الخميس، 17 يناير 2013

MCQs In Clinical Pharmacology

Q 1

You are discussing anticonvulsant therapy with a group of medical students on rounds.
The statement you are MOST likely to include in your discussion is that:

A. azithromycin should not be prescribed with carbamazepine
B.  gabapentin has significant drug interactions
C.  lamotrigine frequently causes a benign, self-limited rash
D.  phenobarbital has little impact on school performance
E.  valproic acid is commonly associated with behavioral changes

Answer

A


  All antiepileptic drugs probably have some effect on behavior and school performance, with phenobarbital causing cognitive impairment and behavioral side effects most frequently (in up to 50% of children). Of the commonly used anticonvulsants, valproic acid is least likely to affect behavior and cognitive performance adversely. However, it can be associated with weight gain, thrombocytopenia, tremor, and fulminant hepatic failure, particularly in children younger than age 3 years who are receiving multiple antiepileptic medications.

            Carbamazepine, one of the most commonly used anticonvulsants in childhood, rarely causes significant leukopenia or hepatotoxicity and seldom produces hyponatremia. Macrolides such as erythromycin and azithromycin should be used very cautiously or, if possible, avoided in children receiving carbamazepine because these drugs compete for hepatic metabolism, leading to increasing carbamazepine levels and acute toxicity. Phenytoin is similar to carbamazepine in efficacy for seizures, but it is used less commonly in children because of significant cosmetic adverse effects, including hirsutism, gingival hyperplasia, and facial coarsening. Phenytoin is poorly absorbed from the gastrointestinal tracts of infants and metabolized at a variable rate in the liver.

            Lamotrigine is used in a number of refractory seizure disorders and generally is well tolerated, with occasional drowsiness, headache, and blurred vision. However, its use is associated with the development of maculopapular rash that may progress to Stevens-Johnson syndrome (Figure 138A) during the early months of use, especially when administered with valproate. The development of such a rash should prompt immediate drug discontinuation. In an attempt to avoid these reactions, lamotrigine is administered initially at a low dose and very gradually increased over months, particularly if valproate also is being administered.

            Gabapentin, a second or add-on drug for partial seizures, usually is well tolerated. Because it is not metabolized by the liver and is excreted unchanged by the kidneys, it has no significant drug interactions. Adverse effects include very occasional fatigue, dizziness, headache, and weight gain.

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Q 2 :


Of the following, the class of drugs MOST likely to cause bladder outlet obstruction is:


A.  antiarrhythmics

B.  anticholinergics

C.  antihistamines

D.  antipyretics
E.   antitussives

Answer

B


To understand how anticholinergics cause bladder outlet obstruction, it is important to review the muscular anatomy and neural innervation of the bladder. Normal bladder function depends on the central and peripheral nervous systems and the detrusor muscle and external sphincter of the bladder. Muscular fibers in the bladder interdigitate around the bladder neck, resulting in the formation of a sphincter, which controls the outflow of urine. The somatic and autonomic nervous systems (ANS) control bladder function. The ANS involves sympathetic (from T10 and L1) and parasympathetic (from S2 to S4) control. The sympathetic nervous system stimulates alpha- and beta-receptor sites in the bladder smooth muscle. The primary neurotransmitter for sympathetic control is norepinephrine (NE). When NE interacts with alpha receptors in the bladder, the bladder smooth muscle tone increases, allowing for stretch. Stimulation of beta receptors in the bladder by NE results in relaxation of the detrusor muscle. Thus, NE allows the bladder to expand, thereby accommodating the inflow of urine from the kidneys and ureters. The primary neurotransmitter of the parasympathetic nervous system is acetylcholine (ACH). Release of ACH from the parasympathetic nervous system results in bladder contraction. Combined with reduced output from the sympathetic nervous system, the bladder releases urine into the urethra.

            Because ACH is a cholinergic substance, anticholinergic medications may counteract its effects, including promotion of bladder emptying. For patients taking anticholinergic medication, the bladder is under only sympathetic control, with a net result of prolonged bladder filling and expansion. In the absence of bladder emptying, spasms inevitably ensue. The effect is identical to that seen in children who have spinal cord lesions at S2 to S4, in which parasympathetic stimulation is reduced.

            Treatment for bladder spasms due to anticholinergic therapy is discontinuation of the medication. Antiarrhythmics, antihistamines, antipyretics, and antitussives all have significant adverse effects, but they do not include abnormalities in neural stimulation of the urinary bladder.

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Q 3 :


The parents of an adopted 3-year-old Guatemalan boy are concerned about his bowel movements. He usually has one formed bowel movement a day. However, about once a week, it is loose. He has had no apparent abdominal pain and no vomiting. His height and weight are at the 30th percentile for age. Laboratory examination of a direct fecal smear reveals eggs of Ascaris lumbricoides.
Of the following, the BEST initial management for the boy is administration of:

A. iodoquinol
B. mebendazole
C. metronidazole
D. praziquantel
E. thiabendazole

Answer

B


Recommended treatment regimens for children who have uncomplicated gastrointestinal ascariasis include oral albendazole, mebendazole, or pyrantel pamoate. Cautious use of piperazine is indicated for children who have a heavy worm load, especially in the presence of intestinal biliary obstruction. Piperazine causes a neuromuscular paralysis of the worm, preventing migration and promoting excretion. Intestinal or biliary obstruction may require surgical intervention. External massage of an obstructing intestinal worm bolus is preferred over intestinal incision.

            Iodoquinol is the drug of choice for asymptomatic amebiasis. Metronidazole is used most commonly for the treatment of trichomonas, giardiasis, and amebiasis. Praziquantel is used for the treatment of schistosomiasis, cysticercosis, and flukes. Thiabendazole has been used for the treatment of cutaneous larva migrans and strongyloides.

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Q 4:



A term newborn is being treated with 3.5 mg/kg intravenous infusion of gentamicin over 30 minutes for Escherichia coli sepsis. The dosing interval is every 24 hours. A trough serum concentration 30 minutes before the fourth dose is 0.9 mg/L, and a peak serum concentration 30 minutes after completion of infusion of the fourth dose is 20 mg/L.

Of the following, the MOST appropriate next step is to:

A. administer furosemide
B. decrease gentamicin dose
C. discontinue gentamicin
D. increase gentamicin dosing interval
E. replace gentamicin with tobramycin

Answer

B


The desired peak serum concentration of gentamicin is 5 to 12 mg/L, which is less than that measured for the infant described in the vignette. The appropriate adjustment for a peak serum concentration that is higher than the desired range is to decrease the dose of the antibiotic.

            Furosemide has no role in the treatment of gentamicin overdosage or toxicity. In fact, the addition of furosemide increases the potential risk of oto- and nephrotoxicity.

            Discontinuing gentamicin is likely to lead to incomplete treatment of sepsis, and it may place the infant at risk for the complications of partially treated sepsis.

            The desired trough serum concentration of gentamicin is 0.5 to 1.0 mg/L, and the concentration reported for the infant in the vignette is within that desired range. Therefore, no adjustment in the dosing interval is warranted.

            The pharmacokinetics, antimicrobial profile, and adverse effects of tobramycin are similar to those of gentamicin. Replacing one aminoglycoside with another is unlikely to be of any benefit.

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