By Amany Helmy Hasanin Assistant Professor of Clinical Pharmacology Pharmacodynamic-2 By Amany Helmy Hasanin Assistant Professor of Clinical Pharmacology

Student Activity Intrinsic activity is, a drug’s ability to elicit: a) Strong receptor binding b) Weak receptor binding c) Response d) Excretion e) Distribution

Agonists A drug (chemical) that is able to alter the conformation of a receptor in such a way that it elicits a response in the system

Agonists Types Full Agonist Partial Agonist Inverse Agonist

Full Agonist Agonist binds to receptors to activate them Agonist possess affinity and efficacy

Partial Agonist (Agonist-Antagonist) In presence of agonist works as antagonist

Inverse Agonist Agonist Antagonist

Graded dose response curve Emax 100% Response 50% ED50 Dose (Log) Graded dose response curve

Graded (quantitative) dose response curve Drug A Drug B Emax 100% Response 50% ED50 ED50 Dose (Log)

Emax The maximal effect produced by the drug (= the maximum value of the dose-response curve) Efficacy

The dose that produces 50% of the maximum therapeutic effect Effective dose fifty ED50 The dose that produces 50% of the maximum therapeutic effect

Slope The middle portion of the curve (it reflects the effect of the drug produced by one unit of the dose)

Efficacy (Emax) Potency (ED50 and slope) Data we can get from graded dose response curve Efficacy (Emax) Potency (ED50 and slope)

Graded (quantitative) dose response curve Drug A Drug B Emax Response 50% ED50 ED50 Dose (Log)

Graded dose response curve Drug A 100% Emax Drug B 100% Emax Response 50% 50% ED50 ED50 Dose (Log)

Antagonist binds to receptors prevents Affinity without efficacy Agonist to bind Affinity without efficacy

Graded dose response curve 100% Response 50% ED50 Dose (Log) Graded dose response curve

Compete with agonists for the same recognition site of the receptors Types of Receptor Antagonists Competitive Compete with agonists for the same recognition site of the receptors

competitive antagonist Graded dose response curve Agonist+ competitive antagonist Agonist alone Emax Response 50% ED50 ED50 Dose (Log)

Types of Receptor Antagonists (Cont.) Noncompetitive Prevent binding of the agonist or prevent activation of the receptor by the agonist

Non-competitive antagonist Graded dose response curve Agonist alone Emax Agonist+ increasing doses of Non-competitive antagonist Response Dose (Log)

Is there any clinical application competitive and non competitive antagonist

Are there other types of antagonists The action of a ligand can be reversed by non-receptor antagonists

Antagonist interact chemically with the agonist away from receptor Chemical antagonist Antagonist interact chemically with the agonist away from receptor Negative charges on heparin are neutralized by positive charges on protamine sulfate (heparin antidote)

Physiological antagonist Antagonist by acting on different receptors induce the opposite actions of the agonist

Histamine H receptors Epinephrine

Non-receptor Mediated Mechanisms Drugs Acting on Enzymes Drugs Acting on Plasmatic Membranes Drugs Acting on the Genetic Apparatus Drugs Acting on Subcellular Structures Drugs Acting by Physical Means Drugs Acting by Chemical Action May affect permeability, carrier systems, transport processes or enzyme systems in the plasmatic membrane antifungal drugs increase permeability of fungal plasmatic membrane Drus acting on genetic apparatus Antibiotics (e.g. aminoglycosides, chloramphenicol & tetracyclines) inhibit bacterial protein synthesis Anticancer Drugs affect DNA synthesis or function Drugs acting on subcellular structures Mitochondria: salicylates uncouple oxidative phosphorylation Microtubules: Antimitotic agents

Drugs Acting on Enzymes

Drugs Acting on Plasmatic Membranes Affect permeability, carrier systems, transport processes or enzyme systems in the plasmatic membrane

Drugs Acting on the Genetic Apparatus

Drugs Acting on Subcellular Structures Mitochondria Microtubules

Drugs Acting by Physical Means Demulcents (soothing): a substance that relieves irritation of the mucous membranes by forming a protective film, lozenges

Drugs Acting by Physical Means (Cont.) Adsorbents: a substance that adsorbs another charcoal adsorbs gases and toxins in intestine

Drugs Acting by Physical Means (Cont.) Lubricants: liquid paraffin is used in constipation Osmosis: osmotic diuretics e.g. Mannitol

Drugs Acting by Chemical Action Antacids neutralize HCL in peptic ulcer Citrates interact with calcium to inhibit blood coagulation

Drugs Acting by Chemical Action (Cont.) Protamine sulfate neutralizes heparin by its positive charges Heparin Protamine

Drugs Acting by Chemical Action (Cont.) Chelation Desferroxamin (multiple blood transfusion)

At the end I am expecting from you to be able to Compare efficacy and potency of two drugs Identify and compare between different types of agonist Specify and compare between different types of antagonist