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UCSD BIMM 118 - PHARM Problemset

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1) Estimate the behavior of this drug in the body during:a) Oral absorptionb) Liver passage (potential phase I + II reactions)a) Good (drug is generally lipophilic)b) Phase I: a. Ester hydrolysisb. Oxidationc. Demethylation Phase II:a. Glucoronidationb. Sulfation2) Which drug has the higher efficacy?Both drugs have the same efficacy (they achieve the same maximal response), however, drug A has the higher potency (less drug is required to achieve maximalefficacy).A 35 kg child in an ER on an i.v. infusion requires immediate treatment with the antiarrhythmic drug procainamide.The textbook lists the following pharmakokinetic values for procainamide in a 70 kg adult: Vd = 130 LClearance = 36 L / hrOral availability = 83%Therapeutic concentration = 5 mg/L1. What iv loading dose should be administered?2. What constant infusion rate is required to maintain the therapeutic concentration?3. What is the predicted half-life of the drug in the child?Answers:The patient is half the weight of the average adult => Vd and clearance will be ~ one half the given values. Drug is given i.v. => oral availability irrelevant:1. Loading dose = Vd x Cp = 130L/2 x 5 mg/mL = 325 mg2. Infusion rate = Cl x Cp = (36 L / hr)/2 x 5 mg/mL = 90 mg/hr3. T1/2 = ln2 x Vd/Cl = 0.693 x 130 L / 36 L/hr = 2.5 hrsPROBLEM SET 2:Which of the drugs qualifies as a partial agonist?Drug C: even at the highest concentration, only a fraction of the maximal response can be achievedA patient appears in the emergency room with a history of ingesting vinegar at a party where marijuana was smoked. The pH of his urine was found to be 2.0. What effect would this pH have had on 11-nor delta9-THC carboxylic acid (THC-COOH), a weak acid metabolite of marijuana? A. the THC-COOH would be ionized B. the concentration of THC-COOH in urine would be decreased C. the concentration of THC-COOH in urine would be increasedD. the excretion of THC-COOH would be facilitated E. none of the above B. the concentration of THC-COOH in urine would be decreased:Lowering the pH of the urine (increasing urine H ion concentration) would increase the percentage of THC that is unionized (e.g. THC-COO- + H+ -> THC-COOH). This will increase passive re-absorption of the drug (lack of “trapping” in the urine) across cell membranes in the kidney, and lower the amount that stays in the renal filtrate (urine).The full effect of digoxin in slowing the heart rate after a single i.v. dose may require 6-8 hours to develop. Which of the following is the most likely explanation? A. rapid renal clearance B. long distribution phase C. extensive protein binding D. long elimination half-life E. small volume of distribution B. long distribution phase: It takes 6-8 hours for digoxin in the plasma to equlibrate (distribute into) peripheral tissues such as the heart. Thus the peak effect is delayed after giving a loading dose of digoxin Phenobarbital and warfarin were administered together to a patient with a myocardial infarction over a period of 7 days. During this time, the warfarin dosage was adjusted to get a 20% increase in coagulation time. On day 8, the patient discontinued the phenobarbital but continued to take the warfarin for the next 2 weeks. What effect would be expected with respect to warfarin? A. plasma level would be increased B. plasma level would be decreased C. prothrombin time would be decreased D. warfarin binding to plasma protein would be decreased A. plasma level would be increased:Phenobarbital is a good inducer of cytochrome P-450, a major drug-metabolizing enzyme. Discontinuation of phenobarbital will result in a decrease in this effect, lower levels of drug-metabolizing enzymes, and increased plasma levels of warfarin. Eliminating phenobarbital would also not decrease the amount of warfarin binding to plasma proteins.PROBLEM SET 3:1) Captopril blocks: A. angiotensin II receptors B. angiotensin II formation C. bradykinin receptors D. bradykinin formation E. alpha1 adrenergic receptorsB) Captopril is an ACE (Angiotensin Converting Enzyme) inhibitor. Bradykinin is metabolized by ACE, therefore its levels would increase, not decrease.2) Sodium nitroprusside: A. is used to lower blood pressure in a hypertensive emergency B. increases smooth muscle cAMP levels C. has a slow onset and long duration of action D. is given orally E. inhibits nitric oxide formationA) Nitroprusside is given i.v. to lower blood pressure. It has a rapid action and short half life and is therefore useful in titrating blood pressure to a desired level by altering its rate of infusion.3) A patient arrives in the ER after attempting suicide by taking a precription drug overdose with the following symptoms:Tachycardia; widened pupils; dry, flushed skin; dry mouthWhich of the drug(s) on his nightstand are likely to be responsible for these symptoms:A. FurosemideB. DigitoxinC. AtenololD. AtropinE. CaptoprilD) The symptoms are consistent with the actions a muscarinic parasympatholyticdrug 4) Would furosemide increase of decrease the effects of digoxin? Increase: Diuretics cause a loss of potassium, resulting in lower potassium concentrations. Potassium competes with digoxin for binding the the Na+/K+ antiporter system => reduced K+ means less competition => increased effect of digoxin.5) A patient starts treatment with probenecid for his gout, however, his condition seems to worsen rather than improve. What is a likely cause for this problem? Uricosuric agents at subtherapeutic concentrations inhibit excretion as well as reabsorption of uric acid. At therapeutic levels, inhibition of reabsorption dominates over inhibition of


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