Pharmacology Past Paper 2024 PDF

Pharmacology 2024 Dr.Elramady Dr.Elramady 4 Pharmacology 2024 Dr.Elramady   Distribution  Distribution:  After absorption of a drug, it is usuall...

Pharmacology 2024 Dr.Elramady Dr.Elramady 4 Pharmacology 2024 Dr.Elramady   Distribution  Distribution:  After absorption of a drug, it is usually distributed through the different tissues & body fluid compartments: a) The plasma b)Interstitial fluid c)Intracellular fluid  Four basic patterns of drug distribution: 1-Single compartment (intravascular):  Drug is confined in the blood compartment.  Drug of high molecular weight e.g. heparin & dextran.  Drugs are bounded to plasma protein 2- Two compartments (intravascular + interstitial):  Drugs can pass capillary wall but cannot pass cell membrane.  Drugs are localized mainly in the extracellular fluid  e.g. quaternary ammonium compounds, insulin and certain ions as sodium, chloride, bromide & sulphate 3- Multi-compartment (extracellular + intracellular):  Drugs that can filtrate.  Drugs can pass cell membrane which are lipid soluble.  Drugs of low MW & water soluble compounds including  saticylates & urea, barbiturates, tertiary amines  (physostigmine) 4-Tissue reservoirs:  Hair → arsenic  thyroid→ iodine  bone→ Ca++  fat→ thiopentone 3  Pharmacology 2024 Dr.Elramady  liver→ chloroquine.  Apparent volume of distribution ( Vd ):  Vd is a pharmacological term used to quantify the distribution of a drug between plasma and the rest of the body after oral or parenteral dosing.  Vd is hypothetical volume at which the drug should be distributed to obtain the estimated concentration of the drug. Total amount of the drug in the body (M)  Vd = Plasma concentration of the drug (C)  To estimate the amount of the drug in the body M = Vd x C  Vd may be increased in a) renal failure (fluid retention) b)liver failure (increased body fluid - decreased plasma protein binding)  Vd may be decreased in dehydration.  Drugs highly bound to plasma proteins small Vd.  Drugs highly bound to tissue proteins high Vd.  Digoxin No need for dialysis slow clearance  Binding of drugs to Plasma Protein:  Most drugs binds reversibly to plasma protein.  Albumin is the major binding plasma protein.  The protein bound fraction is : -inactive pharmacologically -not active. -not filtered -not metabolized -not excreted -acts as depot form.  The free fraction of the drug is : -active -filtered- metabolized -excreted.  Drugs extensively bound to plasma proteins phenylbutazone, dicoumarol, tolbutamide , long acting sulphonalmide, thiopentone, and diazoxide 4 Pharmacology 2024 Dr.Elramady  Drug interactions: Aspirin, phenytoin, sulfonamide drugs displace these drugs from their protein binding sites:  Oral anticoagulants e.g. warfarin hemorrhage.  Oral hypoglycemic e.g.tolbutamide hypoglycemia.  Bilirubin in neonates e.g. jaundice & kernicterus  Passage of drugs to the CNS The passage of drugs into the CNS is limited by Blood Brain Barrier (BBB).  lipid cellular barrier composed of brain capillary endothelium which lacks water channels and the adjacent Glial tissue.  Only lipid soluble (non-ionized) drugs can pass BBB along their concentration gradient  Inflammation e.g. meningitis & encephalitis increases permeability of BBB e.g. penicillin.  the endothelial cells in brain capillaries are packed so tightly that there are no intercellular clefts.  The tight junctions have a high electrical resistance, providing a barrier to ions.  there are no fenestrae.  there is little or no pinocytosis in brain capillary endothelial cells.  -Only water, small lipophilic molecules and actively transported substances cross the BBB. -Because glucose, vitamins and many amino acids can only cross the BBB endothelial cells by active transport.  -the endothelial cells of the BBB have 2 to 4 times as many mitochondria as other endothelial cells . -The mitochondria also assist in maintaining electrochemical gradients and tight junction complexes.  Passage of drugs to the foetus Lipid soluble (non-ionized) drugs can pass placental barrier.  Drugs that don’t pass placenta easily 1. Water soluble drugs. 2. Drugs of high molecular weight. 3. Drugs are destroyed by placental enzymes e.g. MAO.  Drugs that pass placental barrier may cause: 1. Teratogenicity tetracyclines & thalidomide 2. Neonatal asphyxia morphine &barbiturates 3