Drugs Block 3 Flashcards
Escitalopram
long-term tx for anxiety; slow/long-acting, targets serotonin reuptake transporters in brain; long t1/2, high Vd, even though high Cl, low serum-protein binding, 10 days to max effect. Metabolized by CYP1C9.
Alprazolam
acute-tx for anxiety; fast/short-acting; targets GABA receptors in brain; low Vd, short t1/2, lower Cl, high serum protein binding, time to peak effect only 1hr
Mannitol
an osmotic diuretic that increases urine flow, reduces drug reabsorption, increasing drug elimination.
***Gentamicin
nephrotoxic drug that reduces renal fxn and decrease renal elimination
Probenecid
reduces secretion of penicillin G and other anions, like furosemide, by competing for OAT/MRP transporters.
St. John’s Wort
an inducer of cytochrome P450 (3A4) and p-glycoproteins that promotes metabolism of drugs (cyclosporin, erythromycin). and therefore decreases plasma concentration these drugs.
Cimetidine
aka Tagamet; H2 receptor antagonist used to reduce acid secretion (to tx GERD) that also inhibits most CYP450’s; thereby inhibiting drug metabolism and therefore increasing plasma drug concentration. Also reduces hepatic blood flow which may affect drug clearance.
At high doses may have anti-androgenic effect; enlargement of breast tissue in males (gynecomastia) and spontaneous flow of breast milk (galactorrhea) in females; may induce confusion in elderly
Digoxin
a cardiac glycoside that has positive inotropic and negative chronotropic effects; mechanism of action is by blocking Na/K/ATPase; used to tx CHF, certain arrhythmias and tachycardia. Digoxin will decrease renal clearance of other drugs (quinidine, clarithromycin, ritonavir). It’s half life is 1/3 that of digitoxin.
Digitoxin
Same as digoxin but missing an -OH group, therefore less polar than digoxin; t1/2 is 3x a long as digoxin’s. No saturable binding to plasma protein.
Inulin
an indicator used to measure GFR; freely filtered in the kidney and neither secreted/absorbed. Also is not metabolized in the lumen or synthesized endogenously.
***Creatinine
Metabolite produced in skeletal muscle, is freely filtered and also slightly secreted in the tubule; can be used to estimate GFR, but will overestimate due to secretion.
PAH
Non-endogenous drug that is used to measure effective renal plasma flow; it is freely filtered and almost completely secreted so 90% of the drug is extracted in one pass!
Famotidine
aka Pepcid, an H2 receptor antagonist used to reduce acid secretion. Does NOT inhibit CYP450 like the other H2R antags do.
Omeprazole
H/K/ATPase inhibitor that is one of the most potent acid suppressors; used to tx GERD, ulcers, Zollinger-Ellison syndrome, an H. pylori infections; administered as a prodrug that is converted to its active form once inside the acidic compartment of parietal cells; supplied in delayed-release an enteric-coated formulas (protects against pre-absorption). Very few side effects, but may interfere with CYP450 metabolism of diazepam, phenytoin, warfarin, and cyclosporin.
Ranitidine
aka Zantac; an H2 receptor inhibitor that blocks acid secretion, used to tx GERD.
***Esomeprazole
aka Nexium, the S-isomer of omeprazole, also a PPI. Eliminated less rapidly with an increased half-life compared to omeprazole; therefore may have therapeutic advantage.
Diphenhydramine
aka Benadryl; an H1R antagonist used to treat/prevent allergic rhinitis and urticaria; used to tx atopic dermatitis for sedating and anti-pruritic properties. Also used to tx motion sickness (also a muscarinic antagonist)
Dimenhydrinate
aka Dramamine; an H1R antagonist used to treat/prevent allergic rhinitis and urticaria
Fexofenadine
aka Allegra, an H1 receptor antagonist that selectively blocks histamine-induced contraction of bronchiolar or GI smooth muscle; the active (a non-toxic) metabolite of terfenadine. Does not cross BBB.
Terfenadine
An H1 receptor antagonist used to tx allergic rhinitis, metabolized by CYP450; taken off the market because when taken with CYP450 inhibitors (grapefruit juice, cimetidine, ranitidine) the levels of terfenadine were toxic and lead to long QT and lethal ventricular arrhythmias.
Chloroquine
Used to tx/prevent malaria; highly lipophilic, super high Vd, high Cl, very long half life (214 hrs!!) resulting in drug accumulation and lots of side effects. High ion trapping in acidic vesicles.
*** reason the drug has a long t1/2 despite having a high clearance is its super high Vd.
Fentanyl
Analgesic often administered via transdermal patch due to high lipophilicity
Phenytoin
Anti-seizure medication; highly lipophilic so administered as the more soluble prodrug (Fosphenytoin) via IV, and later converted to active form. Substrate of CYP2C9. Nonsaturable binding to plasma protein. Non-linear PK in the therapeutic range.
Verapamil
L-type Ca2+ channel inhibitor used to tx angina, tachycardia, and A-fib; has high pKa, so remains in it’s charged (protonated state) at lower pH.
lidocaine
Local anesthetic and antiarrhythmic, with short half-life (less than 2 hrs), so must be administered via continuous IV drip. Low bioavailability (35%). Can give loading dose (100-200 mg/kg) over ~5 min to tx CHF w/ maintenance of 3 mg/min.
Morphine
Metabolite of codeine; has low bioavailability (24%), low lipophilicity so cannot be delivered transdermally.
***Warfarin
Anticoagulant; inhibitor of VKORC1; high bioavailability; a substrate of CYP450 (2C9); >99% protein bound, can saturate plasma-binding proteins, thereby increasing free-fraction of drug at higher doses. Half-life is 32 hrs. Variants in CYP2C9 and VKORC1 greatly affect dosing for Warfarin;
Erythromycin
Antibiotic; high pKa (8.8), possible saturation-binding to plasma proteins. Metabolized by CYP34A, so concomitant tx with P450 inhibitors can lead to long QT syndrome.
Codeine
Narcotic analgesic; gets metabolized to morphine by CYP2D6.
Propofol
anesthetic, high lipophilicity; short duration of action (15 minutes) compared to half-life of 16 hrs, can be explained by redistribution of drug from highly perfused tissues (brain) to poorly perfused tissues (fat)
Atenolol
selective B1 antagonist used as antiarrhythmic/antianginal, used to HTN, migraine HA’s, and glaucoma.
Fairly low Vd, low oral bioavailability (56%)
Ethanol
Very water soluble, mostly absorbed in gut but also via vapor in lung; Vd is equivalent to TBW, 0.6 L/kg. Blood levels depend on 1st pass metabolism (why drinking while eating lowers your blood alcohol level, because eating slows down gastric emptying). Metabolized mostly by alcohol dehydrogenase (ADH), non linear PK that is saturated at 120 mg/kg/hr.
Acetaldehyde is toxic metabolite of ethanol that is normally metabolized to acetic acid by aldehyde dehydrogenase; this enzyme is polymorphic low/absent in Asians.
Ethanol results in low NAD:NADH ratio leading to an increase in lactate and uric acid, as well as increase in reactive oxygen species that can decrease glutathione levels.
Can alter water balance by inhibiting secretion of vasopressin, leading to diuresis.
Ethanol can inhibit CYP450 at high doses, thereby increasing bioavailability of drugs metabolized by the enzyme. Also, CYP450 can oxidize ethanol in NADPH and O2 dependent manner, so at high doses EtOH can increase its own metabolism.
Chronic EtOH exposure depletes a person of cofactor necessary to metabolize acetaminophen (via phase II) so this drives acetaminophen metabolism via dehydration rxn which results in toxic metabolite!
Aspirin (salicylate)
non-linear PK
Penicillin G
Antibiotic; non-linear PK.
Squill
Herbal drug that contains cardiac glycoside, can be used to tx CHF or atrial fibrillation.
Oleander
Herbal drug that contains cardiac glycoside, can be used to tx CHF or atrial fibrillation
Senna
Herbal drug that leads to potassium loss and enhances inhibitory effects of digoxin on Na/K/ATPase, can lead to toxicity.
Fomepizol
Alcohol dehydrogenase inhibitor, blocks metabolism of EtOH; used to tx alcohol poisoning with ethylene glycol, methanol, etc.
Hydrochlorothiazide/Chlorothiazide
Anti-hypertensive and diuretic of DCT, NCC inhibitor in DCT; blocks NaCl reabsorption, thereby decreasing urine diluting capacity of nephron; promotes Ca2+ reabsorption; K+-depleting; enhances inhibitory effects of digoxin on Na/K/ATPase. Longer t1/2 than LD’s.
Common side effects are hypokalemia, metabolic acidosis, and hyponatremia.
Ritonavir
Anti-viral used in tx of HIV; inhibits P-glycoprotein transporter in kidney as well as CYP3A4 and may result in drug accumulation (digoxin).
Digoxin Immune Fab
Ovine digoxin antibody used to tx digoxin toxicity; effective in 30-60 minutes; has greater affinity for digoxin than that of the sodium pump.
Ketoconazole
Antifungal that inhibits CYP34A.
***Rifampin
Anti-tubercular drug that also is an inducer of CYP3A4; increases clearance of cyclosporin, erythromycin, and some steroids in OCP’s.
***Saquinavir
Tx for HIV; metabolized by CYP34A; the soft gel form (Fortovase) has greater bioavailability than Invirase since it saturates intestinal CYP34A.
Tolbutamide
Oral sulfonylurea drug that induces insulin release from pancreatic Beta-cells thus lowering blood glucose levels. Peak concentration 3-4 hours after administered. Excreted by kidneys at 75% inactive metabolite.
***Zolpidem
aka Ambien; a non-benzodiazepine sleep aid; t1/2 of 2.1 hrs, so given as extended release tablet that increases AUC over 8 hr sleep period. Oral bioavailability of 70%.
Acetazolamide
relatively weak PCT diuretic; carbonic anhydrase inhibitor; causes self-limited NaHCO3- diuresis, leading to metabolic acidosis; used to tx glaucoma, altitude sickness, and metabolic/urinary alkalosis.
Bumetanide
very potent loop diuretic used to tx edema (2’ to CHF); works by inhibiting NKCC in Ascending L of H; promotes Na+ and K+ excretion, as well as Ca2+ excretion; shorter t1/2 than DCT diuretics; protein-bound anion that gets secreted into PCT; impairs ability of kidneys to produce very concentrated or very dilute urine.
Side effects: hypokalemia, metabolic acidosis, hyponatremia.
Torsemide
very potent loop diuretic used to tx edema (2’ to CHF); works by inhibiting NKCC in Ascending L of H; promotes Na+ and K+ excretion, as well as Ca2+ excretion; shorter t1/2 than DCT diuretics; protein-bound anion that gets secreted into PCT; impairs ability of kidneys to produce very concentrated or very dilute urine.
Side effects: hypokalemia, metabolic acidosis, hyponatremia.
Furosemide
very potent loop diuretic used to tx edema (2’ to CHF); works by inhibiting NKCC in Ascending L of H; promotes Na+ and K+ excretion, as well as Ca2+ excretion; shorter t1/2 than DCT diuretics; protein-bound anion that gets secreted into PCT; impairs ability of kidneys to produce very concentrated or very dilute urine.
Side effects: hypokalemia, metabolic acidosis, hyponatremia. Enhances inhibitory effects of digoxin on Na/K/ATPase.
Metolazone
Anti-hypertensive and diuretic of DCT, NCC inhibitor in DCT; blocks NaCl reabsorption, thereby decreasing urine diluting capacity of nephron; promotes Ca2+ reabsorption; K+-depleting; enhances inhibitory effects of digoxin on Na/K/ATPase. Longer t1/2 than LD’s.
Common side effects are hypokalemia, metabolic acidosis, and hyponatremia.
Chlorthalidone
Anti-hypertensive and diuretic of DCT, NCC inhibitor in DCT; blocks NaCl reabsorption, thereby decreasing urine diluting capacity of nephron; promotes Ca2+ reabsorption; K+-depleting; enhances inhibitory effects of digoxin on Na/K/ATPase. Longer t1/2 than LD’s.
Common side effects are hypokalemia, metabolic acidosis, and hyponatremia.
Amiloride
moderate potency CD diuretic, ENaC Inhibitor; blocks Na reabsorption, thereby increasing the positive lumenal membrane potential which halts K+ secretion (K+ sparing)
Side effects include HypErkalemia and mild natriuresis.
Spironolactone
moderate potency CD diuretic, aldosterone antagonist. Blocks Na+ reabsorption and K+ secretion mediated by aldosterone.
Side effects include hypErkalemia, gynecomastia (man boobs), and mild natriuresis.
Eplerenone
moderate potency CD diuretic, aldosterone antagonist. Blocks Na+ reabsorption and K+ secretion mediated by aldosterone.
Side effects include hypErkalemiam and mild natriuresis.
Triamterene
moderate potency CD diuretic, ENaC Inhibitor; blocks Na reabsorption, thereby increasing the positive lumenal membrane potential which halts K+ secretion (K+ sparing)
Side effects include HypErkalemia and mild natriuresis.
Ethacrynic Acid
very potent loop diuretic used to tx edema (2’ to CHF); works by inhibiting NKCC in Ascending L of H; promotes Na+ and K+ excretion, as well as Ca2+ excretion; shorter t1/2 than DCT diuretics; protein-bound anion that gets secreted into PCT; impairs ability of kidneys to produce very concentrated or very dilute urine.
Side effects: hypokalemia, metabolic acidosis, hyponatremia.
Nicotine
Induces activity of CYP1A2, the P450 that metabolizes caffeine and theophylline.
Procaine
aka Novocaine; local anesthetic; gold standard for 50 years; slow onset/short lived (ester linkage); lasts 0.5-1 hr; has maximum dose 3-4X higher than other LA’s. Administered via spinal, infiltration, peripheral nerve block
Erythromycin
Antibiotic; substrate of CYP3A4; when it’s metabolism is inhibited can lead to long QT syndrome.
Methylphenidate
ADHD drug; standard delivery route is oral, but duration of action is 2-5 hours, so multiple doses needed per day. Extended release oral dose can have up to 12 hours of therapeutic effect. Also administered as a transdermal patch with a theraupeutic duration of 9 hours.
