V. DRUGS USED IN HYPERTENSIVE EMERGENCIES Hypertensive emergencies are signaled by signs o

   V. DRUGS USED IN HYPERTENSIVE EMERGENCIES

       Hypertensive emergencies are signaled by signs of severe and rapidly
   progressing damage to several important organs: the brain (en-
   cephalopathy), the retina (hemorrhages, exudates), the kidney
   (hematuria, proteinuria, azotemia) and the heart (heart failure, angina,
   ECG signs of ischemia). Because of the ominous prognosis, blood pressure
   (which is usually elevated into the 200-300/140-160 range) must be
   reduced rapidly (within a few hours) in hospital, preferably in an in-
   tensive care unit.  The most powerful hypotensive drugs available are
   the agents of choice in this situation. These include vasodilators such
   as nitroprusside, diazoxide, and nifedipine, and the ganglion blocker
   trimethaphan. The combination alpha-plus-beta blocking drug labetalol
   has been used with some success.  Adverse effects that would be in-
   tolerable in chronic therapy are of little consequence in this life-   
   threatening situation.  Tachycardia may be controlled, as in chronic hy-
   pertension, with beta-blockers. Fluid retention is managed with diuretics.
   Agents that are still labeled but are probably obsolete for use in hy-
   pertensive emergencies include methyldopa and hydralazine.



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   A. Nitroprusside. Nitroprusside is a very powerful and rapidly acting
   vasodilator. Although its mechanism is not fully understood, it is prob-
   ably similar to that of the nitrate vasodilators. A major advantage is
   that its very short half-life permits precise control of the blood pres-
   sure by simple adjustment of the intravenous drip rate. Nitroprusside
   decomposes in the blood and releases cyanide, which may cause toxicity
   if administration is prolonged or dosage is high.
   Indications:
   * Hypertensive crisis
   * Production of controlled hypotension for neurologic surgery.
   * Unlabeled: Severe refractory congestive heart failure (see Chapter 4)
   * Unlabeled: Relief of severe vasospasm caused by ergot overdosage.
   Contraindications and Warnings:
   * (Warning) According to the package insert, nitroprusside should be
   used with caution in patients with hepatic or renal insufficiency
   Adverse Reactions and Overdose Toxicity:
   * Marked hypotension, tachycardia, retrosternal pain.
   * Cyanide toxicity may occur if dosage limits (see Table 5-5) are ex-
   ceeded. Excessive hypotension and metabolic acidosis are early signs.
   Dyspnea, headache, and loss of consciousness follow.


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   * Treatment of cyanide toxicity is by administration of nitrites (see
   cyanide poisoning, Chapter 24), followed by sodium thiosulfate.
   Hydroxocobalamin has also been used to treat or prevent cyanide toxicity
   associated with nitroprusside use.
   Interactions:
   * Hypotensive agents: additive interaction.

   B. Trimethaphan:  Trimethaphan is a ganglion blocking agent and has the
   extremely high efficacy associated with that drug group. It is only used
   parenterally.
   Indications:
   * Hypertensive emergencies
   * Production of controlled hypotension in neurosurgery.
   * Temporary management of dissecting aneurysm (unlabeled).
   Contraindications and Warnings:
   * (Warning) This drug is not useful in the management of hypertension of
      toxemia.





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   Adverse Reactions, Toxicity and Overdosage:
   * Orthostatic hypotension is present at both therapeutic and toxic
   doses: the patient should be in bed with the head raised for optimum ef-
   fect and blood pressure must be continuously monitored. If pressure drop
   is excessive, the head of the bed can be lowered to improve cerebral
   perfusion.
   Interactions: Increased effect in patients receiving any other
   antihypertensive drug.

   C. Diazoxide: Diazoxide is related to the thiazide diuretics and shares
   with them  the  adverse  effects  of  hyperglycemia  and hyperuricemia.
   However, this drug causes a marked and prolonged vasodilatation that is
   useful in the management of hypertensive emergencies.   
   Indications:
   * Hypertensive emergencies.
   Contraindications and Warnings:
   * Hypersensitivity to sulfonamides.
   * (Warning) Diazoxide is ineffective in pheochromocytoma.




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   Adverse Reactions, Toxicity, and Overdosage:
   * Excessive decrease in blood pressure, especially with the previously
   recommended 300 mg bolus dose. The Trendelenberg position and, if neces-
   sary, sympathomimetics may be used to reverse excessive hypotension.
   * Hyperglycemia, requiring treatment only in diabetics.
   * Sodium retention and hyperuricemia can occur but, since therapy is for
   a short period of time, is rarely of clinical significance.
   Interactions: (Rarely significant since the drug is usually given as a
   single dose and repeated only a few times)
   * Warfarin and similar anticoagulants are displaced from plasma protein
   binding sites by diazoxide.
   * Other hypotensive agents are potentiated by diazoxide.
   * Metabolism of phenytoin is accelerated by diazoxide.









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