Fundamentals of Pharmacology

For health science students

Compiled by

Doctor Asad Ali Arif

Doctor of Pharmacy, M. Phil Pharmaceutical Chemistry

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 Fundamentals of Pharmacology

Preface
Pharmacology is a medical science that forms a backbone of the
medical profession as drugs form the corner stone of therapy in
human diseases. This book on pharmacology is primarily for health
science students such as pharmacy technician (B-Category), health
officer, nursing, midwifery and laboratory technology students.
However, other health professionals whose career involves drug
therapy or related aspects should also find much of the material
relevant.
I hope that this material will be a valuable companion of a
fundamental understanding in a most fascinating area of clinical
knowledge, pharmacology.

Asad Ali Arif

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 Fundamentals of Pharmacology

Dedication

All that I have done is only due to protection and ability endowed to
me by Allah Almighty.
I am thankful to and fortunate enough to get constant encouragement,
support and guidance from my parents and family who helped me in
successfully compiling this handbook.
I heartily thank Sir Mahmood Sadiq who created an opportunity for
students to get standard education at their doorstep and for teachers to
teach professional skills and knowledge in a creative environment

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 Fundamentals of Pharmacology

DIRECTOR’S MESSAGE
I take the pleasure in welcoming you to the family of Muslim group of
colleges.
The Muslim group of colleges has a remarkable history of twenty five years to
serve the fertile land of Punjab. Our endeavors have been acknowledged at
regional and national level as well. By the grace of Allah, we have been given
with presidential awards for consecutive three times.
Our mission is committed to providing an innovative, academic, cultural, and
pragmatic excellence by empowering our future leaders in a holistic
environment. In recent times, paramedical health sciences has fueled desire to
upgrade modern health care system. By keeping this view in mind, we have
stepped forward to set about a pogramme of paramedical health sciences in
different districts of Punjab. In this regard, we have successfully inaugurated
quality campuses in Hafizabad, cheniot, Sangla hill, Gujrat, Mandi bahudin and
Sargodha. And so far, we are looking forward to extend our project in other
districts of Punjab. We have qualified and expert professional faculty to carry
out educational activities. I congratulate you for being the part of this wonderful
group. May you see dreams and fulfill them with everlasting blessing of Allah.
Ameen.

Mahmood sadiq dhooter

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 Fundamentals of Pharmacology

Contents
Chapter Names Page number

Chapter 1 Introduction to pharmacology 06

Chapter 2 Posology 19

Chapter 3 Autonomic nervous system 25

Chapter 4 Central nervous system drugs 42

Chapter 5 Cardiovascular system drugs 53

Chapter 6 Gastrointestinal drugs 65

Chapter 7 Respiratory drugs (system) 72

Chapter 8 Gento urinary system drugs 77

Chapter 9 Introduction to chemotherapy drugs 81

Chapter 10 Drugs used as anesthetics 88

Chapter 11 Autacoids and their antagonist 91

Chapter 12 Toxicology 94

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Chapter :1

INTRODUCTION/ BASIC CONCEPTS OF

PHARMACOLOGY
Definition of Pharmacology
Pharmacology is the study of the interactions between the living system and various
substances (drugs). Living system means, either the whole living being or part of the living
being (e.g. isolated tissues of animals).
INTERACTIONS
Interactions are of two types. These are—
1. What the body does to the drug, i.e. Pharmacokinetics, which includes—
a. Absorption
b. Distribution
c. Biotransformation
d. Excretion
2. What the drug does to the body, i.e. Pharmacodynamics
Major components of pharmacodynamic study are—
a. Effects of the drug
b. The mechanism of drug action
c. Quantitative interrelationship between drug dose and drug effect.
So the two important branches of pharmacology are—
1. Pharmacokinetics
2. Pharmacodynamics
Other branches of pharmacology are—
1. Experimental pharmacology is the study of drugs in animals other than human
being.
2. Clinical pharmacology is the scientific study of drugs in cases of human being.
Pharmacy is the study of preparation and dispensing of drug.
3. Toxicology deals with poison and poisoning.
4. Pharmacognosy deals with the botanical sources of drugs.
5. Therapeutics is the practical application of drugs in the treatment and prevention of
diseases.
Chemotherapy
6. is the subdivision of pharmacology, dealing with drugs that can destroy
invading organisms without destroying the host. It also includes drug treatment of
neoplastic diseases.

Routes of Drug Administration

The route of drug administration is defined as a path by which a drug, fluid, poison, or other
substance is taken into body
It is determined primarily by
 The properties of drug (water or lipid solubility, ionization etc)
 The therapeutics objectives (the desirability of a rapid onset of action or the need for
long term administration)

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There are three major routes of drug administration

1. Enteral (oral, sublingual and rectal)

2. Parenteral (IV, IM, SC etc.)
3. Others (inhalation, intranasal, topical etc.)
Enteral
Enteral administration is entry of drug through alimentary canal. Enteral route includes

a. Oral
b. Sublingual
c. Rectal

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Oral route
Giving drug by mouth is called oral route

Note
In oral administration delivery of drug into circulation is slow, so that rapid, high blood
concentration are avoided and adverse effects are less

Sublingual
Placement of drug under the tongue is called sublingual, it allows a drug to diffuse into the
capillary network and, therefore, to enter the systemic circulation directly for example
glyceryl trinitrate in angina. Irritation of oral mucosa, and excessive salivation are main
disadvantages of this route

Rectal administration
This pathway uses the rectum as a route of administration for medication and other fluids,
which are absorbed by the rectum's blood vessels, and flow into the body's circulatory
system. Glycerin (laxative) suppositories for insertion into the rectum.

Parenteral
 Parenteral administration means any non-oral means of administration. This route is
well known for following uses
 for drugs that are not absorbed well from the GIT (heparin)
 For drugs that are unstable in the GIT (insulin).
 Parenteral administration is also used for treatment of unconscious patients and
under situations that require a rapid onset of action.
There are three major routes of parenteral administration

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Examples
 Intravenous (IV) (directly into a vein)
 Intramuscular (IM) (into, a muscle)
 Intra dermal (ID) (applied within the layers of the skin for example small pox
vaccine)
 Subcutaneous (SC) ( into subcutis )
 Intra peritoneal (IP) ( through the peritoneum. The peritoneum is a thin,
transparent membrane that lines the walls of the abdominal (peritoneal) cavity
 Intra arterial (IA) (entry by way of an artery)
 Intra cardiac (IC) (into the heart muscles or ventricles)
 Intra thecal (IT) ( into the spinal canal, or into the subarachnoid space so that it
reaches the cerebrospinal fluid )
 Intra articular or joint (IJ) (direct into joints)
 Intra bone marrow (IBM) ( into bone marrow cells)

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Other Routes Of Drug Administration

 Inhalation
Drugs administered by inhalation through the mouth must be atomized into smaller
droplets so that the drugs can pass through the windpipe (trachea) and into the lungs. ...
Inside the lungs, they are absorbed into the bloodstream.

 Intranasal
A route by which drugs are insufflated through the nose.
 Topical
A route in which there is application to body surfaces such as the skin or mucous
membranes to treat ailments via a large range of classes including creams, foams, gels,
lotions, and ointments

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Pharmacokinetics

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Drug Absorption
is generally defined as the rate and extent to which the drug moves from its site of
administration to its intended target (site) of action. The chemical composition of a drug, as
well as the environment into which a drug is placed, work together to determine the rate
and extent of drug absorption.

The rate and efficiency of absorption depend on the route of administration. For IV
delivery, absorption is complete, that is the total dose of drug reaches the system
circulation. The need for absorption is bypassed entirely. For drug absorption to occur, a
drug must cross biologic barriers (e.g. epithelial/endothelial cells, etc.). Only a few drugs
move across cellular barriers in an “active” way; that is, a way that requires energy (ATP)
(Active diffusion) and moves the drug from an area of low concentration to an area of
higher concentration. On the other hand, most drugs cross cellular barriers via passive
diffusion; that is, drugs simply move from an area of higher concentration to an area of
lower concentration by diffusing through cell membranes. This type of drug movement
does not require any energy expenditure.
Drugs that are un-ionized will be better able to diffuse through a lipid cellular membrane,
cross a biologic barrier, and enter the bloodstream (e.g. be absorbed) compared to drugs
that are ionized. Thus, a key take-home point is: a drug that is a weak acid will be best
absorbed in an acidic environment (because it gains a proton and becomes un-ionized) and
basic drugs.

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Sites of Absorption
About 80% of drugs are taken orally, therefore, GIT is the main site of drug absorption, in
addition drug can be introduced into the systemic circulation through intramuscular or
subcutaneous site skin and respiratory tract.
Pinocytosis
This type of drug delivery transports drugs of exceptionally large size across the cell
membrane. Specific receptors for transport drugs must be present for this process to work.it
includes two main processes
1. Endocytosis involves engulfment of a drug molecule by the cell membrane and
transport into the cell by pinching off the drug filled vesicle. For example transport of
vitamin B 12 across the gut wall.
2. Exocytosis is the reverse of endocytosis and is used by cells to secrete many
substances by a similar vesicle formation process.
Drug Distribution
It involves the movement of drug molecules from circulatory fluid to the other areas of the
body and gets entry to interstium fluid (extracellular fluid). It includes the sites of action,
sequestration and elimination. Drug distribution is the process by which a drug reversibly
leaves the bloodstream, and enters the interstitium () and/ or the cell of the tissues.
Distribution of drugs begins when it enters blood (i.e. absorbed) and is completed when the
drug has reached all the possible sites where it can go. For example, Thiopental sodium after
IV administration reaches the RAS system of the brain (site of action), exists in a higher
concentration than plasma in adipose tissue (site of sequestration) and attains in kidneys
(site of elimination) for removal from the body.
Factors modifying drug distribution
1. Blood Flow
The rate of blood flow to the tissue capillaries varies widely as a result of the unequal
distribution of cardiac output to the various organs. Blood flow to the brain, liver, and
kidney is greater than that to the skeletal muscles; adipose tissue has a still lower rate of
blood flow. More drugs are delivered to greater blood flow areas. The almost immediate
anesthetic effect (unconsciousness) of Thiopental sodium is due to its rapid uptake by the
brain. Recovery of consciousness then occurs within minutes, because adipose tissue and
muscle continue to absorb the drug, the concentration of drug in brain decreases.
2. Capillary Permeability
 It varies widely in various tissues
 In brain capillary endothelial cells are continuous and have no slit junction, so that
only lipid soluble (unionized) drug can cross.
 In liver and spleen a large part of basement membrane is exposed by large
discontinuous capillary through which large plasma protein can pass.

3. Binding Of Drug to Plasma Protein

Drug molecules may bind to plasma protein (usually albumin). Most drugs while in the blood
remains bound with plasma proteins and other substances. Bound drugs are
pharmacologically inactive, only the free, unbound drug can act on target site in the tissues.
Bound drug stays in vascular space and is not metabolized or eliminated.

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Apparent Volume of Distribution

The volume of distribution (VD, also known as apparent volume of distribution) is the
theoretical volume that would be necessary to contain the total amount of an administered
drug at the same concentration that it is observed in the blood plasma.
A drug rarely associates exclusively with only one of the water compartments of the body.
Instead, the vast majority of drugs distribute into several compartments, often avidly
binding cellular compartments. For example, lipids (abundant in adipocytes and cell
membranes), protein (abundant in plasma and within cells), or nucleic acids (abundant in
the nuclei of cells). Therefore, the volume into which drugs distribute is called the apparent
volume of distribution.

VD = Dose administered / Plasma Concentration of drug

Drug Metabolism
Drugs are mostly eliminated by biotransformation and/or excretion into the urine or bile.
The process of metabolism transforms lipophilic drugs into more polar readily excretable
products.
ORGANS INVOLVED
1. Major: Liver
2. Intermediate: Lungs, kidney and intestinal mucosa
3. Minor: Leukocyte, spleen, eye, brain and gonads.

Reaction of Drug Metabolism

The kidney cannot efficiently eliminate lipophilic drugs that readily cross cell membrane and
are reabsorbed in the distal tubules. Therefore lipid soluble agents must first be
metabolized in the liver using two general sets of reaction, called Phase I and Phase II.
The microsomal enzymes play a pivotal role in biotransformation. The microsomal enzymes
of the liver, which are part of the smooth endoplasmic reticulum, convert many lipid-soluble
drugs and foreign compounds into more water-soluble metabolites. These enzymes are
located in the lipophilic membranes of endoplasmic reticulum of the liver and other tissues.

Phase I
Phase-I reaction function to convert lipophilic molecules into more polar molecules
by the exposing a polar functional group. Mainly it is oxidation, but sometimes there
is reduction or hydrolysis.
a) Oxidation: Microsomal oxidation involves the introduction of an oxygen and/or
the removal of a hydrogen atom or hydroxylation of drug molecule e.g. conversion of
salicylic acid into gentisic acid.
b) Reduction: The reduction reaction will take place by the enzyme reductase which
catalyze the reduction of azo (-N=N-) and nitro (-NO2) compounds e.g. prontosil
converted to sulfonamide.
c) Hydrolysis: Drug metabolism by hydrolysis is restricted to esters and amines (by
esterases and amidases) are found in plasma and other tissues like liver. It means
splitting of drug molecule after adding water e.g. pethidine undergoes hydrolysis to
form pethidinic acid. Other drugs which undergo hydrolysis are atropine and
acetylcholine

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Phase II
This phase consists of conjugation reactions. If the metabolites from Phase I metabolism is
sufficiently polar, it can be excreted by the kidneys, However, many Phase I metabolites are
too lipophilic to be retained in the kidneys tubules. A subsequent conjugation reaction with
an endogenous substrate such as sulfuric acid, acetic acid, or amino acid result in polar and
more water soluble compounds, that excreted by the kidney. The reactions are—
mentioned in following lines
Glucuronide conjugation: It is the most common and most important conjugation reaction
of drugs. Drugs which contain
a) Hydroxyl, amino or carboxyl group undergo this process e.g.
phenobarbitone.
b) c) Sulfate conjugation: Sulfotransferase present in liver, intestinal mucosa
and kidney, which transfers sulfate group to the drug molecules e.g. phenols,
catechols,
c) Acetyl conjugation: The enzyme acetyl transferase, which is responsible for
acetylation, is present in the kupffer cells of liver. Acetic acid is conjugated to
drugs via its activation by CoA to form acetyl CoA. This acetyl group is then
transferred to-NH2 group of drug e.g. dapsone, isoniazid.
d) Glycine conjugation: Glycine conjugation is characteristic for certain
aromatic acids e.g. salicylic acid, isonicotinic acid, p-amino salicylic acid.
These drugs are also metabolized by other path ways.
e) Methylation: Adrenaline is methylated to metanephrine by catechol-o-
methyl transferase etc.

Drug Elimination
The process whereby a drug is removed from the body after producing its effects with or
without the process of metabolism. Most of the drugs are eliminated from the body after
metabolism but some drugs do not follow the process, e.g. Digoxin, Ephedrine, Proctalol and
Inhalation anesthetics.
ORDERS OF KINETICS
During the movement of drug molecules from one site to another or its metabolic change, it
may follow:
i. First order kinetics
ii. ii. Zero order kinetics.
First order kinetics (Exponential clearing)—A constant fraction of drug is eliminated per unit
time.
Zero order (Linear clearing)—A constant quantity of drug is eliminated per unit time
PROCESS OF ELIMINATION
Drugs are eliminated by two ways—
a. Metabolism b. Excretion
Metabolism and excretion taken together constitute elimination. Three processes are
involved in renal excretion of drugs as:
a. Passive glomerular filtration—directly proportional to the excretion. Only the drug which
is not bound with the plasma proteins can pass through glomerulus. All the drugs which
have low molecular weight can pass through glomerulus e.g. digoxin, ethambutol, etc.

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b. Active tubular secretion—inversely proportional to excretion.The cells of the proximal

convoluted tubule actively transport drugs from the plasma into the lumen of the tubule
e.g. acetazolamide, benzyl penicillin, dopamine
c. Passive tubular reabsorption—directly proportional to excretion. The reabsorption of
drug from the lumen of the distal convoluted tubules into plasma occurs either by simple
diffusion or by active transport. When the urine is acidic, the degree of ionization of basic
drug increase and their reabsorption decreases. Conversely, when the urine is more
alkaline, the degree of ionization of acidic drug increases and the reabsorption decreases

Routes of Elimination

Kidney
Most drugs, particularly water-soluble drugs and their metabolites, are eliminated largely by
the kidneys in urine. Therefore, drug dosing depends largely on kidney function.

Liver
It can secrete drugs or their metabolites into bile that are lost in feces. However, some drug
may be reabsorbed in intestine to again enter the circulation.in this way the action of drugs
prolong.

GIT
Some drugs are excrete through GIT
Thiocynates, iodides and mercury in saliva
Morphine through passive diffusion in stomach

Lungs
Gaseous and volatile general anesthetic is excreted in expired air.

Others Routes
 Sweat (alcohol, heavy metals ,salicylic acid, benzoic acid).excretion through skin may
lead to urticaria and dermatitis
 Breast milk: alcohol is excreted only to a limited extent in breast milk. in addition,
metformin is sometimes detectable in low levels in the serum of breastfed infants.
 Salivary secretion: Compounds excreted in saliva are caffeine, theophylline,
phenytoin etc. Bitter taste felt in mouth is indication of salivary excretion.
 Tears : excretion through this route is quantitatively not so important

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Pharmacodynamics
Most drugs exert their effects, both beneficial and harmful, by interacting with receptors
that are, specialized target macromolecules present on the cell surface or intracellulraly.
Receptors bind drugs and initiate events leading to alterations in biochemical and / or
biophysical activity of a cell and consequently, the function of an organ. Drugs may interact
with receptors in many different ways. Drugs may bind to enzymes, nucleic acids or
membrane receptors.

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Major Receptors Families

Receptors are part of the cells that can interact with a drug or endogenous material so that
a series of chemical events occur leading to the biological effect of the drug. Thus, enzymes
and structural protein can be considered to be pharmacological receptors.

1. Ligand-Gated Ion Channels Receptors

These are responsible for regulation of the flow of ion across cell membrane. The activity of
these channels is regulated by the binding of a ligand to the channel. Normally they remain
closed but when the ligand gets attached with the acetylcholine receptors (AChR) the
channel opens up. Now, Na+ ions from extracellular fluid (ECF) enter the muscle cells
through the channel, this ultimately results in development of action potential (AP).
Nicotinic receptor (Nn, Nm) and Gamma aminobutyric acid (GABA) receptors are important
examples of ligand-gated receptors.

2. G-Protein Coupled Receptors

A second family of receptors consists of G protein-coupled receptors. These receptors
contain a single peptide; these receptors are linked to a G protein having three subunits,
alpha, beta, and gamma subunit. Binding of the appropriate ligand to the extra-cellular
region of the receptor activates the G protein.

3. Enzyme Linked Receptors

A third major family of receptors consists of those having cytosolic enzyme activity as an
integral component of their structure or function. Binding of a ligand activates or inhibits
this cytosolic enzyme activity.

4. Intracellular Receptors
The fourth family of receptors is called intra cellular receptors. These receptors are either in
the cytoplasm or in the nucleolus gives response by increasing the gene transcription.

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Chapter :2

Posology

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Posology
The word posolgy is derived from Greek, posos - how much and logos –science. So we can
say it is branch of pharmacology which deals with dosage of drugs

Drug
A medicine or other substance which has a physiological effect when ingested or otherwise
introduced into the body.

Pro-Drug
It refers to compounds that, on administration, must undergo chemical conversion by
metabolic processes before becoming an active pharmacological agent. (Levodopa into
dopamine)

Placebo
It refers to an inactive substance or preparation given to satisfy the patients symbolic need
(psyche need) for drug therapy, and used in controlled studies to determine the efficiency of
medicinal substance.
Dose
Amount of drug taken each time by an individual or a quantity to be administrated at one
time. (20mg, 10mg, 2drops etc)
Dosage
The amount of a drug given to an individual per unit body weight or the determination and
regulation of the size, frequency and number of doses.
Dosage Types

Therapeutic Dose
Average dose for an adult to produce a therapeutic effect is called therapeutic dose.

a. Loading Dose
Loading dose: The loading dose is one or a series of doses that may be given at the onset of
therapy with the aim of achieving the target concentration rapidly.
Maintenance dose: To maintain target concentration, the rate of drug administration is
adjusted such that the rate of input equals to rate of loss. It is such a dose used to maintain
the therapeutic effect or concentration in blood plasma is called maintenance dose.

b. Maximal Tolerated Dose

Largest dose of a drug that can be taken safely.

c. Toxic Dose
Amount of drug, which produces undesirable harmful effect of serious nature, is called toxic
dose.

d. Fatal Dose
A dose that produces death is called fatal dose.

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Dose Calculation
Adult dose is for a person between the age of 18-60years. Children are given small dose.
Children dose may be calculated as a fraction of adult dose.

Young’s Formula
Young’s formula is used to calculate doses for children (2-17years old) based on the adult
dose.

Child’s Dose=

Clark’s Formula
Clark’s formula is used to calculate doses especially for infants (birth to 1year old) by using
weight of infant in pounds (lbs).

Infant Dose=

Dose Response relationship

The exact relationship between the dose and the response depends on the biological object
under observation and the drug employed. When a logarithm of dose as abscissa and
responses as ordinate are constructed graphically, the “S” shaped or sigmoid type curve is
obtained.
The lowest concentration of a drug that elicits a response is minimal dose, and the largest
concentration after which further increase in concentration will not change the response is
the maximal dose
1. Graded dose effect: As the dose administered to a single subject or tissue increases, the
pharmacological response also increases in graded fashion up to ceiling effect.
- It is used for characterization of the action of drugs. The concentration that is required to
produce 50 % of the maximum effect is termed as EC50 or ED502.
2. Quantal dose effect: It is all or none response, the sensitive objects give response to small
doses of a drug while some will be resistant and need very large doses. The quantal dose
effect curve is often characterized by stating the median effective dose and the median
lethal dose.
Median lethal dose or LD50: This is the dose (mg/kg), which would be expected to kill one
half of a population of the same species and strain.
Median effective dose or ED50: This is the dose (mg/kg), which produces a desired
response in 50 per cent of test population.
Therapeutic index: It is an approximate assessment of the safety of the drug. It is the ratio
of the median lethal dose and the median effective dose. Also called as therapeutic window
or safety.
Therapeutic index (T. I) = LD50 /ED50
The larger the therapeutic index, the safer is the drug. Penicillin has a very high therapeutic
index, while it is much smaller for the digitalis preparation.

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Half life:
Half life (t1/2) of a drug is the time taken for the concentration of drug in the blood or
plasma to decline to half of original value or the amount of drug in the body to be reduced
by 50%. It has two phases i.e half-life of distribution and half-life of elimination.
A half-life value can be readily determined for most drugs by administering a dose of the
drug to a subject, taking blood samples at various time intervals and then assaying the
samples., For example if a blood level of drug A is 8.6 mg/ml at 10 minutes and 4.3 mg/ml at
60 minutes, so the half – life of that drug is 50 minutes.

Factors Modifying The Action And Dosage Of Drug

Many factors influence the dosage and action of drug. If the drug is too small, the drug will
not produce the desired action. If it is too large it will produce toxic effects, which are not
desirable.
Following are important factors, which influence the action and dosage of drug.

 Age
 Body weight
 Sex
 Routes of administration
 Time of administration
 Dosage form
 Absorption, Distribution and excretion of drug
 Pathological condition
 Tolerance
 Combination of drugs (synergism, antagonism)
Age
Adult dose is for a person between the ages of 18-60years. Children are given small dose.
We use young’s formula and Clark’s formula to calculate dose for children and infant. Above
60years of age the dose should be decreased 3/4th of adult dose. The pharmacokinetics of
many drugs changes with age. Thus gastric emptying is prolonged and the gastric pH
fluctuates in neonates and infant, further the liver capacity to metabolize drugs is low, renal
function is less developed and the proportion of body water is higher in the newborn and
the neonates. Hence children may not react to all drugs in the same fashion as young adults.
With a few exceptions, drugs are more active and more toxic in the new born than the
adults. Elderly are sensitive to the drugs like hypnotics, tranquilizers, phenylbutazone,
diazepam, pethidine etc. doses in children and infants are calculated using clark’s and
young’s formula

Body Weight
For abnormal body weight the dose of the drug should be suitably adjusted according to the
weight of the patient. The average dose is mentioned either in terms of mg per kg body
weight or as the total single dose for an adult weighing between 50-100kg.

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Sex
Doses for the women should be less than man because women are usually having more
effect than men. Pregnancy, menstruation and lactation periods should keep in mind while
adjusting dosage. Drugs producing pelvic congestion should be avoided during
menstruation e.g. drastic purgatives. Drugs which may stimulate the uterine smooth
muscle, are contraindicated during pregnancy like tetracyclines, phenytoin, Warfarin,
lithium. They may produce direct or indirect teratogenic effect. Most of the lipid soluble
drugs get into breast milk. Therefore the drugs, which are excreted in the milk and harm the
infant health should be, avoided by breast-feeding mothers e.g. sulphonamides,
tetracyclines, aspirin, etc.

Routes Of Administration
When drug is given intravenously onset of action is rapid orally given drug have slow onset
action. Oral dose of drug always greater than when it is given parenterally and dose for
subcutaneous or intramuscular injection is greater than intravenous.

Time of Administration
Presence of food in stomach delays the absorption of drug onset action is slow some drugs
can cause irritant, nausea and vomiting while given in empty stomach. Hypnotics are more
effective when given at bedtime.

Dosage Form of Drug (Preparation)

Onset action is rapid when the drug is given in liquid or as a powder as compared to drug
given inform of a tablet of pill.

Absorption, Distribution And Excretion Of Drug

Drugs, which are rapidly absorbed and excreted quickly, cannot maintain effective
concentration for therapeutic effect. Drugs, which are quickly absorbed but excreted slowly,
may produce toxic effect.

Pathological Condition
When liver or kidneys are not functioning properly the dose should be decreased to avoid
toxic effects.
Tolerance
It is unusual resistance to ordinary dose of the drug-increased dose is often required to
obtain desired therapeutic effects.
Tachyphylaxis:
Rapid development of tolerance on repeated administration is called tachyphylaxis

Combination of Drugs
When two or more than two drugs are given together action may be increased or
decreased.
Drug synergism
When the therapeutic effect of two drugs are greater than the effect of individual drugs, it
is said to be drug synergism.
It is of two types.

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Additive effect:
When the total pharmacological action of two or more drugs administered together is
equivalent to the summation of their individual pharmacological actions is called additive
effect.
i.e A + B = AB
e.g. Combination of ephedrine and aminophyllin in the treatment of bronchial asthma.
Potentiation effect
When the net effect of two drugs used together is greater than the sum of individual
effects, the drugs are said to have potentiation effect. i.e AB > A + B
e.g. Trimethoprim+sulfamethoxazole

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Chapter: 3

Nervous system

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Autonomic Nervous System (ANS)

ANS along with the endocrine system coordinates the regulation and integration of bodily
function. ANS is concerned with regulation of visceral function. So it is otherwise called
involuntary nervous system.

Neuron
Neuron is defined as the basic structural and functional unit of the nervous system.
Neuron is like any other cell in the body having nucleus and all the organelles in the
cytoplasm.

However it is different from other cells by two ways:

1. Neuron has branches or processes called axon and dendrites.
2. Neuron does not have centrosome, so it cannot undergo division.
Classification Of Nerve Cells
On the basis of functions the nerve cells are classified into two types
1. Motor Neuron (Efferent)
2. Sensory Neuron (Afferent)
Motor Neuron (Efferent)
Neurons, which carry the motor impulses from central nervous system to the peripheral
effectors organ like muscles, gland, and blood vessels. Motor neurons are also known as
efferent nerve cells; generally these neurons have long axons and short dendrites.
Sensory Neuron (Afferent)
These neurons carry the sensory impulses from periphery to the CNS generally these have
short axons and long dendrites.
Receptor
Pharmacology defines a receptor as any biological molecule to which a drug binds and
produces a measurable response. Thus, enzymes and structural protein can be considered
to be pharmacological receptors.

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Neurotransmitters
Neurotransmitter is a chemical substance that acts as the mediator for the transmission of
nerve impulse from one neuron to another neuron through a synapse.
Communication between nerve cells and between nerve cells and effector organs occurs
through the release of specific chemical signals called neurotransmitters.
Local Mediators
Most cells in the body secrete chemicals that act locally. These chemical signals are rapidly
destroyed or removed; therefore, they do not enter the blood and are not distributed
throughout the body etc Histamine.

Hormones
Specialized endocrine cells secrete hormones into the bloodstream where they travel
throughout the body exerting effects on broadly distributed target cells in the body.

Anatomy of ANS
Efferent Neurons
Efferent neurons carry nerve impulse from CNS to the effector organs by way of two types
of efferent neurons.
The first nerve cell is called preganglionic neuron, its cell body is located within the CNS, and
it emerges from brainstem or spinal cord, and makes a synaptic connection in ganglia. These
ganglia function as relay station between preganglionic neuron and a second nerve cell
called postganglionic neuron. Cell body of second neuron is originates from ganglion and
terminates on effector organs such as smooth muscles of the viscera, cardiac muscle and
the exocrine glands.

Afferent Neurons
Afferent neurons of ANS bring nerve impulse back to CNS from periphery
Sympathetic Neurons
The efferent ANS is divided into the sympathetic and parasympathetic nervous system, as
well as the enteric NS.
Anatomically they originate in the CNS and emerge from two different spinal cord regions.
The preganglionic neurons of the sympathetic system come from thoracic and lumber
regions of the spinal cord. Preganglionic neurons are short in comparison to the
postganglionic neurons. Axons of the postganglionic neurons extend from ganglia to the
tissues that they innervate and regulate.
Parasympathetic Neurons
The parasympathetic preganglionic fibers arise from cranium (cranial nerve 3, 7, 9 and 10)
and from sacral region of the spinal cord and synapse in ganglia near or on the effector
organs. In contrast to the sympathetic system the preganglionic fibers are long and
postganglionic ones are short, with the ganglia close to or within the organ innervated.
Enteric Neurons
The enteric nervous system (ENS) is the third division of the autonomic NS. It is a collection
of nerve fibers that innervate the gastrointestinal tract (GIT), pancreas and gallbladder. This
system functions independently of the CNS and controls the motility, exocrine and
endocrine secretions and microcirculation of GIT.

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Action of
Sympathetic and Parasympathetic Nervous System on Effecter Organs

Organ Sympathetic Action Parasympathetic Action

Contraction of iris sphincter
Contraction of iris redial
muscle (Pupil contracts)
muscle (Pupil dilate)
Eye Contraction of ciliary muscle
Relaxation of ciliary
(lens accommodates for near
muscles
vision)
Increase rate Decrease rate
Heart
Increase contractility Decreased contractility
Blood Vessels (skeletal
Dilate …
muscle)
Blood Vessels (skin, mucous
Constriction …
membrane)
Rennin secretion (β1
Kidney …
increase, α1 decrease)
Constrict
Trachea & Bronchioles Dilate
Increase secretions
Contraction of sphincters
Increased muscle motility and
Gastrointestinal Decrease in muscle motility
tone
and tone
Genitalia (male) Stimulation ejaculation Stimulates erection
Genitalia (female) Relaxation of uterus …
Salivary Gland Thick, viscous secretion Large watery secretion

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Epinephrine & Nor-

Adrenal Medulla …
epinephrine secreted
Lacrimal Gland … Stimulates tears

Prototype Drug Definition

A first or preliminary form of drug from which other forms of drugs are developed or copied
is called prototype drug.

Drugs affecting the autonomic nervous system are divided into two groups according to the
type of neuron involved in their mechanism of action.

 Cholinergic Drugs Or Parasympathetic Drugs

 Adrenergic Drugs Or Sympathetic Drugs

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Now we will discuss cholinergic drug/parasympathetic drugs, these drugs are classified
into…

 Colinergic agonist or parasympathetomimetic

 Colinergic antagonist or parasympathetolytic

Cholinergic Agonists
Cholinergic drugs are also called parasympathomimetics because their effect mimics the
effect of parasympathetic nerve stimulation. Administration of these drugs will result in an
increase in the parasympathetic activities in the systems innervated by cholinergic nerves.
There are two groups of cholinergic drugs:
1. Direct-acting: bind to and activate muscarinic or nicotinic receptors (mostly both) and
include the following subgroups: a. Esters of choline: methacholine, carbachol, betanechol
b. Cholinergic alkaloids: pilocarpine, muscarine, arecoline, nicotine
2. Indirect-acting: inhibit the action of acetylcholinesterase enzyme
a. Reversible: neostigmine, physostigmine, edrophonium
b. Irreversible: Organophosphate compounds; echothiophate
The actions of acetylcholine may be divided into two main groups:
1. Nicotinic actions- those produced by stimulation of all autonomic ganglia and the
neuromuscular junction
2. Muscarinic actions- those produced at postganglionic cholinergic nerve endings

Acetylcholine (Direct Acting)

ESTERS OF CHOLINE
ACETYLCHOLINE
It is the prototypical cholinergic agent. It functions as neurotransmitter at all cholinergic
sites in the body; because of its unique pharmacokinetic properties, it has never been used
in medical therapeutics; the discussion which follows is for academic exercise. Acetylcholine
has both muscarinic and nicotinic activities.
Pharmacokinetics
Acetylcholine is poorly absorbed from the gastric mucosa; therefore it is ineffective if given
orally. The recommended way of administration is parenteral. In the blood it is rapidly
hydrolyzed by the enzyme cholinesterase into acetic acid and choline; this makes its
duration of action very short and unreliable for therapeutic purposes.
Pharmacodynamics
As mentioned earlier it has two types of actions: nicotinic and muscarinic;
the muscarinic actions are of main interest and are discussed below.
i. Cardiovascular system
Heart-- slow heart rate
Blood vessels-- vasodilator
Blood pressure-- falls because of the effect on the heart and blood revels
ii. Gastrointestinal tract: It stimulates the tone and motility of the Gl tract but the
sphincters will be relaxed
iii. Urinary tract: It stimulates the detrusor muscle and relaxes the internal urethral
sphincter resulting in evacuation of bladder
iv. Bronchioles: It increase bronchial secretion and brings about bronchoconstriction
v. Eye- It has two effects- miosis and accommodation for near objects because of
stimulation of the constrictor pupillae and ciliary muscles respectively.

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vi. Exocrine glands- it stimulates salivary, gastric, bronchial, lachrymal and sweat gland
secretions.
SYNTHETIC CHOLINE ESTERS
These are synthetic derivatives of choline and include metacholine, carbachol and
betanechol. These drugs have the following advantages over acetylcholine:
 They have longer duration of action,
 They are effective orally as well as parenterally
 They are relatively more selective in their actions.
CARBACHOL
Pharmacokinetics
It is completely absorbed from the gastro intestinal tract and is stable towards hydrolysis by
cholinesterase enzyme; therefore it can be given both orally and parenteraly with almost
similar dosage.
Pharmacodynamics
It has similar actions to those of acetylcholine with pronounced effects on the gastro
intestinal tract and the urinary bladder
Indications
 Glaucoma
 Retention of urine (postoperative)

BETANECHOL
This drug is similar to carbachol in all parameters, i.e., pharmacokinetics,
pharmacodynamics and clinical indications; it has a better advantage over carbachol
because it has fewer side effects as a result as lack of nicotinic actions.

CHOLINERGIC ALKALOIDS
1. Those with chiefly nicotinic actions include nicotine, lobeline etc. 2. Those with chiefly
muscarinic actions include muscarine, pilocarpine, etc.
PILOCARPINE
Pharmacokinetics
This drug is readily absorbed from the gastrointestinal tract and it is not hydrolyzed by
cholinesterase enzyme. It is excreted partly destroyed and partly unchanged in the urine.
Pharmacodynamics
The drug directly stimulates the muscarinic receptors to bring about all the muscarinic
effects of acetylcholine.
Indications
• Glaucoma
Adverse Effects of Cholinergic Drugs
Diarrhea, Miosis, Nausea, Urinary urgency, Bradycardia, Bronchoconstriction, AV block,
Flushing, Salivation

ANTICHOLINESTERASE DRUGS
The commonly used cholinesterase inhibitors fall into three chemical groups: 1. Simple
alcohols bearing quaternary amines, e.g., edrophonium 2. Carbamate and related
quaternary or tertiary amines, e.g., neostigmine, physostigmine 3. Organic derivatives of
phosphates, e.g., isofluorophate, echothiophate

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PHYSOSTIGMINE (Indirect Acting, Reversible)

Pharmacokinetics
This drug is completely absorbed from the gastrointestinal and is highly distributed
throughout the body; it can pass the blood brain barrier.
Pharmacodynamics
Inhibits the enzyme cholinesterase; therefore, it increases and prolongs the effect of
endogenous acetylcholine at the different sites.It has no direct effect on cholinergic
receptors.
Indications
 Glaucoma
 Atropine over dosage
Adverse Effects Of Physostigmine
When high doses are used fall in cardiac output may occur. The cause of death in
physostigmine poisoning is respiratory failure.

NEOSTIGMINE
Pharmacokinetics
This drug is poorly absorbed from the gastro intestinal tract and is poorly distributed
throughout the body; it cannot pass the blood brain barrier.
Pharmacodynamics
Just like physostigmine, it inhibits cholinesterase enzyme; but unlike physostigmine, it has a
direct nicotinic action on skeletal muscles.
Indications
 Myasthenia gravis
 Paralytic Ileus
 Reversal of effect of muscle relaxants, e.g. tubocurarine
 Post operative urine retention
Organophosphates
such as echothiophate, isofluorophate, etc. combine with cholinesterase irreversibly and
thus hydrolysis is very slow.
They may be used in glaucoma. Other organophosphates like parathion and malathion are
used as insecticides.

Echothiophate (Indirect Acting, irreversible)

A number of synthetic organophosphate compounds (organo-phosphorus compound) have
the capacity to bind covalently to acetylcholinesterase. This result is a long lasting increase
in acetylcholine at all sites where it is released.

Mechanism Of Action
Echothiophate is an organophosphate that covalently binds with acetylcholinesterase. After
binding this enzyme permanently inactivated. Restoration of acetylcholinesterase activity
requires the synthesis of new enzyme molecules.

Action Of Echothiophate
As acetylcholine released, it does not destroyed due to inactivation of acetylcholinesterase.
Acetylcholine gets accumulated in the body to exert both muscarinic and nicotinic actions.
Due to muscarinic action there will be miosis, salivation, sweating, bradycardia vasodilation

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and fall in blood pressure. Due to nicotinic actions there are muscle twitching in the whole
body. Due to central effect there is restlessness confusion.

Therapeutic Uses
An ophthalmic solution of the drug is used directly in the eye for the chronic treatment of
open angle glaucoma.

Cholinergic Antagonists
(Parasympatholytic Drugs)
Anticholinergics block the effects of acetylcholine and other cholinergic drugs at cholinergic
receptors of effector cells.
Anticholinergics fall into two major families:
1. Antinicotinics which include ganglion blockers such as hexamethonium,
trimethaphan, etc., and neuromuscular blockers such as gallamine, tubocurarine,
pancuronium, Succinylchoine ,Mecamylamine etc.
2. Antimuscarinics include tertiary amines such as atropine, scopolamine, tropicamide,
etc, andquaternary amines such as propantheline, ipratropium, benztropine, etc.
ATROPINE
Atropine is found in the plant Atropa belladonna and it is the prototype of muscarinic
antagonists.
Pharmacokinetics
Atropine is absorbed completely from all sites of administration except from the skin wall,
where absorption is for limited extent; it has good distribution. About 60% of the drug is
excreted unchanged in urine.
Pharmacodynamics
Atropine antagonizes the effect of acetylcholine by competing for the muscarinic receptors
peripherally and in the CNS; therefore the effects of atropine are opposite to the
acetylcholine effects.
Organ system Effects:
CNS: -lower doses produce sedation
-higher doses produce excitation, agitation and hallucination
Eyes:
- relaxation of constrictor pupillae (mydriasis)
- relaxation or weakening of ciliary muscle (cycloplegia-loss of the ability to
accommodate)
CVS: - blocks vagal parasympathetic stimulation (tachycardia)
- vasoconstriction
Respiratory: - bronchodilatation and reduction of secretion
GIT: - decreased motility and secretions
GUS: - Relaxes smooth muscle of ureter and bladder wall; voiding is slowed.
Sweat Glands: - suppresses sweating
Clinical Indications
 Pre anesthetic medication -to reduce the amount of secretion and to prevent
excessive vagal tone due to anesthesia.
 As antispasmodic in cases of intestinal, biliary, and renal colic Heart block
 Hyperhidrosis
 Organophosphate poisonings

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Side effects
 Dryness of the mouth,
 tachycardia and blurred vision
 Retention of urine
Contraindication
 Glaucoma
 Bladder outlet obstruction.
Adverse Effects
Depending on the dose atropine may cause dry mouth, blurred vision, constipation, increase
in temperature, effect on the CNS include restlessness, confusion.

HYOSCINE (SCOPOLAMINE)
This drug has the same effect as atropine except for some differences which includes:- - It
has shorter duration of action - It is more depressant to the CNS. - All other properties are
similar to atropine.
It has certain advantage over atropine.
These include:
 Better for preanesthetic medication because of strong antisecretory and antiemetic
action and also brings about amnesia
 Can be used for short- travel motion sickness

Mecamylamine (Ganglionic Blockers)

Ganglionic blockers specifically act on the nicotinic receptors of both parasympathetic and
sympathetic autonomic ganglia. These drugs block the entire output of the ANS at the
nicotinic receptor. Ganglionic blockers rarely used therapeutically. However they often
serve as tools in experimental pharmacology.

Mechanism of Action
Mecamylamine produces a competitive nicotinic blockade of the ganglia.

Pharmacokinetics
The duration of action is about 10 hours after a single administration. It has good oral
absorption.

Therapeutic Actions
It is primarily used to lower blood pressure in emergency situations.

Neuromuscular Blockers
These drugs blocks acetylcholine at neuromuscular junctions. These neuromuscular blockers
are structural analogs of acetylcholine. These drugs are clinically useful during surgery for
producing complete muscle relaxation.

Tubocurarine (Non-Depolarizing (Competitive) Blockers)

Mechanism Of Action
Non-depolarizing neuromuscular blocking drugs interact with the nicotinic receptors to
prevent the binding of acetylcholine. These drugs thus prevent depolarizing of the muscles

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and inhibit muscular contraction. Because these agents compete with acetylcholine at the
receptor that’s why also called competitive blockers.

Therapeutic Uses
These blockers are used therapeutically as adjuvant drugs in anesthesia during surgery to
relax skeletal muscle. These agents are also used to facilitate intubations as well as during
orthopedic surgery.

Pharmacokinetics
All neuromuscular blocking agents are injected intravenously. They penetrate membrane
very poorly and do not enter cells or cross the blood brain barrier, many drugs are not
metabolized. They excreted in urine unchanged.

Succinylcholine (Depolarizing Agents)

Mechanism Of Action
The depolarizing neuromuscular blocking drug succinylcholine attaches to the nicotinic
receptor and act like acetylcholine. This drug remains attached to the receptor for longer
time and providing a constant stimulation of the receptor.

Action
Succinylcholine initially produces short lasting twitching of the muscle (fasciculation)
followed within a few minutes by paralysis. The drug does not produce a ganglionic block
except at high doses.

Therapeutic Uses
Because of its rapid onset and short duration of action, succinylcholine is useful when rapid
endotracheal intubation is required during the anesthesia. For example if aspiration of
gastric contents is to be avoided during intubations.

Pharmacokinetics
Succinylcholine is injected intravenously its duration of action is short therefore usually
given by continuous infusion.

Adverse Effects
Hyperthermia, Hyperkalemia

Adrenergic Agonists
(Sympathomimetics)
ADRENERGIC DRUGS
As their name suggests, these drugs resemble sympathetic nerve stimulation in their effects;
they may be divided into two groups on the basics of their chemical structure.
1. Catecholamines: -these are compounds which have the catechol nucleus.
Catecholamines have a direct action on sympathetic effectors cells through interactions
with receptor sites on the cell membrane. The group includes adrenaline, noradrenaline,
dopamine, isoprenaline, and dobutamine.
2. Noncatecholmines: - lack the catechol nucleus.

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They may directly act on the receptors or may indirectly release the physiologic
catecholaminese.g. ephedrine, phenylephrine, amphetamine

Adrenergic drugs, like cholinergic drugs, can be grouped by mode of action and by the
spectrum of receptors that they affect.
a) Direct mode of action: directly interact with and activate adrenoreceptors, e.g.,
adrenaline and noradrenaline
b) Indirect mode of action: their actions are dependent on the release of endogenous
catecholamines. This may be i. Displacement of stored catecholamies from the
adrenergic nerve endings, e.g., amphetamine, tyramine
c) Inhibition of reuptake of catecholamines already released, e.g. cocaine, tricyclic
antidepressants
Organ-system Effects of Activation of the Adrenergic System
1. CVS:
a) Heart: increased rate and force of contraction, increased cardiac output,
myocardial demand, and AV conduction
b) Blood Vessels and Blood pressure: constriction of blood vessels in the
skin and mucous membranes
c) Dilatation of skeletal muscle vessels - Adrenaline increases systolic and
decreases diastolic blood pressure at low doses but increases both at
higher doses - Noradrenaline increases both systolic and diastolic blood
pressure
2. Smooth Muscle:
a) Bronchi: relaxation.
b) Uterus: relaxation of the pregnant uterus
c) GIT: relaxation of wall muscles and contraction of sphincters
d) Bladder: relaxation of detrusor muscle; contraction of sphincter and trigone muscle
3. Eye:
a) mydriasis;
b) reduction of intraocular pressure in normal and glacucomatous eyes
4. Respiration:
a) Bronchodilatation; relief of congestion; mild stimulation of
respiration
5. Metabolic: Increased hepatic glycogenolysis; decreased peripheral glucose
intake; increased free fatty acids in the blood (lipolysis)
6. CNS: excitement, vomting, restlessness
7. Skeletal muscle: facilitation of neuromuscular transmission and vasodilatation

The adrenergic drugs affect receptors that are stimulated by norepinephrine or epinephrine.
Some adrenergic drugs act directly on the adrenergic receptors (adrenoceptor) by activating
it and said to be sympathomimetics.

ADRENALINE
This is the prototype of adrenergic drugs and is produced in the body by the cells of the
Adrenal medulla and by chromaffin tissues.

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Pharmacokinetics
Adrenaline is rapidly destroyed in the gastrointestinal tract, conjugated, and oxidized in the
liver. It is therefore ineffective when given orally and should be given intramuscularly or
subcutaneous. Intravenous injection is highly dangerous and is likely to precipitate
ventricular fibrillation. The drug may however, be given by nebulizer for inhalation when its
relaxing effect on the bronchi is desired or it may be applied topically to mucus membranes
to produce vasoconstriction. Because of the extensive metabolism of the drug in liver, little
is excreted unchanged in the urine.
Pharmacodynamics
Adrenaline directly stimulates all the adrenergic receptors both and brings about effects of
sympathetic nerve stimulation. Its action may be divided in to two, depending on the type of
receptor stimulated.
The α effects consist of vasoconstriction in skin and viscera, mydriasis, platelet aggregation
and some increase in blood glucose. The ß effects consists of increased contractility and rate
of heart with a decreased refractory period (ß1), vasodilatation in muscles and coronary
vessels (ß2), bronchial relaxation (ß2) uterine relaxation (ß2), hyperglycemia, lactic acidemia
and increased circulating free fatty acids.
Indications
1. Acute bronchial asthma
2. Anaphylaxis
3. Local haemostatic to stop bleeding in epistaxis
4. With local anesthesia to prolong the action
5. Cardiac arrest
Adverse reactions
1. Anxiety, restlessness, headache tremor
2. Anginal pain
3. Cardiac arrhythmias and palpitations
4. Sharp rise in blood pressure 5. Sever vasoconstriction resulting in gangrene of extremities
6. Tearing, conjunctival hyperemia

NOR ADRENALINE
Nor adrenaline is the neurochemical mediator released by nerve impulses and various drugs
from the postganglionic adrenergic nerves. It also constitutes 20% of the adrenal medulla
catecholamine out put.
Pharmacokinetics
Like adrenaline, noradrenaline is ineffective orally so it has to be given intravenously with
caution. It is not given subcutaneous or intramuscularly because of its strong
vasoconstrictor effect producing necrosis and sloughing. The metabolism is similar to
adrenaline; only a little is excreted unchanged in urine.
Pharmacodynamics
Nor adrenaline is a predominantly α receptor agonist with relatively less β agonist action
when compared to adrenaline.
Indication
Nor adrenalines is used as hypertensive agent in hypotensive states
E.g. During spinal anesthesia or after sympathectomy.
Adverse effects include:
Anxiety, headache, bradycardia are common side effects - Severe Hypertension in sensitive
individuals - Extravasation of the drug causes necrosis and sloughing.

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ISOPRENALINE DOPAMINE, DOBUTAMINE

These are the other catecholamines which have similar properties to adrenaline and
noradrenaline.
Dopamine is naturally occurring and is a precursor of noradrenaline. The other two-
isoprenaline and dobutamine- are synthetic. These drugs have advantage over the others
because they are more selective in their action so that they have fewer side effects than
adrenaline and nor adrenaline. Dopamine and dobutamine are very useful drugs for the
treatment of shock.
NON- CATECHOLAMINES
Most of the non- catecholamines function by releasing the physiologic catecholamines from
the postganglionic nerve endings
EPHEDRINE
Pharmacokinetics
Ephedrine in absorbed from the gastrointestinal tract and from all parenteral sites. It has a
good distribution through out the body and is resistant to hydrolysis by the liver enzymes.
Major proportion of the drug is excreted unchanged in the urine. Because of its stability to
metabolism it has long duration of action than the catecholamines.
Pharmacodynamics
Ephedrine stimulates both α and β receptors. This effect is partly by a direct action on the
receptors and partly indirectly by releasing noradrenaline from its tissue stores the effect of
the drug to various organs and systems is similar to that of adrenaline. It is also a mild CNS
stimulant.
Indications:
1. Bronchial asthma: - usually as a prophylactic for prevention of attacks
2. Nasal decongestion
3. Mydriasis
4. Heart block
5. Nocturnal enuresis
Side effects
The side effects are similar to those of adrenaline; but in addition it may produce insomnia
and retention of urine.
Contraindications
They are the same as Adrenaline.

Amphetamine (Indirect Acting)

Amphetamine is a non-catecholaminergic sympathetic amine that shows quite similar
effects as cocaine.

Mechanism of Action
Amphetamine shows their effect on CNS and peripheral nervous system by releasing intra
cellular stores of catecholamine. Amphetamine also inhibits monoamine oxidase (MAO)
that’s why high levels of catecholamine are readily released into synaptic spaces and
response increased.
Therapeutic Uses
Attention deficit hyperactivity disorder (ADHD)
Some young children re lack the ability to be involved in any one activity for longer than few
minutes. The drug prolongs the patient’s span of attention.

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Narcolepsy
Narcolepsy is a rare sleep disorder. Patient is usually treated with drugs such as
amphetamine.

Pharmacokinetics
Amphetamine is completely absorbed from the GIT, metabolized by the liver and excreted in
the urine.

Adverse Effects
Insomnia, irritability, weakness, dizziness, and tremor.
Amphetamine causes cardiac arrhythmias, hypertension, angina pain, headache, excessive
sweating, nausea, and diarrhea.

Adrenergic Antagonists
(Sympatholytic Agents/Drugs)
A large number of drugs inhibit the activity of the sympathetic nervous system. These drugs
are called adrenergic antagonists or sympatholytics.
These adrenergic blocking drugs may be classified into groups based on their site of action.
Adrenrgic receptor blockers may be considered in two groups:
1. Drugs blocking the ą adrenergic receptor
2. Drugs blocking theβ Adrenergic receptor
These drugs prevent the response of effectors organs to adrenaline, noradrenaline and
other sympathomimetic amines whether released in the body or injected. Circulating
catecholamines are antagonized more readily than are the effects of sympathetic nerve
stimulation. The drugs act by competing with the catechoamines for α or β receptors on the
effectors organs. They don’t alter the production or release of the substances.
α- Adrenergic blockers
Alpha adrenergic receptor antagonists may be reversible or irreversible.
 Reversible antagonists dissociate from the receptors e.g. phentolamine, tolazoline,
prazosin,yohimbine, etc.
 Irreversible antagonists tightly bind to the receptor so that their effects may persist
long after the drug has been cleared from the plasma e.g. phenoxybenzamine
 Drugs Affecting Neurotransmitter Uptake Or Release e.g. Reserpine

Pharmacologic Effects:
Alpha receptor antagonist drugs lower peripheral vascular resistance and blood pressure.
Hence, postural hypotension and reflex tachycardia are common during the use of these
drugs. Other minor effects include miosis, nasal stuffiness, etc.
Prazosin
This is an effective drug for the management of hypertension. It has high affinity for alpha1
receptor and relatively low affinity for the alpha2 receptor. Prazosin leads to relaxation of
both arterial and venous smooth muscles due to the blockage of alpha1 receptors. Thus, it
lowers blood pressure, reduces venous return and cardiac output. It also reduces the tone
of internal sphincter of urinary bladder.
Indications:
- Essential hypertension
- Raynaud’s syndrome

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-Benign prostatic hyperplasia

Adverse effect
α 1 blockers may cause dizziness, lack of energy, nasal congestion, headache, orthostatic,
hypotension.
β - ADRENERGIC BLOCKING DRUGS
The β - adrenergic receptor blocking drugs in use may be classified by their selectivity for
receptors in different tissues.
1. Drugs blocking all the β receptor effects of adrenaline (non-selective beta blockers) e.g.
propanalol, pinadolol, timolol etc
2. Drugs blocking mainly the β1 effects (those on the heart) with less effect on the bronchi
and blood vessels (beta1-selective blockers), e.g. atenolol, practalol acebutalol, etc.
PROPRANOLOL
Propranolol is a non- selective β adrenergic blocker; it has also other actions like membrane
stabilization.
Pharmacokinetics
Propranolol is almost completely absorbed following oral administration. However, the liver,
leaving only 1/3 rd of the dose to reach the systemic circulations, metabolizes most of the
administered dose. It is bound to plasma to the extent of 90-95%. It is excreted in the urine.
Pharmacodynamics
The drug has the following main actions.
1. Cardiovascular system
• Bradycardia • Reduces force of contraction • Reduces blood pressure
2. Respiratory system
Bronchoconstriction
3. Metabolic system
Hypoglycemia
4. Central nervous system
Anti-anxiety action
5. Eye
Decrease the rate of Aqueous humor production
6. Kidneys:
Decrease renin secretion
Indications
• Cardiac arrhythmias • Hypertension • Prophylaxis against angina • Myocardial
infarction • Thyrotoxicosis • Anxiety states (suppression of the physical manifestations
of situational anxiety) • Prophylaxis against migraine attacks • Glaucoma

Adverse reactions
• GI disturbances like nausea, vomiting • Heart failure • Heart block • Hypotension and
severe bradycardia • Bronchospasm • Allergic reaction • Vivid dreams night mare and
hallucinations • Cold hands • Withdrawal symptoms in case of abrupt discontinuation •
Masking of hypoglycemia in diabetic patients and sexual impairment
Contraindications and Precautions:
• Bronchial asthma • Diabetes mellitus • Heart failure • Peripheral vascular disease

Reserpine (Drugs Affecting Neurotransmitter Release Or Uptake)

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 Autonomic Nervous System (ANS) UNIT-III

Mechanism Of Action
Reserpine blocks the Mg2+ ATP-dependent transport of biogenic amine, norepinephrine,
dopamine and serotonin from the cytoplasm into storage vesicles in the adrenergic nerves
of all body tissues.

Therapeutic Uses
Reserpine is used in the treatment of hypertension mild to moderate. Reserpine causes a
slowly developing falling blood pressure.

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 Central Nervous System (CNS) UNIT-IV

Chapter: 4

Central nervous system

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 Central Nervous System (CNS) UNIT-IV

Central Nervous System (CNS)

The central nervous system (CNS) is the part of the nervous system consisting of the brain
and spinal cord. The CNS is so named because it integrates the received information and
coordinates and influences the activity of all parts of the bodies
Drugs Affecting The CNS
Drugs acting on CNS may be CNS depressants or CNS stimulants. Depressants are more
important pharmacologically and therapeutically than stimulants. Most drugs that affect the
CNS act by altering some step in the neurotransmission process.
Drugs affecting the CNS may act presynaptically by influencing the production, storage,
release or termination of action of neurotransmitters. Other agents may activate or block
postsynaptic receptors.

However, we will discuss prototype drugs used in different CNS related diseases.

1. Neurodegenerative Diseases
2. Anxiolytic And Hypnotic Drugs
3. CNS Stimulants
4. Antidepressant
5. Neuroleptics Drugs
6. Antiepileptic Drugs

Neurodegenerative Diseases
Parkinsonism:
Parkinsonism is characterized by a combination of rigidity, bradykinesia, tremor, and
postural instability. It is due to the imbalance between the cholinergic and dopaminergic
influences on the basal ganglia. Thus, the aim of the treatment is either to increase
dopaminergic activity (by dopamine agonist) or to decrease cholinegic (antimuscarinic
drugs) influence on the basal ganglia.
Levodopa
Levodopa, the immediate metabolic precursor of dopamine, does penetrate the blood brain
barrier, where it is decarboxylated to dopamine. Levodopa is rapidly absorbed from the
small intestine. Food will delay the appearance of levodopa in the plasma. Levodopa should
be taken on an empty stomach. Levodopa has an extremely short half-life (1 to 2 hours).
It is extensively metabolized by peripheral dopa decarboxylase, hence given in combination
with carbidopa, a peripheral dopa decarboxylase inhibitor.
When levodopa is given without carbidopa it causes vomiting (which is due to stimulation of
emetic center to dopamine) and CVS disorder (tachycardia, ventricular extrasystoles, atrial
fibrillation)
Adverse Effects
Trachycardia, Nausea, vomiting, hypotension, brownish color of saliva and urine.
Abnormal involuntary movements, mood change, depression
Dopamine agonists
The enzymes responsible for synthesizing dopamine are depleted in the brains of
Parkinsonism patients, and drugs acting directly on dopamine receptors may therefore have

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 Central Nervous System (CNS) UNIT-IV

a beneficial effect additional to that of levodopa. There are a number of dopamine agonists
with antiparkinsonism activity.
e.g: Bromocryptine
Monoamine Oxidase Inhibitors: Selegiline (deprenyl), a selective inhibitor of monoamine
oxidase B, hinders the breakdown of dopamine; as a result, it prolongs the antiparkinsonism
effect of levodopa. Selegiline has only a minor therapeutic effect on parkinsonism when
given alone. It may reduce disease progression.
Amantadine
Amantadine, an antiviral agent, was by chance found to have antiparkinsonism properties.
Its mode of action in parkinsonism is unclear, but it may potentiate dopaminergic function
by influencing the synthesis, release, or reuptake of dopamine.

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 Central Nervous System (CNS) UNIT-IV

Anxiolytic And Hypnotic Drugs

Anxiolytic drugs are used to treat the symptoms of anxiety, where as hypnotic drugs used to
treat insomnia. The same drugs are used for both purposes.
Classes of anxiolytic and hypnotic drugs:
The main groups of the drugs are:
1. Benzodiazepines. Benzodiazepines are the most important group, used as sedative and
hypnotic agents.
2. 5- HT1A receptor agonist (e.g. buspirone). It is recently introduced anxiolytic.
3. Barbiturates (phenobarbitone). They are nowadays less commonly used as
sedativehypnotics.
4. β -adrenoceptor antagonists (e.g. propranolol). They are used to treat some forms of
anxiety, where physical symptoms (sweating, tremor, and tachycardia), are troublesome.
They are not used as hypnotics.
Benzodiazepines
Benzodiazepines are well absorbed when given orally. They bind strongly to plasma
proteins, however, many of them accumulate gradually in the body fat (i.e. they are highly
lipid soluble). Benzodiazepines are inactivated by the liver and excreted in the urine.
Classification
Based on their duration of action roughly divided into
1. short acting (flurazepam, triazolam),
2. medium acting (alprazepam, lorazepam)
3. and long acting compounds (diazepam, chlordiazepoxide, clonazepam).
Pharmacodynamics
Act by binding to a specific regulatory site on the GABAA receptor, thus enhancing the
inhibitory effects of GABA.
Central nervous system effects of benzodiazepines include:
1. Reduction of anxiety and aggression.
2. Sedation and induction of sleep.
3. Reduction of muscle tone and coordination.
4. Anticonvulsant effects.
Clinical Uses • Treatment insomnia • Anxiety • Preoperative mediations • Acute alcohol
withdrawal • As anticonvulsants • Chronic muscle spasm and spasticity
Unwanted effects • Toxic effects due to acute overdosage causes prolonged sleep. •
Unwanted effects occurring during normal therapeutic use includes: drowsiness, confusion,
amnesia, and impaired motor coordination.
• Tolerance and dependance: i.e. stopping benzodiazepines treatment after weeks or
months causes an increase in symptoms of anxiety.
5 - HT1A receptor agonist
Buspirone is a potent agonist of. 5 - HT1A receptors. Anxiolytic effects take days to weeks to
develop. Buspirone does not cause sedation, motor incoordiation and withdrawal effects.
The main side effects are nausea, dizziness, headache, and restlessness.
Barbiturates
They are non-selective CNS depressants, which produce effects ranging from sedation and
reduction of anxiety, to unconsciousness and death from respiratory and cardiovascular
failure.
They are potent inducers of hepatic drug metabolizing enzymes, hence likely to cause drug
interaction. Tolerance and dependance occur, more than benzodiazepines

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 Central Nervous System (CNS) UNIT-IV

Classification of barbiturates
Ultra short acting
- acts within seconds and duration of action 30 min
- thiopental ,methohexital sodium
short acting
- acts within minutes and duration of action 2 hrs
- phenobarbitone
- hexobabritone
intermediate acting
- effects last 3-5 hrs
- butabarbitone
- amobarbitone
long acting
- effects last for 6 hrs
- phenobarbitone
- mephobarbitone
Mechanism Of Action-
Barbiturates act by enhancing action of GABA, but less specific than benzodiazepines.

Actions
Depression of CNS
At low doses, the barbiturates produce sedation (Have a calming effect and reduce
excitement). At higher doses, the drugs cause hypnosis, followed by anesthesia (loss of
feeling or sensation), and, finally, coma and death. Thus, any degree of depression of the
CNS is possible, depending on the dose.

Respiratory Depression
Barbiturates suppress the hypoxic and chemoreceptor response to CO 2 and overdosage is
followed by respiratory depression and death.

Therapeutic Uses

Anesthesia
Selection of a barbiturate is strongly influenced by the desired duration of action. The ultra
short-acting barbiturates, such as thiopental, are used intravenously to induce anesthesia.

Anticonvulsant
Barbiturates are used in long-term management of seizures, status epilepticus, and
eclampsia.

Anxiety
Barbiturates have been used as mild sedatives to relieve anxiety, nervous tension, and
insomnia.
Adverse Effects
Drowsiness, impaired concentration, and mental and physical sluggishness tremors, anxiety,
weakness, restlessness, nausea and vomiting, death can occur due to overdoses for many
decades.

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Central Nervous System (CNS) UNIT-IV

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 Central Nervous System (CNS) UNIT-IV

CNS Stimulants

Large number of drugs may stimulate different parts of brain and

in large doses they may stimulate all parts of brain. CNS Available Brands in the
stimulants have diverse clinical uses and are important as drugs Market
of abuse. Coramin-G Cap. (Nicotine)

Following prototype drugs are used as CNS stimulants.

Psychomotor Stimulants
 Cocaine
 Nicotine

Hallucinogens
Lysergic Acid Diethylamide (LSD)

Cocaine (Psychomotor Stimulants)

Cocaine is a widely available and highly addictive drug that is currently abused daily by more
than 3million people.

Mechanism Of Action
Cocaine inhibits the reuptake of monoamines (nor epinephrine, serotonin and dopamine).
The inhibition of reuptake of monoamine by the cocaine potentiates and prolongs the CNS
and peripheral action of these monoamines.

Actions
The behavioral effects of cocaine result from powerful stimulation of cortex and brainstem.
It also causes tremors and convulsions.

Hyperthermia
Hyperthermia can also cause by cocaine.

Therapeutics Uses
Cocaine has a local anesthetic action. Cocaine is applied topically as a local anesthetic during
eye, ear, nose and throat surgery. Cocaine is the only local anesthetic that causes
vasoconstriction.

Pharmacokinetics
Cocaine is often self-administered by chewing, intranasal, smoking or intravenous onset of
action is most rapid.

Adverse Effects
Anxiety, depression, seizures, cardiac aarrhythmias.

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 Central Nervous System (CNS) UNIT-IV

Nicotine (Psychomotor Stimulants)

Nicotine is the active ingredient in tobacco. It is most widely used CNS stimulant.

Mechanism Of Action
In low doses, nicotine causes ganglionic stimulation by depolarization. At high doses,
nicotine causes ganglionic blockade.

Action

CNS
Nicotine is highly lipid soluble and readily cross the blood brain barrier. It improves
attention, learning, problem solving and reaction time.

Peripheral Effects
The peripheral effects of nicotine are complex. It increases blood pressure and heart rate.
Use of tobacco is harmful in hypertensive patients.

Pharmacokinetics
Because nicotine is highly lipid soluble absorption readily occur via oral mucosa, lungs, GIT
and skin. Clearance of nicotine involves metabolism in the lung and the liver and urinary
excretion.

Adverse Effects
High blood pressure trachycardia, diarrhea, tremors

Hallucinogens (Lysergic Acid Diethylamide, LSD)

Mechanism Of Actions
Multiple sites in the CNS are affected by lysergic acid diethylamide (LSD). The drug shows
serotonin agonist activity at presynaptic receptor in the midbrain.

Pharmacological Effects
Activation of the sympathetic nervous system causes pupillary dilation, increased blood
pressure and increased body temperature.

Adverse Effects
Adverse effects include hyper-reflexia, nausea and muscular weakness.

Antidepressants
Depression is a serious disorder and its symptoms are intense feeling of sadness,
hopelessness and inability to experience pleasure in usual activities.

Types of antidepressant drugs

1. Tricyclic antidepressants (TCAs) (amitryptaline,imipiramine)
2. Monoamine oxidase inhibitors (MAOI)(selegiline,phenelzine)
3. 5-HT uptake inhibitors (nefazodone)
4. Atypical antidepressants (Mirtazapine,amoxapine,bupropion)
5. Selective Serotonin Re-uptake Inhibitors(Fluoxetine, paroxetine, sertraline)

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 Central Nervous System (CNS) UNIT-IV

6.Serotonin/norepinephrine Re-uptake Inhibitors(Duloxetine)

Pharmacokinetics
Tricyclic antidepressants are well absorbed upon oral administration because of their
lipophilic nature. They are widely distributed in body. These drugs have variable half-lives
from 4 to 17 hours metabolism occurs in liver and excreted from urine.
Fluoxetine (Selective Serotonin Reuptake Inhibitors (SSRIs)) is well absorbed. The MAO
inhibitors are readily absorbed from the gastrointestinal tract and excreted rapidly in the
urine. Metabolites of serotonin / norepinehrine re uptake inhibitor are excreted in the
urine. Food delays the absorption of the drug. The half-life is 12 hours.

Mechanisms of action
TCAs block the uptake of amines (noradrenaline and 5-HT) by nerve terminals by
competition for the carrier transport system. In addition, TCAs block α1- adrenoceptors,
muscarinic, histamine (H1) and 5-HT receptors.
Monoamine oxidase inhibitors (MAOI): Tranylcypromine selectively inhibits MAO-A. MAOI
causes a rapid and sustained increase in the 5-HT, noradrenaline and dopamine.
Selective 5-HT uptake inhibitors: fluoxetine, fluvoxamine lack antimuscarinic and
cardiovascular effects. The SSRI block the reuptake of serotonin, leading to increased
concentration of the neurotransmitter in the synaptic cleft and increased postsynaptic
neuronal activity. Atypical antidepressant drugs have no common mechanisms of action,
some are monoamine uptake blockers, but others act by unknown mechanisms.
Clinical Indications:
The major indication of TCAs are endogenous depression, panic attacks, Phobic and
obsessional states (clomipramine) and bed-wetting in children. MAOIs are used in severe
depression refractory to other treatment and phobias.

Adverse Effects:
Postural hypotension, dry mouth, blurred vision, constipation, urine retention, sedation,
are the most important side effects of TCAs. MAOI cause postural hypotension, atropine-like
effects, weight gain, and CNS stimulation causing restlessness, tremor, and insomnia.

Neuroleptics Drugs OR Antipsychotic Drugs

Neuroleptics drugs are used primarily to treat schizophrenia. They are also used in other
psychotic states such as manic states. Psychotic illness is characterized by delusion,
hallucinations, thought disorder, social withdrawal and flattering of emotional response.
Antipsychotics are a group of drugs used mainly for treating schizophrenia

Schizophrenia
Schizophrenia is caused by increased dopamine activity in mesolimbic pathway and
mesocortical pathway. During schizophrenia, glutamic acid activity in mid brain is decreased
and now there is a new emergence of role of serotonin in the development of
schizophrenia.

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 Central Nervous System (CNS) UNIT-IV

Classification
1. Typical Neuroleptics (Low Potency)
Chlorpromazine
thioridazine

2. Typical Neuroleptics (High Potency)

Haloperidol
flupenthixol

3. Atypical Neuroleptics
Clozapine
sulpiride

Pharmacokinitics
Most antipsychotic drugs are readily but incompletely absorbed. Many of these drugs
undergo significant first-pass metabolism. Very little of any of these drugs is excreted
unchanged, as they are almost completely metabolized to more polar substances.

Mechanism of Action
Dopamine Receptor Blocking In the Brain
All of the older and new Neuroleptics drugs block dopamine receptor in the brain and the
periphery. The Neuroleptics drugs bind to these receptors to varying degrees.
Serotonin Receptor Blocking Activity in The Brain
Some of these drugs also inhibit serotonin receptors.

Clinical uses
Schizophrenia • Mania • Vomiting

Adverse Reactions
Extrapyramidal reactions • Seizures • Autonomic nervous system effects (antimuscarinic
effects, orthostatic hypotension) • Metabolic and Endocrine Effects (weight gain,
hyperprolactinemia, infertility, loss of libido and impotence)

Antiepileptic Drugs
Epilepsy
In epilepsy there is a sudden excessive and rapid discharge in grey matter of the brain.
Epilepsy is not a single entity it is collection of different seizure types and syndromes
originating from several mechanisms. This abnormal electrical activity may result in variety
of events including loss of consciousness, abnormal movements, and odd behavior.
Seizures have been classified into two groups.

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 Central Nervous System (CNS) UNIT-IV

1. Partial or focal seizures

2. Generalized seizures(grand mal and petit mal)

Mechanism of action
Anticonvulsant drugs act by two mechanisms
 by reducing electrical excitability of cell membrane
 by enhancing GABA mediated synaptic transmission.
The main drugs used in the treatment of epilepsy are
phenytoin, carbamazepine, valproate, ethosuximide, phenobarbitone and gaba analogs
Phenytoin
It is commonly used antiepileptic drug. It is effective against different forms of partial and
generalized seizures; however it is not effective in absence seizures.
Well absorbed when given orally. It is metabolised by the liver. It is liver enzyme inducer and
therefore, increases the rate of metabolism of other drugs. Phenytoin block voltage-gated
sodium channels. At very high concentration, Phenytoin can block voltage-dependent
calcium channel.
Main side effects are sedation, confusion, gum hyperplasia, skin rash, anaemia, nystagmus,
and diplopia.
Carbamazepine
It is derived from tricyclic antidepressant. Its pharmacological action resembles those of
phenytoin, however, it is chiefly effective in the treatment of partial seizure. It is also used in
the treatment of trigeminal neuralgia and manic-depressive illness.
It is powerful inducer of liver microsomal enzymes, thus accelerates the metabolism of
phenytoin, warfarin, oral contraceptives and corticosteroids.
Carbamazepine causes sedation, mental disturbances and water retention.
Valproate
Valproate is chemically unrelated to the other antiepileptic drugs. The mechanism of action
is unknown. It is used in grand mal, partial, petit mal and myoclonic seizure.
Relatively has few side effects, however, it is potentially hepatotoxic. It is non sedating.
Ethosuximide
Has fewer side effects and used in the treatment of absence seizures.
Phenobarbitone
It is well absorbed after oral administration and widely distributed. Renal excretion is
enhanced by acidification of the urine. Phenobarbitone is liver enzyme inducer and hence
accelerates the metabolism of many drugs like oral contraceptives and warfarin.
The clinical use of phenobarbitone is nearly the same as that of phenytoin. The most
important unwanted effect is sedation.
Benzodiazepines:
Clonazepam and related compounds, clobazam are claimed to be relatively selective as
antiepileptic drugs. Sedation is the main side effect of these compounds, and an added
problem may be the withdrawal syndrome, which results in an exacerbation of seizures if
the drug is stopped.
Gabapentin (GABA Analogues)
Gabapentin is an analog of GABA. However it does not act at GABA receptors nor enhance
GABA actions, nor it converted into GABA. It precise mechanism of action is not known.
Gabapentin does not bind to plasma protein and is excreted unchanged through kidneys.

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 Cardiovascular System (CVS) UNIT-V

Chapter: 5

Cardiovascular system

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 Cardiovascular System (CVS) UNIT-V

Cardiovascular System (CVS

Major Diseases Related To Cardiovascular System

1. Heart Failure
2. Arrhythmias
3. Angina
4. Hypertension

Heart Failure
Congestive heart failure occurs when there is an inability of the heart to maintain a cardiac
out put sufficient to meet the requirements of the metabolising tissues.
Heart failure is usually caused by one of the following:
Ischaemic heart disease,
Hypertension,
Heart muscle disorders, and
Valvular heart disease.
Drugs used to treat heart failure can be broadly divided into:
A. Drugs with positive inotropic effect.
B. Drugs without positive inotropic effect.
A. Drugs with positive inotropic effect:-
Drugs with positive inotropic effect increase the force of contraction of the heart muscle.
These include:
• Cardiac glycosides,
• Bipyridine derivatives,
• Sympathomimetics, and
• Methylxanthines
Cardiac glycosides
Cardiac glycosides comprise a group of steroid compounds that can increase cardiac out put
and alter the electrical functions. Commonly used cardiac glycosides are digoxin and
digitoxin.
The mechanism of inotropic action of cardiac glycosides is inhibition of the membrane-
bound Na+/K+ ATPase often called the “Sodium Pump”. This results in an increased
intracellular movement of sodium and accumulation of sodium in the cells. As a
consequence of the higher intracellular sodium, decreased transmembrane exchange of
sodium and calcium will take place leading to an increase in the intracellular calcium that
acts on contractile proteins.
All cardiac glycosides exhibit similar pharmacodynamic properties but do differ in their
pharmacokinetic properties. For example, digitoxin is more lipid soluble and has long half-
life than digoxin.
Therapeutic uses
• Congestive heart failure • Atrial fibrillation, • Atrial flutter, and • Paroxysmal atrial
tachycardia.
Toxicity of cardiac glycosides include:
 Gastrointestinal effects such as anorexia, nausea, vomiting, diarrhoea
 Cardiac effects such as bradycardia, heart block, arrhythmias

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 Cardiovascular System (CVS) UNIT-V

 CNS effects such as headache, malaise, hallucinations, delirium, visual disturbances

(yellow vision)
Mild toxicities such as gastrointestinal and visual disturbance can be managed by reducing
the dose of the drug.
2. Bipyridine derivatives, e.g. amrinone, milrinone.
These drugs possess both positive inotropic effect and vasodilator effects.
The suggested mechanism of action is inhibition of an enzyme known as phophodiesterase,
which is responsible for the inactivation of cyclic AMP. Inhibition of this enzymes result in an
increase in cAMP. Bipyridine derivatives are used in cases of heart failure resistant to
treatment with cardiac glycosides and vasodilators.
3. Beta - adrenergic stimulants e.g. dobutamine, dopamine
The increase in myocardial contractility by beta stimulants increase the cardiac out put.
However, positive chronotropic effect of these agents minimizes the benefit particularly in
patients with ischaemic heart disease. The positive inotropic effect of dobutamine is
proportionally greater than its effect on heart rate. It is reserved for management of acute
failure.
4. Methylxanthines, e.g. theophylline in the form of aminophylline
Aminophylline has a positive inotropic effect, bronchodilating effect and a modest effect on
renal blood flow.
It is used for management of acute left ventricular failure or pulmonary edema.
B. Drugs without positive inotropic effect. These include:
• Diuretics, e.g. hydrochlorothiazide, furosemide
• Vasodilators, e.g. hydralazine, sodium nitroprusside
• Angiotensin converting enzyme inhibitors e.g. captopril, enalapril
Diuretics
Diuretics are first – line drugs for treatment of patients with heart failure. In mild failure, a
thiazide may be sufficient but are ineffective at low glomerular filtration rates. Moderate or
severe failure requires a loop diuretic.
In acute failure, diuretics play important role by reducing ventricular preload. The reduction
in venous pressure causes reduction of edema and its symptoms and reduction of cardiac
size which leads to improved efficiency of pump function.
Vasodilators
The vasodilators are effective in acute heart failure because they provide a reduction in
preload (through venous dilation), or reduction in after-load (through arteriolar dilation), or
both.
Hydralazine
It has a direct vasodilator effect confined to arterial bed. Reduction in systemic vascular
resistance leads to a considerable rise in cardiac out put.
Sodium nitroprusside
It is a mixed venous and arteriolar dilator used also for acute reduction of blood pressure.
relaxation of smooth muscle of blood vessels by direct action..
Pharmacokinetics
Onset of action occurs within 1 minute of intravenous administration.
Adverse Effects
Headache, nausea, vomiting
Vasodilator agents are generally reserved for patients who are intolerant of or who have
contraindications to ACE inhibitors.

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 Cardiovascular System (CVS) UNIT-V

Angiotensin converting enzyme (ACE) inhibitors

Captopril is ACE inhibiters agents that block the ACE activity. As ACE convert angiotensin-I
into angiotensin-II, which is a powerful vasoconstrictor. Captopril and other ACE inhibitors
decrease vascular resistance and blood pressure. These agents also diminish the rate of
bradykinin inactivation, which is a vasodilator.
Pharmacokinetics
ACE inhibitors absorbed in GIT. The presence of food may decrease absorption so they
should be given empty stomach except for Captopril.
Adverse Effect
Dry cough, abdominal pain, skin rash, hypotension, and renal insufficiency. ACE inhibitor
should not be used in pregnant women, because they are fetotoxic.

Antianginal Drugs
Angina pectoris (pain or discomfort in the chest),(pectoris= chest or breast) is on of the
major symptoms of heart disease. It is sudden, severe, pressing chest pain radiating to the
neck, jaw and arms. It is caused by coronary blood flow that is insufficient to meet the
oxygen demand of the myocardium leading to ischemia.

Types Of Angina

Angina occurs in the following forms

1. Stable Angina/ Typical Angina
2. Unstable Angina
3. Variant Angina

Stable Angina
It is the most common form of angina and therefore is called typical angina pectoris. It is
characterized by a burning and heavy feeling in the chest. It is produced by physical activity,
emotional excitement or any other cause of increased cardiac workload. Typical angina
pectoris is promptly relieved by rest or nitroglycerin (a vasodilator).

Unstable Angina
Unstable angina lies between stable angina and myocardial infarction. In unstable angina
chest pains occur with increased frequency. The symptoms are not relieved by rest or
nitroglycerin. Unstable angina requires hospital admission.

Variant Angina
Variant angina is an uncommon pattern of episodic angina that occurs at rest and due to
coronary artery spasm. Symptoms are caused by decreased blood flow to the heart muscles
due to the spasm of coronary artery. Variant angina relieved by coronary vasodilators such
as nitroglycerine and calcium channel blockers.
Drugs used in angina pectoris
1. Organic nitrates e.g. nitro-glycerine, isosorbide dinitrate, etc.
2. Beta adrenergic blocking agents e.g. propranolol, atenolol, etc.
3. Calcium channel blocking agents e.g. verapamil, nifedipine, etc.
4. Miscellaneous drugs e.g. aspirin, heparin, dipyridamole.

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 Cardiovascular System (CVS) UNIT-V

1. Organic nitrates: organic nitrates are potent vasodilators and successfully used in therapy
of angina pectoris for over 100 years.
The effects of nitrates are mediated through the direct relaxant action on smooth muscles.
Nitrates are believed to act by mimicking the vasodilator action of endothelium derived
relaxing factor (EDRF) identified as nitric oxide. Vasodilating organic nitrates are reduced to
organic nitrites, which is then converted to nitric oxide.
The action of nitrates begins after 2-3 minutes when chewed or held under tongue and
action lasts for 2 hours. The onset of action and duration of action differs for different
nitrates and varying pharmaceutical preparations.
Adverse effects include flushing, weakness, dizziness, tachycardia, palpitation, vertigo,
sweating, syncope localized burning with sublingual preparation and contact dermatitis with
ointment.
Therapeutic uses: prophylaxis and treatment of angina pectoris, post myocardial infarction,
coronary insufficiency, acute LVF (left ventricle failure)
2. Adrenergic blocking agents
Exercise and emotional excitement induce angina in susceptible subject by the increase in
heart rate, blood pressure and myocardial contractility through increased sympathetic
activity. Beta receptor blocking agents prevent angina by blocking all these effects. In most
patients the net effect is a beneficial reduction in cardiac workload and myocardial oxygen
consumption e.g. atenolol, propranolol metoprolol, labetolol.
Adverse effects: Lethargy, fatigue, rash, cold hands and feet, nausea, breathlessness,
nightmares and bronchospasm. Selective beta blockers have relatively lesser adverse
effects.
Therapeutic uses other than angina include hypertension, Cardiac arrhythmias.
3. Calcium channel blockers:
calcium is necessary for the excitation contraction coupling in both the cardiac and smooth
muscles. Calcium channel blockers appear to involve their interference with the calcium
entry into the myocardial and vascular smooth muscle, thus decreasing the availability of
the intracellular calcium e.g. nifedipine, felodipine, verapamil and diltiazem.
4. Miscellaneous drugs,e.g. Acetylsalicylic acid
Acetylsalicylic acid (aspirin) at low doses given intermittently decreases the synthesis of
thromboxne A2 without drastically reducing prostacylin synthesis. Thus, at the doses of 75
mg per day it can produce antiplatelet activity and reduce the risk of myocardial infarction
in anginal patients.

Antiarrhythmic Drugs
Anti - arrhythmics
Electrophysiology of cardiac muscle: the pathophysiological mechanisms responsible for
the genesis of cardiac arrhythmias are not clearly understood. However, it is generally
accepted that cardiac arrhythmias arise as the result of either of a) Disorders of impulse
formation and/ or b) Disorders of impulse conduction.
Pharmacotherapy of cardiac arrhythmias
Antiarrhythmic drugs are used to prevent or correct cardiac arrhythmias (tachyarrhythmias).
Drugs used in the treatment of cardiac arrhythmias are traditionally classified into:
Class (I): Sodium channel blockers which include quinidine, lidocaine, phenytion, flecainide,
etc.
Class (II): Beta adrenergic blockers which include propranolol, atenolol, etc.

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Class (III): Potassium channel blockers e.g. amiodarone, bretylium.

Class (IV): Calcium channel blockers e.g. verapamil, etc.
Class (V): Digitalis e.g.digoxin. .

Pharmacological Action
Class – I drugs
Quinidine: Quinidine is an alkaloid and shows many of the action of quinine such as anti
malarial, antipyretic, depression. Quinidine blocks sodium channels. It reduces the maximal
rate of depolarization (phase o) depresses spontaneous phase 4 diastolic depolarization
slow conduction and prolong the effective refractory period of arterial and ventricular so
that there is an increase in threshold for excitability. In general quinine is a cardiac
depressant. It decreases automaticity, excitability and conduction velocity and depressed
contractility.
It is well absorbed orally
Adverse effects: It has low therapeutic ratio. Main adverse effects are SA block, cinchonism,
severe headache, diplopia and photophobia.
Lidocaine, which is used commonly as a local anaesthetic blocks both open and inactivated
sodium channel and decreases automaticity. It is given parenterally.
Adverse effects: excessive dose cause massive cardiac arrest, dizziness, drowsiness, seizures,
etc.
Class –II drugs: Beta-adrenergic receptor blockers
Propranolol: Myocardiac sympathetic beta receptor stimulation increases automaticity,
enhances A.V. conduction velocity and shortens the refractory period. Propranolol can
reverse these effects. Beta blockers may potentiate the negative inotropic action of other
antiarrhythmics.
Therapeutic uses: This is useful in tachyarrhythmias, in pheochromocytoma and in
thyrotoxicosis crisis.
Class – III: Potassium channel blockers
AMIODARONE:
Action
Amiodarone contains iodine and is related structurally to thyroxin. It has complex effect
showing class I, II, III and IV actions.
Its dominant effect is prolongation of the action potential duration and the refractory
period. Amiodarone has anti anginal as well as anti arrhythmic activity.

Therapeutic Uses
Amiodarone is effective in the treatment of severe refractory supra ventricular and
ventricular trachy arrhythmias. Despite its side effect Amiodarone is the most commonly
employed antiarrhythmic.

Pharmacokinetics
Amiodarone is incompletely absorbed after oral administration. The drug is unusual in
having prolonged half-life of several weeks and it distributes extensively in adipose tissue.

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 Cardiovascular System (CVS) UNIT-V

Adverse Effects
Amiodarone shows a variety of toxic effects. Some common side effects are GIT disturbance,
tremor, dizziness, lover toxicity, photosensitivity, muscle weakness, skin discoloration
caused by iodine accumulation in the skin.
Verapamil (Class-IV, Ca2+ Channel Blockers This drug is used in the treatment of refractory
supraventriculat tachyarrhythmias and ventricular tachyarrhythmias. It depresses sinus,
atrial and A.V nodal function.
The main adverse effects of this drug are anorexia, nausea, abdominal pain, tremor,
hallucinations, peripheral neuropathy, A.V. block
Class IV drugs: Calcium channel blockers
Verapamil:
Mechanism of Action
Verapamil inhibits slow channel calcium ion transport across the myocardial cell membrane
it also reduces intracellular calcium concentration in smooth muscle cells of the coronary
and peripheral vasculature. It is absolutely contraindicated in patients on beta blockers,
quinidine or disopyramide.

Pharmacological Action
Verapamil depress SA and AV nodal functions. Slow AV conduction is its major action
making it useful as anti arrhythmic agent. It reduces coronary and peripheral vascular
resistance. It increases coronary blood flow. Verapamil increases myocardial oxygen supply
by increasing coronary blood flow. Simply we can say Verapamil has anti arrhythmic, anti
anginal and antihypertensive properties.

Pharmacokinetics
Verapamil is rapidly and almost completely absorbed after oral administration. It undergoes
extensive first pass metabolism in the liver. It is highly bound by plasma proteins. Its half-life
is 3 to 6 hours.

Therapeutics Uses
Verapamil is more effective in the treatment of arterial arrhythmias than ventricular
arrhythmias. It is also very useful in the treatment of angina pectoris and hypertension.

Adverse Effects
Constipation is the most common side effect. Nausea, vomiting, headache, weakness and
gastric disturbance may occur when given IV; Verapamil may cause severe hypotension, and
bradycardia.
.
Class - V drugs:
Digoxin causes shortening of the atrial refractory period with small doses (vagal action) and
a prolongation with the larger doses (direct action). It prolongs the effective refractory
period of A.V node directly and through the vagus. This action is of major importance in
slowing the rapid ventricular rate in patients with atrial fibrillation Any cardiac rhythm other
than the normal is called arrhythmia. For example cardiac arrhythmias may cause the heart
to beat too slowly (bradycardia) or to beat too rapidly (tachycardia) or to beat irregularly.

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 Cardiovascular System (CVS) UNIT-V

Antihypertensive
Hypertension is group of symptoms, characterized by elevated blood pressure. Cardiac
output and total peripheral resistance determine the blood pressure.
Anti hypertensive therapy involves non-pharmacological intervention as well as specific
drugs treatments. Dietary sodium restriction, exercise, weight loss, behavior are some
factors that effect B.P.

Antihypertensive drugs
a. General consideration:-
Hypertension is defined as an elevation of arterial blood pressure above an arbitrarily
defined normal value. The American Heart Association defines hypertension as arterial
blood pressure higher than 140/90mmHg (based on three measurements at different
times).
Hypertension may be classified in to three categories, according to the level of diastolic
blood pressure:
 Mild hypertension with a diastolic blood pressure between 95-105 mmHg
 Moderate hypertension with a diastolic blood pressure between 105 – 115mmHg
 Severe hypertension with a diastolic blood pressure above 115mmHg.

Two factors which determine blood pressure are cardiac out put (stroke volume x heart
rate) and total peripheral resistance of the vasculature. Blood pressure is regulated by an
interaction between nervous, endocrine and renal systems
Elevated blood pressure is usually caused by a combination of several abnormalities such as
psychological stress, genetic inheritance, environmental and dietary factors and others.
Patients in whom no specific cause of hypertension can be found are said to have essential
hypertension or primary hypertension (accounts for 80-90 % of cases).
Secondary hypertension arises as a consequence of some other conditions such as,
atherosclerosis, renal disease, endocrine diseases and others.
antihypertensive therapies.
The central issue of antihypertensive therapy is to lower arterial blood pressure,
irrespective of the cause.
1. Non pharmacological therapy of hypertension
Several non-pharmacological approaches to therapy of hypertension are available. These
include:

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 Cardiovascular System (CVS) UNIT-V

• Low sodium chloride diet

• Weight reduction
• Exercise
• Cessation of smoking
• Decrease in excessive consumption of alcohol
• Psychological methods (relaxation, meditation …etc)
• Dietary decrease in saturated fats.
The sensitivity of patients differs to these non-pharmacological approaches, but, on the
average, only modest reductions (5 to 10 mmHg) in blood pressure can be achieved.

2. Pharmacological therapy of hypertension.

Currently available drugs lower blood pressure by decreasing either cardiac output (CO) or
total peripheral vascular resistance (PVR) or both although changes in one can indirectly
affect the other.
A) Diuretics, which lower blood pressure by depleting the body sodium and reducing blood
volume. Diuretics are effective in lowering blood pressure by 10 – 15 mmHg in most
patients.
Diuretics include:
a) Thiazides and related drugs, e.g. hydrochlorthiazide bendrofluazide, chlorthalidone, etc.
Initially, thiazide diuretics reduce blood pressure by reducing blood volume and cardiac out
put as a result of a pronounced increase in urinary water and electrolyte particularly sodium
excretion. With chronic administration (6-8weeks), they decrease blood pressure by
decreasing peripheral vascular resistance as the cardiac out put and blood volume return
gradually to normal values.
b) Loop diuretics, e.g. furosemide, ethacrynic acid, etc.
The antihypertensive effect is mainly due to reduction of blood volume.
Loop diuretics are indicated in cases of severe hypertension which is associated with renal
failure, heart failure or liver cirrhosis.
c) Potassium sparing diuretics, e.g. spironolactone
They are used as adjuncts with thiazides or loop diuretics to avoid excessive potassium
depletion and to enhance the natriuretic effect of others. The diuretic action of these drugs
is weak when administered alone.
B) Sympathoplegic agents (Depressants of sympathetic activity).
Based on the site or mechanism of action sympathoplegic drugs are divided into:
a) Centrally acting antihypertensive agents e.g. methyldopa, clonidine
Centrally acting sympathetic depressants act by stimulating α2 - receptors located in the
vasomotor centre of the medulla. As a result, sympathetic out flow from the medulla is
diminished and either total peripheral resistance or cardiac out put decreases. .
b) Adrenoceptor antagonists, e.g propranolol (beta blocker), prazosin (alpha blocker),
labetalol (alpha and beta blocker).
β – Blockers antagonize beta, receptors located on the myocardium and prevent the cardio
acceleration, which follows sympathetic stimulation.
The rate and force of myocardial contraction is diminished, decreasing cardiac out put and
thus, lowering blood pressure. An additional effect which can contribute to a reduction of
blood pressure is that renin release is mediated by β receptors. Therefore, receptor

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 Cardiovascular System (CVS) UNIT-V

blockade prevents angiotensin II formation and associated aldosterone secretion, resulting

in a decrease in total peripheral resistance and blood volume.

c) Alpha adrenergic blocking

The principal action of alpha adrenergic blocking drugs is to produce peripheral vasodilation.
Alpha blockers reduce arterial pressure by dilating both resistance and capacitance vessels.
alpha-adrenergic antagonists, treat conditions such as high blood pressure and benign
prostatic hyperplasia. ... Because alpha blockers also relax other muscles throughout the
body, these medications can help improve urine flow in older men with prostate problems.
d) Direct vasodilators. These include:- • Arterial vasodilators, e.g. hydralazine •
Arteriovenous vasodilators, e.g. sodium nitroprusside
Hydralazine: It dilates arterioles but not veins. It is used particularly in severe hypertension.
The most common adverse effects are headache, nausea, anorexia, palpitations, sweating
and flushing which are typical to vasodilators.
Sodium nitroprusside: It is a powerful vasodilator that is used in treating hypertensive
emergencies as well as severe cardiac failure.
It dilates both arterial and venous vessels, resulting in reduced peripheral vascular
resistance and venous return.
Nitroprusside rapidly lowers blood pressure and it is given by intravenous infusion.
The most serious toxicities include metabolic acidosis, arrhythmias, excessive hypotension
and death.

D) Angiotensin converting enzyme inhibitors, e.g. captopril, enalapril, etc. The prototype is
captopril. Captopril inhibits angiotensin converting enzyme that hydrolyzes angiotensin I
(Inactive) to angiotensin II (Active), a potent vasoconstrictor, which additionally stimulates
the secretion of aldosterone. It lowers blood pressure principally by decreasing peripheral
vascular resistance.
The adverse effects include maculopapular rash, angioedema, cough, granulocytopenia and
diminished taste sensation.
Enalapril is a prodrug with effects similar to those of captopril.
E) Calcium channel blockers, e.g. nifedipine, verapamil, nicardipine, etc.
The prototype is verapamil.
The mechanism of action in hypertension is inhibition of calcium influx in to arterial smooth
muscle cells, resulting in a decrease in peripheral resistance.
Verapamil has the greatest cardiac depressant effect and may decrease heart rate and
cardiac out put as well.
The most important toxic effects for calcium channel blockers are cardiac arrest,
bradycardia, atrioventricular block and congestive heart failure.

F) Angiotensin Receptor Antagonist

Losartan and its longer acting metabolite, E-3174, lower blood pressure by antagonizing the
renin-angiotensin-aldosterone system (RAAS); they compete with angiotensin II for binding
to the type-1 angiotensin II receptor (AT1) subtype and prevents the blood pressure
increasing effects of angiotensin II.

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 Cardiovascular System (CVS) UNIT-V

Diuretics

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Cardiovascular System (CVS) UNIT-V

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 Gastrointestinal Drugs UNIT-VI

Chapter: 6

Gastrointestinal drugs

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 Gastrointestinal Drugs UNIT-VI

Gastrointestinal Drugs
Gastro Intestinal Tract is concerned with the function of ingesting and absorbing nutrients
and excreting unabsorbed and waste products.

Here we will discuss prototype drugs used to treat three common medical conditions
involving the gastrointestinal (GI) tract:

1. Peptic ulcers and gastroesophageal reflux disease

2. Diarrhea
3. Constipation
4. Emesis

Drugs Used To Treat Peptic Ulcer Disease

Drugs used in Acid-peptic disease:

Acid-peptic disease includes peptic ulcer (gastric and duodenal), gastroesophageal reflux
and Zollinger – Ellison syndrome. Peptic – ulcer disease is thought to result from an
imbalance between cell – destructive effects of hydrochloric acid and pepsin and cell-
protective effects of mucus and bicarbonate on the other side. Pepsin is a proteolyic enzyme
activated in gastric acid, also can digest the stomach wall. A bacterium, Helicobacter pylori is
now accepted to be involved in the pathogenesis of ulcer. In gastroesophageal reflux, acidic
stomach contents enter into the esophagus causing a burning sensation in the region of the
heart; hence the common name heartburn, or other names such as indigestion, dyspepsia,
pyrosis, etc. Zollinger-Ellison syndrome is caused a tumor of gastrin secreting cells of
pancreas characterized by excessive secretion of gastrin that stimulates gastric acid
secretion.

The disorders can be treated by drugs, which are able to:

1. Neutralize gastric acid (HCl) e.g. magnesium hydroxide
2. Reduce gastric acid secretione.g. cimetidine
3. Enhance mucosal defences e.g sucralfate
4. Exert antimicrobial action against H.pylori e.g. clarithromycin, Metronidazol
5. Proton Pump Inhibitors e.g. Omeprazole)

6. Prostaglandins Analogue e.g. Misoprostol

A. Neutralize gastric acid (HCl)

Antacids are alkaline substances (weak bases) that neutralize gastric acid (hydrochloric acid)
They react with hydrochloric acid in the stomach to produce neutral or less acidic or poorly
absorbed salts and raise the PH of stomach secretion, and above PH of 4, pepsin is inactive.
Antacids are divided into systemic and nonsystemic
 Systemic, e.g. sodium bicarbonate are absorbed into body fluids and may alter acid –
base balance. It can be used in the treatment of metabolic acidosis.

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 Gastrointestinal Drugs UNIT-VI

 Non systemic, do not alter acid – base balance significantly. They are used as gastric
antacids; and include aluminium, magnesium and calcium compounds e.g. (Al(OH)3,
MgS2O3 , Mg(OH)2, CaCO3).

The most commonly used antacids, are mixtures of aluminium hydroxide and magnesium
hydroxide (e.g. Gelusil, Maalox etc).
Aluminum hydroxide antacids are used in the treatment of peptic ulcer disease, and they
may also promote healing of duodenal ulcers.
Aluminum hydroxide mostly excreted in feces. Small amounts absorbed are excreted by the
kidneys. They are used as last-line therapy for acute gastric ulcers
Adverse Effects
Antacids tend to cause constipation, stomach pain, loss of appetite, and muscle weakness.

B. Gastric acid secretion inhibitors (antisecretory drugs):

HCl is secreted by parietal cells of the gastric mucosa which contain receptors for
acetylcholine, histamine and gastrin that stimulate the secretion. Antagonists of
acetylcholine, histamine and gastrin inhibit acid secretion Antisecretory drugs include:
a) H 2-receptors blocking agents such as cimetidine, ranitidine, famotidine, nizatidine.
Cimetidine is the proto type of the group.
 The histamine H2-receptor antagonists cimetidine, act selectively on H2 receptors in
the stomach, blood vessels, and other sites, but they have no effect on H1 receptors.
They are competitive antagonists of histamine and are fully reversible
 Histamine H2-receptor antagonists are equally effective in promoting the healing of
duodenal and gastric ulcers.
 Low doses of H2 antagonists, currently available for over-the-counter sale, appear to
be effective for the prevention and treatment of heartburn (gastroesophageal
reflux).
 Cimetidine and the other H2 antagonists are given orally, distribute widely
throughout the body and are excreted mainly in urine
Common adverse effects: muscular pain, headache, dizziness, anti- androgenic effects at
high doses such as impotence, gynecomastia, menstrual irregularities.

b) Proton pump inhibitors such as, omeprazole, lansoprazole, etc. inhibit the H+/K+
ATPase, or more commonly just gastric proton pump of the gastric parietal cell.
 Proton pump inhibitors are used in the treatment of peptic ulcer, these
agents suppressing acid production and healing peptic ulcers. These agents
are also successfully used with antimicrobial agents for the peptic ulcer
treatment.
 Adverse Effects: These agents are generally well tolerated. Increased
concentration of viable bacteria in the stomach has been reported with
continued use of these agents.

C. Cytoprotective (mucosal protective) agents.

Locally active agents help to heal gastric and duodenal ulcers by forming a protective barrier
between the ulcers and gastric acid, pepsin, and bile salts. It also stimulates prostaglandin
release as well as mucus and bicarbonate output, and it inhibits peptic digestion. They do

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 Gastrointestinal Drugs UNIT-VI

not alter the secretion of gastric acid. These drugs include sucralfate and colloid bismuth
compounds. (e.g. tripotassium, dicitratobismuthate). Colloidal bismuth compounds
additionally exert bactericidal action against H.pylori
Sucralfate
Sucralfate effectively heals duodenal ulcers and is used in long-term maintenance therapy to
prevent their recurrence.

Pharmacokinetics
Little of the drug is absorbed systemically. It is very well tolerated; it has a very short serum
half-life of 1 h and is excreted almost completely by the kidneys.

Adverse Effects
Less serious side effects of sucralfate may include stomach pain, constipation, diarrhea,
nausea, and vomiting.

D.Antimicrobial
Other drugs that can to eradicate H.pylori such as amoxicillin, metronidazole, clarithromycin
and tetracycline are included in the anti-ulcer treatment regimens. Patients with peptic
ulcer disease (both duodenal and gastric ulcers) who are infected with H. pylori, which is a
Gram- negative, microaerophilic bacterium found in the stomach requires antimicrobial
treatment.
E.Protaglandins have both antisecretory and mucosal protective effects.
Example: Misoprostol- used for prevention of NSAID – induced ulcer.
A. Misoprostol seems to inhibit gastric acid secretion by a direct action
on the parietal cells through binding to the prostaglandin receptor.
It Increases secretion of mucus and bicarbonate.
B. Therapeutic Action
It is an effective anti-ulcer agent. It is clinically effective only at
higher doses that diminish gastric acid secretion
C. Adverse Effects
The most common adverse effects of misoprostol are uterine
contractions, diarrhea and nausea.

Prototype Drugs Used To Treat Diarrhea

Anti diarrheal are used in the treatment of diarrhea, defined as the frequent expulsion of
liquid or semi liquid stools → hinders absorption of fluids and electrolytes. Increased
motility of the gastrointestinal tract and decreased absorption of fluid are major factors in
diarrhea.
Most common antidiarrheal drugs used to treat acute diarrhea include antimotility agents,
and adsorbents.

A. Opiates and opiate derivatives are the most effective. They

decrease diarrhea by slowing propulsive movements in small and
large intestine. Morphine is effective but not used due to severe
potential adverse effects.

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 Gastrointestinal Drugs UNIT-VI

B. Loperamide (Antimotility Agents) Loperamide is widely used to

control diarrhea. They inhibit acetylcholine release and decrease
peristalsis. At the usual doses, they lack analgesic effects. Side
effects include drowsiness, abdominal cramps, and dizziness. They
should not be used in young children or in patients with severe
colitis.
C. Adsorbent – demulcent products such as kaolin – pectin
preparation may be included in antidiarrheal preparations.
Adsorbent agents, such as aluminum hydroxide are used to control
diarrhea. Presumably, these agents act by adsorbing intestinal
toxins or microorganisms and/or by coating or protecting the
intestinal mucosa. They can interfere with the absorption of other
drugs.
Drugs Used To Treat Constipation
Laxatives are commonly used for constipation to accelerate the movement of food through
the gastrointestinal tract. Most common and important laxatives are listed below.
Difference between Laxatives and cathartics (purgatives)
Laxatives and cathartics are drugs used orally to evacuate the bowels or to promote bowel
elimination (defecation).
The term laxative implies mild effects, and eliminative of soft formed stool. The term
cathartic implies strong effects and elimination of liquid or semi liquid stool. Both terms are
used interchangeably because it is the dose that determines the effects rather than a
particular drug.
Example:-
Castor oil laxative effect= 4ml
Cathartic effect = 15-60ml
Laxative and cathartics are arbitrarily classified depending on mode of action as:
A. Bulk forming laxatives: are substances that are largely unabsorbed from the
intestine. They include hydrophilic colloids such as psyllium, bran, methylcellulose,
etc. When water is added, the substances swell and become gel-like which increases
the bulk of the fecal mass that stimulates peristalsis and defecation.
B. Osmotic laxatives such as lactulose, magnesium sulfate, magnesium hydroxide,
sodium phosphate, etc. also belong to bulk – forming laxatives.
These substances are not efficiently absorbed, thus creating a stronger than usual solution
in the colon which causes water to be retained. The increase in pressure and volume causes
stimulation of peristalsis.
Lactulose (Saline And Osmotic Laxatives)
Lactulose is a semisynthetic disaccharide sugar that also acts as an osmotic laxative. It is a
product that cannot be hydrolyzed by intestinal enzymes. Oral doses are degraded in the
colon by colonic bacteria into lactic, formic, and acetic acids. This increases osmotic
pressure, causing fluid accumulation, colon distension, and soft stools.

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 Gastrointestinal Drugs UNIT-VI

C. Stimulant (irritant) laxati ves (cathartics):are substances that are themselves irritant
or contain an irritant substance to produce purgation. Individual drugs are castor oil,
bisacodyl, phenolphthalein, cascara sagrada, glycerine, etc. They are the strongest
and most abused laxative products that act by irritating the GI mucosa and pulling
water into the bowel lumen. The feces is moved too rapidly and watery stool is
eliminated as a result. Glycerine can be administered rectally as suppository only.
Castor Oil (Irritants And Stimulants)
This agent is broken down in the small intestine to ricinoleic acid, which is very irritating to
the stomach and promptly increases peristalsis.
D. Fecal softners – Decrease the surface tension of the fecal mass to allow water to
penetrate into the stool. They have detergent – like property e.g. docusate. They
may also decrease water absorption through intestinal wall.
Docusate (Stool Softeners)
Stool softeners emulsified with the stool produce softer feces and ease passage. They may
take days to become effective and are often used for prophylaxis rather than acute
treatment. Stool softeners should not be taken with mineral oil because of the potential for
absorption of the mineral oil.
E. Lubricant laxatives e.g. liquid paraffin (mineral oil). It lubricates the intestine and is
thought to soften stool by retarding colonic absorption of fecal water.

Antiemetics
Vomiting is a protective reflex mechanism for eliminating irritant of harmful substances
from upper GIT.
Causes of Vomiting

 Pregnancy
 Motion sickness
 GI obstruction
 Peptic ulcer
 Drug toxicity
 Renal failure
 Hepatitis

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 Gastrointestinal Drugs UNIT-VI

Drug Used To Treat Emesis

drugs used to prevent or treat nausea and vomiting.
Nausea is an unpleasant sensation of abdominal discomfort accompanied by a desire to
vomit.
Vomiting is the expulsion of stomach contents through the mouth Nausea may occur
without vomiting and vomiting may occur without prior nausea, but the two symptoms
most often occur together. Vomiting occurs when the vomiting center in the medulla
oblongata is stimulated. Dopamine and acetylcholine play a major role in stimulating the
vomiting center. To a certain extent, vomiting is a protective mechanism which can result
from various noxious stimuli.

Anti emetic agents

Most antiemetic agents relieve nausea and vomiting by acting on the vomiting center, CTZ,
cerebral cortex, vestibular apparatus, or a combination of these.
Antiemetic drugs include:
A. D2 Receptor Antagonist (Metoclopramide, Domperidone)
B. Sedative Hypnotics (Barbiturates, Benzodiazepines)
(See in Anxiolytic And Hypnotic Drugs)
C. Antimuscarinics (Scopolamine)
D. H1 Receptor Antagonists (Meclizine, Dimenhydrinate)

(D2 Receptor Antagonist)

Metoclopramide
Mechanism Of Action
Metoclopramide centrally block dopamine D2 receptors in CTZ, it also enhances action of
acetylcholine at muscarinic nerve ending in gut.
Therapeutic Uses
Metoclopramide is used in the treatment of nausea and vomiting associated with GI
disorders, before emergency anesthesia and in gastroesophageal reflux.
Adverse Effects
Restlessness, diarrhea

(H1 Receptor Antagonists)

Dimenhydrinate
Mechanism Of Action
Dimenhydrinate is a H1 antihistaminic or antiemetic agent.
Therapeutic Uses
It provides relief of symptoms of vomiting, allergic reactions such as rash, watery eyes,
runny nose, itchy eyes and sneezing. It may also be used to treat motion sickness, relief of
anxiety or tension and sleeplessness.
Adverse Effects
Dizziness, Headache, Drowsiness, and Fatigue

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 Respiratory System UNIT-VII

Chapter: 7

Respiratory system

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 Respiratory System UNIT-VII

Respiratory System

The respiratory system includes the upper airway passages, the nasal cavities, pharynx and
trachea as well as the bronchi and bronchioles. Drug therapy of pulmonary disorders is
generally directed towards altering a specific physiologic function.

Common Diseases Related To Respiratory System

1. Asthma
2. Allergic Rhinitis
3. Cough
Now we will discuss prototype drugs of each disease…

Asthma
Asthma is an inflammatory disease of the airways characterized by episodes of acute
bronchoconstriction causing shortness of breath, cough, chest tightness, wheezing, and
rapid respiration.
Pathogenesis
There are two types of bronchial asthma i.e extrinsic and intrinsic.
Extrinsic asthma is associated with history of allergies in childhood, family history of
allergies, hay fever, or elevated IgE.
Intrinsic asthma occurs in middle-aged subjects with no family history of allergies, negative
skin tests and normal serum IgE.
PHARMACOTHERAPY OF BRONCHIAL ASTHMA
Drug used in the treatment of bronchial asthma can be grouped into three main categories:
1. Bronchodilators
a. β- Adrenergic agonists which include: ƒ

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 Respiratory System UNIT-VII

 Non selective β-agonists e.g. adrenaline ƒ

 Selective β-agonists e.g. salbutamol
b. Methylxanthines; theophylline derivatives
c. Muscranic receptor antagonists e.g. Ipratropium bromide
2. Mast cell stabilizers, e.g. cromolyn sodium, nedocromil, ketotifen
3. Antiinflammatory agents: corticosteroids
Drugs Used To Treat Asthma
Bronchodilator
β –adrenergic agonist
Mechanism of Action
β-Agonists stimulate adenyl cyclase and increase formation of cAMP in the airway tissues.
They have got several pharmacological actions important in the treatment of asthma
- Relax smooth muscles
- Inhibit release of inflammatory mediator or broncho constricting substances from mast
cells.
- Inhibit microvasculature leakage
Pharmacokinetics
Adrenergic Agonists Most clinically useful β2 agonists have a rapid onset of action (5 to 30
minutes) and provide relief for 4 to 6 hours
Side effects
Tremors, anxiety, insomnia, tachycardia, headache, hypertension and etc.
Methylxanthines; theophylline derivatives
The three important methylxanthines are theophylline, theobromine, and caffeine. The
theophylline preparations most commonly used for therapeutic purposes is aminophylline
(theophylline plus diethylamine).
Mechanism of Action
They inhibit phosphodiesterase (PDE) enzyme leading to increased cAMP level.
Pharmacokinetics
Most preparations are well absorbed from gastro intestinal tract and metabolized by liver
Adverse Effects:
Anorexia, nausea, vomiting, abdominal discomfort, headache, anxiety, insomnia, seizures,
arrhythmias
MUSCRANIC RECEPTOR ANTAGONISTS
Mechanism of Action
Muscarinic antagonist competitively inhibit effect of acetylcholine at muscarinic receptors –
hence block the contraction of air way smooth muscle and the increase in secretion of
mucus that occurs in response to vagal activity e.g atropine sulfate
Corticosteroids
Inhaled corticosteroids (ICS) are the drugs of first choice in patients with any degree of
persistent asthma (mild, moderate, or severe). The corticosteroids commonly used are
hydrocortisone, predinisolone, beclomethasone, triamcinolone and etc.
Mechanism of action
They are presumed to act by their broad anti inflammatory efficacy mediated in part by
inhibition of production of inflammatory mediators.
Side effects: -
 Osteoporosis
 Sodium retention and hypertension

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 Respiratory System UNIT-VII

 Cataract
 Impairment of growth in children
 Susceptibility to infection like oral candidiasis, tuberculosis
MAST CELL STABILIZERS e.g cromolyn sodium
Mechanism of action
 Stabilize the mast cells so that release of histamine and other mediators is inhibited
through alteration in the function of delayed chloride channel in cell membrane.
Clinical uses - Exercise and antigen induced asthma - Occupational asthma
Side effects
 Poorly absorbed so minimal side effect
 Throat irritation, cough, dryness of mouth, chest tightness and wheezing

Leukotriene Antagonists
Montelukast

Montelukast (Leukotriene Antagonists)

It blocks the effects of cysteinyl leukotrienes..
Pharmacokinetics
The drug is orally active. Greater than 90 percent of drug is bound to plasma protein. The
drug is extensively metabolized, and their metabolites undergo biliary excretion.
Adverse Effects
Elevations in serum hepatic enzymes, headache and dyspepsia

Allergic Rhinitis
Rhinitis is an inflammation of the mucous membranes of the nose and is characterized by
sneezing, itchy nose/eyes, watery rhinorrhea, and nasal congestion. An attack may be due
to inhalation of an allergen such as dust, pollen, or animal dander. The foreign material
interacts with mast cells which, release mediators, such as histamine that promote
bronchiolar spasm and mucosal thickening from edema and cellular infiltration.

Prototype Drugs Used To Treat Allergic Rhinitis

 β -Adrenergic Agonists
 Antihistamines
 Corticosteroids (see in Asthma)
 Montelukast (see in Asthma)
β-Adrenergic Agonists
Short-acting β-Adrenergic agonists constrict dilated arterioles in the nasal mucosa and
reduce airway resistance. Longer-acting β-Adrenergic agonists are also available. When
administered as an aerosol, these β-Adrenergic agonists nasal formulations should be used
no longer than 3 days due to the risk of rebound nasal congestion.
Antihistamines (H1-Receptor Blockers)
Antihistamines are the most frequently used agents in the treatment of sneezing and watery
rhinorrhea associated with allergic rhinitis. H1-histamine receptor blockers are useful in
treating the symptoms of allergic rhinitis caused by histamine release.

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 Respiratory System UNIT-VII

ANTI-TUSSIVES
Cough is a protective reflex, which serves the purpose of expelling sputum and other irritant
materials from the respiratory airway.
Types:
1. Useful productive cough o Effectively expels secretions and exudates
2. Useless cough o Non-productive chronic cough o Due to smoking and local irritants
Anti-tussives are drugs used to suppress the intensity and frequency of coughing.
Two Types of Anti-tussives:
1. Central anti- tussives - Suppress the medullay cough center and may be divided
into two groups:
 Opoid antitussive e.g. codeine, hydrocodeine, etc
 Non opoid antitussives e.g. dextromethorphan
2. Peripheral antitussives - Decrease the input of stimuli from the cough receptor in
the respiratory passage. Demulcents coat the irritated pharyngeal mucosa and exert
a mild analgesic effect locally. e.g: Demulcents e.g. liquorices lozenges, honey
3. Local anesthetics e.g. lidocaine aerosol
CODEINE
Codeine is a narcotic relatively less addicting drug and central antitussive agen and it’s main
side effects are dryness of mouth, constipation and dependence.
DEXTROMETROPHAN
Dextromethorphan is an opoid synthetic antitussive, essentially free of analgesic and
addictive properties and the main side effects are respiratory depression
Expectorant is a drug that aid in removing thick tenacious mucus from respiratory passages,
e.g. Ipecac alkaloid, sodium citrate, saline expectorant, guanfenesin, potassium salts
Mucolytics are agents that liquefy mucus and facilitate expectoration, e.g.acetylcysteine.
DECONGESTANTS are the drugs that reduce congestion of nasal passages, which in turn
open clogged nasal passages and enhances drainages of the sinuses.
e.g phenylephrine, oxymetazoline etc.

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 Genitourinary System UNIT-VIII

Chapter: 8

Gento-urinary system

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Genitourinary System
The term "genitourinary" actually refers to two different systems. Urinary refers to the
system responsible for removal waste products of metabolism from the bloodstream.
Genito refers to the genital organs and the reproductive system.

Diuretics
Diuretics are drugs, which increase renal excretion of salt and water: are principally used to
remove excessive extracellular fluid from the body. Diuretics can be used as first-line drug
therapy for hypertension. Low-dose diuretic therapy is safe, inexpensive, and effective in
preventing stroke, myocardial infarction, and congestive heart failure. Recent data suggest
that diuretics are superior to β-blockers for treating hypertension in older adults.
Approximately 180 liters of fluid is filtered from the glomerulus into the nephron per day.
The normal urine out put is 1-5 liters per day. The remaining is reabsorbed in different areas
of nephron. There are three mechanisms involved in urine formation

Classification of diuretics:-
Most of the diuretics used therapeutically act by interfering with sodium reabsorption by
the tubules. The major groups are:
I. Thiazides and related diuretics: e.g. chlorthiazide, Hydrochlorothiazide
chlorthalidone, bendrofluazide, etc.
II. Loop diuretics: e.g. bumetanide, furosemide, ethacrynic acid, etc.
III. Potassium sparing diuretics e.g. triamterene, amiloride , spironolactone, etc.
IV. Carbonic anhydrase inhibitors e.g. acetazolamide
V. Osmotic diuretics e.g. mannitol, glycerol
1. Thiazide diuretics act by inhibiting NaCl symport at the distal convoluted tubule.
They decrease Na+ reabsorption increase the concentration of urine.
Pharmacokinetics
These drugs are effective orally half-life is 40 hours these drugs secreted by urine.
Clinical use
They are used in hypertension, edema of hepatic, renal and cardiac origin.

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 Genitourinary System UNIT-VIII

Adverse effect
Epigastric distress, nausea, vomiting, weakness, fatigue, dizziness, impotence, jaundice, skin
rash, hypokalemia, hyperuricemia, hyperglycaemia and visual disturbance.
2. Loop diuretics:
Loop diuretics like frusemde inhibit Na+- K – 2Cl symporter in the ascending limb.
Adverse effects: Hypokalemia, nausea, anorexia, vomiting epigastric distress, fatigue
weakness muscle cramps, drowsiness. Dizziness, hearing impairment and deafness are
usually reversible.
Pharmacokinetics
Loop diuretics are administered orally or parenterally. They are secreted into the urine.
Therapeutic uses: acute pulmonary edema, edema of cardiac, hepatic and renal disease.
Hypertension, cerebral edema, in drug overdose it can be used to produce forced diuresis to
facilitate more rapid elimination of drug.
3. Potassium sparing diuretics
Mechanism of action: Potassium sparing diuretics (spironolactone, triamterene, amiloride)
are mild diuretics causing diuresis by increasing the excretion of sodium, calcium and
bicarbonate but decrease the excretion of potassium.
Adverse effects: G.I. disturbances, dry mouth, rashes confusion, orthostatic hypotension,
hyperkalaemia. Hyponatraemia
Therapeutic uses: These agents are used as diuretics with an additional advantage that is
retention of K.

4. Carbonic anhydrase inhibitors:

These drugs like acetazolamide inhibit the enzyme carbonic anhydrase in renal tubular cells
and lead to increased excretion of bicarbonate, sodium and potassium ions in urine. In eye it
results in decrease information of aqueous humor. Therefore these are used in treatment of
acute angle glaucoma. Less commonly, acetazolamide can be used in the prophylaxis of
acute mountain sickness.
adverse effects of these agents are drowsiness, hypokalemia, metabolic acidosis and
epigastric distress.
5. Osmotic diuretics:
Osmotic diuretics are used to affect increased water excreted rather than Na excretion.
These drugs like mannitol and glycerine (glycerol) are freely filtered at the glomerulus and
are relatively inert pharmacologically and undergo limited reabsorption by renal tubule.
These are administered to increase significantly the osmolality of plasma and tubular fluid.
Some times they produce nausea, vomiting, electrolyte imbalances. They are used in
cerebral edema and management of poisoning. Mannitol is not absorbed when given orally
and should only be given intravenously.

Ritodrine (Beta-2 Agonist, Uterine Muscles Relaxant)

Mechamism of Action
Ritodrine is a selective beta-2 receptor agonist that developed specifically for use as a
uterine relaxant.

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Therapeutic Uses
Ritodrine used for smooth muscle (uterine muscle) relaxant to decrease uterine activity and
delay uncomplicated premature labor.
Side Effects
Fast heart rate, headache, nervousness, anxiety, nausea and vomiting

Oxytocin (Uterine Muscles Contractants)

Mechamism of Action
Oxytocin increase in intracellular calcium levels thus stimulates rhythmic contractions of the
uterus.

Therapeutic Uses
Oxytocin use as a smooth muscle (uterine muscle) contractant.

Side Effects
Allergic reaction,nausea, vomiting, swelling of the mouth, face, lips, or tongue

Ergotamine (Ergot Alkaloid, Uterine Muscles Contractants)

Mechanism of Action
Ergotamine constricts smooth muscles like blood vessels and uterine muscles.

Therapeutic Uses
Ergotamine constricts uterine muscles. Ergotamine is also used to treat headache pain and
other symptoms associated with migraines.

Side Effects
Allergic reaction, nausea, vomiting, swelling of the mouth, face, lips, or tongue

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 Introduction To Chemotherapy UNIT-IX

Chapter: 9

Introduction of chemo therapy

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 Introduction To Chemotherapy UNIT-IX

Introduction To Chemotherapy
Chemotherapy is the use of chemical agents (either synthetic or natural) to destroy
infective agents (microorganisms’ i.e bacteria, fungus and viruses, protozoa, and
helminthes) and to inhibit the growth of malignant or cancerous cells. The chemical
substances used for this purpose are called chemotherapeutics agents.

Chemotherapeutic agents: are chemical which are intended to be toxic for parasitic cell but
non toxic to the host, such selective toxicity depends on the existence of exploitable
biochemical difference between the parasite and the host cell.
Antimicrrobials: are chemical agents (synthetic/natural) used to treat bacterial, fungal and
viral infections.
Antibiotics: are substances produced by various species of microorganisms (bacteria, fungi,
actinomycetes) that suppress the growth of other microorganisms. Antimicrobial drug
exhibits selective toxicity. I.e. the drug is harmful to the parasite without being harmful to
the host.
Bactericidal versus bacteriostatic action: When antimicrobial agents lead to the death of
the susceptible microbe (e.g. bacteria) it is said have bactericidal action but when it merely
inhibits the growth and therefore spread of the microbial population it is said to have
bacteriostatic action.

Drugs Used In Chemotherapy

1. Antibacterial drugs
2. Antiviral drugs
3. Antiprotozoal drugs
4. Anthelmintics
5. Antifungal drugs
6. Antitubercular drugs
7. Antileprotic drugs
8. Anticancer drugs

ANTIMICROBIAL DRUGS
Mechanisms of antimicrobial drug action:
1. Inhibition of cell wall synthesis
2. Cell membrane function inhibitors
3. Inhibition of protein synthesis
4. Inhibition of nucleic acid synthesis
5. Antimetabolites
Antibacterial agents
Cell wall synthesis inhibitors
Members the group: Beta-lactam antibiotics, vancomycin, bacitracine, and cycloserine
Beta-lactam antibiotics: Penicillins, cephalosporins, carbapenems, and monobactams are
members of the family. All members of the family have a beta-lactam ring and a carboxyl
group resulting in similarities in the pharmacokinetics and mechanism of action of the group

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members. They are water-soluble, elimination is primary renal and organic anion transport
system is used.
Penicillins
Penicillins have similar structure, pharmacological and toxicological properties. The
prototype of penicillins is penicillin G and is naturally derived from a genus of moulds called
penicillium.
Classification: Penicillins can be classified into three groups:
1. Natural Penicillins: Penicillin G and penicillin V are natural penicillins. Penicillin G
is the drug of choice for infections caused by streptococci, meningococci, enterococci
etc
2. Antistaphylococcal Penicillins: [Methicillin, Nafcillin, isoxazolyl penicillins
(Oxacillin, cloxacillin, and dicloxacillin
3. Extended-spectrum penicillins: Aminopenicillins (ampicillin, amoxicillin),
Carboxypenicillins (Carbenicillin, ticarcillin, effective at lower doses), and
Ureidopenicillins (piperacillin, mezlocillin, and azlocillin)

Adverse Reactions: Skin rashes, fever, bronchospasm, Oral lesions, diarrhea, nephritis and
platelet dysfunction Cephalosporins
Cephalosporins can be classified into four generations depending mainly on the spectrum of
antimicrobial activity.
First-generation compounds have better activity against gram-positive organisms and the later
compounds exhibit improved activity against gram-negative aerobic organisms.
First-generation cephalosporins
Members: Cefadroxil, cefazolin, cephalexin, and cephalothin.
Second-generation cephalosporins
Members: Cefaclor, cefamandole, and cefuroxime. All second-generation cephalosporins are
less active against gram-positive bacteria than the first-generation drugs; however, they have
an extended gram-negative coverage.
Third-generation cephalosporins
Members: cefotaxime, ceftazidime, ceftriaxone, and proxetil.

Fourth-generation cephalosporins (e.g.cefepime)

It is similar to third-generation agents
Adverse Effects: Cephalosporins are sensitizing and may elicit a variety of hypersensitivity
reactions that are identical to those of penicillins.
Monobactams contain a monocyclic beta-lactam ring(e.g. aztreonam).
Carbapenems include imipenem and meropenem and have a broad spectrum of activity
(against most Gram-positive and negative bacteria).
Beta-lactamase inhibitors: (clavulanic acid, sulbactam, and tazobactam).
They have no antimicrobial activity, and usually combined with beta lactamase labile
antibiotics, irreversibly inhibit beta-lactamases. Examples: Ticarcillin and clavulanate,
Ampicillin and sulbactam, Amoxicillin and clavulanate [Augmentin]
Vancomycin
Vancomycin is active only against gram-positive bacteria, particularly staphylococci. It
inhibits cell wall synthesis.
Bacitracin
Bacitracin is active against gram-positive microorganisms.
Cycloserine
Cycloserine inhibits many gram-positive and gram-negative organisms, but it is used almost
exclusively to treat tuberculosis caused by strains of M tuberculosis.

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Cell Membrane Function Inhibitors

Antimirobials such as polymyxins acting on gram negative bacteria and affects the
functional integrity of the cytoplasmic membrane, macromolecules and ions escape from the
cell and cell damage and death occurs. The two most well known agents are poymyxin B and
colistin.
Protien Synthesis Inhibitors
Protien synthesis inhibitors are divided into two groups: bacteriostatic and bactericidal.
Chloramphenicol, macrolides, clindamycin (Lincosamides), and tetracyclines are
bacteriostatic whereas aminoglycosides are bactericidal.
Chloramphenicol
Chloramphenicol is a bacteriostatic broad-spectrum antibiotic that is active against both
aerobic and anaerobic gram-positive and gram-negative organisms.
Tetracyclines
The tetracyclines are a large group of drugs with a common basic structure and activity.
Tetracyclines are classified as short acting (chlortetracycline, tetracycline, oxytetracycline),
intermediate acting (demeclocycline and methacycline), or long-acting (doxycycline and
minocycline) based on serum half-lives.
Macrolides: include erythromycin, clarithromycin and azithromycin.
Aminoglycosides:
Members: Streptomycin, neomycin, kanamycin, amikacin, gentamicin, netilmicin
Nucleic Acid Synthesis Inhibitors
Nalidixic acid
Nalidixic acid is the first antibacterial quinolone.
Quinolones are synthetic fluorinated analogs of nalidixic acid, that nucleic acid
synthesis.Ofloxacin and ciprofloxacin inhibit gram-negative cocci and bacilli.
Trimethoprim-Sulfamethoxazole( Cotrimoxazole)

Antiviral Drugs
Viral replication consists of several steps: (1) adsorption to and penetration into susceptible
host cells; (2) uncoating of viral nucleic acid; (3) synthesis of early, regulatory proteins, eg,
nucleic acid polymerases; (4) synthesis of RNA/ DNA; (5) synthesis of late, structural
proteins; (6) assembly (maturation) of viral particles; and (7) release from the cell.
Antiviral agents can potentially target any of these steps. Most of the antiviral agents
currently available act on synthesis of purines and pyrimidines (step 4); reverse
transcriptase inhibitors block transcription of the HIV RNA genome into DNA, thereby
preventing synthesis of viral mRNA and protein. The protease inhibitors act on synthesis of
late proteins and packaging (steps 5 and 6). Antiviral drugs are used to treat infections
caused by viruses. Viruses do not contain cell wall and cell membranes and its replication
depends on the metabolic processes of the host cell therefore they are not affected by
antimicrobial agents.
Acyclovir, Ganciclovir, Foscarnet are anti herpes.
Antiretroviral Agents
There are four different classes of antiretroviral agents commercially available currently:
Nucleoside reverse transcriptase inhibitors (NRTI)(Zidovudine), Protease
inhibitors(Indinavir), Nonnucleoside reverse transcriptase inhibitors (NNRTI) Delavirdine
(DLV ), and Fusion inhibitors (Enfuvirtide (T-20)

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 Introduction To Chemotherapy UNIT-IX

Antiprotozoal Drugs
Antiprotozoal Drugs used to treat protozoals infections. Protozoal infections are common
among people in underdeveloped countries, where sanitary conditions, hygienic practices
etc are inadequate with increased world travel protozoal diseases such as malaria,
amebiasis, and trypanosomiases are spreading.

Drug Classification
The antimalarial drugs are classified by their selective actions on the parasite's life cycle.
1) Tissue schizonticides: drugs that eliminate tissue schizonts or hypnozoites in the liver
(eg, primaquine). 2) Blood schizonticides: drugs that act on blood schizonts (eg,
chloroquine, amodiaquine,
2) proguanil, pyrimethamine, mefloquine, quinine) .
3) Gametocides are drugs that prevent infection in mosquitoes by destroying
gametocytes in the blood (eg, primaquine for P falciparum and chloroquine for P
vivax, P malariae, and P ovale
4) Sporonticidal agents are drugs that render gametocytes noninfective in the mosquito
(eg, pyrimethamine, proguanil).
Adverse Effects: Gastrointestinal symptoms, mild headache, pruritus, anorexia, malaise,
blurring of vision, and urticaria are uncommon, irreversible retinopathy, ototoxicity, and
myopathy.

Anthelmintics Drugs
Anthelmintics are drugs used for eradication of worms from the body. An anthelmintic,
which kills the worm, is called vermicide. If the drug is merely noxious to the worms and
causes them to be expelled from the body, it is called a vermifuge.
Treatment of Amebiasis
1. Asymptomatic Intestinal Infection: The drugs of choice, diloxanide furoate and
iodoquinol. Alternatives are metronidazole plus iodoquinol or diloxanide.
2. Intestinal Infection: The drugs of choice, metronidazole and a luminal amebicide.
3. Hepatic Abscess: The treatment of choice is metronidazole. Diloxanide furoate or
iodoquinol should also be given to eradicate intestinal infection whether or not
organisms are found in the stools. An advantage of metronidazole is its effectiveness
against anaerobic bacteria, which are a major cause of bacterial liver abscess.

Antifungal Drugs

ANTIFUNGAL AGENTS
The antifungal drugs fall into two groups:
1. Antifungal antibiotics and
2. synthetic antifungals.
Antifungal antibiotics
Amphotericin B
Mechanism of Action: Amphotericin B binds to ergosterol (a cell membrane sterol) and
alters the permeability of the cell by forming amphotericin B-associated pores in the cell
membrane. The pore allows the leakage of intracellular ions and macromolecules,
eventually leading to cell death.

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 Introduction To Chemotherapy UNIT-IX

Adverse Effects: fever, chills, muscle spasms, vomiting, headache, hypotension (related to
infusion), renal damage and Anaphylaxis, liver damage, anemia occurs infrequently.
Nystatin
Nystatin has the same pore-forming mechanism of action. It is too toxic for systemic use and
is only used topically.
Griseofulvin
Griseofulvin is a fungistatic and used is in the treatment of dermatophytosis.
Synthetic Antifungal Agents
 Flucytosine
 Azoles
Azoles are synthetic compounds that can be classified as imidazoles and triazoles. The
imidazoles consist of ketoconazole, miconazole, and clotrimazole. The triazoles include
itraconazole and fluconazole.
The antifungal activity of azole drugs results from the reduction of ergosterol synthesis by
inhibition of fungal cytochrome P450 enzymes.
ANTIMYCOBACTERIAL DRUGS
Mycobacterial infections are the most difficult of all bacterial infections to cure.
Mycobacteria are slowly growing organisms (can also be dormant) and thus completely
resistant to many drugs, or killed only very slowly by the few drugs that are active. The lipid-
rich mycobacterial cell wall is impermeable to many agents.
Antimycobacterial drugs can be devided into these groups: drugs used in the treatmen of
tuberculosis, and drugs used in the treatment of leprosy.
Drugs Used In Tuberculosis

First-Line Antimycobacterial Drugs

Members: Isoniazid (INH), rifampin, pyrazinamide, ethambutol, and streptomycin are the
five first-line agents for treatment of tuberculosis. INH and rifampin are the two most active
drugs.
Isoniazid (INH)
INH inhibits synthesis of mycolic acids, which are essential components of mycobacterial cell
walls. INH is readily absorbed from the gastrointestinal tract, and it diffuses readily into all
body fluids and tissues.
Adverse Reactions: INH-induced hepatitis is the most frequent major toxic effect ,Peripheral
neuropathy is more likely to occur in slow acetylators and patients with predisposing
conditions such as malnutrition, alcoholism, diabetes, AIDS, and uremia. Neuropathy is due
to a relative pyridoxine deficiency. INH promotes excretion of pyridoxine, and this toxicity is
readily reversed or can be prevented by administration of pyridoxine. Rifampin
Rifampin is administered together with INH, ethambutol, or another antituberculous drug in
order to prevent emergence of drug resistant mycobacteria.
Ethambutol
Ethambutol inhibits synthesis of mycobacterial cell wall. Ethambutol is well absorbed from
the gut. It accumulates in renal failure.
Pyrazinamide
Pyrazinamide (PZA) is a relative of nicotinamide, stable, slightly soluble in water. Drug is
taken up by macrophages and kills bacilli residing within this acidic environment.
Streptomycin

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 Introduction To Chemotherapy UNIT-IX

Most tubercle bacilli are inhibited by streptomycin. Streptomycin penetrates into cells
poorly, and thus it is active mainly against extracellular tubercle bacilli.

Antileprotic Drugs
Leprosy is caused by mycobacterium leprae. I t can be treated dapsone, rifampin,
clofazimine, ethionamide, etc. Dapsone
Dapsone (diaminodiphenylsulfone) is the most widely used drugs in the treatment of
leprosy and it inhibits folate synthesis. Sulfones are well absorbed from the gut and widely
distributed throughout body fluids and tissues. Excretion into urine is variable, and most
excreted drug is acetylated.
Side effects
Fever, pruritus, and rashes occur. Erythema nodosum often develops during dapsone
therapy in lepromatous leprosy. Hemolysis and methemoglobinemia can occur.

Antineoplastic agents
Cancer refers to a malignant neoplasm or new growth. Cancer cells manifest uncontrolled
proliferation, loss of function due to loss of capacity to differentiate. There are three
approaches for the management of cancer:
1. Radiotherapy
2. Surgery
3. Chemotherapy
Anticancer drugs are broadly classified into two:
 cytotoxic drugs and
 hormones.
Cytotoxic drugs are further classified into:
 Alkylating agents and related compounds (e.g. cyclophosphamide, lomustine,
thiotepa, cisplatin): These groups of drugs act by forming covalent bonds with DNA
and thus impending DNA replication.
 Antimetabolites (e.g. methotrexate, fluorouracil, mercaptopurine): These drugs
blocks or destabilize pathways in DNA synthesis.
 Cytotoxic antibiotics (e.g. Doxorubucin, bleomycin, dactinomycin): These drugs
inhibit DNA or RNA synthesis or cause fragmentation to DNA chains or interfere
with RNA polymerase and thus inhibit transcription.
 Plant derivatives (e.g. vincristine): Inhibits mitosis
Hormones and their antagonists are used in hormone sensitive tumors (eg. glucocorticoids
for lymphomas, oestrogens for prostatic cancer, tamoxifen for breast tumors).
General toxic effects of anticancer drugs: • Bone marrow toxicity. • Impaired wound
healing. • Sterility. • Loss of hair. • Damage to gastrointestinal epithelium

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 Introduction To Drugs Used In Anesthetics UNIT-X

CHAPTER: 10

ANESTHETIC DRUGS

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 Introduction To Drugs Used In Anesthetics UNIT-X

Introduction To Drugs Used In Anesthetics

Anesthesia is insensitivity to pain, especially as artificially induce by the administration of
gases or drugs before a surgical operation.
Classification according to area of body
1. General Anesthesia
General anesthesia is a total unconsciousness of the body achieved by the drugs that affects
the whole body. It is used for major surgical operations.
2. Local Anesthesia
Anesthesia that affects a limited area of the body and is used for minor surgical operations
e.g. dental procedures
Classification on the basis of route of administration
General anesthetics are administered by inhalation or by intravenous routes. They are
classified into two on the basis of their route of administration as inhalation and intravenous
anesthetics.
1. Inhalation anesthetics
The main agents are: Halothane, nitrous oxide, enflurane and ether.
1. Halothane: Is the most widely used agent, highly lipid soluble, potent. It causes
arrhythmia, hangover and the risk of liver damage is high if used repeatedly. More over,
Bradycardia, Malignant hyperthermia, Isoflurane, Desflurane, Sevoflurane

2. Nitrous oxide: Oderless and colourless gas. It is rapid in action and also an effective
analgesic agent. Its potency is low, hence must be combined with other agents. It is a
relatively free of serious unwanted effects.
3. Ether: Has analgesic and muscle relaxant properties. It is highly explosive, causes
respiratory tract irritation, postoperative nausea and vomiting. It is not widely used
currently.
2. INTRAVENOUS ANESTHETICS
Intravenous anesthetics act much more rapidly, producing unconsciousness in about 20
seconds, as soon as the drug reaches the brain from the site of its injection. These agents
used for induction of anaesthesia followed by inhalation agent. The main induction agent in
current use is: thiopentone, etomidate, propofol, ketamine and short acting benzodiazepine
(midazolam).
Thiopentone: Thiopentone is a barbiturate with very high lipid solubility. After intravenous
administration the drug enters to tissues with a large blood flow (liver, kidneys, brain, etc)
and more slowly to muscle. It causes cardiovascular depression.
Etomidate: It is more quickly metabolized and the risk of cardiovascular depression is less
compared to thiopentone.
Benzodiazepines including diazepam, lorazepam, and midazolam are used in general
anesthetic procedures. Compared with intravenous barbiturates, benzodiazepines produce
a slower onset of central nervous system effects.
Opioid analgesic anesthesia: Opioid analgesics can be used for general anesthesia, in
patients undergoing cardiac surgery and fentanyl and its derivates are commonly used for
these purposes.
Preanesthetic medication: It is the use of drugs prior to the administration of anaesthetic
agent with the important objective of making anaesthesia safer and more agreable to the
patient. The drugs commonly used are, opioid analgesics, barbiturates, anticholinergics, anti
emetics and glucocorticoids.

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 Introduction To Drugs Used In Anesthetics UNIT-X

Lidocaine (Local Anesthetics)

Pharmacokinetics
Local anesthetics are usually administered by injection into dermis and soft tissues located
in the area of nerves. Thus, absorption and distribution are not as important in controlling
the onset of effect. Local anesthetics abolish sensation and, in higher concentrations, motor
activity in a limited area of the body.

Mechanism Of Action
The primary mechanism of action of local anesthetics is blockade of voltage-gated sodium
channels.
Therapeutic Uses
Lidocaine is probably the most commonly used. Local anesthetics cause vasodilatation,
which leads to rapid diffusion away from the site of action and results in a short duration of
action when these drugs are administered alone. By adding the vasoconstrictor epinephrine
to the local anesthetic, the rate of local anesthetic diffusion and absorption is decreased.
This both minimizes systemic toxicity and increases the duration of action.

Adverse Effects
Neural toxicity, allergic reactions, depresses cardiac pacemaker activity, excitability, and
conduction.

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 Introduction To Toxicology UNIT-XII

Chapter: 11

Introduction of Autocoids and their

Antagonists

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 Introduction To Toxicology UNIT-XII

Introduction To Autacoids And Their Antagonists

INTRODUCTION
“Autacoids” (Greek “self-remedy”) is a collective term for various endogenous peptides,
prostaglandins, leukotrienes, and cytokines. These are sometimes also called local
hormones. They play important roles in physiologic processes and also have several
pharmacological significances.
1. Histamine
It is a potent tissue amine widely distributed in plant and animal tissues and in the venoms
of bees. In man, it is formed by decarboxylation of histidine and major portion is stored in
mast cells and basophils.
Mechanisms of Action: It acts on 2 major types of receptors a. Stimulation of H1 receptors
results in smooth muscle contraction, increased vascular permeability, and mucus
production. Both types of receptors are involved in vascular dilatation and edema
formation.
Pharmacological Actions:
1. Cardiovascular system
Histamine produces dilatation of capillaries and venules accompanied by a fall in blood
pressure.
2. Smooth Muscles: Histamine directly stimulates the smooth muscles of various tissues
including the bronchi and uterus.
3. Exocrine Glands: It is a powerful stimulant of HCl secretion by the gastric mucosa.
4. CNS: Histamine is formed locally in the brain and is believed to be a “waking amine”,
acting by “increasing the sensitivity of large cerebral areas to excitation inputs”
1. Antihistaminc Drugs
These drugs competitively block histamine receptors and are of two types:
1. H1 receptor antagonists
2. H2 receptor antagonists (used in the treatment of acid-peptic disease)
H1 Receptor Antagonists
Classification of H1 recepror antagonists:
a. Potent and sedative: such as diphenhydramine and promethazine.
b. Potent but less sedative: such as cyclizine and chlorpheniramine
c. Less potent and less sedative: such as pheniramine
d. Non-sedative: such as terfenadine, loratadine, and cetrizine.
Pharmacological Actions:
Antihistaminic Actions:-they block histamine effects at various sites. Most of them produce
CNS depression resulting in sedation, drowsiness, inability to concentrate, and disturbances
of coordination.
Pharmacokinetics:
They are well-absorbed following oral and parenteral administration. And are mainly
metabolized by the liver; degradation products are removed in the urine.
Therapeutic Uses:
1. Allergic Disorders:-Including urticaria, seasonal hay fever, atopic and contact
dermatitis, mild blood transfusion reactions.
2. Somnifacients
Many first generation antihistamines have strong sedative properties and are used in
the treatment of insomnia.

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 Introduction To Toxicology UNIT-XII

Adverse Effects:
Are usually mild. Most common is sedation. The most common anticholinergic adverse
effect is dryness of the mouth. They may themselves occasionally cause allergic reactions.
2. 5-Hydroxytreptamine (Serotonin)
5-HT causes constriction of renal, splanchnic, meningeal, and pulmonary arteries and veins
and venules, but dilatation of the blood vessels of skeletal musles, coronaries, and skin
capillaries. It also stimulates smooth muscles, especially of the intestines. Serotonin is
widely distributed in the CNS, serving as a neurotransmitter.
Side effects
Disturbances in sleep, mood, sexual behavior, motor activity, pain perception, migraine,
temperature regulation, endocrine control, psychiatric disorders and extra-pyramidal
activity.
Serotonin Agonists:
Sumatriptan is a selective agonist of 5-HT1 receptors and is highly effective in treating acute
attacks of migraine, but is not useful in the prevention. It relieves the nausea and vomiting,
but the headache may recur, necessitating repeated administrations.
Buspirone another serotonin agonist, is a useful effective anxiolytic agent.
Serotonin Antagonists:
a. Methysergide: blocks the actions of 5-HT on a variety of smooth muscles. It also has a
weak direct vasoconstrictor effect. It is an effective prophylactic agent for migrainous
headaches.
b. Cyproheptadine: is a potent antagonist of 5-HT and to a smaller extent of histamine and
acetylcholine. It is mainly used to relieve the itching associated with skin disorders such as
allergic dermatitis.
3. Prostaglandins:
They were named so because of their presumed origin from the prostate gland. Human
seminal fluid is the richest known source, but they are also present in various tissues. PG E2
and PG F2 are the two main prostaglandins. They play an important role in the development
of the inflammatory response in association with other mediators.
Pharmacological actions
Abortion
Several of the prostaglandins used as abortifacients (agents causing abortion).
Prostaglandins have the advantages of stimulating uterine contractions at any stage of
pregnancy.

Peptic Ulcer
Prostaglandins protect the mucous membrane of stomach. Misoprostol is sometimes used
to inhibit the secretion of gastric acid.

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Chapter: 12

Toxicology

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Introduction To Toxicology
Toxicology is defined as the study of the adverse effects of chemicals on living organisms
Toxicology is concerned with the deleterious effects of chemical and physical agents on all
living systems. The terms poison, toxic substance and toxicant are synonymous. The most
important axiom of toxicology is that “the dose makes the poison”, indicating that any
chemical or drug can be toxic if the dose or exposure becomes high enough.
Poisoning occurs by non-therapeutic substances such as household and environmental
agens, and due to over-dosage of therapeutic substances. Poison may be ingested
accidentally or deliberately. A difficult challenge to the health care provider is the
identification of the toxicant and limited availability of antidotes. Thus, the health care
provider in most cases may be limited with symptomatic therapy.
“Treat the patient, not the poison” remains the most basic and important principle of
clinical toxicology.
A toxic response can occur within minutes or after a delay of hours, days, months or years.
Acute toxicities are of particular interest for practicing health care provider.
General measures in poisoning
The treatment of a poisoned patient requires a rapid and genuine approach.
There are three principles underlying the management of poisoning:
1. Life support
2. Drug identification
3. Drug elimination and detoxification
Life support
Life support and supportive care is first line treatment. Drug overdose or poisoning by other
chemicals can often manifest itself as an acute clinical emergency. The kinds of life-
threatening emergencies include seizures, cardiac arrhythmias, circulatory shock and coma.
Massive damage to liver, lungs or kidneys can also lead to death with in a relatively short
period of time. Immediate supportive measures may take precedence over identification
and detoxification of the offending agent. Therefore, maintenance of vital functions such as
respiration, circulation, suppression of seizures, etc. is given priority.
Drug identification
The amount taken may have to be deduced from a combination of client history, clinical
manifestations and laboratory findings. The general approaches employed to reduce
systemic absorption of an ingested poison where the client still has an intact gag reflex is to
administer an emetic (eg. Syrup of epecac), a cathartic (eg. Magnesium sulphate), an
adsorbent (eg. Activated charcoal) or a combination of these. Within clinical environment,
more invasive procedures such as gastric lavage and haemodialysis can be performed.
Dug eliminiation and detoxification
Poisons normally are eliminated by hepatic biotransformation, renal excretion, or a
combination of these mechanisms. We can enhance drug elimination by using forced
dieresis, hemodialysis and hemoperfusion.

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Specific antidotes can also be used as detoxifying agents. Antidotes are available against
poisoning with the following substances and are able to reverse the toxic manifestations.

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