Lecture 1
Pharmacology 1
Level 2 – 2024/2025
Dr. Khaled Kandel
General Pharmacology
What is Pharmacology? What is the Drug?
➢ Pharmacology is the study of effect of chemicals (drugs) on living ➢ A drug is more than a pill. It is a compound of chemical elements
tissues and how those chemicals help diagnose, treat, and prevent that interacts with the body’s chemistry causing a chain reaction
disease or correct the pathophysiology of living tissues. of events.
➢ The term pharmacology is derived from two Greek words: ➢ Drugs are given to achieve a therapeutic effect.
✓ Pharmakon → the Greek word for drugs. ➢ However, most drugs also have side effects.
✓ Logos → the Greek word for science. ✓ Some side effects are desirable and some are not.
Medical uses for drugs Drug Sources
1) Therapeutic use.
1) Plants
2) Diagnostic use.
➢ A number of plants have medicinal qualities and have been used
3) Replacement use.
for centuries as natural remedies for injuries and illnesses.
4) Preventive or Prophylactic use.
2) Animals
➢ Hormone e.g. Insulin.
3) Minerals
Pharmacology
➢ Pharmacology includes the study of:
A. Pharmacodynamics
B. Pharmacokinetics
✓ Define the term pharmacokinetics:
▪ The movement of drugs within the body from dosage to elimination.
✓ Pharmacokinetics encompasses the absorption, distribution, metabolism, and excretion of drugs (ADME).
A. Pharmacodynamics
➢ Pharmacodynamics refers to the action of the drug at the cellular level.
➢ This includes:
a) The binding of a drug to its receptor or binding site.
b) The relationship of dose and therapeutic level to the physiologic response.
c) The relationship of drug action and efficacy to dosage interval.
Receptor Drug
➢ Receptor → Any cellular macromolecule that a neurotransmitter or ➢ Drug → A chemical substance that interacts with a receptor to
drug binds to initiate its effects. produce a physiologic effect.
➢ The endogenous function of a receptor is to participate in ➢ The ability to bind to a receptor is mediated by the chemical
neurotransmission or physiologic regulation. structure of the drug that allows it to interact with complementary
➢ Humankind has learned that drugs can be given to activate or block surfaces on the receptor.
these receptors to produce a variety of effects
➢ Notice how the amino acids that make up the receptor protein
contribute functional groups to allow a neurotransmitter or
drug to bind to this receptor.
Drug Actions Drug Effects
➢ Action occurs when drug binds to receptor and this action may be: ➢ Most drugs bind to cellular receptors.
a) Ion channel is opened or closed. ➢ Initiate biochemical reactions.
b) Second messenger is activated. ➢ Pharmacological effect is due to the alteration of an intrinsic
✓ cAMP, cGMP, Ca++, inositol phosphates, etc. physiologic process and not the creation of a new process.
✓ Initiates a series of chemical reactions.
c) Normal cellular function is physically inhibited.
d) Cellular function is “turned on”.
Ligands
➢ They are molecules attach selectively bind to particular receptors.
➢ Endogenous receptors are naturally occurring receptors within the body that respond to endogenous ligands, which are molecules produced
by the body itself.
➢ Exogenous receptors are receptors that respond to ligands originating from outside the body. These ligands can be drugs, toxins, or other
foreign substances.
➢ Receptors can be activated either by endogenous or exogenous, leads to change in the biological response.
a) Full agonist b) Partial agonist c) Inverse agonist
✓ The ligands that increase the activity of ✓ These ligands partially increase the ✓ A drug that binds to the same receptor as
the receptors & produce the maximal activity of the receptors but do not an agonist but induces a pharmacological
response. produce the maximal response like full response opposite to that of the agonist
agonist even when present in excess (negative intrinsic activity).
amount.
✓ Ex. Morphine, mimics the action of ✓ Ex. Buspirone, is an anxiolytic drug, used to ✓ Ex. Β-carboline produce anxiety due to
endorphins at opioid receptors. treat an anxiety disorder. stimulation of GABA receptors.
➢ A neutral antagonist has no activity in the absence of an agonist or inverse agonist but can block the activity of either.
Targets of Drug actions (PROTEIN TARGETS FOR DRUG BINDING)
➢ Four main kinds of regulatory protein are commonly involved as primary drug targets, namely:
1) Receptors → e.g. adrenergic or cholinergic
2) Ions channel → e.g. Ca channel blockers
3) Enzymes → e.g. MAOIs
4) Carriers → e.g. digitalis/ATPase enzyme
What is the role of the receptor in the selectivity of drug action?
➢ The molecular size, shape, and charge of a drug in relation to that of the receptor determines the degree of binding of the drug to that
receptor.
➢ This has been referred to as the "lock and key" effect.
➢ Thus, specific changes in the structure of a drug may dramatically influence the type of receptor to which it bind subsequently altering
the potency of the drug and its physiologic effects.
1) Receptors
➢ They are protein structure present on the mammalian cell or within the cells.
➢ Receptors are the sensing elements in the system of chemical communications that
coordinates the function of all the different cells in the body.
a) Direct control of ions channels receptors b) G-protein coupling receptors
➢ The nicotinic acetylcholine receptor, a ligand-gated ion channel. ➢ Ex of ligands → serotonin, adrenergic amines, muscarinic acetylcholine,
➢ The receptor molecule is depicted as embedded in a rectangular peptide hormones, odorants, photons
piece of plasma membrane, with extracellular fluid above and ➢ Effector increases conc. of 2nd messenger (cAMP, Ca++, etc.).
cytoplasm below. ➢ Ex: Effector enzyme adenylyl cyclase converts ATP to cAMP.
➢ Composed of five subunits (two , one , one , and one ), the receptor
opens a central transmembrane ion channel when acetylcholine
(ACh) binds to sites on the extracellular domain of its subunits.
c) Tyrosine kinase linked receptor d) Intracellular receptors or Lipid soluble receptors
➢ Or A lipid soluble ligand (drug) crosses the membrane and acts on an
intracellular receptor.
➢ Ex: corticosteroids, mineral corticoids, sex steroids, vitamin D, and
thyroid hormone.
➢ Therapeutic consequences:
✓ Effects of these drugs can last hours or days even when drug
has been stopped.
➢ Or Ligand binds to the extracellular domain of the transmembrane
receptor which in turn is bound to and activates tyrosine kinase in
the cytoplasm.
➢ Ex of ligands → insulin.
2) Ion channels
3) Enzymes
4) Carriers
• Unlike carrier proteins, ion channels do not undergo conformational changes during
the transport process.
• Instead, they form a pore or channel through which ions can flow.
• Examples of carrier proteins include glucose transporters (GLUT), sodium-
potassium pumps (Na+/K+-ATPase), and neurotransmitter transporters (e.g., serotonin
transporter).
Spare receptor
➢ Generally, maximal drug activity is obtained when there is a full occupancy of all receptors by the drug.
➢ In some cases, however a maximal response is attained by a concentration of the agonist that does not results full occupancy of the
complements of available receptors in such case the receptors are spare receptors.
➢ Receptors may be considered spare when the maximal response is elicited by an agonist at a concentration that does not produce full
occupancy of the available receptors.
➢ Spare receptors are significant, because they increase both the sensitivity and speed of a tissue’s responsiveness to a ligand or drug.
➢ This allow low affinity agonists to produce full response at low concentration. So they are economically significant.
Receptor regulation
A) Receptor upregulation B) Receptor downregulation
➢ Long term using of β blocker in hypertension and sudden withdrawal, ➢ Occur in using drug for long term.
resulted in increase in BP. ➢ e.g. β2 agonist in treatment of bronchial asthma, its bronchodilator
➢ Due to exposure of cell to catecholamine will sensitize synthesis of effect will decrease due to decrease in receptors or desensitization
new androgenic receptors. of receptors.
