A 30-year-old woman undergoes abdominal surgery. In spite of minimal tissue damage, complete ileus (absence of bowel motility) follows, and she complains of severe bloating. She also finds it difficult to urinate. Mild cholinomimetic stimulation with bethanechol or neostigmine is often effective in relieving these complications of surgery. Neostigmine and bethanechol in moderate doses have significantly different effects on which one of the following?
(A) Gastric secretory cells
Because neostigmine acts on the enzyme cholinesterase, which is present at all cholinergic synapses, this drug increases acetylcholine effects at nicotinic junctions as well as muscarinic ones. Bethanechol, on the other hand, is a direct-acting agent that activates muscarinic receptors regardless of whether the receptors are innervated or not. The muscarinic receptors on vascular endothelial cells are not innervated and respond only to direct-acting drugs. The answer is B.
JR, a 35-year-old farm worker, is admitted to the emergency department suffering from insecticide poisoning. Parathion has which one of the following characteristics?
(A) It is inactivated by conversion to paraoxon
(B) It is less toxic to humans than malathion
(C) It is more persistent in the environment than DDT
(D) It is poorly absorbed through skin and lungs
(E) If treated early, its toxicity may be partly reversed by pralidoxime
The “-thion” organophosphates (those containing the P=S bond) are activated, not inactivated, by conversion to “-oxon” (P=O) derivatives. They are less stable than halogenated hydrocarbon insecticides of the DDT type; therefore, they are less persistent in the environment. Parathion is more toxic than malathion. It is very lipid-soluble and rapidly absorbed through the lungs and skin. Pralidoxime has very high affinity for the phosphorus atom and is a chemical antagonist of organophosphates. The answer is E.
Ms Brown, a 28-year-old accountant, has been treated for myasthenia gravis for several years. She reports to the emergency department complaining of recent onset of weakness of her hands, diplopia, and difficulty swallowing. She may be suffering from a change in response to her myasthenia therapy, that is, a cholinergic or a myasthenic crisis. Which of the following is the best drug for distinguishing between myasthenic crisis (insufficient therapy) and cholinergic crisis (excessive therapy)?
Any of the cholinesterase inhibitors (choices B, C, or E) would effectively correct myasthenic crisis. However, because cholinergic crisis (if that is what is causing the symptoms) would be worsened by a cholinomimetic, we choose the shortest-acting cholinesterase inhibitor, edrophonium. The answer is B.
A crop duster pilot has been accidentally exposed to a high concentration of a highly toxic agricultural organophosphate insecticide. If untreated, the cause of death from such exposure would probably be
(B) Gastrointestinal bleeding
Respiratory failure, from neuromuscular paralysis or CNS depression, is the most important cause of acute deaths in cholinesterase inhibitor toxicity. The answer is E.
Mr Green has just been diagnosed with dysautonomia (chronic idiopathic autonomic insufficiency). You are considering different therapies for his disease. Pyridostigmine and neostigmine may cause which one of the following in this patient?
(D) Irreversible inhibition of acetylcholinesterase
(E) Reduced gastric acid secretion
Cholinesterase inhibition is typically associated with increased (never decreased) bowel activity. (Fortunately, many patients become tolerant to this effect.) The answer is C.
Parasympathetic nerve stimulation and a slow infusion of bethanechol will each
(A) Cause ganglion cell depolarization
(B) Cause skeletal muscle end plate depolarization
(D) Increase bronchial smooth muscle tone
Choice (E) is not correct because the vagus slows the heart. Parasympathetic nerve stimulation does not cause vasodilation (most vessels do not receive parasympathetic innervation), so choice (C) is incorrect. Ganglion cells and the end plate contain nicotinic receptors, which are not affected by bethanechol, a direct-acting muscarinic agonist. Efferent fibers in the vagus may cause bronchoconstriction. The answer is D.
Actions and clinical uses of muscarinic cholinoceptor agonists include which one of the following?
(A) Bronchodilation (treatment of asthma)
(B) Miosis (treatment of narrow angle glaucoma)
(C) Decreased gastrointestinal motility (treatment of diarrhea)
(D) Decreased neuromuscular transmission and relaxation of skeletal muscle (during surgical anesthesia)
(E) Increased sweating (treatment of fever)
Muscarinic agonists cause accommodation and cyclospasm, the opposite of paralysis of accommodation (cycloplegia). Although not drugs of choice, in acute angle-closure glaucoma, this may result in a desirable increased outflow of aqueous and decreased intraocular pressure. Parasympathetic nerve stimulation and a slow infusion of bethanechol, these agents may cause bronchospasm but have no effect on neuromuscular transmission. They may cause diarrhea and must not be used in its treatment. Muscarinic agonists may also cause sweating, but drug-induced sweating is of no value in the treatment of fever. The answer is B.
Which of the following is a direct-acting cholinomimetic that is lipid-soluble and is used to facilitate smoking cessation?
Varenicline is a lipid-soluble partial agonist at nicotinic receptors and is used to reduce craving for tobacco in smokers. The answer is E.
A 3-year-old child is admitted to the emergency department after taking a drug from her parents’ medicine cabinet and swallowing multiple tablets. The signs suggest that the drug is a cholinomimetic with little or no vascular effect, little or no CNS effect, and a duration of action of about 2–4 h. Which of the following is the most likely cause of these effects?
The fact that the drug has no vascular effect suggests that it is an indirect-acting agent. Neostigmine is the prototypical indirect-acting cholinomimetic; it is a quaternary (charged) substance with poor lipid solubility and little or no CNS action; its duration of action is about 2–4 h. Physostigmine is similar but has good lipid solubility and significant CNS effects. The answer is C.
Which of the following is the primary second-messenger process in the contraction of the ciliary muscle when focusing on near objects?
(A) cAMP (cyclic adenosine monophosphate)
(C) Depolarizing influx of sodium ions via a channel
(D) IP3 (inositol 1,4,5-trisphosphate)
Cholinomimetics cause smooth muscle contraction mainly through an action on M3 Gq-coupled receptors resulting in the release of intracellular calcium. This release is triggered by an increase in IP3 acting on IP3 receptors in the endoplasmic reticulum. The answer is D.