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- Edward M Lerner Small Miracles (pdf)
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glionic sympathetic nerves. This demonstrates a com- (B) Hydrochlorothiazide
plex action potential that consists of a fast EPSP fol- (C) Trimethaphan
lowed by a slow IPSP followed by a slow EPSP and (D) Methyldopa
finally by a late very slow EPSP. (E) Spironolactone
1. In Professor Smith s demonstration, the mediator of 5. Ganglionic blocking agents are rarely used because
the fast EPSP is of the numerous side effects they may produce. One
(A) Dopamine such side effect is
(B) Neuropeptide Y (A) Increased stimulation of the genital tract
(C) Serotonin (B) Urinary hesitation or urgency
(D) Angiotensin (C) Vasoconstriction
(E) Acetylcholine (D) Increased cardiac output
2. In Professor Smith s demonstration, the slow EPSP (E) Mydriasis
and slow IPSP can both be blocked by prior admin-
istration of ANSWERS
(A) Prazosin 1. E. The principal neurotransmitter released from
(B) Sumatriptan preganglionic nerve terminals in all autonomic gan-
(C) Atropine glia is acetylcholine. It acts on the postganglionic
(D) Losartan cell body to activate a nicotinic cholinergic receptor
(E) Chlorpromazine resulting in a fast EPSP. Dopamine or norepineph-
3. In Professor Smith s demonstration, the receptor rine or both are the mediators released from SIF
most likely mediating the slow EPSP is cells or interneurons. Neuropeptide Y is a peptide
(A) Nicotinic cholinergic neurotransmitter. Angiotensin and serotonin are
(B) Muscarinic cholinergic modulatory mediators. These last three contribute
(C) -Adrenergic to the late very slow EPSP.
(D) P2X Purinergic 2. C. The slow EPSP results from activation of
(E) -Adrenergic muscarinic cholinergic receptors on SIF cells or in-
14 Ganglionic Blocking Drugs and Nicotine 147
terneurons, which release norepinephrine or 5. E. The effect of ganglionic blockade depends upon
dopamine from their terminals. These catechol- the predominant autonomic tone exerted within
amines then cause a slow IPSP in the ganglionic cell various organ systems. Since the activity of the
body. Therefore, both the slow EPSP and subse- parasympathetic nervous system predominates in
quent slow IPSP would be prevented by the mus- the eye, the effect of ganglionic blockade is mydria-
carinic antagonist atropine. Prazosin is an 1- sis, not miosis. Similarly, stimulation of the genital
adrenergic antagonist; sumatriptan is a serotonin tract and urinary retention would be decreased.
5HT1D agonist; losartan is an angiotensin receptor Since sympathetic nervous system activity predomi-
antagonist; and chlorpromazine is a dopamine an- nates in blood vessels and the ventricles, vasodila-
tagonist. Only atropine would block both the slow tion and a decreased cardiac output would follow
EPSP and the slow IPSP. ganglionic blockade.
3. B. The receptor contributing to the slow EPSP is a
muscarinic cholinergic receptor and is activated by SUPPLEMENTAL READING
ACh. The nicotinic cholinergic receptor mediates Benowitz NL (ed). Nicotine Safety and Toxicity. New
the fast EPSP, an -receptor may mediate the slow York: Oxford University Press, 1998.
IPSP, and a P2X receptor and a -adrenergic recep- Clementi F, Fornasari D, and Gotti C. (eds). Neuronal
tor do not appear to be involved in the complex ac- Nicotinic Receptors. Berlin: Springer Verlag, 2000.
tion potentials seen at autonomic ganglia. Elfvin L-G, Lindh B and Höokfelt T. The chemical neu-
4. C. Trimethaphan is a ganglionic blocking agent that roanatomy of sympathetic ganglia. Annu Rev
will lower blood pressure very rapidly. Hydralazine Neurosci 1993;16:471 507.
is a vasodilator; hydrochlorothiazide and spirono- Fant RV, Owen CC, and Henningfield JE. Nicotine re-
lactone are diuretics; and methyldopa is a sympa- placement therapy. Prim. Care 1999;26:633 652.
tholytic acting in the central nervous system. All of Lee EW and D Alonzo GE. Cigarette smoking, nico-
these drugs are used clinically as antihypertensive tine addiction and its pharmacological treatment.
agents. None work as rapidly as trimethaphan. Arch Intern Med 1993;153:34 48.
Clinically, however, either nitroprusside or clonidine Sargent PB. The diversity of neuronal nicotine acetyl-
is used much more commonly than trimethaphan in choline receptors. Annu Rev Neurosci
this situation. 1993;16:403 443.
Case Study Smoking Cessation
patient who has been a heavy smoker (2 packs You explain that nicotine replacement can be car-
Aof cigarettes per day for 30 years) comes to ried out with chewing gum (nicotine polacrilex),
you for advice to quit smoking. You inform your pa- transdermal patches (e.g., Nicoderm, Habitrol),
tient that sudden cessation of smoking will result in nasal spray (Nicotrol NS), or vapor inhaler
withdrawal symptoms that may include restlessness, (Nicotrol Inhaler). The objective of the nicotine re-
irritability, anxiety, tension, stress, intolerance, placement is to obtain a sustained plasma nicotine
drowsiness, frequent awakenings from sleep, fatigue, concentration that is lower than the venous blood
depression, impotence, confusion, impaired concen- concentrations after smoking. It is known that arte-
tration, gastrointestinal disturbances, decreased rial blood concentrations immediately following cig-
heart rate, and impaired reaction times. You advise arette smoke inhalation can be as much as 10 times
your patient that successful cessation of tobacco use the venous concentration. You decide on a nicotine
requires attention to both the positive and negative patch and combine this strategy with counseling
(withdrawal) reinforcement properties of nicotine and motivational therapy from a professional
and tobacco use. You plan, therefore, to combine trained in such methods. It is quite likely that the
both psychological and pharmacological treatment. combination of the patch plus counseling will ulti-
What are some therapeutic approaches you can mately result in a successful cessation of smoking in
suggest? your patient after a couple of relapses. During a
second relapse period, you may wish to consider
ANSWER: Several options are available for the phar-
combining the antidepressant drug bupropion with
macological approach, including nicotine replace-
the other forms of treatment.
ment and antidepressant drugs (e.g., bupropion).
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