KRYSTAL JANE B. SALINAS BSN 2.
Date: June 22, 2019
NCM 106 PHARMACOLOGY
Define the following:
Pharmacology
> is the branch of biology concerned with the study of drug or medication action, where a drug can be
broadly defined as any man-made, natural, or endogenous (from within the body) molecule which exerts
a biochemical or physiological effect on the cell, tissue, organ, or organism (sometimes the word
pharmacon is used as a term to encompass these endogenous and exogenous bioactive species). More
specifically, it is the study of the interactions that occur between a living organism and chemicals that
affect normal or abnormal biochemical function.
Pharmacotherapeutic
> Pharmacotherapeutics is the clinical purpose or indication for giving a drug.It is the study of the
therapeutic uses and effects of drugs in patients. The focus of pharmacotherapy is the patient, not the
drug or the disease.
Pharmacokinetics
> Pharmacokinetics is the way the body acts on the drug once it is administered. It is the measure of the
rate (kinetics) of absorption, distribution, metabolism and excretion (ADME). All the four processes
involve drug movement across the membranes. To be able to cross the membranes it is necessary that
the drugs should be able dissolve directly into the lipid bilayer of the membrane; hence lipid soluble
drugs cross directly whereas drugs that are polar do not.
Pharmacodynamic
> The word pharmacodynamics is from two Greek words pharmakon: Drug
and dynamikós : force or power
Thus, pharmacodynamics is the study of the effects of drugs.Whether we are talking about
pharmaceutical therapeutics or recreational drugs, people take drugs to achieve a desired
pharmacological effect. And two key questions often asked prior to taking the drug are: “Howlong before
I feel the effect?” and “How long will the effect last?” Both of these questions can be answered by using
pharmacodynamic analyses.Most drugs are developed based on the theory that the drug interacts with a
biological structure (eg, receptor, enzyme, transporter, etc.), and that interaction leads to a specific effect
on the body. The strength and length of this interaction determines how quickly the drug initiates the
effect, and how long the effect lasts.
For example
¤ Penicillin is recognized as one of the first drugs to enter mass production, leading to a significant
reduction of bacterial infections across the world. Penicillin is an antibiotic, which means it kills bacteria.
The penicillin molecule binds to a bacterial enzyme (DD-transpeptidase) that creates “cross-links” in the
bacterial cell wall, preventing the cross-linking action. Thus penicillin prevents bacteria from creating
strong cell walls, in effect killing the bacteria. The interaction between penicillin and the DD-
transpeptidase enzyme depends on the amount of penicillin present. When large amounts of penicillin
are available, the enzyme is completely blocked. When small amounts of penicillin are available, the
enzyme resumes normal function. Thus the bacterial-killing activity of penicillin changes as drug levels in
the body change. This is considered the “pharmacodynamics” of penicillin. Using this information,
physicians can properly prescribe the penicillin dosing frequency to ensure high drug levels over the
course of treatment.
4 Stages of Movement
1. Absorption
Absorption is the movement of a drug from its site of administration into the blood. Most drugs are
absorbed by passive absorption but some drugs need carrier mediated transport. Small molecules
diffuse more rapidly than large molecules. Lipid soluble non – ionized drugs are absorbed faster.
Absorption is affected by blood flow, pain stress etc.
• Acidic drugs such as asprin will be better absorbed in the stomach whereas basic drug ike morphine
will be absorbed better in the intestine. Most of the absorption of the drug takes place in the small
intestine. Since the surface area of the stomach is much smaller than that of the intestine. Most of the
drugs are absorbed in the small intestine since the amount of time that the drugs spend in the stomach
is less and also the surface area of the stomach is small. If a basic drug is taken after a meal then the
activity of the drug can be reduced whereas if an acidic drug is taken after a meal then the action of the
can be noticed much more quickly, owing to the gastric absorption.There are some substances that are
partly soluble in water and it is these that will be absorbed and then an equivalent amount will be
absorbed from the undissolved portion. Thus complete absorption will take place. There are bile salts
present in the intestine which will aid in salvation of the drug and their resultant absorption. Drugs that
are amphipathic have no problem in getting absorbed. There are some drugs that are completely
insoluble in water such drugs float as globules in the intestine but the bile salts will emulsify these into
small enough particles such that absorption can take place. E.g. vitamins. Some of the drugs are similar
to compounds found in the body for e.g. thyroxine and such drugs can be absorbed into the system by
active transport.
When drugs are injected into the muscle, subcutaneous layer absorption still has to take place but it is
less dependent on the chemical nature of the drugs since the drugs are absorbed into the circulatory
system through the small pores in the capillary walls.
2. Distribution
Distribution is the movement of drugs throughout the body. Determined by the blood flow to the
tissues, it is ability of the drug to enter the vasculature system and the ability of the drug to enter the cell
if required.
3 .Metabolism or Biotransformation
It is the process of transformation of a drug within the body to make it more hydrophilic so that it can be
excreted out from the body by the kidneys. This needs to be done since drugs and chemicals are foreign
substances in our body. If the drug continues to be in the lipohilic state and is going to be filtered by the
glomerulus then it will be reabsorbed and remain in the body for prolonged periods. Hence metabolism
deals with making the drug more hydrophilic such that it can be excreted out from the body. In some
cases the metabolites can be more active than the drug itself e.g. anxiolytic benzodiazepines.Some
enzymes are highly specific and will breakdown only compounds that they recognize for e.g. glucose
dehydrogenase. But there are some enzymes such as pepsin which are not specific and will breakdown
most soluble proteins into smaller polypeptides or amino acids. This enzyme and many other proteolytic
enzymes attack the peptide bond that joins the amino acids to make proteins, and in this way break the
protein down.
Two types of enzymes are involved in metabolism:
Phase I Metabolism
These enzymes modify the drug chemically by processes such as oxidation, reduction and hydrolysis or
by the removal and addition of an active group.
Phase II Metabolism
These include the conjugation of a drug or a phase I metabolite with a polar group to render it possible
for excretion. e.g. sulphates and glucuronide
4. Excretion
Excretion is the removal of the substance from the body. Some drugs are either excreted out unchanged
or some are excreted out as metabolites in urine or bile. Drugs may also leave the body by natural routes
such as tears, sweat, breath and saliva. Patients with kidney or liver problem can have elevated levels of
drug in the system and it may be necessary to monitor the dose of the drug appropriately since a high
dose in the blood can lead to drug toxicity.
Type of Drug Therapy
Antimetabolites
Antimetabolites mimic the building blocks of DNA or RNA that cancer cells need to survive and grow.
When the cancer cell uses an antimetabolite instead of the natural substances, it can't produce normal
DNA or RNA and the cell dies.
Antimitotics
Antimitotics damage cancer cells by blocking a process called mitosis (cell division), which prevents
cancer cells from dividing and multiplying.
Antitumor Antibiotics
Antitumor antibiotics prevent cell division by either binding to DNA to prevent the cells from duplicating
or inhibiting RNA synthesis.
Asparagine-Specific Enzymes
Some enzymes can prevent cancer cells from surviving.
Bisphosphonates
Bisphosphonates are used to treat high levels of calcium in the blood caused by certain cancers,
including myeloma. Bisphosphonates won't slow or stop the spread of cancer, but they can slow bone
breakdown, increase bone thickness and reduce bone pain and fracture risk.
Chemotherapy
widely used treatment for cancer. The term chemotherapy refers to the drugs that prevent cancer cells
from dividing and growing. It does this by killing the dividing cells.
DNA-Damaging Agents (Antineoplastics) and Alkylating Agents
DNA-damaging agents (antineoplastics) and alkylating agents react with DNA to change it chemically and
keep it from allowing cell growth.
DNA-Repair Enzyme Inhibitors
DNA-repair enzyme inhibitors attack the cancer cell proteins (enzymes) that normally repair damage to
DNA. DNA repair is a normal and vital process within the cell. Without this repair process, the cancer cell
is much more susceptible to damage and cannot grow.
Histone Deacetylase Inhibitors
Histone deacetylase inhibitors attack cancer cells by targeting the proteins that support DNA in the cell
nucleus.
Hormones (Corticosteroids)
Certain hormones (corticosteroids) can kill lymphocytes. They're believed to work by blocking cell
metabolism through their effect on specific genes. In high doses, these synthetic hormones — relatives
of the natural hormone cortisol — can kill malignant lymphocytes.
Hypomethylating (Demethylating) Agents
Hypomethylating (demethylating) agents interfere with cancer cell duplication by slowing or reversing
hypermethylation. Methylation is a critical part of cell growth and replication. This process sometimes
speeds up in cancer cells.
Immunomodulators
Immunomodulators influence the immune system function by suppressing or stimulating immune
response.
Janus-Associated Kinase (JAK) Inhibitors
JAK inhibitors block the enzymes JAK1, JAK2, JAK3 and tyrosine kinase 2, which play a role in the cell-
signaling process that leads to the inflammatory and immune responses seen in certain diseases. JAK
inhibitors interrupt the signaling pathway.
Monoclonal Antibodies
Monoclonal antibodies are laboratory-produced proteins that target specific antigens on the cancer cell's
surface to interfere with the cell's function and destroy it. Some monoclonal antibodies are combined
with a toxin or radioactive substance.
Phosphoinositide 3-kinase inhibitors (PI3K inhibitors)
PI3K (phospho inositide 3 kinases) inhibitors are a group of closely related kinase proteins. They act like
switches in the cell – turning on other proteins. Switching on PI3Ks may make cells grow and multiply, or
trigger the development of blood vessels, or help cells to move around. In some cancers PI3K is
permanently switched on, which means that the cancer cells grow uncontrollably. Researchers are
developing new treatments that block (inhibit) PI3K. They hope this will stop the cancer cells growing
and make them die.
Proteasome Inhibitors
Proteasome inhibitors are designed to limit the effects of a cell structure called a proteasome. When a
proteasome doesn't function properly, the cell dies. Cancer cells may be more susceptible to the effects
of proteasome inhibition than normal cells.
Tyrosine Kinase Inhibitors
Tyrosine kinase inhibitors block the action of a specific, abnormal protein that gives cancer cells the
signal to grow.
Adverse Reaction
In pharmacology, any unexpected or dangerous reaction to a drug. An unwanted effect caused by the
administration of a drug. The onset of the adverse reaction may be sudden or develop over time.Also
called an adverse drug event (ADE), adverse drug reaction (ADR), adverse effect or adverse event.
Types of Adverse Reaction
There are several different types:
¤ Dose-related ¤ Allergic ¤ Idiosyncratic
Dose-related adverse drug reactions represent an exaggeration of the drug's therapeutic effects. For
example, a person taking a drug to reduce high blood pressure may feel dizzy or light-headed if the drug
reduces blood pressure too much. A person with diabetes may develop weakness, sweating, nausea, and
palpitations if insulin or an oral antidiabetic drug reduces the blood sugar level too much. This type of
adverse drug reaction is usually predictable but sometimes unavoidable. It may occur if a drug dose is
too high (overdose reaction), if the person is unusually sensitive to the drug, or if another drug slows the
metabolism of the first drug and thus increases its level in the blood (see Drug Interactions). Dose-
related reactions are usually not serious but are relatively common.
Allergic drug reactions are not dose-related but require prior exposure to a drug. Allergic reactions
develop when the body's immune system develops an inappropriate reaction to a drug (sometimes
referred to as sensitization). After a person is sensitized, later exposures to the drug produce one of
several different types of allergic reaction. Sometimes doctors do skin tests to help predict allergic drug
reactions.
Idiosyncratic adverse drug reactions result from mechanisms that are not currently understood. This
type of adverse drug reaction is largely unpredictable. Examples of such adverse drug reactions include
rashes, jaundice, anemia, a decrease in the white blood cell count, kidney damage, and nerve injury that
may impair vision or hearing. These reactions tend to be more serious but typically occur in a very small
number of people. Affected people may have genetic differences in the way their body metabolizes or
responds to drugs.
Drug Interaction
> A drug interaction is a reaction between two (or more) drugs or between a drug and a food, beverage,
or supplement. Taking a drug while having certain medical conditions can also cause a drug interaction.
For example, taking a nasal decongestant if you have high blood pressure may cause an unwanted
reaction.
A drug interaction can make a drug less effective, increase the action of a drug, or cause unwanted side
effects.
Pharmacokinetic Drug-drug Interactions
Duration and intensity of drug action in both target and non-target tissues is predicated on the drug’s
plasma level and ability to reach intended or unintended receptors. In addition to dosage, the plasma
level of a drug is modulated by the drug’s rate of absorption, distribution, metabolism, and clearance.6
These rates may be altered, i.e., induced or inhibited by concomitant drug therapy (Table 2). It is of note
that some pharmacokinetic drug-drug interactions may at times be harnessed to optimize a drug’s
therapeutic effect.
Table 2. Pharmacokinetic Drug-drug Interactions.
Type Examples of Mechanisms
Absorption Drug A causes vasoconstriction at the site of administration and interferes with the
systemic absorption of drug B administered at the same site
Drug A delays gastric emptying and the systemic absorption of drug B absorbed
primarily in the intestine
Drug A neutralizes gastric acid (elevates gastric pH) and prevents the absorption of
drug B
Drug A forms chelates or complexes with drug B and prevents its absorption
Distribution Drug A competes for plasma protein binding with drug B and increases its plasma
level
Drug A blocks the transport of drug B into hepatocytes and increases its plasma level
Drug A blocks the transport of drug B into the intestinal lumen and increases its
plasma level
Metabolism rug A induces a CYP450 isoenzyme responsible for the metabolism of drug B and
decreases its plasma level
Drug A, inhibits a CYP450 isoenzyme responsible for the metabolism of drug B and
increases its the plasma level
Drug A inhibits CYP450-independent oxidation and causes accumulation of toxic
intermediary metabolites of drug B
Renal clearance Drug A competes for renal tubular transport with drug B and
increases its elimination half-life
Biliary clearance Drug A increases the synthesis of biliary proteins involved in
the conjugation of drug B and decreases its plasma level
Renal clearance Drug A competes for renal tubular transport with drug B and increases its elimination
half-life
Biliary clearance Drug A increases the synthesis of biliary proteins involved in the conjugation of drug
B and decreases its plasma level
Consider the pharmacokinetic ADR between opioid analgesics and APAP. The opioid by binging to μ-
receptors in the gastrointestinal tract increases the tone of the anterior portion of the stomach,
decreases gastric motility, and delays the absorption of APAP, which takes place in the intestine. Another
example, which affects metabolism, is the interaction between metronidazole and alcohol.
Metronidazole inhibits the oxidation of an intermediary toxic metabolite of alcohol and causes severe
nausea and vomiting.
Pharmacodynamic Drug Interactions
Pharmacodynamic interactions can occur when two or more drugs have mechanisms of action that
result in the same physiological outcome. Pharmacodynamic interactions can be categorized broadly as:
synergistic (when the effect of two drugs is greater than the sum of their individual effects); antagonistic
(when the effect of two drugs is less than the sum of their individual effects); additive (when the effect
of two drugs is merely the sum of the effects of each); and sequence-dependent (when the order in
which two drugs are given governs their effects). Although pharmacodynamic interactions are relatively
common in clinical practice, adverse effects can usually be minimized if the interactions are anticipated
and appropriate counter-measures taken.
Drug Legislation
From drug possession to drug trafficking, a look at laws regulating controlled substances.Drug laws and
drug crimes have gotten lots of attention in the past decade. Laws in every state and at the federal level
prohibit the possession, manufacture, and sale of certain controlled substances -- including drugs like
marijuana, methamphetamine, ecstasy, cocaine, and heroin.
Illegal Drugs vs. Legal Drugs
The legality of a drug often depends on how it is being used -- or what it is being used for. For example,
amphetamines are used to treat attention deficit disorder, barbiturates help treat anxiety, and marijuana
can help alleviate cancer-induced nausea. But unprescribed and unsupervised use of these substances
(and many others) is thought to present a danger to individuals and to society in general. So, for
decades, lawmakers have stepped in to regulate the use, abuse, manufacture, and sale of illegal drugs.
Federal, State, and Local Drug Laws
Though there is a longstanding federal strategy in place to combat the abuse and distribution of
controlled substances, each state also has its own set of drug laws. One key difference between the two
is that while the majority of federal drug convictions are obtained for trafficking, the majority of local
and state arrests are made on charges of possession. Out of these state and local arrests, over half are
for the possession of marijuana.
Another difference between federal and state drug laws is the severity of consequences after a
conviction. Federal drug charges generally carry harsher punishments and longer sentences. State arrests
for simple possession (i.e. possession without intent to distribute the drug) tend to be charged as
misdemeanors and usually involve probation, a short term in a local jail, or a fine -- depending on the
criminal history and age of the person being charged.
Categories of Scheduled Control Substances
Controlled Substances are chemicals, pharmaceutical agents, etc., that have been identified by the
United States Department of Justice/Drug Enforcement Administration (DEA) as having the potential for
abuse. These substances have been categorized by the federal government into five “schedules”, or
categories based on their medicinal use and potential for abuse.
Schedule Categories:
Schedule 1 - drugs with little or no accepted medical use and a high potential for abuse (e.g., heroin,
LSD)
Schedule 2 – drugs with a high potential for abuse and potential for physical or severe psychological
dependance (e.g. morphine, codeine)
Schedule 3 – drugs with lower potential for abuse than Schedule 1 or 2 agents, but with the potential for
physical or psychological dependence (e.g. combination drugs such as vicodin® and Tylenol® with
codeine, anabolic steroids)
Schedule 4 – drugs with lower potential for abuse than Schedule 3 agents (e.g., diazepam,midazolam)
Schedule 5 – drugs with lower potential for abuse than Schedule 4 agents – primarily combination
products containing limited amounts of codeine (e.g., cough syrup)
Rights in Drug Administration
One of the recommendations to reduce medication errors and harm is to use the “five rights”: the right
patient, the right drug, the right dose, the right route, and the right time. When a medication error does
occur during the administration of a medication, we are quick to blame the nurse and accuse her/him of
not completing the five rights. The five rights should be accepted as a goal of the medication process not
the “be all and end all” of medication safety.
Judy Smetzer, Vice President of the Institute for Safe Medication Practices (ISMP), writes, “They are
merely broadly stated goals, or desired outcomes, of safe medication practices that offer no procedural
guidance on how to achieve these goals. Thus, simply holding healthcare practitioners accountable for
giving the right drug to the right patient in the right dose by the right route at the right time fails
miserably to ensure medication safety. Adding a sixth, seventh, or eighth right (e.g., right reason, right
drug formulation, right line attachment) is not the answer, either.”
