CHAPTER 7- MEDICINES AND PHARMACOLOGY

do not pass through liver first

based on lipid solubility through the epidermis

restricted to nonionized, lipid soluble drugs

Albumin- largely responsible for binding drugs (PCN and warfarin 90% bound)

will displace unconjugated bilirubin in newborns

tetracycline and heavy metals

constant amount of drug is eliminated regardless of dose

drug eliminated proportional to dose

5 half-lives

• 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

• 1) fraction of unchanged drug reaching the systemic circulation
• 2) assumed to be 100% for intravenous drugs, less for other routes (i.e. oral)

drug level at which desired effect occurs in 50% of patients

drug level at which death occurs in 50% of patients

effect at an unusually lose dose

tolerance after only a few doses

dose required for effect

ability to achieve result without untoward effect

(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.

• 1) cimetidine
• 2) isoniazide
• 3) ketoconazole
• 4) erythromycin
• 5) cipro
• 6) flagyl
• 7) allopurinol
• 8) verapamil
• 9) amiodarone
• 10) MAOIs
• 11) disulfiram

• 1) cruciform vegetables
• 2) EtOH
• 3) insecticides
• 4) cigarrette smoke
• 5) phenobarbital (barbituates)
• 6) dilantin
• 7) theophylline
• 8) warfarin

P450 system transforms aromatic hydrocarbons into carcinogens

Kidney- most important organ for eliminating most drugs (glomerular filtration and tubular secretion)

more water soluble and more likely to be elimintated in unaltered form

more fat soluble and more likely to be metabolized before excretion

• 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

• 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

• (phenergan, antiemetic)-
• 1) causes tardive dyskinesia (inhibits dopamine receptors)
• Tx: diphenhydramine (benadryl)

• (reglan, prokinetic)
• 1) dopamine receptor blocker that can be used to increase gastric motility and gut motility in general

• (zofran)
• 1- serotonin receptor inhibitor; antiemetic

• 1) proton pump inhibitor
• 2) blocks H/K ATPase in stomach

• 1) histamine H2 receptor blocker
• 2) decrease acid in stomach

somatostatin analogue that is longer acting

• 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

• 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

causes transient interruption of the AV node

• 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

• 1) may prolong life in patients with severe LV failure
• 2) reduce risk of MI and atrial fibrillation postoperatively

• 1) acetylcholine antagonist
• 2) increases heart rate

• 1) inhibit adrenal steroid synthesis
• 2) used in patients with adrenocortical Ca

• 1) analogue of GnRH and LHRH
• 2) Inhibits release of LH and FSH from pituitary when given continuously (paradoxic effect)

• 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

• 1) inhibits prostaglandin production
• 2) used to close patent ductus arteriosus (PDA) in children and used in patients with gout

• 1) PGE1 derivative, a protective prostaglandin used to prevent peptic ulcer disease
• 2) consider use in patients on chronic NSAIDs

inhibit prostaglandin synthesis and lead to decreased mucus and HCO3- secretion and increased acid production (mechanism of ulcer formation in patients on NSAIDs

• 1) can cause extrapyramidal manifestations
• 2) inhibits dopamine receptors

• 1- tinnitus
• 2- headaches
• 3- nausea/vomiting

• 1st - respiratory alkalosis
• 2nd- metabolic acidosis

nausea

N-acetylcysteine

• 1) used for sepsis
• 2) mechanism is fibrinolysis
• 3) drug inactivates the inhibitor of protein C, creating activated protein C