PDF Pharmacology Lecture Notes - Pharmaco-dynamics

Pharmacology Pharmaco-dynamics LECTURE (1) Pharmaco-dynamics (1) DR. El-Sawy 0  Pharmacology...

Pharmacology Pharmaco-dynamics LECTURE (1) Pharmaco-dynamics (1) DR. El-Sawy 0  Pharmacology Pharmaco-dynamics Introductory definitions  A basic science. Medical  Deal with small molecules used to prevent, diagnose, or pharmacology treat diseases.  The science concerned with use of drugs in humans. Clinical pharmacology  Involves interaction between drug & patient.  Any chemical molecule that can interact with body systems drug and produce effect. drug-body interactions ‫الامتصاص‬ ‫بيش تغل ازاي‬ ‫التوزيع‬ ‫بيعمل اي‬ ‫التكسري‬ ‫الاخراج‬ DR. El-Sawy 1  Pharmacology Pharmaco-dynamics Definition:  The effect of drug on body.  A drug may produce its effects through: Direct mechanism Interaction with : Interaction with : : body control systems Certain metabolic (regulatory proteins) pathways A. Receptors. 1. Chemical B. Ion channels. mechanisms. C. Enzymes. 2. Physical D. Carrier molecule. mechanisms. Definitions:  Protein macromolecules. Receptors  Combine with a drug, they may be activated or blocked.  Any molecule that can combine with the receptors. Ligand A ligand that activates the receptor  agonist. A ligand that blocks the receptor  antagonist.  The empathy of the receptor to the ligand. Affinity  It determines the number of receptors occupied by the drug. DR. El-Sawy 2  Pharmacology Pharmaco-dynamics Types of receptors Ion channel-Linked receptors G-protein-linked receptors: (direct ligand-gated ion channels):  The receptor is an ion channel consists of  The receptor consists of 7 membrane subunits. 5 transmembrane subunits  Binding of agonist to the extracellular part of receptor (a1, α2, β, γ, δ).  activation of intracellular G-protein.  Binding of agonist to the extracellular  When G-protein is activated  its α subunit binds to part of receptor  opening of channel GTP to be phosphorylated and bring stimulatory or for a specific ion. inhibitory response.  Response of these receptors is very fast  Response is slower than ion channel receptors  Duration is very short.  Duration is longer. Structure DR. El-Sawy 3  Pharmacology Pharmaco-dynamics  Nicotinic Ach receptors in motor end- plate:  Stimulatory G-protein (Gs) : The ion channel opens for Na ions in leads to increase adenyl cyclase enzyme  ↑ CAMP response to stimulation by Ach.  activation of protein kinases. Examples: B1 and B2-adrenergic receptors.  Inhibitory G-protein (Gi) : leads to decrease adenyl cyclase enzyme  ↓ CAMP inhibition of protein kinases. Examples Examples: α2- adrenergic receptors and M2 muscarinic receptors.  Gama aminobuteric acid (GABA) receptors in brain:  Gq-coupled receptors: The ion channel opens for Cl ions in response to stimulation by GABA. ↑ inositol triphosphate (IP3) & diacylglycerol (DAG). IP3 increases free intracellular Ca2+. Examples: α1-adrenergic receptors, M1 and M3 muscarinic receptors. DR. El-Sawy 4  Pharmacology Pharmaco-dynamics Tyrosine kinase (TK)-linked receptors Intracellular receptors  Consists of 2 large domains:  They are located inside the cell either in cytoplasm or 1. Extracellular hormone-binding domain directly on DNA. 2. Intracellular TK-binding domain  They regulate transcription of genes in nucleus or connected by a transmembrane mitochondria. segment.  Their agonist must enter inside the cell to reach them. Structure  Binding of agonist to hormone-binding  They have two important features: domain causes activation of intracellular 1. Their response is slow (time is required for synthesis domain to activate TK enzyme → of new proteins). activation of several proteins known as 2. Their effects persist for long time after the agonist is "signaling proteins". removed. Examples Insulin receptors. receptors for corticosteroids, sex hormones, thyroxin, etc. DR. El-Sawy 5  Pharmacology Pharmaco-dynamics Types of drug-receptor bonds hydrogen bond ionic bond covalent bond (electrostatic)  Attraction between  Electrical attraction  If occurred between two hydrogen. between two opposing drug and receptor, the charges. receptor becomes permanently blocked.  Weak  Strong  Very strong  Reversible  Reversible.  Irreversible.  When a drug combines with a receptor, this may lead to : Agonist effect Antagonist effect  Means that the drug  Means that the drug combines with the combines with the receptor receptor but gives no response, and prevents and gives response. the receptor from binding to another drug. DR. El-Sawy 6  Pharmacology Pharmaco-dynamics Dose response relationship Types of responses to drugs: Graded response Quantal response  The response is increased  The response is doesn't increase proportionally to dose of agonist. proportionally to agonist.  But it is all-or-none response.  Prevention of convulsions by anti-  Response of the heart to adrenaline. epileptic drugs.  It is the response to most drugs.  It is response to few drugs.  The response could not be tested in  The response could be tested in one one animal and must be tested in a or more animals. group of animals. DR. El-Sawy 7