Pharmacology - An Illustrated Review
Questions & Answers
1. Atropine blocks the action of
2. Drugs that possess antimuscarinic activity are contraindicated in patients with
3. A 52-year-old woman became angry with her spouse and ingested a bottle of pesticide containing parathion, an organophosphate compound. She was brought to the emergency room within 30 minutes. A nasogastric lavage was performed immediately. The patient's symptoms progressed to include miosis, diaphoresis, salivation, lacrimation, defecation, and bronchorrhea. Which of the following drug pairs would comprise part of the treatment for this poisoning episode?
A. Atropine and pralidoxime
B. Nitroglycerin and hydrochlorothiazide
C. Phenylephrine and isoproterenol
D. Propranolol and theophylline
E. Tubocurarine and lidocaine
For questions 4 to 8, refer to the pathway for catecholamine synthesis that follows. A to D represent the enzymes involved in the steps of that pathway.
4. Dopa decarboxylase catalyzes which step in the pathway above?
5. Dopamine-β-hydroxylase catalyzes which step in the above pathway?
6. Tyrosine hydroxylase catalyzes which step in the above pathway?
7. Phenylethanolamine-n-methyltransferase (PMNT) catalyzes which step in the above pathway?
8. The rate-limiting step in catecholamine synthesis is:
9. Direct inhibition of norepinephrine release is accomplished via
A. α1-adrenergic receptor stimulation
B. α2-adrenergic receptor stimulation
C. β1-adrenergic receptor stimulation
D. β2-adrenergic receptor stimulation
10. Antihypertensive action of clonidine in the central nervous system (CNS) occurs via
A. activation of α1-adrenergic receptors
B. activation of α2-adrenergic receptors
C. activation of β1-adrenergic receptors
D. activation of β2-adrenergic receptors
E. activation of muscarinic receptors
11. Which of the following blocks the blood pressure effects of norepinephrine but does not interfere with the presynaptic actions of norepinephrine to modulate its own release?
12. A 54-year-old man with benign prostatic hypertrophy is experiencing uncontrollable leakage of small amounts of urine. Drug treatment to reduce prostatic hypertrophy is initiated, but it will take several weeks to alleviate the overflow incontinence. Which of the following agents will act directly in the bladder to decrease outflow obstruction and increase urinary flow rates so that a more rapid therapeutic response may be obtained?
13. An alternative approach to that taken in question 12 may be to activate the postganglionic parasympathetic responses of the bladder. Which of the following drugs would have this effect?
The following information refers to Questions 14 to 17.
In a dog anesthetized with pentobarbital, recording electrodes are placed on
I Carotid sinus baroreceptor nerve fibers
II Splanchnic (sympathetic) nerve fibers (preganglionic)
III Inferior cardiac (sympathetic) nerve fibers (postganglionic)
IV Vagal (parasympathetic) nerve fibers
Answer choices A to E show the changes (if any) in firing rates that would be expected to occur at nerves I to IV following the administration of the last drug in each series of drugs listed in questions 14 to 17. Presume that sufficient time for the actions of the premedicating agents has been allowed and that the last agent is then given intravenously.
Key. ⇑ = increase of nerve activity; ⇓ = decrease nerve activity; ⇔ = no change in neural firing.
14. Propranolol and atropine, then phenylephrine
Answers and Explanations
1. D Atropine is a muscarinic cholinergic receptor antagonist. Of the listed agents, acetylcholine is the only one that is an agonist at cholinergic receptors. Thus, atropine blocks the actions of acetylcholine at the muscarinic subtype of cholinergic receptor (p. 49).
A. Dopamine is an agonist at dopaminergic receptors.
B. Norepinephrine is an agonist at adrenergic receptors.
C. Serotonin is an agonist at serotonin receptors.
D. Histamine is an agonist at histamine receptors.
2. A Antimuscarinic anticholinergics may worsen glaucoma and are therefore contraindicated in patients with this condition (p. 52).
A. Antimuscarinic anticholinergics tend to produce constipation, an effect that would be helpful in diarrhea, therefore it is not contraindicated for this condition.
B. C and D. Antimuscarinic anticholinergics have little or no effect on blood pressure and gout.
3. A Treatment for organophosphate poisoning involves giving atropine to block the muscarinic effects plus pralidoxime to reactivate acetylcholinesterase thereby permitting acetylcholine degradation (p. 48).
A. Nitroglycerine is a venodilator and hydrochlorothiazide is a thiazide diuretic. Neither are indicated for organophosphate poisoning.
B. Phenylephrine is a direct-acting α adrenergic receptor agonist. Isoproterenol is a β1 and β2 adrenergic receptor agonist. Neither are indicated for organophosphate poisoning.
C. Propranolol is a nonselective β adrenergic receptor antagonist. Theophylline is a drug used in asthma therapy that acts in many different ways, including being a β receptor agonist. Neither are indicated for organophosphate poisoning.
D. Tubocurarine is a nondepolarizing neuromuscular nicotinic receptor antagonist. Lidocaine is a local anaesthetic agent.
4. B Dopa decarboxylase catalyzes the conversion of dopa to dopamine (p. 38).
5. C Dopamine-β-hydroxylase catalyzes the conversion of dopamine to norepinephrine (p. 38).
6. A Tyrosine hydroxylase catalyzes the conversion of tyrosine to dopa (p. 38).
7. D Phenylethanolamine-n-methyltransferase (PMNT) catalyzes the conversion of norepinephrine to epinephrine (p. 39).
8. A The rate-limiting step in catecholamine synthesis is conversion of tyrosine to dopa by tyrosine hydroxylase (p. 38).
9. B Activation of α2 receptors located on presynaptic terminals of sympathetic neurons inhibits the release of norepinephrine (p. 41, table 4.2).
A. Stimulation of α1-receptors causes vasoconstriction.
B. Stimulation of β1-receptors increases heart rate, force, and velocity of contraction.
C. Stimulation of β2- receptors causes brochodilation.
10. B Clonidine is a selective α2 agonist that acts in the CNS to decrease sympathetic outflow to the periphery. This decreased sympathetic tone leads to decreased blood pressure by lowering total peripheral resistance (p. 58).
11. C Norepinephrine increases blood pressure by activation of α1 receptors thereby producing vasoconstriction. Its release is regulated by presynaptic α2 receptors. Prazosin is an α1-receptor antagonist that blocks the blood pressure effects of norepinephrine but does not interfere with its presynaptic actions (p. 60).
A. Dopamine increases blood pressure by acting on α1-receptors to produce vasoconstriction.
B. Terbutaline is a β2 -receptor agonist used as a bronchodilator that produces minimal effects on blood pressure.
C. Pindolol is a nonselective β -adrenergic receptor a ntagonist.
12. C Urinary outflow is regulated by norepinephrine acting on α1-adrenergic receptors on the bladder sphincter causing contraction. Doxazosin is an antagonist at α1-adrenergic receptors and will therefore cause dilation of the bladder sphincter, decreasing outflow obstruction, and increasing urine flow rates (p. 60).
A. Clonidine is a selective α2 agonist that acts in the CNS to decrease sympathetic outflow to the periphery. This decreased sympathetic tone leads to decreased blood pressure by lowering total peripheral resistance. It does not decrease outflow obstruction and increase urinary flow rates.
B. Epinephrine stimulates α1, α2 and β2 adrenoceptors and so would contribute to the contraction of the bladder sphincter, not lessen it (via α1 effects).
C. Pyridostigmine is an indirect-acting parasympathomimetic that inhibits acetylcholinesterase, thereby increasing concentrations of acetylcholine, and enhancing cholinergic function. It does not decrease outflow obstruction and increase urinary flow rates.
D. Yohimbine is an α2-receptor antagonist. It has no important clinical use.
13. B Bethanechol is a direct-acting parasympathomimetic at muscarinic receptors on the bladder sphincter and detrusor muscle. Activation of these receptors will cause relaxation of the sphincter and contraction of the detrusor muscle that expels urine, thus increasing urinary flow (p. 46).
A. Atropine is a muscarinic cholinergic receptor antagonist which would have the opposite effects to bethanechol.
B. Succinylcholine is a nicotinic receptor antagonist at the neuromuscular junction.
C. Trimethaphan blocks nicotinic receptors of both sympathetic and parasympathetic ganglia.
14. B Propranolol is a nonselective β adrenergic receptor antagonist. Atropine is a muscarinic cholinergic receptor antagonist. These agents are given to prevent reflex changes in cardiac output in response to phenylephrine (pages 49 and 60). Phenylephrine will increase blood pressure by direct activation of α1-adrenerigc receptors. This will increase the baroreceptor firing rate (I) and activate the baroreceptor reflex, leading to decreased sympathetic outflow (II, III) and increased parasympathetic outflow (IV).
15. B The addition of reserpine, which prevents storage and causes depletion of neuronal norepinephrine, will have no effect on the response to phenylephrine, which acts directly on α1-adrenergic receptors (p. 62).
16. E Hexamethonium is a ganglionic blocking agent that blocks nicotinic receptors of both sympathetic and parasympathetic ganglia, so there will be no change in postganglionic sympathetic nerve activity (p. 48).
17. C Phenoxybenzamine is an irreversible noncompetitive antagonist at both α1- and α2-adrenergic receptors. It will thus prevent phenylephrine from having any effect (p. 60).