CHAPTER 7- MEDICINES AND PHARMACOLOGY

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CHAPTER 7- MEDICINES AND PHARMACOLOGY
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CHAPTER 7- MEDICINES AND PHARMACOLOGY
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  1. Sublingual and rectal drugs:
    do not pass through liver first
  2. Skin absorption-
    based on lipid solubility through the epidermis
  3. CSF absorption
    restricted to nonionized, lipid soluble drugs
  4. What protein largely responsible for binding drugs:
    Albumin- largely responsible for binding drugs (PCN and warfarin 90% bound)
  5. Sulfonamides
    will displace unconjugated bilirubin in newborns
  6. What drugs get stored in bone?
    tetracycline and heavy metals
  7. 0 order kinetics:
    constant amount of drug is eliminated regardless of dose
  8. 1st order kinetics:
    drug eliminated proportional to dose
  9. How many half-lives does it take for drug to reach steady state?
    5 half-lives
  10. Volume of distribution:
    • 1) amount of drug in the body divided by amount of drug in plasma or blood
    • 2) drugs with high volume of distribution have higher concentrations in the extravascular compartment (i.e. fat tissue) compared with intravascular concentrations
  11. Bioavailability:
    • 1) fraction of unchanged drug reaching the systemic circulation
    • 2) assumed to be 100% for intravenous drugs, less for other routes (i.e. oral)
  12. What is ED50?
    drug level at which desired effect occurs in 50% of patients
  13. What is LD50?
    drug level at which death occurs in 50% of patients
  14. Hyperactive-
    effect at an unusually lose dose
  15. Tachyphylaxis-
    tolerance after only a few doses
  16. Potency-
    dose required for effect
  17. Efficacy-
    ability to achieve result without untoward effect
  18. Microsomal drug metabolism:
    (hepatic cell endoplasmic reticulum, P450 system)

    • Phase I: demethylation, oxidation, reduction, hydrolysis reactions (mixed function oxidases, requires NADPH/oxygen)
    • Phase II: glucuronic acid (#1) and sulfates attached (forms water-soluble metabolite); often inactive and ready for excretion. Biliary excreted drugs may become deconjugated in intestines with reabsorption, some in active form.
  19. Inihibitors of P450:
    • 1) cimetidine
    • 2) isoniazide
    • 3) ketoconazole
    • 4) erythromycin
    • 5) cipro
    • 6) flagyl
    • 7) allopurinol
    • 8) verapamil
    • 9) amiodarone
    • 10) MAOIs
    • 11) disulfiram
  20. Inducers of P450:
    • 1) cruciform vegetables
    • 2) EtOH
    • 3) insecticides
    • 4) cigarrette smoke
    • 5) phenobarbital (barbituates)
    • 6) dilantin
    • 7) theophylline
    • 8) warfarin
  21. What does P450 do to aromatic hydrocarbons?
    P450 system transforms aromatic hydrocarbons into carcinogens
  22. What is the most important organ for eliminating most drugs?
    Kidney- most important organ for eliminating most drugs (glomerular filtration and tubular secretion)
  23. Polar drugs (ionized)-
    more water soluble and more likely to be elimintated in unaltered form
  24. Nonpolar drugs (nonionized)-
    more fat soluble and more likely to be metabolized before excretion
  25. Gout:
    • 1) caused by uric acid buildup; end product of purine metabolism
    • 2) Colchicine- anti-inflammatory; binds tubulin and inhibits migration
    • 3) Indomethacin- anti-inflammatory
    • 4) Allopurinol- xanthine oxidase inhibitor, blocks uric acid formation from xanthine
    • 5) Probenecid- increases renal secretion of uric acid
  26. Lipid lowering agents:
    • 1) Cholestyramine- can bind vitamin K and cause bleeding tendency
    • 2) HMG-Co reductase inhibitors (statin drugs)- can cause liver dysfunction, rhabdomyolysis
    • 3) Niacin (inhibits cholesterol synthesis)- can cause flushing. Tx: ASA
  27. GI drugs (slides to follow):
  28. Promethazine:
    • (phenergan, antiemetic)-
    • 1) causes tardive dyskinesia (inhibits dopamine receptors)
    • Tx: diphenhydramine (benadryl)
  29. Metoclopramide
    • (reglan, prokinetic)
    • 1) dopamine receptor blocker that can be used to increase gastric motility and gut motility in general
  30. Ondansetron
    • (zofran)
    • 1- serotonin receptor inhibitor; antiemetic
  31. Omeprazole:
    • 1) proton pump inhibitor
    • 2) blocks H/K ATPase in stomach
  32. Cimetidine/ranitidine
    • 1) histamine H2 receptor blocker
    • 2) decrease acid in stomach
  33. Octreotide:
    somatostatin analogue that is longer acting
  34. Cardiac drugs (to follow):
  35. Digoxin:
    • 1) inhibits Na/K ATPase and increases myocardial calcium
    • 2) increased atrial contraction rate by slows AV conduction
    • 3) also acts as an inotrope
    • 4) decreased blood flow to intestines- has been implicated in causing mesenteric ischemia
    • 5) Hypokalemia- increased sensitivity of heart to digitalis; can precipitate arrhythmias or AV block
    • 6) Is not cleared with dialysis
    • 7) Other side effects:
    • 1- visual changes (yellow hue)
    • 2- fatigue
    • 3- arrhythmias
  36. Procainamide
    • 1) Can cause:
    • 1- lupus-like syndrome
    • 2- pulmonary fibrosis
    • 3- torsades

    • 2) Magnesium- used to treat torsades
    • 3) follow drug levels and QT intervals: >400ms is concerning
    • 4) Normal procainamide level: 4-12ug/mL
    • 5) Normal NAPA (N-acetyl procainamide) level: <30ug/mL
  37. Adenosine:
    causes transient interruption of the AV node
  38. ACE (angiotensin-converting enzyme) inhibitors- Captopril
    • 1) best single agent shown to reduce mortality in patients with CHF
    • 2) can prevent CHF post MI
    • 3) can prevent progression of renal dysfunction in patients with hypertension and DM
    • 4) can precipitate renal failure in patients with renal artery stenosis
  39. Beta-Blockers:
    • 1) may prolong life in patients with severe LV failure
    • 2) reduce risk of MI and atrial fibrillation postoperatively
  40. Atropine
    • 1) acetylcholine antagonist
    • 2) increases heart rate
  41. Metyrapone and aminoglutethimide
    • 1) inhibit adrenal steroid synthesis
    • 2) used in patients with adrenocortical Ca
  42. Leuprolide:
    • 1) analogue of GnRH and LHRH
    • 2) Inhibits release of LH and FSH from pituitary when given continuously (paradoxic effect)
  43. Vasopressin (ADH)
    • 1) acts on V1 receptors found on vascular smooth muscle (constriction)
    • 2) can be used in patients with gastrointestinal bleeding by reducing intestinal blood flow
  44. Indomethacin
    • 1) inhibits prostaglandin production
    • 2) used to close patent ductus arteriosus (PDA) in children and used in patients with gout
  45. Misoprostol
    • 1) PGE1 derivative, a protective prostaglandin used to prevent peptic ulcer disease
    • 2) consider use in patients on chronic NSAIDs
  46. NSAIDs
    inhibit prostaglandin synthesis and lead to decreased mucus and HCO3- secretion and increased acid production (mechanism of ulcer formation in patients on NSAIDs
  47. Haldol:
    • 1) can cause extrapyramidal manifestations
    • 2) inhibits dopamine receptors
  48. ASA poisoning:
    • 1- tinnitus
    • 2- headaches
    • 3- nausea/vomiting

    • 1st - respiratory alkalosis
    • 2nd- metabolic acidosis
  49. Gadolinium side effect?
    nausea
  50. Tylenol overdose treatment:
    N-acetylcysteine
  51. What is activated protein C (Xigris) used for?
    • 1) used for sepsis
    • 2) mechanism is fibrinolysis
    • 3) drug inactivates the inhibitor of protein C, creating activated protein C

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