Pharmacodynamics PDF

Pharmacodynam ics  Dose- response curve The response to increasing doses of an agonist or antagonist are plotted graphically. It can measure the following: Efficacy: is the maximum effect (Emax) which can be obtained from a large dose of the drug. Potency: is the amoun...

Pharmacodynam ics  Dose- response curve The response to increasing doses of an agonist or antagonist are plotted graphically. It can measure the following: Efficacy: is the maximum effect (Emax) which can be obtained from a large dose of the drug. Potency: is the amount (dose) of drug or concentration in the plasma that can produce a similar effect by a dose of another drug  EC50 (Effective concentration): is the concentration that produce 50% of the maximum effect. ED50 (Effective dose): is the dose that produces the response of 50% of subjects LD50 (Lethal dose): is the dose that cause death in 50% of subjects  Therapeutic index Is the ratio between the average maximum tolerated dose LD50 and the average minimal effective dose ED50 TI= LD50/ ED50 It indicates the margin of safety in use of a drug The higher the TI the safer the drug  Type of receptor proteins A. ligand gated ion cannels: Ionotropic receptors They are membrane receptors that compose an ion channel with ligand binding site (receptor) in the extracellular domain that stimulate the opening of the channel. It increases Na, K permeability and possibly generates an action potential. Typically are these the receptors which fast neurotransmitters acts (milliseconds). E.g. nicotinic Ach receptor, GABA A receptor B. G-protein coupled receptors Know as metabotropic receptor, they are membrane receptors They either stimulate an enzyme or a channel The receptor is coupled with G protein  G-proteins comprises 3 subunits; α, β, γ. The α subunit consists of GTPase, which catalyzes the conversion of GTP to GDP and break down. the G-proteins releasing the α subunit then the α-GTP diffuse in the membrane and associate with various enzymes causing activation or inactivation. This process is terminated when the α subunit is recombined with the β, γ subunits  Classes of G- protein : Gi, Gs, Gq. Gs & Gi either stimulate or inhibit enzyme Adenylate cyclase. Gq activates phospholipase C (PLC) Example: cholera toxin acts by Gs pertusis toxin acts by Gi Targets of G- proteins: 1- adenylate cyclase (cAMP) 2- Phospholipase C PLC (IP3 “inositol trisphosphate” and diacylglycerol ”DAG”) 3- Ion channels (Ca+2 and K+) C- Kinase- linked and related receptor: They mediate the action of many different mediators including growth factors, cytokines, and hormones (insulin) They have a common structure, a large extracellular (ligand- binding) domain connected by an α- helix to an intracellular domain (effector) D- Nuclear receptors These are ligand for: steroid hormones, thyroid hormones, vt.D and retinoic acid as well as lipid-lowering drugs and antidiabetics From its name it is found in the nucleus (intracellular) so the ligand must enter the cell. The compounds are usually lipophilic so they readily cross the lipid-bilayer. They are important for gene expression, alter protein synthesis and drug metabolizing enzymes. They are the slowest  Other GATING mechanisms: 1- Voltage- gating channels: They open when the membrane is depolarized (i.e. excitation) in the activation phase It is short lasting They are either Na+, K+, Ca+2 voltage- gated channel 2- Calcium releasing channels: They lie on the membrane of the endoplasmic reticulum