C. Highly hydrophilic drugs have poor oral bioavailability, because they are poorly absorbed due to their inability to cross the lipid-rich cell membranes. Highly lipophilic (hydrophobic) drugs also have poor oral bioavailability, because they are poorly absorbed due their insolubility in aqueous stomach fluids and therefore cannot gain access to the surface of cells. Therefore, drugs that are largely hydrophobic, yet have aqueous solubility have greater oral bioavailability because they are readily absorbed.

A. A muscarinic agonist binds to and activates muscarinic receptors in the heart, endothelial cells (blood vessels), the gut, and iris sphincter (eye) and urinary bladder wall muscles, in addition to several other tissues. Activation of muscarinic receptors by an agonist causes a reduction in heart rate, constriction of circular muscles in the iris sphincter leading to constriction of the pupil (miosis), increased GI motility (hence, diarrhea, not constipation), and contraction of bladder muscles leading to an increase (not decrease) in urination frequency. In the endothelial cells of blood vessels, muscarinic activation produces release of nitric oxide that causes vasorelaxation and a reduction (not increase) in blood pressure.

A. Stimulation of α1 receptors, mostly found in the blood vessels, causes vasoconstriction and increase in blood pressure. Stimulation of α2 receptors on the sympathetic presynaptic terminal reduces the release of norepinephrine. β2 receptors are not found in the heart, so activation of β2 receptors does not affect heart rate. Stimulation of β2 receptors found in the bronchial tissues causes bronchodilation, not bronchoconstriction.

C. This is a potentially fatal situation. It is important to administer a diuretic that will reduce fluid accumulation in the lungs and, thus, improve oxygenation and heart function. The loop diuretics are most effective in removing large fluid volumes from the body and are the treatment of choice in this situation. In this situation, furosemide should be administered intravenously. The other choices are inappropriate.

A. The cough is most likely an adverse effect of the ACE inhibitor enalapril. Losartan is an ARB that has the same beneficial effects as an ACE inhibitor but is less likely to produce a cough. Nifedipine, prazosin, and propranolol do not cause this side effect.

D. Lipid-soluble drugs readily cross the blood–brain barrier because they can dissolve easily in the membrane of endothelial cells. Ionized or polar drugs generally fail to cross the blood–brain barrier because they are unable to pass through the endothelial cells, which do not have slit junctions.

B. Muscarinic agonists (for example, ACh, pilocarpine) contract the circular smooth muscles in the iris sphincter and constrict the pupil (miosis). Anticholinesterases (for example, neostigmine, physostigmine) also cause miosis by increasing the level of ACh. Muscarinic antagonists, on the other hand, relax the circular smooth muscles in the iris sphincter and cause dilation of the pupil (mydriasis).

B. α2 Agonists activate α2 receptors located in the presynaptic terminal of sympathetic neurons and cause a reduction in the release of norepinephrine from sympathetic nerve terminals. This leads to a reduction in blood pressure. α2 Agonists such as clonidine and methyldopa are therefore used as antihypertensive agents

C. Acetazolamide is used prophylactically for several days before an ascent above 10,000 feet. This treatment prevents the cerebral and pulmonary problems associated with the syndrome as well as other difficulties, such as nausea.

D. Prazosin produces first-dose hypotension, presumably by blocking α1 receptors. This effect is minimized by initially giving the drug in small, divided doses. The other agents do not have this adverse effect.

D. A drug will reach steady state in about four to five half-lives. Thus, for this drug with a half-life of 10 hours, the approximate time to reach steady state will be 40 hours.

C. Since there is already a deficiency in brain cholinergic function in Alzheimer’s disease, inhibiting cholinergic receptors or inhibiting the release of ACh will worsen the condition. Activating the acetylcholinesterase enzyme will increase the degradation of ACh, which will again worsen the condition. However, inhibiting the acetylcholinesterase enzyme will help to increase the levels of ACh in the brain and thereby help to relieve the symptoms of Alzheimer’s disease.

D. α1 Receptors are located on the postsynaptic membrane in the effector organs such as blood vessels. α2 Receptors are mainly found on the presynaptic sympathetic nerve terminals, where they inhibit the release of norepinephrine when activated. β1 Receptors are found in the heart, in addition to some other tissues, and cause increase in heart rate and contractility when activated. β2 receptors are found in the lungs, in addition to some other tissues, and cause relaxation of bronchial smooth muscles when activated. β3 Receptors are found in adipose tissue and are involved in lipolysis.

C. Spironolactone antagonizes aldosterone, which in turn prevents salt/water retention, cardiac hypertrophy, and hypokalemia. Spironolactone has endocrine effects on hormones but not on glucose.

C. The side effect profile of β-blockers, such as metoprolol, is characterized by interference with sexual performance and decreased exercise tolerance. None of the other drugs is likely to produce this combination of side effects.

Correct answer = A. As a general rule, weak acid drugs such as phenobarbital can be eliminated faster by alkalization of the urine. Bicarbonate alkalizes urine and keeps phenobarbital ionized, thus decreasing its reabsorption

C. Muscarinic agonists such as ACh, pilocarpine, and bethanechol contract the circular muscles of iris sphincter and cause constriction of the pupil (miosis), whereas muscarinic antagonists such as atropine and tropicamide prevent the contraction of the circular muscles of the iris and cause dilation of the pupil (mydriasis). α-Adrenergic antagonists such as phentolamine relax the radial muscles of the iris and cause miosis.

E. Norepinephrine activates both α1 and β1 receptors and causes an increase in heart rate and blood pressure. A drug that prevents the increase in blood pressure caused by norepinephrine should be similar to carvedilol that antagonizes both α1 and β1 receptors. Prazosin is an α1 antagonist, clonidine is an α2 agonist, and propranolol and metoprolol are β antagonists, and these drugs cannot completely prevent the cardiovascular effects of norepinephrine.

C. Hypokalemia is a common adverse effect of the thiazides and causes fatigue and lethargy in the patient. Supplementation with potassium chloride or foods high in K+ corrects the problem. Alternatively, a potassiumsparing diuretic, such as spironolactone, may be added. Calcium, uric acid, and glucose are usually elevated by thiazide diuretics. Sodium loss would not weaken the patient.

D. Increasing the dose of lisinopril or adding a second medication from a different class (such as a calcium channel blocker or diuretic) would be appropriate steps to control the blood pressure. Adding an ARB as the second medication is not recommended. ARBs have a similar mechanism of action to ACE inhibitors, and combination therapy may increase the risk of adverse effects.

A. For IV infusion, Loading dose = (Vd) × (desired steady-state plasma concentration). The Vd in this case corrected to the patient’s weight is 70 L. Thus, Loading dose = 70 L × 2.5 mg/L = 175 mg.

C. Sarin is an organophosphate cholinesterase inhibitor. It causes an increase in ACh levels in tissues that leads to cholinergic crisis by the activation of muscarinic as well as nicotinic receptors. Most of the symptoms of cholinergic crisis are mediated by muscarinic receptors and, therefore, the muscarinic antagonist atropine is used as an antidote for sarin poisoning. Cholinergic agonists such as pilocarpine, carbachol, physostigmine (indirect agonists), and nicotine will worsen the symptoms of sarin poisoning.

A. If β-blocker therapy is stopped abruptly, that could cause angina and rebound hypertension. This could be due to the up-regulation of β receptors in the body. β-Blockers do not cause direct vasorelaxation. Therefore, they do not decrease peripheral resistance and are less likely to cause orthostatic hypotension. Propranolol is a nonselective β-blocker (not cardioselective). Cardioselective β-blockers antagonize only β1 receptors and do not worsen asthma as they do not antagonize β2 receptors.

Hydrochlorothiazide is effective in increasing calcium reabsorption, thus decreasing the amount of calcium excreted, and decreasing the formation of kidney stones that contain calcium phosphate or calcium oxalate. However, hydrochlorothiazide can also inhibit the excretion of uric acid and cause its accumulation, leading to an attack of gout in some individuals. Furosemide increases the excretion of calcium, whereas the K+-sparing osmotic diuretics, spironolactone and triamterene, and urea do not have an effect.

C. Hydralazine is an appropriate choice for a hypertensive pregnant patient. ACE inhibitors, ARBs, and the direct renin inhibitor, aliskiren, are all contraindicated in pregnancy due to their potential for fetal harm.
Did you choose Fenoldopam? Why you are right! This is the Dopamine agonist that could also be used!