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nation with a diuretic. A vasodilator can be added to the sion, which follows abrupt withdrawal of clonidine ther-
clonidine diuretic regimen in the treatment of resistant apy. This posttreatment hypertension appears to be the
forms of hypertension. Such drug combinations can be result of excessive sympathetic activity. The genesis of
quite effective, since the reflex increases in heart rate the syndrome is not well understood. A contributing
and cardiac output that result from vasodilator adminis- factor may be development of supersensitivity in either
tration are reduced or negated by clonidine-induced de- the sympathetic nerves or the effector organs of the car-
creases in heart rate and cardiac output. diovascular system due to the clonidine-caused chronic
For severely hypertensive patients, clonidine has reduction in sympathetic activity. Thus, when the drug is
been used in combination with a diuretic, a vasodilator, abruptly withdrawn, an exaggerated response to nor-
and a -blocker. Some care must be taken, however, be- mal levels of activity may occur. If treatment with
cause the coadministration of clonidine and a -blocker clonidine is terminated gradually, rebound hyperten-
may cause excessive sedation. Clonidine is especially sion is unlikely. Patients should be warned of the danger
useful in patients with renal failure, since its duration of of abruptly discontinuing clonidine treatment.
Study Questi ons
1. A 55-year-old patient has been referred to you. She 3. Which of the following antihypertensive drugs is
complains about a skin rash and a cough. In the contraindicated in a hypertensive patient with a
course of history taking, she tells you that she takes pheochromocytoma?
high blood pressure medication but she doesn t re- (A) Metyrosine
member the name. You suspect a drug toxicity. (B) Labetalol
Which of the following antihypertensive agents is (C) Prazosin
the patient most likely taking? (D) Phenoxybenzamine
(A) Captopril (E) Guanethidine
(B) Nifedipine 4. Which of the following antihypertensive agents
(C) Prazosin would decrease renin release?
(D) Propanolol (A) Prazosin
(E) Clonidine (B) Clonidine
2. Which of the following compounds depends least (C) Captopril
upon the release of EDRF (nitric oxide) from en- (D) Nitroprusside
dothelial cells to cause vasodilation? (E) Diazoxide
(A) Bradykinin
(B) Histamine ANSWERS
(C) Minoxidil 1. A. Although many drugs can evoke a reaction such
(D) Hydralazine as a rash, a rash and a dry cough are well-recog-
(E) Acetylcholine nized side effects of angiotensin converting enzyme
238 III DRUGS AFFECTING THE CARDIOVASCULAR SYSTEM
(ACE) inhibitors, such as captopril. Up to 20% of periphery and therefore reduces the sympatheti-
these patients may develop a cough with ACE in- cally induced stimulation of renin release. The sym-
hibitors. The cause is not known for certain, but it pathetic effect on renin release is mediated by -
may be related to the accumulation in the lungs of receptors, so prazosin, an -blocker would not de-
bradykinin or other inflammatory mediators. crease release. Captopril is an ACE inhibitor and is
Inhibiting ACE leads to an increase in bradykinin, likely to enhance renin release, although it would
which is normally broken down by this enzyme. The prevent the effects of renin by reducing the forma-
rash was originally attributed to a sulfhydryl group tion of angiotensin II. Nitroprusside and diazoxide
in captopril but is known to occur with other are directly acting vasodilators and will promote
non sulfhydryl-containing ACE-inhibitors. renin release reflexively.
2. C. The vasodilation caused by bradykinin, hista-
mine, hydralazine, and acetylcholine depends in part SUPPLEMENTAL READING
upon nitric oxide release from the endothelium. Dosh SA. The treatment of adults with essential hyper-
Minoxidil activates K channels, which results in tension. J Fam Pract 2002:51;74 80.
vascular smooth muscle hyperpolarization and Friedman AL. Approach to the treatment of hyperten-
thereby relaxation. sion in children. Heart Dis 2002; 4;47 50.
3. E. Guanethidine does not normally cause release Hansson L. Why don t you do as I tell you?
of catecholamines from the adrenal medulla. Compliance and antihypertensive regimens. Int J
However, it may provoke the release of cate- Clin Pract 2002;56:191 196.
cholamines from pheochromocytoma. This action Kaplan NM. Kaplan s Clinical Hypertension (8th Ed.).
plus its ability to antagonize neuronal uptake of cat- Philadelphia: Lippincott Williams & Wilkins, 2002.
echolamines could trigger a hypertensive crisis. The Drugs for hypertension. Med Lett Drugs Ther
other drugs are good choices to lower blood pres- 1995;37:45 50.
sure in a patient with pheochromocytoma: metyro- Edvmsson L and Uddman R. (eds.). Vascular
sine, by decreasing synthesis; labetalol, by blocking Innervation and Receptor Mechanisms. San Diego:
both the - and -effects of the catecholamines; Academic, 1993.
prazosin and especially phenoxybenzamine, by in- Sixth Report of the Joint National Committee on
troducing a fairly long -blockade. Prevention, Detection, Evaluation, and Treatment
4. B. Clonidine is an antihypertensive because it de- of High Blood Pressure. Arch Intern Med
creases sympathetic outflow from the CNS to the 1997;157:2413 2446.
Case Study Hypertensive Emergency
50-year-old woman is seen in the emergency needs to be hospitalized and receive drug therapy [ Pobierz całość w formacie PDF ]

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