1. Which of the following is not used in treatment of pulmonary hypertension?
A. Beta blocker
2. Which of the following causes persistent leucopenia?
3. SIADH is caused by the following drugs except?
4. Which one of the following is a side effect of 2 agonist?
5. A 3-year-old child is brought to the emergency de¬partment having just ingested a large overdose of promethazine, an antihistaminic drug. Prometh¬azine is a weak base with a pKa of 9.1. It is capable of entering most tissues, including the brain. On physical examination, the heart rate is 100/min, blood pressure 110/60 mm' Hg, and respiratory rate 20/min. In this case of promethazine overdose,
(A) Urinary excretion would be accelerated by administration of NH4Cl, an acidifying agent
(B) Urinary excretion would be accelerated by giv¬ing NaHCO3, an alkalinizing agent
(C) Absorption of the drug would be faster from the stomach than from the small intestine
(D) Hemodialysis is the only effective therapy
6. If the plasma concentration of a drug declines with "first-order kinetics," this means that
(A) There is only 1 metabolic path for drug dispo¬sition
(B) The half-life is the same regardless of the plasma concentration
(C) The drug is largely metabolized in the liver after oral administration and has low bioavail¬ability
(D) The rate of elimination is proportionate to the rate of administration at all times
7. Dose-response curves are used for drug evaluation in the animal laboratory and in the clinic. Quantal dose response curves are
(A) Used for determining the therapeutic index of a drug
(B) Used for determining the maximal efficacy of a drug
(C) Obtainable from the study of intact subjects but not from isolated tissue preparations
(D) Used to determine the statistical variation (standard deviation) of the maximal response to the drug
8. Which of the following statements about spare re¬ceptors is MOST correct?
(A) Spare receptors, in the absence of drug, are sequestered in the cytoplasm
(B) Spare receptors may be detected by finding that the drug-receptor interaction lasts longer than the intracellular effect
(C) Spare receptors influence the maximal efficacy of the drug-receptor system
(D) Spare receptors may be detected by the finding that the EC50 is smaller than the Kd for the agonist
9. Which of the following terms best describes the an¬tagonism of leukotrienes bronchoconstrictor effect (mediated at leukotriene receptors) by terbutaline (acting at adrenoceptors) in a patient with asthma?
(A) Pharmacologic antagonist
(B) Partial agonist
(C) Physiologic antagonist
(D) Chemical antagonist
10. You have diagnosed asthma in a 19-year-old pa¬tient with recurrent, episodic attacks of bron-chospasm with wheezing. Avoidance of allergens has been tried unsuccessfully. She is to receive therapy with several drugs. You are concerned about drug interactions caused by changes in drug metabolism in this patient. Drug metabolism usu¬ally results in a product that is
(A) More likely to distribute intracellularly
(B) Less lipid soluble than the original drug
(C) More likely to be reabsorbed by kidney tubules
(D) More lipid soluble than the original drug
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1. Ans. (A) Beta Blocker
Because the pulmonary artery pressure in PPH increases dramatically with exercise, patients should be cautioned against participating in activities that demand increased physical stress.
• Digoxin may increase cardiac output and lower circulating levels of norepinephrine.
• Diuretic therapy relieves peripheral edema and may be useful in reducing RV volume overload in the presence of tricuspid regurgitation.
• Resting and exercise pulse oximetry should be obtained, as oxygen supplementation helps to alleviate dyspnea and RV ischemia in patients whose arterial oxygen saturation is reduced.
• Anticoagulant therapy is advocated for all patients with PPH since thrombin deposition occurs in the pulmonary circulation; thrombin can serve as a growth factor to promote the disease process.
• One retrospective study and one prospective study demonstrated that the anticoagulant warfarin increases survival of patients with PPH. The dose of warfarin is generally titrated to achieve an INR of two to three times control.
OTHER DRUGS USEFUL ARE:
• Calcium Channel Blockers
• Prostacyclins Epoprostenol
• Endothelin Receptor Antagonists e.g. Bosentan
2. Ans. (D). Carmustine
Carmustine causes persistent neutropenia with a delayed nadir.
Carmustine of BCNU is a mustard gas-related α-chloronitrosourea compound used as an alkylating agent in chemotherapy. It is used in the treatment of several types of brain cancer (including glioma, glioblastoma multiforme, medulloblastome and astrocytoma), multiple myeloma and lymphoma (Hodgkin’s and non-Hodgkin). carmustine for injection is marketed under the name BiCNU by Bristol-Myers Squibb.
3. Ans. D. Cisplatin
Definition: AVP excess associated with hyponatremia without edema or hypovolemia. The AVP excess is inappropriate in the face of hypo-osmolality.
Drugs Causing SIADH
1. Intravenous cyclophosphamide*
3. Vincristine or vinblastine
6. Tricyclic antidepressants or serotonin-reuptake inhibitors
7. Monoamine oxidase inhibitors
10. Narcotics, opiate derivatives
4. Ans. D. Hypokalemia
2 agonist cause hypokalemia by enhancing K + uptake into muscles, thus used in hyperkalemic familial periodic paralysis.
5. Ans. A. Urinary excretion would be accelerated by administration of NH4Cl, an acidifying agent
Questions that deal with acid-base (Henderson ¬Hasselbalch) manipulations are common. Since absorption involves permeation across lipid mem¬branes, we can treat an overdose by decreasing ab-sorption from the gut and reabsorption from the tubular urine by making the drug less lipid soluble. Ionization attracts water molecules and decreases lipid solubility. Promethazine is a weak base, which means that it will be more ionized (proto¬nated) at acid pH than at basic pH. Choice C sug¬gests that the drug would be more ionized at pH 7.4 than at pH 2.0: clearly wrong. Choice D says (in effect) that the more ionized form will be ab¬sorbed faster, which is incorrect. A and B are op¬posites because NH4Cl is an acidifying salt and sodium bicarbonate an alkalinizing one. From the point of view of test strategy, opposites always de¬serve careful attention and, in this case, encourage us to exclude E, a distracter. Because an acid envi¬ronment favors ionization of a weak base, we should give NH4Cl. The answer is A.
6. Ans. B. The half-life is the same regardless of the plasma concentration
5. "First-order" means that the elimination rate is proportionate to the concentration perfusing the organ of elimination. The half-life is a constant. The rate of elimination is proportionate to the rate of administration only at steady state.
7. Ans. A. Used for determining the therapeutic index of a drug
Graded (not quanta!) dose-response curves must be used to determine maximum efficacy (maximal response). Quantal dose-response curves show only the frequency of occurrence of a specified re-sponse, which may be therapeutic (ED) or toxic (TD). Dividing the TD50 by the ED so gives the therapeutic index.
8. Ans. D. Spare receptors may be detected by the finding that the EC50 is smaller than the Kd for the agonist
5. While some types of receptors appear to be se¬questered in the cytoplasm under certain condi¬tions, there is no difference between "spare" and other receptors. Spare receptors may be defined as those which are not needed for binding drug to achieve the maximal effect. Spare receptors influ¬ence the sensitivity of the system to an agonist be¬cause the statistical probability of a drug-receptor interaction increases with the total number of re¬ceptors. They do not alter the maximal efficacy. If they do not bind an agonist molecule, spare recep¬tors do not activate an effector molecule. EC50 less than Kd is an indication of the presence of spare receptors.
9. Ans. C. Physiologic antagonist
Because terbutaline interacts with adrenoceptors and leukotriene with leukotriene receptors, terbu¬taline cannot be a pharmacologic antagonist of leukotriene. Because the results of adrenoceptor activation oppose the effects of leukotriene recep¬tor activation, terbutaline must be a physiologic antagonist.
10. Ans. B. Less lipid soluble than the original drug
Biotransformation usually results in a product that is less lipid soluble.