Effects On Drugs

Effects On Drugs

1. absorption :route IV>IM>SC>PO -from lung after inhalation is very quick due to L.S. Aو H.b.S -destruction :digestive enzyme in GIT destruct insulin

   • 1-passive diffusion :- Movement .Across. Concentration gradient without energy, carrier,not saturable *lipid Soluble D penetrate Lbilayer while water soluble pass via channel
   • 2-facilitated p D:- carrier to facilitate non Lipid Soluble D to diffuse across phospholipid layer of cell m until concentration equal,no energy
   • 5-exocytosis: the reverse of endocytosis

2. 3-active: Transport .of. subtance across the phospholipid L of cm against concentration g energy is required -Atp hydrolysis is required

3. 4-endocytosis :- (pinocytosis) suitable for Large.or very Lipid insoluble molecules .g peptides ,vB12 _the Drug molecule bind to receptor on cm with engulfment (internalization) by invagination (in-folding) form vesicle and release into cytoplasm

4. factors:- (bt.Gd ) 1-b=bF(CHF⬇) 2-T=total S area available for absorption و more in intestine than microvilli 3-g=gastric motility and contact time (absorption of drug ⬇diarrhea 4-d =Degree of ionization (non ionized lipophilic readily absorbed *acidic D :-stomach *alkaline:-intestine

5. distribution: -process drug leave b stream وenter interstitial (extracellular fluid )

   • 1-blood flow: brain liver kidney greater than skeletal m, adipose t the lower
   • 2-capillary permeability:- -structure of Cappillaresو chemical nature of drug -bbb :lipid soluble d penetrate cNS while ionized or polar fail
   • plasmaوT bining to plasma protein :-1-reversible binding to plasma protein sequesters in a non diffusible formو slow their transfer out of V.C 2-Bound d are inactive only the free unbound act on target sites elicit biological response be available to elimination 3-high extraction cuz low p b وlow extraction cuz so depend on p binding 4-decrease in concentration of albumin lead to ulter phrama of drug that are highly b to albumin 5-the drugs u keep eye on : warfarin diazepam 6-most drugs b to pp (album an acidic glyco p) 7-acidic d b to albumin و basic to acidic glycoprotein
   • lipid solubility: as L.S of drug increase وas plasma binding increase و free fractions decrease and thus clearance decrease
   • apparent volume of distribution : drug rare associate with only one water compartment of Body instead vast majority distribute in several compartments as lipids وproteins و nucleic acid

6. biotransformation metabolism: 1-b of D to more hydrophilic melocue is required for elimination from body 2-B reaction produce polar hydrophilic biological inactive m more readily excreted و metabolism retain biological activity may be toxic oçcur in liver sometimes liver lung GIT

   • phase1: -parent d is alter by introduce a functional .g (oh, NH,sH) by( oxidation reduction hydrolysis ) -drug by phase 1lose pharmacological activity, 1- their products:- directly in urine و 2-react with endogenous compounds to form water.Soluble .Conjugate phase2) *phase one :-use in :- cytochrome p450oxidase O2و reductase وNADPH
   • phase2:- conjugation R:-form covalent linkage بين parent .c وfunctional g as sulfate acetate amino acid -conjugates are polar biological inactive conjugate excreted urine -high molecular weight excret in bile then conjugate bond cleaved by intestinal flora release back systemic .C called ( enterohaptic recirculation) *glucuronidation most common وimportant -drug possesses oH HN2 cooH may enter phase 2 become more conjugated without prior phase
   • enzyme induction:-synthesis of liver microsomal cytochrome p450 enhanced by specific drugs leading increase metabolism decrease in plasma concentration
   • enzyme inhibition :microsomal cytochrome p450 can be inhibited by specific drugs leading ⬇in metabolism ⬆plasma.concentration of drug as cimetidine, ketoconazole chloramphenicol

7. drug elimination and excretion : -1-ex of D و bio products occur in kindey but the portion not bound to albumin is filtered at the glomerulus and secret into tubules by T.C 2-as water is reabsorb as the concentration of drug and metabolites in the tubules rise above in that in the plasma , reabsorb of D occur into body If ,it's sufficiency Lipid Soluble to cross Tubular Cell membrane of -lung:excretion only volatile or gaseous -bile:mediate by protein transports then intestinal tract -many drugs in sweat saliva breast

   • kinetics of D elimination :- 1-zero order elimination rate is independent of plasma concentration *a constant amount of D is eliminated per unit time and have no fixed half life و straight line as ethanol phenytoin 2-first-order rate: directly proportional to plasma level the highis amont the more rapid *most drugs follow that pattern -constant fraction is eliminated per unit of time follow exponential decay -time to eliminate 50%of given amount