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Pharm Module 5.pdf

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Department
Pharmacology
Course
Pharmacology 2060A/B
Professor
Dr.Mike
Semester
Fall

Description
PHARMACOKINETICS▯–▯EXCRETION▯ 5.1▯ROUTES▯OF▯DRUG▯EXCRETION▯ Drug▯Excretion▯ ▯ Is▯the▯removal▯of▯parent▯drug▯and▯drug▯metabolites▯from▯the▯body.▯ ▯ ▯ ▯ ▯ ▯ ▯ Renal▯Drug▯Excretion▯ ▯ The▯kidneys▯account▯for▯the▯majority▯of▯drug▯ excretion.▯ ▯ Healthy▯kidneys▯serve▯to▯limit▯the▯duration▯and▯ intensity▯of▯drug▯effects.▯ ▯ Decreased▯kidney▯function▯prolongs▯the▯ duration▯of▯action▯and▯intensity▯of▯drug▯effects.▯ ▯ The▯Nephron ▯ ▯ ▯ The▯basic▯structural▯and▯functional▯unit▯of▯the▯ kidney.▯ ▯ Regulates▯water,▯electrolyte▯and▯drug▯excretion.▯ ▯ Controls▯blood▯volume,▯blood▯pressure,▯blood▯pH▯ and▯solute▯(including▯drug)▯excretion.▯▯ ▯ ▯ ▯ ▯ 5.2▯FACTORS▯AFFECTING▯RENAL▯DRUG▯EXCRETION ▯ ▯ 1) Glomerular▯Filtration▯ 2) Tubular▯Secretion▯ 3) Tubular▯Reabsorption▯▯ 1) Glomerular▯Filtration▯ ▯ ▯ Drugs▯enter▯the▯kidney▯from▯the▯renal▯ artery.▯ ▯ Hydrostatic▯pressure▯within▯glomerular▯ capillaries▯forces▯low▯molecular▯weight▯ drugs▯into▯the▯renal▯tubules.▯ ▯ Glomerular▯filtration▯rate▯is▯~▯120▯ 2 ml/min/1.73▯m ▯or▯about▯20%▯of▯total▯ renal▯plasma▯flow.▯ ▯ Lipid▯solubility▯and▯pH▯do▯not▯affect▯ glomerular▯filtration▯of▯drugs.▯ ▯ Only▯non▯protein▯bound▯(i.e.▯free)▯ drugs▯are▯filtered▯at▯the▯glomerulus.▯▯ ▯ 2) Tubular▯Secretion▯ ▯ ▯ Drugs▯not▯filtered▯by▯the▯glomerulus▯leave▯ the▯glomeruli▯by▯the▯efferent▯arteriole.▯ ▯ The▯efferent▯arterioles▯divide▯to▯form▯ capillaries▯that▯surround▯the▯proximal▯ tubule.▯▯ ▯ Drugs▯can▯be▯secreted▯from▯the▯blood▯ surrounding▯the▯tubules▯into▯the▯lumen▯of▯ the▯proximal▯tubule.▯ ▯ Drug▯secretion▯in▯the▯kidney▯primarily▯occurs▯ by▯two▯transport▯systems,▯one▯for▯weak▯acids▯ and▯one▯for▯weak▯bases.▯ ▯ 3) Tubular▯Reabsorption▯ ▯ ▯ ▯ As▯drugs▯move▯toward▯the▯distal▯tubule,▯their▯ concentration▯increases.▯ ▯ This▯is▯primarily▯due▯to▯the▯actions▯of▯the▯loop▯of▯henle▯ which▯functions▯to▯concentrate▯tubular▯solutes.▯ ▯ Once▯in▯the▯distal▯tubule▯the▯drug▯concentration▯often▯ exceeds▯the▯concentration▯in▯the▯blood▯that▯immediately▯ surrounds▯the▯distal▯tubule.▯ ▯ If▯the▯drug▯is▯uncharged▯or▯lipid▯soluble,▯its▯able▯to▯leave▯ the▯tubule▯and▯be▯reabsorbed▯back▯into▯the▯blood.▯▯ ▯ The▯Effect▯of▯Age▯on▯Renal▯Function▯ ▯ ▯ Kidney▯function▯is▯low▯in▯ newborn▯infants.▯▯ Typical▯glomerular▯ filtration▯rate▯(GFR)▯of▯ newborns▯40▯ mL/min/1.73▯m 2.▯▯By▯ two▯years▯old▯the▯GFR▯ reaches▯that▯of▯a▯ healthy▯adult▯(120▯ 2 mL/min/1.73m ).▯ ▯ As▯we▯age▯renal▯function▯ decreases.▯▯ ▯ If▯renal▯function▯is▯ decreased,▯renal▯drug▯ excretion▯is▯decreased.▯ ▯ 5.3▯BILIARY▯DRUG▯EXCRETION ▯ ▯ ▯ Some▯drugs▯are▯eliminated▯into▯the▯bile▯and▯ ultimately▯excreted▯in▯the▯feces.▯ ▯ Characteristics▯of▯drugs▯eliminated▯in▯the▯bile▯ include:▯ ▯ ▯▯▯▯▯1)▯▯molecular▯weight▯>▯300▯Da▯▯ 2)▯have▯both▯polar▯and▯lipophilic▯groups▯▯▯▯ (amphipathic▯molecules)▯ 3)▯are▯g
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