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ETHNOPHARMACHOLOGY

ETHNOPHARMACHOLOGY. Caucasians (Lower Plasma level of TCA) Maximal Haloperidol concentration following RT Asian> Caucasians (Lin at al 1983) CYP2D6 Caucasians higher rate of poor metabolizers (7%), East Asian lower (1%) Ultrarapid metabolizers North Africans (33%) needing high dosages

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ETHNOPHARMACHOLOGY

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  1. ETHNOPHARMACHOLOGY • Caucasians (Lower Plasma level of TCA) • Maximal Haloperidol concentration following RT Asian> Caucasians (Lin at al 1983) • CYP2D6 Caucasians higher rate of poor metabolizers (7%), East Asian lower (1%) Ultrarapid metabolizers North Africans (33%) needing high dosages • 40% of Asians and 60% South American Native Indians lack Aldehyde Dehydrogenase • Caucasion better SSRI response (long form 5_HT transporter polimorphism)

  2. ETHNOPHARMOCHOLOGY

  3. GENDER DIFFERENCES

  4. PHARMACOKINETICS What happens to drugs once administered (What the body does to the drug) Routes of administration: enteral (oral, rectal and SL) and parenteral (IM, IV, intrathecal, peritoneal, inhalation, skin). Advantages and disadvantages. How single and multiple dosing of different formulations affect plasma concentration---Time relationship Bioavailability: How much of a given drug reaches its target, It depends on Absorption/ Distribution/ Metabolism / Excretion Distribution: Free and bound , BBB crossing → target tissue and other tissue First-Order Kinetic: Rate of absorption or elimination is directly proportional to the amount of drug remaining. (The higher the plasma concentration the longer remains in the body) Zero-order kinetic: a fixed amount of drug is absorbed or eliminated for each unit of time independent of drug concentration (e.g saturation of enzymes or controlled released)

  5. METABOLISM 1-Aims to produce polar compounds for renal elimination 2-Liver is the main site 3-Metabolise to active compounds=Phase 1 or inactive Phase 2 4-First pass Metabolism= Drugs is absorbed from GI into portal circulation and metabolized in liver before reaching systemic circulation EXCRETION 1-Ionised states allows passive diffusion 2-Ph affect rate of elimination

  6. METABOLISM Chemical transformation by the body: reducing lipid solubility and altering biological activity. Eg: Diazepam→Oxazepam. By hepatomicrosomal and nonmicrosomal enzyme systems and two phases: phase I and phase II Phase 1: Oxdn, redn, hydrolysis →may or may not be active but shorter T1/2 Phase 2: Combining with endogenous molecules, usually glucoronides→ ↑H2O soluble. Now, if MW 300+ then through bile or otherwise → blood→ kidneys. Also in plasma, lung, kidney and skin.

  7. P450 INDUCTION OR INHIBITION Inducers Inhibitors Carbamazepine Phenytoin Burbiturates Chronic EtOH Cigarette smoking Others such as Rifampicin, griseofulvin Ranitidine Ciprofloxacin Erythromycin Valproate Fluoxetine, paroxetin TCAs Antipsychotics

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