Basic Pharmacology

College of Medical Technology

Manila Central University
Jover D. Francisco, RPh
Instructor
DRUG ACTIONS

Most drugs bind to cellular receptors, where they initiate a series of biochemical reactions that alter the cells
physiology.

Pharmacology at the Cellular level

Drug Receptors proteins or glycoproteins that are present on the cell surface, on an organelle within a cell, or in
the cytoplasm.

When a drug binds to a receptor, one of the following actions is likely to occur:
1. Ion channel is opened or closed
2. Biochemical messengers, often called second messengers (cAMP, cGMP, Ca
++
, inositol phosphates) are
activated. Tranduce the signal stimulated by the drug.
3. A normal cellular function is physically inhibited. eg DNA synthesis, bacterial cell wall production
4. A cellular function is turned on. Eg steroid promotion of DNA transcription

The Receptor theory of Drug Action:
1. Langley and Ehrlich 1
st
proposed that drug actions were mediated by chemical receptors
2. Drug Response Theory

Clarks Theory (1933)
1. Drug response is proportional to the number
of receptors occupied.
2. Assumed that all drug-receptor interactions
were reversible.
3. Assumed that drug binding to receptors
represented only a fraction of the availably
drugs.
4. Assumed that each receptor bound only one
drug.

DEFINITION OF TERMS

Stephensons Modified Theory
1. Drug response depends on both the affinity of
a drug for its receptors and the drugs efficacy.
2. Described spare receptors. Proposed that
maximal response can be achieved even if a
fraction of receptors are unoccupied.
Affinity strength of binding between a drug and its receptor
Dissociation Constant measure of a drugs affinity for a given receptor. It is the concentration of drug required in
solution to achieve 50% occupancy of its receptors. Units are expressed in molar concentration.
Agonist drugs w/c alter the physiology of a cell by binding to plasma membrane or intracellular receptors.
Usually, a number of receptors must be occupied by agonists before a measurable change in cell
function occurs.
Strong Agonist causes maximal effects even though it may only occupy a small fraction of receptors on a cell.
Weak Agonist must be bound to many more receptors than a strong agonist to produce the same effect.
Partial Agonist drug that fails to produce maximal effects, even when all the receptors are occupied
Antagonist inhibit or block responses caused by agonists.
Competitive Antagonist competes with agonist for receptors. High dose agonist is required to achieve receptor
occupancy. Competitive antagonism is said to be surmountable.
Non Competitive Antagonist binds to a site other than the agonist-binding domain. Induces a conformational
changein the receptor such as the agonist no longer recognizes the agonist-binding domain. Considered
insurmountable.
Irreversible Antagonist (Non equilibrium competitive) also insurmountable. Competes with agonists for the
agonist-binding domain. In contrast to competitive antagonist, it permanently combines with the receptor.

Basic Pharmacology
College of Medical Technology
Manila Central University
Jover D. Francisco, RPh
Instructor
Physiological Antagonism two agonist,in unrelated reactions, cause opposite effects. Cancels one another.
Antagonism by Neutralization two drugs bind to one another, when combined, both drugs are inactive.


Pharmacology at the Organism Level

Efficacy degree to w/c a drug is able to induce maximal effects.
-used to compare drugs with diff mechanism but same effect.
eg. If drug A reduces blood pressure by 20mm and drug B reduces blood pressure by 10mm, then Drug A
has greater efficacy than Drug B.

Potency amount of drug required to produce 50% of the maximal response that the drug is capable of inducing.
- Compare drugs within a chemical class
eg. Morphine and codeine are both capable of relieving post-operative pain, a smaller dose of morphine
than codeine is required to achieve this effect.

Pharmacology at the Population Level

Before new drugs can be approved for marketing, their efficacy and safety must be tested in animal and human
population studies.

Effective Concentration 50% - the concentration of drug which induces a specified clinical effect in 50% of the
subjects to which the drug is administered.

Lethal Dose 50% - The concentration of drug which induces death in 50% of the subjects to which the drug is
administered.

Therapeutic Index a measure of the safety of a drug. Calculated by dividing the LD
50
by the ED
50.


Margin of Safety the margin between therapeutic and lethal doses of a drug.


Undesirable Effects of Drugs

Tolerance represents a decreased response to a drug. Clinically, it is seen when the dose of a drug must be
increased to achieved the same effect.
Metabolic drug is metabolized more rapidly after chronic use.
Cellular decreased number of drug receptors, known as down regulation
Behaviorallearning to hide signs of drugs effect. eg alcoholics learns to hide signs of drinking to avoid
being caught

Dependence occurs when a patient needs a drug to function normally. Detected when cessation of the drug
produces withdrawal symptoms. Eg. Chronic use of laxatives inorder to have normal bowel movement, coffee in
the morning to start the day.

Withdrawal occurs when a drug is no longer administered to a dependent patient. The symptoms of withdrawal
are often the opposite of the effects achieved by the drug.