INTRODUCTION TO PHARMACOLOGY

DEFINITION: Pharmacology is the science that deals with the study of drugs and their interaction with the living
systems.
The word Pharmacology is derived from Greek – pharmaco means drug and logos means study.

DRUG: Drug is a substance used in the diagnosis ,prevention or treatment of disease.

PHARMACOKINECTICS: Pharmacokinectics is the study of the absorption distribution ,metabolism and excretion
of drugs, i.e what the body does the drug (in Greek kinesis = movement).

PHARMACODYNAMICS : Pharmacodynamics is the study of the effect of the drugs on the body and their
mechanism of action, i.e what the drug does the body.

THERAPEUTICS: Therapeutics deals with the use of drugs in the prevention and treatment of disease.

TOXICOLOGY : Toxicology deals with the adverse effect of the drug and also the study of poisons, i.e detection,
prevention and treatment of poisoning [Toxico =poison in Greek.

CHEMOTHERAPHY : Chemotherapy is the use of chemicals for the treatment of infections. the term anow also
includes the use of chemical to treat malignancies.

PHARMACY: Pharmacy is the science of identification , compounding and dispensing of drugs .It also includes
collection, isolation, purification, synthesis and Standardization of medical substances.

SOURCES OF DRUGS
The sources of drugs could be natural or synthetic

NATURAL SOURCES:
1. PLANTS, e.g Atropine ,Morphine ,Quinine, digoxine, pilocarpine, physostigmine.
2. ANIMALS, e.g . Insulin, heparin, gonadotrophins and antitoxic sera.
3. MINERALS, Magnesium sulphate, Aluminium hydroxide, iron, sulphur and radio active isotopes.
4. MICROORGANISMS, Antibacterial agents are obtained from some bacteria and fungi. we thus have pencillins,
cephalosporins, tetracycline and other antibiotics.
5. HUMAN: some drugs are obtained from man, e.g Immunoglobulin from blood,growth hormone from
anterior pituitary and chorionic gonadotrophins from the urine of pregnant woman.

SYNTHETIC : Most drugs are now synthesized .e.g quinolones, omeprazole, sulfonamides, pancuronium,
neostigmi ne. Many drugs are obtained from cell culture, e.g urokinase from cultured kidney cells. some are now
produced by recombinant DNA technology, e.g human insulin, tissue plasmogen activator and some drugs by
Hybridoma technique, e.g monoclonal antibodies.

ROUTES OF DRUG ADMINISTRATION

Drugs may be administered by various routes, the choice of the route in a given patient depends on the
properties of the drug and the patients requirements. A knowledge of advantage and disadvantage of the routes
of drug administration is essential.The route can be broadly divided into: Enteral,
Parenteral,
Rectal and Others

ENTERAL ROUTE (ORAL INGESTION ) This is the most common ,oldest and safest routes of drug administration. the
large surface area of the GI, the mixing of its content and the differences in pH at different parts of the gut help
effective absorption of the drugs given orally. Oral refers to two methods of administration: applying topically to the
mouth, swallowing for absorption along the gastrointestinal (GI) tract into systemic circulation. PO (from the Latin per
os) is the abbreviation used to indicate oral route of medication administration

ADVANTAGE
1. Safest route
2. Most convenient - can be self- administered, pain free, easy to take
 3. Most economical
4. Drugs can be self-administered
5. Non-invasive route

DISADVANTAGES
1. Onset of action is slower as absorption needs time.
2. Some drugs may not be absorbed due to certain physical characteristics, e.g streptomycin.
3. There may be irregularities in absorption.
4. Irritation to the GIT may lead to vomiting.
5. Some drugs may be destroyed by gastric juices.e.g insulin.
6. Cannot be given to unconscious and uncooperative patients.
7. Some drugs may undergo extensive first pass metabolism in liver.
8. Patients may forget to take the tablet which is the practical problem.
9. effect too slow for emergencies.
10. unpleasant taste of some drugs

First-pass Effect The first-pass effect is the term used for the hepatic metabolism of a pharmacological agent when it
is absorbed from the gut and delivered to the liver via the portal circulation. The greater the first-pass effect, the less
the agent will reach the systemic circulation when the agent is administered orally. Food and G-I motility can affect
drug absorption. Often patient instructions include a direction to take with food or take on an empty stomach.
Absorption is slower with food (milk and milk products) for tetracyclines and penicillins, etc. However, for propranolol
bioavailability is higher after food, and for griseofulvin absorption is higher after a fatty meal.

Oral Dosage Forms Common dose forms for oral administration, tablets , capsules, liquids , solutions suspensions,
syrups, elixirs

PARENTERAL ROUTE;- Here the drugs are directly delivered into tissue fluids or blood.

ADVANTAGE
1. Action is more rapid and predictable than oral administration.
2. These routes can be employed in unconscious or uncooperative patients.
3. Gastric irritant can be given parenterally and therefore irritation to the GIT can be avoided.
4. It can be used in patients with vomiting or those unable to swallow
5. In emergencies parenteral routes are very useful.
6. Digestion by the gastric and intestinal juices and the first pass metabolism are avoided

DISADVANTAGES
1. A-sepsis must be maintained.
2. Injection may be painful.
3. More expensive less safe and inconvenient.
4. Injury to nerve and other tissues may occur.

Parenteral route include:

1. Injections
2. 2.Inhalation
3. Intramuscular
4. subcutaneous
5. Trans-dermal route
6. Trans-mucosal route
7. Intra-dermal

Intra-dermal; These drug are injected into the layers of the skin eg: BCG vaccine, Smallpox vaccine.

Subcutaneous (SC) injection; Here the drug is deposited in the SC tissue, e.g.insulin, heparin. As this tissue is less
vascular, absorption is slow and largely uniform and this make the drug long- acting.

DISADVANTAGES
As SC tissue is richly supplied by nerves, irritant drugs cannot be injected.
Drugs can also be administered subcutaneously as :

1. Dermojet : In this method ,a high velocity jet of drug solution is projected from a fine orifice using a gun .The
solution gets deposited in the SC tissue from where it is absorbed. As needle is not required this method is
painless. It is suitable for vaccines.

2. pellet implantation : Small pellets packed with drugs are implanted SC. The drug is slowly released for weeks
or months to provide constant blood levels,e.g, testosterone, desoxycortocosterone acetate.
3. sialistic implants : The drug is packed in sialistic tubes and implanted SC. The drug gets absorbed over
months to provide constant blood levels, e.g .hormones and contraceptives. The empty non-biodegradable
implant has to be removed.

INTRAMUSCULAR: Aqueous solution of the drug is injected into one of the large skeletal muscle – deltoid, triceps,
gluteus or rectus femoris. Absorption into the plasma occurs by simple diffusion, large molecules enter through
the lymphatic channels. As the muscle are vascular ,absorption is rapid and quite uniform.

Drugs are absorbed faster from the deltoid region than gluteal region especially in women. The volume of
injection should not exceed 10ml. For infants rectus femoris is used instead of gluteus which is not
well-developed till the child start walking. oily solution or suspension, the absorption is slow and steady. Soluble
substances ,Mild irritant ,depot preparations , suspensions and colloids can be injected by this route.

ADVANTAGES
Intramuscular route is reliable.
Absorption is rapid.

DISADVANTAGES
IM injection may be painful.
It may result in an abscess.
Risk of nerve injury –irritant solutions can damage the nerve if injected near the nerve.
The needle may also puncture the blood vessel.

INTRAVENOUS (IV); Here, the drug is injected into one of the superficial veins so that it directly reaches the
circulation and is immediately available for action.

Drug can be given IV as :

1. A bolus: the drug is dissolved in a suitable amount of vehicle and injected slowly. An initial large dose is given,
e.g . heparin.
2. slowly : over 15-20 min, e.g. aminophylline.
3. slow infusion: when constant plasma concentration are required, e.g.oxytocin in labor or when large volumes
have to be given, e.g. dextrose, saline.

ADVANTAGES
IV route is useful in emergencies because the drug is immediately available for action.
It gives 100% bioavailability.
Large volume and irritants can be given,they quickly diluted in blood.
Rapid dose adjustments are possible-if unwanted effectes occur,infusion can be stopped.

DISADVANTAGES
Once injected ,the drug cannot be withdrawn.
Irritation of the vein may cause thrombophlebitis.
Self medication is difficult.
The solution should be sterile and strict aseptic measures should be taken.

Administration of IV solutions
Maintain strict asepsis.
Before starting infusion the IV line should be flushed with saline.
Watch for sign of extravasation of fluid and thrombophlebitis.
Make sure that there are no air bubbles in syringe and tubing.
Intraperitonial: Peritonium offers a large surface area for absorption, This route is also used for peritonial
dialysis.

Intrathecal: Drugs can be injected into the subarachnoid space for action on the CNS, e.g. spinal
anesthetics.some antibiotics and corticosteroids are also injected by this route to produce high local
concentrations.

Intra-articular: Drugs are injected directly into a joint for the treatment of arthritis and other diseases of the
joints.strict aseptic precautions are required, e.g. hydrocortisone is injected into the affected joint,in rheumatoid
arthritis.

Intra-arterial: Here the drug is injected directly into the arteries.it is used only in the treatment of peripheral
vascular disease, local malignancies and angiograms.

Intramedullary: This route involves injection into a bone marrow; now this rarely used.

Inhalation: Volatile liquids and gases are given by inhalation, e.g GA. Solution of drug particles and the fine
droplets are inhaled as aerosol, e.g . Salbutamol, Inhaled drugs and vapour may act and absorbed on the
pulmonary epithlium and mucous membranes of the respiratory tract.

ADVANTAGES
Almost instaneous absorption of the drug is achieved because large surface area of the lungs.
Hepatic first pass metabolim is avoided.
Absorption and excretion through lunges.

DISADVANTAGES
Irritant gases may enhance pulmonary secretions and should be avioded by this route.

TRANSDERMAL ROUTE: Highly lipid soluble drugs can be applied over the skin for slow and prolonged absorption,
e.g nitroglycerin ointment in angina pectoris, Adhesive units, inunction, iontophoresis and jet injection are some
forms of transdermal drug delivery.

ADVANTAGES
Duration of action is prolonged.
Provide constant plasma levels.
Patient compliance is good.

Inunction: In this route of administration the drug is rubbed in to the skin and it gets absorbed to produce
systemic effects.

Iontophoresis: In this procedure, galvanic current is used for bringing about penetration of lipid insoluble drugs
into the deeper tissues where its action is required, e.g. salicylates, fluoride iontophoresis is used in the
treatment of dental hypersensitivity.

Jet injection: As absorption of drug occurs across the layers of the skin.

TRANSMUCOSAL: Drug are absorbed across the mucous membranes. It includes sublingual, nasal and rectal
routes.

Sublingual: Here, the tablet or pellet containing the drug is placed under the tongue. it dissolved and the drug is
absorbed across the sublingual mucosa, e.g. Nitroglycerin, nifedipine, buprenorphine.

ADVANTAGES
Absorption is rapid –within minutes the drug reaches the circulation.
First pass metabolism is avoided.
After the desired effect is obtained, the drug can be spat out to avoid the unwanted effects.

DISADVANTAGES
Buccal ulceration can occur.
Nasal: Drugs can be administered through nasal route .e.g. Oxytocin spray, oxymetazoline, budesonide for
allergic rhinitis.

Rectal : Rectum has a rich blood supply and drugs can cross the rectal mucosa to be absorbed for systemic
effect.

Drugs absorbed from the upper part of the rectum are carried by the superior hemorrhoidal vein to the portal
circulation. e.g indomethacin, chlorpromacine, diazepam can be given rectally.

ADVANTAGES
Gastric irritation is avoided.
Can be administered by unskilled persons.
Useful in geriatric patient and others with vomiting and those unable to swallow.

DISADVANTAGES
Irritation of the rectum can occur.
Absorption may be irregular and unpredictable.(enema )

Enema is the administration of a drug in liquid form into the rectum. enema may be evacuant or retension
enema;

Evacuant enema: In order to empty the bowel, about 600ml of soap water is administered per rectum. it is given
prior to surgeries, obstetric procedures and radiological examination of gut.

Retention enema: The drug is administered with about 100ml of fluids and is retained in the rectum for local
action.e.g prednisolone enema in ulcerative colitis.

TOPICAL: Drugs may be applied on the skin for local action as ointment ,cream , gel ,powder, paste, etc. drugs
may also be applied on the mucous membrane eg. the eyes, ears, and nose as ointment ,drops and sprays. Drugs
may be administered as suppository for rectum, bougie for urethra and pessary (oval shape) and douche for
vagina.e.g antifungal pessaries in vaginal candidiasis.

SPECIAL DRUG DELIVERY SYSTEM

In order to improve drug delivery, to prolong the duration of action and improve the patient compliance, special
drug delivery system are used. some such systems are
ocusert,
progestasert,
transdermal adhesive unit,
prodrug,
osmotic pumps,
computerized pumps and methods using monoclonal antibodies and liposomes as carriers.

Ocusert: Ocusert systems are thin elliptical units that contains the drug reservoir which slowly release the drug
by diffusion.e.g pilocarpine ocusert used in glaucoma is placed under the lid and can deliver the pilocarpine for 7
days.

Progestasert: is inserted into the uterus where it delivers progesterone constantly for one year.

Trans-dermal adhesive units: Prodrug is an inactive form of a drug which gets metabolized to the active
derivative in the body. e.g dopamine.its does not cross BBB but levo dopa a pro-drug crosses BBB and it is
converted to dopamine in the CNS. Bacampicillin a prodrug of ampicillin.

Osmotic pumps are small tablet shape units containing the drug and osmotic substances in two different
chambers. the tablet are swallowed and reaches the gut, water enter into the tablet through SPM. the osmotic
layers swells and pushes the drug slowly.

Computerized miniature pumps: These are Programmed to release drugs at a definite rate and continuously .e.g
insline and anticancer drugs.
Monoclonal antibodies are antibodies that fight against the tumor .

Liposome are phospholipids suspended in aqueous vehicles to form minute vesicles . Drugs encapsulated in
liposomes, mainly used for malignant tumors.

NURSES RESPONSIBILITIES

Ensure the correct drug is administered by the right route and in the right dose.
History of allergy should be taken particularly before parental administration of the drugs.
Monitor the adverse effect.
Drugs should be kept in safe place.
Check the prescription, drug label and the patients name before the administration of drugs.

PHARMACOKINETICS

PHARMACOKINETIC: Pharmacokinetics is the study of the absorption ,distribution , metabolism and excretion of
the drugs, i.e the movement of the drugs into, within and out of the body. once drug is administered it is
absorbed ,i.e .enters the blood, then it is distributed to different parts of the body, reaches the site of action, it is
metabolized and excreted. All these processes involve passage of the drug molecules across various barriers –
like the intestinal epithelium, cell membrane, renal filtering membrane, capillary barrier.
Drugs may be transported across the membrane by passive or active transport.

Passive transport: The drug moves across a membrane without any need for energy.

Active transport: It is the transfer of drugs against a concentration of drugs against a concentration gradient
and needs energy. It is carried by a specific carrier protein. only drugs related to natural metabolites are
transported by this process, e.g levodopa, iron, aminoacids, penicillin and probenecid are given together, the
excretion of penicillin is delayed by probenecid.

ABSORPTION; Absorption is defined as the passage of the drug from the site of administration into the circulation.
for a drug to reach its site of action, it must pass through various membranes depending on the route of
administration .

Absorption occurs by one of the processes i.e passive diffusion or active transport. except for IV route,
absorption is important for all other route of administration. several factor influence the rate and extent of
absorption of a drug. they are:

1. Disintegration and dissolution time: The drug taken orally should break-up into individual particles to be
absorped, then it has to dissolve in the GI fluids. In case of drugs given SC or IM, the drug molecules have to
dissolve in the tissue fluids. liquids are absorbed faster than solids. Delay in disintegration and dissolution result
in delayed absorption.

2. Formulation: Inert substance used with drugs as diluent like starch and lactose may sometimes interfere with
absorption.

3. Particle size: small particle size is important for better absorption of drugs. Drugs like corticosteroids,
griseofulvin, digoxin, asprin and tolbutamide are well absorbed when given as small particles.

4. Lipid solubility: lipid soluble drugs are absorbed faster and better by dissolving in the phospholipids of the cell
membrane.

5. pH and ionization: Ionized drugs are poorly absorbed while unionized drugs are lipid soluble and are well
absorbed. Acidic drugs remain unionized in acidic medium of the stomach and are rapidly absorbed, e.g aspirin,
barbiturates. Basic drugs are unionized when they are reach the alkaline medium of intestine from where they
are rapidly absorbed, e.g pethidine, ephedrine. strong acid and bases are highly ionized and therefore poorly
absorbed, e.g heparin, streptomycin.

6. Area and vascularity of the absorbing surface:larger area of the absorbing surface and more the vascularity –
better is the absorption.Thus most of the drug absorbed from the small intestine.
7. Gastrointestinal motility: Gastric emptying time-if gastric emptying is faster, the passage of the drug to the
intestines is quicker and hence absorption is faster.

First pass metabolism: First pass metabolism is the metabolism of the drug during its passage from the site of
absorption to the systemic circulation. it is also called pre-systemic metabolism or first pass effect.
Drugs given orally may be metabolized in the gut wall and in the liver before reaching the systemic circulation.
the extent of FPM differs from drug to drug and person to person. FPM may result in partial to total inactivation
of the drug. when it is partial, it can be compensated by giving higher dose of particular drug, e.g nitroglycerin,
salbutamol.

Bioavailability; is the fraction of the drug that reaches the systemic circulation following administration of any
route. IV -100% Bioavailability, chlortetracyclinem30%, chloroquin 80%, diazepam 100%.

Bioeqivalence : it is the study of comparison bioavailability of different formulation of the same drug.

Metabolism;- Metabolism or biotransformation is the process of biochemical alteration of the drug in the
body.Body treats most of the drugs as foreign substance and tries to inactivate and eliminate them by various
biochemical reactions.

Theses processes convert the drugs into more polar, water soluble compounds so that they are easily excreted
through the kidneys. e.g frusemide, atenolol. mainly drugs are metabolized in liver some are metabolized
kidney, lungs, blood and skin. the chemical reactions of biotrasformation can take place in two phases,

1. phase I (Non-synthetic reactions) : convert the drug to more polar metabolite by oxidation,reduction,or
hydrolysis.if the metabolites are not water soluble it undergoes phase II reactions.

2. phase II (Synthetic reaction): in this reactions water soluble substance present in the body like glucuronic
acid, sulfuric acid or an aminoacid combine with the drug to form a highly polar compounds it excreted by the
kidneys. large molecules are excreted through the bile.

Excretion;- The major organs of excretion are the kidneys, intestine, biliary system and the lungs. Drugs are small
amounts are excreted in saliva,sweat ,and milk. Renal excretion Kidney is the most important organ of drug
excretion.highly lipid soluble drugs are reabsorbed in in the renal tubules ,so their excretion is slow.

Unabsorbed portion of the orally administered drugs are eliminated through the feces. large water soluble
conjugates are excreted in the bile. The lungs are the main route of elimination for gases and liquids, e.g. GA,
Alcohol.

Plasma half-life (t1/2) is the time taken for the plasma concentration of a drug to be reduced to half its value.

Minimum dose is the smallest dose required to produce a desired therapeutic effect of the drug. Maximum
dose is the largest dose of the drug that can be safely given to a patient without producing harmful effect.

Toxic dose is the dose of the drug which produce undesirable effects in majority of the patients.

Lethal dose is the dose of the drug which can cause death. e.g lethal dose of phenobarbitone is 6-10gm.

PHARMACODYNAMICS

PHARMACODYNAMICS; Pharmacodynamics is the study of actions of the drugs on the body and their mechanism
of action, i.e to know what drugs do and how they do it. Drugs produce their effects by interacting with the
physiological system of the organisms. By such interaction drugs can only modify the rate of function of various
systems. e.g drugs may disrupt the secretions. but they cannot change the basic function of any physiological
system. Thus drugs act by :
1. Stimulation
2. Depression
3. Irritation
4. Replacement
5. Anti-infective or cytotoxic action
6. Modification of the immune status
Stimulation is the in activity of the specialized cells, e.g adrenaline stimulates the heart.

Depression is the in activity of the specialized cells, e.g quinidine depresses the heart.

Irritation : This can occur on all types of tissues in the body and may result in inflammation, corrosion and
necrosis of cells.

Replacement : drugs may be used for replacement when there is deficiency of natural subatances like
hormones ,metabolites or nutrients ,e.g insulin in diabetes, iron in anemia ,vit C in scurvy.

Anti –infective and cytotoxic action: drugs may act by specifically destroying infective organism,e.g penicillin,
cytotoxic effect on cancer cells.

Modification of immune status: vaccines and sera act by improving our immunity while immunosuppressants act
by depressing immunity, e.g glucocorticoids.

Sites and mechanism of drug action Sites

drugs may produce their effects locally or systematically.

Local : drugs may act at the site of application.e.g antibiotics, antifungal agent.

Drugs may act by one or more complex mechanism of action. fundamental mechanism of drug action may be:
Through receptor
Through enzymes and pumps
Through ion channel
By physical action
By chemical interaction
By altering metabolic processes

Through receptor;- Drugs may interact specific receptor in the body through enzymes and pumps.
Drugs may act by inhibition of various enzymes, thus altering the enzyme –mediated reaction, e.g . Allopurinal
inhibits the enzyme xanthine oxidase, acetazolamide inhibit carbonic anhydrase.

Through ion channel. Drugs may interfere with the movement of ions across specific channels, e.g . Ca channel
blocker, K channel blocker.

Physical action;- The action of drug could result from its physical properties. E.g .absorption –activated charcoal
in poisoning.

Chemical interaction;- Drugs may act by chemical reaction. Eg Antacids - Neutralize gastric acids

Alternating metabolic processes;- drugs like antimicrobial alter the metabolic pathway in the micro organism
resulting destruction of MO.e.g sulfonamides interfere with bacterial folic acid synthesis.

Receptor: A receptor is a site on the cell with which an agonist binds to, to bring about a change. Receptor are
proteins, they may be present in the cytoplasm or on the nucleus.

Functions of receptors
The receptor has to identify the compound, and when the compound binds to the receptor, it has convey the
message to bring about a response.

Agonist : An agonist is a substance that binds to the receptor and produce a response.
Antagonist : An antagonist is a substance that binds to the receptor and prevents the action of agonist on the
receptor.
Partial agonist :It binds to the receptor but has low intrinsic activity that is , produce partial response.

Drug synergism and antagonism

When two or more drugs are given concurrently, the effect may be additive, synergistic or antagonistic.
Additive effect : the effect of two or more drugs get added up and the total effect is equal to the sum of their
individual actions.e.g . Ephedrine with theophylline in bronchial asthma.

Synergism : when action of one drug is enhanced or facilitated by another drug the combination is synergistic.
here the total effect of the combonation is greater than the sum of their independent effect. it is often called
‘potentiation’ or supra- additive effect.e.g acetylcholine + physostigmine.

Antagonism : one drug opposing or inhibiting the action of another drug is antagonism. based on the mechanism,
antagonism may be; Chemical antagonism, physiological antagonism, Antagonism at the receptor
level-Reversible (competitive), Irreversible -Non- competitive antagonism

Chemical antagonism: Two substance chemically interact to result in inactivation of the effect, e.g . Antacid like
aluminium hydroxide neutralize gastric acids.

Physiological antagonism: Two drugs act at different sites to produce opposing effect. E.g . Insulin and glucogan
have opposite effects on the blood sugar level.

Antagonism at the receptor level ;- The antagonist inhibits the binding of the agonist to the receptor. such
antagonism may be reversible or irreversible.

Reversible competitive antagonism : The agonist and antagonist compete for the same receptor. By increasing
the concentration of the agonist, the antagonism can be overcome. it is thus reversible antagonism. Ace and
atropine compete at muscarnic receptor. the antagonism can be overcome by increasing the concentration of
Ach at the receptor.

Irreversible antagonism : The antagonist binds so firmly by covalent bonds to the receptor that it dissociate
slowly. it block the agonist. the blockade cannot be overcome by increase the dose of agonist hence it is
irreversible antagonism, e.g. Adrenaline and phenoxybenzamine at- adrenergic receptor.

Factors modifying the drug action

Various factor modifying the drug action. they are

1. body weight : The recommended dose is calculated for medium and built persons. for the obese and
underweight persons, the dose has to be calculated individually.

Dose = body wt (kg)/70 x average adult dose

2. Age : In the new born, the liver and kidney are not fully mature to handle the drugs, e.g barbiturates which
produce sedation in adults may produce excitation in children.

Young's formula, child dose = age (years) x adult dose age +12

3. Sex : The hormonal effects and smaller body size may influence drug response in women. special care is
necessary while prescribing for pregnant and lactating women during menstruation.

4. species and race : response to drug may vary with species and race.e.g. Rabbits are resistant to atropine
need more dose to produce mydriasis.

5. Diet and environment : food interfere with the absorption of the drugs. e.g.tetracycline form complexes with
Ca present in the food and are poorly absorbed.

6. Route of administration : route of administration may modify the pharmacodynamic response.e.g. Mgso
when given orally it is a purgative, in IV it causes CNS depression and has anti-convulsion effects. When applied
topically it reduce local edema.

7. Genetic factor : the enzyme production are genetically controlled. The response of the drugs differ according
to the metabolizing enzymes.

A. Acetylation of drugs : the rate of drug acetylation differs among individuals. people may be fast or slow
acetylators.e.g. INH, sulfonamides and hydralazine.
B. G6PD deficiency : primaquine,sulphones and quinolones can cause hemolysis in such people.
8. Dose : it is interesting to know the response of the drug, the dose is increased the response also increased till
the maximum reached .incase some drugs further increased the drug response is lowered.e.g. Myasthenia
gravis ,neostigmine enhance the muscle power in therapeutic doses in higher the dose it produce muscle
paralysis.

9. Diseases : presence of certain disease can influence drug responses,e.g . Malabsorption –drugs are poorly
absorbed ,liver diseases-rate of metabolism reduced.

10. Repeated dosing :Can result in cumulation, tolerance, tachyphylaxis. Cumulation : Drugs like digoxin
which are slowly eliminated may cumulate resulting in toxicity.
Tolerance : Tolerance is defined as the capacity of the body to become less responsive to a substance. Lethal
dose of Morphine is 250 mg, addict can tolerate morphine in gm.

Trachy phylaxis : is the rapid development of tolerance.when some drugs are administered repeadly at short
interval ,tolerance develops rapidly and is known as tachyphylaxis or acute tolerance.

11. Psychological factor : the doctor patient relationship as well as the nursing care influence the response to a
large extent by acting on the patient psychology. The patients confidence in the doctor may itself be sufficient to
relieve a suffering, particularly the psychomatic disorder. placebo is the inert dosage form with no biological
activity but only resembles the actual preparation in appearance.

12. presence of other drugs : The concurrent use of two or more drugs can influence the response of each
other.