A 50-year-old female has been receiving a diuretic for the treatment of essential hypertension. This drug acts by increasing the calcium content of urine and is the drug of choice for reducing acute pulmonary edema in congestive heart failure. Its side effects include ototoxicity and hyperuricemia. What is the most likely mechanism of action of this drug?
A. Aldosterone receptor antagonist
B. Inhibition of the Na/K/2Cl cotransporter
C. Inhibition of carbonic anhydrase
D. Acts as osmotic diuretic
E. Blocking of the NACL cotransporter
Correct Answer: B
B: Loop diuretics inhibit the Na/K/2Cl cotransporter of the luminal membrane in the ascending limb of the loop of Henle. Therefore, reabsorption of Na, K, and CL is decreased. The loop diuretics are the most efficacious of the diuretic drugs because the ascending limb accounts for the reabsorption of 25–30 % of filtered NaCl and downstream sites are not able to compensate for this increased Na load. Loop diuretics are the drugs of choice for reducing acute pulmonary edema in congestive heart failure. Loop diuretics act promptly, even among patients who have poor function or who have not responded to thiazides or other diuretics. Adverse side effects include ototoxicity, particularly when used in conjunction with the aminoglycoside antibiotics. Furosemide and ethacrynic acid compete with uric acid for the renal and biliary secretary system, thus blocking its secretion, and thereby causing or exacerbating gouty attacks. A: Aldosterone receptor antagonist is incorrect. Spironolactone is a synthetic aldosterone antagonist that competes with aldosterone for intracellular cytoplasmic receptor sites. Because spironolactone chemically resembles some of the sex steroids, it does have minimal hormonal activity and may induce gynecomastia in males and menstrual irregularities in females. C: Inhibition of carbonic anhydrase is incorrect. Acetazolamide inhibits carbonic anhydrase, which is located intracellulary and on the apical membrane of the proximal tubular epithelium. The decreased ability to exchange NA for H in the presence of acetazolamide results in a mild diuresis. The adverse side effects of acetazolamide include metabolic acidosis (mild), potassium depletion, renal stone formation, drowsiness, and paresthesia. D: Acts as osmotic diuretic is incorrect. A number of simple, hydrophilic, chemical substances that are filtered through the glomerulus, such as mannitol and urea, result in some degree of diuresis. This is due to their ability to carry water with them into tubular fluid. Osmotic diuretics are a mainstay of treatment for patients with increased intracranial pressure or acute renal failure due to shock, drug toxicities, or trauma. E: Blocking of the NaCl cotransporter is incorrect. The thiazide derivatives act mainly in the distal tubule to decrease the reabsorption of Na by inhibition of an Na/Cl cotransporter on the luminal membrane. As a result, these drugs increase the concentration of NA and CL in the tubular fluid. Hypokalemia is the most frequent problem encountered with the thiazide diuretics and can predispose patients on digitalis to ventricular arrhythmias. Thiazides increase serum uric acid by decreasing the amount of acid excreted by the organic acid secretory system. The thiazides inhibit the secretion of calcium, sometimes leading to elevated levels of Ca in the blood.
Question 132:
A 7-year-old boy has been suffering from influenza and had been given a drug by his father to decrease his high fever. A few hours later, his father brought him to the emergency room in a comatose state with a papulovesicular rash all over the body, moderate hepatomegaly, and asterixis. Laboratory studies reveal elevated levels of blood ammonia, AST, ALT, and PT. CT scan findings are suggestive for generalized cerebral edema.
The drug the father gave his son is most likely which of the following drugs?
A. Aspirin
B. Acetaminophen
C. Indomethacin
D. Mefenamic acid
E. Diclofenac
Correct Answer: A
A: The syndrome is an acute noninflammatory encephalopathy with hepatic failure. Although the etiology of Reye's syndrome is unknown, the condition typically follows viral illness, particularly upper respiratory tract infection (URTI), influenza, varicella, or gastroenteritis, and is associated with aspirin use during the illness. A dramatic decrease in aspirin use in children has made Reye's syndrome rare. High index of suspicion is critical for diagnosis. Consider Reye's syndrome in any child with vomiting and altered mental status. Pathogenesis is unclear, but it typically involves mitochondrial dysfunction in a viral-infected, sensitized host, usually with exposure to mitochondrial toxins (e.g., salicylates, in >80% of cases). Individuals with low levels of urea cycle enzymes are also at increased risk. Mortality has fallen from 50% to less than 20% as a result of earlier diagnosis, recognition of milder cases, and more aggressive therapy. Signs and symptoms of Reye's syndrome include protracted vomiting, with or without significant dehydration, encephalopathy in afebrile patients with minimal or absent jaundice, and hepatomegaly in 50% of patients. Antiemetics may mask early symptoms. Liver function tests reveal elevation of ammonia levels to as much as 1.5 times normal (up to 1200g/dL) 24-48 hours after the onset of mental status changes; this is the most frequent laboratory abnormality. Transaminases (ALT and AST) increase to 3 times normal. Histologic changes include: hepatocyte cytoplasmic fatty vacuolization, astrocyte edema, loss of neurons, and edema and fatty degeneration in proximal lobules. The American Academy of Pediatrics Committee on Infectious Disease recommends that salicylate not be given to children with chicken pox or influenza B. B: Acetaminophen is incorrect. Acetaminophen acts by prostaglandin synthesis in the CNS, and this explain its antipyretic and analgesic properties, which account for its weak anti-inflammatory activity. Acetaminophen is a suitable substitute for the analgesic and antipyretic effects of aspirin in those patients with gastric complaints and to avoid Reye's syndrome in children. C: Indomethacin is incorrect. Indomethacin is more potent than aspirin as an anti-inflammatory agent (NSAID), but it is inferior to the salicylates at doses tolerated by rheumatoid arthritis patients. D: Mefenamic acid is incorrect. Mefenamic acid has no advantage over the other NSAIDS as anti-inflammatory agents. The side effects of mefenamic acid, such as diarrhea, can be severe and associated with inflammation of the bowel. E: Diclofenac is incorrect. Diclofenac is approved for long-term use in the treatment of rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis.
Question 133:
An 18-year-old female is referred to a dermatologist for treatment of severe acne vulgaris. The dermatologist wants to start her on tetracycline.
What test should the patient have prior to starting treatment?
A. Pregnancy test
B. Chest X-ray
C. Complete blood count
D. Liver function tests
E. Creatine kinase
Correct Answer: A
Pregnancy test. Tetracyclines are effective in the treatment of severe cases of acne. They are however teratogenic. As such, it is imperative to make sure female patients are not pregnant prior to starting this medication. In many instances patients are started on concurrent birth control to mitigate this risk even further. A chest x-ray (B) is an important exam to obtain prior to starting drugs which have pulmonary toxicity as a side effect such as amiodarone. A complete blood count (C) would be useful prior to starting a medication that causes anemia, such as immunosuppressive and chemotherapeutic agents. Liver function tests (D) are important to establish as a baseline prior to starting anti-mycobacterial agents. Creatine kinase levels (E) are used to establish as a baseline prior to starting statins.
Question 134:
A 22-year-old woman adopted a cat. Shortly thereafter, she developed itchy eyes and persistent rhinorrhea. She was clearly allergic to the pet, but desperately wanted to keep it. She tried taking diphenhydramine, but it had intolerable side effects.
Which of the following is a common effect of this type of medication?
A. Decreased intraocular pressure
B. Bradycardia
C. Xerostomia
D. Diarrhea
E. Excessive sweating
Correct Answer: C
Diphenhydramine possesses anticholinergic properties. Xerostomia, or dry mouth, is a common side effect of anti-cholinergic medications, due to anti-muscarinic, parasympatholytic effects. Other adverse reactions may include: ?Mydriasis with blurred vision, photophobia ?Urinary retention ?Constipation ?Anhidrosis ? Hyperthermia ?Tachycardia ?Altered mental status A commonly referenced mnemonic for anti-cholinergic toxicity is "mad as a hatter, red as a beet, dry as a bone, hot as a hare, blind as a bat" to reflect confusion, flushing, dry mouth, hyperthermia and mydriasis, respectively.
Question 135:
An 11-year-old male presents with his mother to your clinic with 5 days of frequent diarrhea, occasionally with streaks of blood mixed in. Stool cultures are pending, but preliminary stool samples demonstrate fecal WBC and RBC.
Assuming the patient is stable enough for outpatient management, what would be the optimal treatment assuming the underlying pathogen is Shigella?
A. Oral Erythromycin
B. Oral Metronidazole
C. Oral Vancomycin
D. An oral quinolone
E. Oral TMP-SMX
Correct Answer: E
Correct: E. Shigella can cause bloody diarrhea, and frequently affects young children and institutionalized patients. The pathogen is highly contagious, and is spread via fecal-oral transmission. The pathogen can lead to severe dehydration, and even cause febrile seizures in young patients. For clinically stable patients who can be managed via outpatient therapy, the optimal treatment is via PO TMP-SMX to decrease the risk of person-to-person transmission. Choice A ?Erythromycin is the first line treatment for bloody diarrhea caused by the pathogen campylobacter. However, for the purposes of decreasing transmissibility of suspected Shigella, TMP-SMX remains the mainstay of therapy. Choices B + C ?Oral metronidazole and oral vancomycin can both be used in the treatment of Clostridium deficile. Alternatively, intravenous metronidazole can be given if the patient is unable to tolerate oral medications. Choice D ?Oral quinolones can be used in cases of bloody diarrhea in which salmonella is the suspected pathogen. Salmonella is caused by the ingestion of contaminated poultry and/or eggs, and can ultimately lead to bacteremia in 510% of cases.
Question 136:
A 23-year-old female presents to your clinic complaining of intermittent throbbing headaches that usually last for several hours and are made worse by the presence of light. She endorses occasional nausea without vomiting during the most severe episodes. Physical examination is unrevealing, and she has no significant past medical history.
Which of the following treatments is considered an abortive therapy for this patient's underlying condition?
A. Sumatriptan
B. Gabapentin
C. Amitriptyline
D. Propranolol
E. Diltiazam
Correct Answer: A
Correct: A. Migraine headaches typically affect females more often than males, and patients most frequently present in their early 20s. Classic symptoms of migraine include throbbing headaches lasting between 2?4 hours in duration, with triggers such as red wine, fasting, stress, and menses. Primary prevention is aimed at the identification and avoidance of triggers. Over the counter NSAIDS can be used if symptoms persist. Failing this, PRN abortive therapy is indicated, including the triptans (e.g. ? sumatriptan) and metoclopramide. Choice B ?Gabapentin is an anticonvulsant that is considered to be a second-line, prophylactic treatment for recurrent migraine headaches. Its utility is limited by its lengthy side effect profile. Choice C ?Amitriptyline, a tricyclic antidepressant, can also be utilized for migraine prophylaxis. However, it will not abort a migraine currently in progress, and extensive side effects limit its use. Choices D + E ?Propranolol and diltiazam are beta-blockers and calcium channel blockers, respectively. As with the anticonvulsants and tricyclic antidepressants, these are considered migraine prophylaxis and will not interrupt a migraine once it has begun.
Question 137:
Your patient, a 25-year-old G1P0 female at 26 weeks gestation presents due to an abnormal glucose tolerance test. One week prior, she was given 50 g of oral glucose and demonstrate a venous plasma glucose level of 156 mg/dL one hour later.
Which of the following is the most appropriate next step of management?
A. Repeat the 50 g oral glucose challenge
B. Administer an oral, 3-hour 100 g glucose dose
C. Advise the patient to follow an American Diabetic Association diet plan
D. Begin insulin treatment
E. Order a fetal ultrasound examination
Correct Answer: B
Gestational diabetes is typically asymptomatic but identified via a 1-hour 50g oral glucose challenge administered at 24?8 weeks of gestation. A venous plasma glucose blood level of>; 140 mg/dL is suggestive, and must be confirmed with a 3-hour 100g oral glucose tolerance test. After administration of the 100g glucose challenge, at least two of the following are required for diagnosis: (1) fasting glucose > 95 mg/dL, (2) one-hour glucose >180 mg/dL, (3) two hour glucose >155 mg/dL, and (4) three hour glucose > 140 mg/dL. Choice A ?To diagnose gestational diabetes, a positive 1-hour 50g oral glucose challenge must be followed up by a three-hour 100g oral glucose challenge. The diagnosis is only confirmed after both challenges are completed and the thresholds are met. Choice C ?Following the diagnosis of gestational diabetes, the first step is strict glycemic control (fasting glucose).
Question 138:
A 67-year-old female presents to your clinic complaining of fatigue, diarrhea, headaches and a loss of appetite. Upon examination you find that she is having some cognitive difficulty. Laboratory results reveal: MCV: 109fL; Hgb: 9g/dL; MMA and homocystine are both elevated. Shilling test is positive.
What is the next best step in the management of this patient?
A. Lifelong folic acid supplementation
B. Lifelong Vitamin B12 supplementation
C. Iron supplementation for 4-6 months
D. Obtain a Coomb's test
E. Give corticosteroids and iron supplementation
Correct Answer: B
Lifelong Vitamin B12 supplementation. Vitamin B12 (cyanocobalamin) deficiency generally presents in patients as fatigue, diarrhea and headaches but can also be the cause of cognitive changes (difficulty concentrating, even mild dementia). Pernicious anemia is a macrocytic anemia, therefore laboratory findings indicate an increased mean corpuscular volume (MCV), with a decreased hemoglobin. A positive Schilling test indicates that the B12 deficiency is due to a lack of intrinsic factor. Lifelong cyanocobalamin supplementation (either orally or via injections) is needed to treat pernicious anemia. A is incorrect. Folic acid deficiency anemia is another common type of macrocytic anemia. However, cognitive deficits are not typically seen with folic acid deficiency. Furthermore, a schilling test would be negative and the methylmalonic acid (MMA) would be normal, rather than elevated. C is incorrect. Iron deficiency anemia causes a microcytic anemia, characterized by a decreased MCV. D is incorrect. A Coomb's test is used to detect autoimmune hemolysis that may be suspected in patients with normocytic anemia (anemia with an MCV in the normal range). E is incorrect. Corticosteroids and iron supplementation are indicated as treatment in hemolytic anemia.
Question 139:
Which of the following NSAIDs is an Enolic acid derivative?
A. Ibuprofen
B. Piroxicam
C. Naproxen
D. Oxaprozin
E. Fenoprofen
Correct Answer: B
The following NSAIDs belong to the propionic acid derivatives group - Ibuprofen - Ketoprofen - Naproxen -Fenoprofen - Flurbiprofen - Oxaprozin whereas piroxicam belongs to the class of Enolic acid derivative which also includes other agents like meloxicam and Nabumetone. They are non-selective COX inhibitors and act by preventing the production of certain prostaglandins.
Question 140:
Which of the following statements is true regarding Drug-receptor bonds?
A. Covalent bonds of drugs with receptors are strong and mostly reversible
B. Covalent bonding is much more common than electrostatic bonding in drug-receptor interactions
C. Electrostatic bonds are stronger than covalent bonds
D. Hydrophobic bonds are weak bonds and they are important in the interactions of highly water soluble drugs with the lipids of cell membranes
E. Bond formation of between the acetyl group of aspirin and cyclo-oxygenase enzyme is a covalent bond
Correct Answer: E
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 acetylsalicylic 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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