Drugs undergo 1 or 2 types of chemical reactions in the liver o Phase I

Drugs undergo 1 or 2 types of chemical reactions in

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Drugs undergo 1 or 2 types of chemical reactions in the liver o Phase I: oxidation, hydrolysis, or reduction to increase water solubility of drug molecules A. Phase I enzymes— Cytochrome P450 isoenzymes (CYP 450 ): i. Developmental/genetic differences in isoenzymes ii. Disease states alter isoenzyme activity such as cystic fibrosis alters CYP 2D9 activity iii. Concurrent therapy w/ inhibitor or inducer may alter the metabolism of a medication o Phase II: conjugation or union of drug molecule with water-soluble substance 4. Prodrugs are inactive compounds that rely on metabolism to become active Elimination: most elimination done by the kidneys 1. Renal: o Glomerular Filtration: drug must be unbound from protein, free drug, water soluble metabolites A. Factors affecting renal excretion: kidney function, age, hydration, c/o o Active tubular secretion o Passive tubular reabsorption 2. GI tract
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o Biliary excretion: After being metabolized in the liver, the metabolite is excreted into the bile. o Some drugs may then be reabsorbed in the intestine. o Enterohepatic cycle o Fecal excretion 3. Lung Excretion o Gases o General anesthetics and volatile liquids o Rate of excretion is based on respiratory rate and pulmonary blood flow 4. Sweat/Salivary Excretion: dermatitis/complain of “taste” 5. Mammary Excretion Ch. 3 I Can PresCribE A Drug Mnemonic o Indication o Contraindications o Precautions o Cost/Compliance o Efficacy o Adverse effects o Dose/Duration/Direction Drug factors influencing drug selection Pharmacokinetic factors o Bioavailability o CYP 450 metabolism o Renal elimination o Dose-concentration curve o Half-life Pharmacodynamic factors o Ease of titration o Therapeutic index i. A narrow therapeutic index is more difficult to manage. ii. A wider therapeutic index is safer and requires less monitoring. Therapeutic factors: evidence from RCTs/clinical trials/practice guidelines, systematic reviews Safety Cost (to patient and to society) Patient factors Provider factors Ch. 4 Off-label prescribing Prescribing for a use not indicated on the official FDA label Legal Decision is based on o Understanding the medication being prescribed o Rational scientific principles o Expert medical opinion (the literature)
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o Controlled clinical trials Controlled Substance Prescribing Precaution Tamper-proof paper Name, National Provider identifier, address, and telephone # on pad DEA (U.S. Drug Enforcement Administration [DEA]) # if controlled substance
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  • Spring '14
  • Henrikson,J
  • Pharmacology, U.S. Drug Enforcement Administration

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