QUESTION: 13

A 55-year-old female is receiving chemotherapy for metastatic carcinoma. She threatens to stop her treatment because of severe nausea and vomiting. The oncologist plans to use prochlorperazine to reduce the nausea and vomiting associated with chemotherapeutic agents. What is the mechanism of action of prochlorperazine?

Serotonin 5-HT3 antagonist
Blocking dopamine receptors
Cannabinoids related
Blockage of prostaglandins
H2 receptor antagonist

Answer(s): B

Explanation:

B: A variety of drugs have been found to be of some value in the prevention and treatment of vomiting, especially cancer chemotherapy-induced vomiting. With the exception of thioridazine, most of the neuroleptic drugs have antiemetic effects that are mediated by blocking D2 dopaminergic receptors of the chemoreceptor trigger zone of the medulla. Phenothiazines, such as prochlorperazine, were the first drugs shown to be effective antiemetic agents and act by blocking dopamine receptors. They are effective against low to moderately emetogenic chemotherapeutic agents (for example, fluorouracil and doxorubicin). Although increasing the dose improves antiemetic activity, side effects, including hypotension and restlessness, are dose limiting. Other adverse reactions include extrapyramidal symptom and sedation. A: Serotonin 5-HT3 antagonist is incorrect. The specific antagonists of the 5-HT3 receptor, ondansetron and granisetron, selectively block 5-HT3 receptors in the periphery and in the brain (chemoreceptor trigger zone). C: Cannabinoids related is incorrect. Cannabinoids are marijuana derivatives including dronabinol and nabilone and are effective against moderately emetogenic chemotherapy. However, they are seldom first-line antiemetics because of serious side effects. D: Blockage of prostaglandins is incorrect. Dexamethasone and methylprednisolone used alone are effective against mildly to moderately emetogenic chemotherapy. Their antiemetic mechanism is not known, but it may involve blockade of prostaglandins. E: H2 receptor antagonist is incorrect. Antagonists of histamine H2 receptor block the action of histamine at all H2 receptors; their chief clinical use is as inhibitors of gastric acid secretion.

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QUESTION: 14

A 27-year-old female with ovarian cancer is undergoing chemotherapy. She develops subsequent renal failure.
Which of the following drugs is most likely responsible for this?

Cyclophosphamide
Bleomycin
Cisplatin
Vinblastine
Vincristine

Answer(s): C

Explanation:

Cisplatin. All chemotherapeutics have similar generalized side effects related to their effects on rapidly growing cells. These include hair loss, nausea, and fatigue. However, many chemotherapeutics have unique toxicities as well which are often tested. Cisplatin (C) is notable for its nephrotoxicity and ototoxicity. Cyclophosphamide (A) is known to cause hemorrhagic cystitis. This is a distinct process from nephrotoxicity. The most noteworthy side effect of bleomycin (B) is pulmonary toxicity that can lead to pulmonary fibrosis. Vinblastine (D) is known for bone marrow suppression. Vincristine (E) causes neuropathy.

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QUESTION: 15

Your patient is a 43-year-old male who is experiencing post-operative voiding difficulty after an elective inguinal hernia repair. His post void residual volume was 280 cc.
Which of the following medications is the most appropriate choice of therapy for this patient?

Bethanechol
Oxybutynin
Phenylephrine
Finasteride
Imipramine

Answer(s): A

Explanation:

The patient is experiencing a common complication of low abdominal surgery. Post-operative urinary retention occurs in almost 25% of patients after low abdominal surgical procedures. A normal post- void residual volume is less than 50 cc or urine. The effects of anesthesia and analgesia both contribute to bladder distension, decreased micturition reflex, reduction of contractility of the detrusor muscle of the bladder, and incomplete voiding. The detrusor muscle of the bladder is stimulated to contract by muscarinic cholinergic agonists. Bethanechol is a muscarinic agonist and is frequently used in this setting to improve bladder emptying. Finasteride is a drug that is a 5 alpha reductase inhibitor indicated for use in patients with bladder outlet obstruction as a result of prostatic hypertrophy. The inhibition of 5 alpha reductase decreases local conversion of testosterone to dihydrotestosterone in the prostate gland, which results in gradual shrinkage over a period of six to twelve months. Phenylephrine is an alpha-adrenergic agonist that is selective for alpha-1 receptors. Activation of the alpha 1 receptors in the bladder results in contraction of the trigone muscle and sphincter. This promotes urinary retention. Oxybutynin is an antimuscarinic agent that is useful for treatment of urge incontinence, and would have a detrimental effect on this patient’s bladder disorder. Imipramine is a medication with anticholinergic properties that would also cause worsening of the patient’s condition. Take home message: Post-operative urinary retention with concomitant incomplete voiding is a complication that results from a decreased micturition reflex, increased vesical sphincter tone, or decreased contractility of the detrusor muscle of the bladder. It can be successfully treated with a muscarinic agonist, such as bethanechol, or with an alpha-1 adrenergic antagonist.

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QUESTION: 16

Which of the following statements is true regarding Drug-receptor bonds?

Covalent bonds of drugs with receptors are strong and mostly reversible
Covalent bonding is much more common than electrostatic bonding in drug-receptor interactions
Electrostatic bonds are stronger than covalent bonds
Hydrophobic bonds are weak bonds and they are important in the interactions of highly water soluble drugs with the lipids of cell membranes
Bond formation of between the acetyl group of aspirin and cyclo-oxygenase enzyme is a covalent bond

Answer(s): E

Explanation:

Drugs mainly interact with the receptors by means of chemical forces or bonds. There are three major types of drug receptor bonds: - Covalent - Electrostatic - Hydrophobic Covalent bonds are very strong bonds and in most of the cases they are irreversible under biologic conditions. For example, the covalent bond between the acetyl group of aspirin and cyclo-oxygenase enzyme (target enzyme present on the platelets) does not breaks easily. The platelet aggregation effect of aspirin lasts long after free acetyl-salicylic acid has disappeared from the blood (about 15 minutes) and it is reversed only by the synthesis of new cyclo-oxygenase enzyme in new platelets which takes a long time. Hence the effect of aspirin is seen after the drug is stopped. Among the drug receptor interactions, electrostatic bond is much more commonly found than covalent bond. The electrostatic bonds vary from relatively strong linkages between permanently charged ionic molecules to weaker hydrogen bonds and very weak induced dipole interactions such as van der Waals force. The electrostatic bonds are weaker than covalent bonds. Hydrophobic bonds are usually very weak bonds and probably important in the interactions of highly lipid soluble drugs with the lipids of cell membranes and perhaps in the interactions of the drugs with the internal walls of receptor “pockets”.

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