Nitroprusside Antihypertensives

Diaz oxide (Hyperstat IV) and nitroprusside (Nitropress) are examples of intravenous (IV) drugs that may be used to treat hypertensive emergencies. A hypertensive emergency is a case of extremely high blood pressure that does not respond to conventional antihypertensive drug therapy. 

Hydrogen cyanide (HCN) is a colorless, rapidly acting, highly poisonous gas or liquid that has an odor of bitter almonds. Most HCN is used as an intermediate at the site of production. Major uses include the manufacture of nylons, plastics, and fumigants. Exposures to HCN may occur in industrial situations as well as from cigarette smoke, combustion products, and naturally occurring cyanide compounds in foods. Sodium nitroprusside (Na2[Fe(CN)5 N0]-2H20), which has been used as an antihypertensive in humans, breaks down into nonionized HCN. 

C. Trimethaphan is a ganglionic blocking agent that will lower blood pressure very rapidly. Hydralazine is a vasodilator hydrochlorothiazide and spironolactone are diuretics and methyldopa is a sympatholytic acting in the central nervous system. All of these drugs are used clinically as antihypertensive agents. None work as rapidly as trimethaphan. Clinically, however, either nitroprusside or clonidine is used much more commonly than trimethaphan in this situation. 

It is usually recommended that ACE inhibitors be continued peri-operatively in common with other antihypertensives. There is some evidence that postoperative haemodynamic stability is improved and renal function protected. Pretreatment with ACE inhibitors may reduce tachyphylaxis to sodium nitroprusside and help to prevent rebound hypertension. On the other hand, there is evidence that ACE inhibitors may predispose to hypotension during anaesthesia and that they reduce cerebral blood flow during any period of systemic hypotension. Furthermore, the response to and recovery from hypotensive episodes due to blood loss or circulatory depletion may be impaired. At present, the advice concerning these drugs would be to continue therapy up to and including the day of operation. Another rare side-effect of ACE inhibitors is angioneurotic oedema, which has occasionally been seen complicating intubation. 

The vasodilating properties of captopril or hydralazine (antihypertensive agents) are mediated by the formation of EDRF or prostaglandin, or both. On the other hand, the vasodilating properties of nitroprusside (an antihypertensive agent) result directly from the formation of cyclic GMP. 

Q9 Sodium nitroprusside can be used to rapidly reduce BP in hypertensive emergencies, but it is not suitable as a regular antihypertensive medication. Why is this ... 

Q9 Sodium nitroprusside acts via the production of NO. It is a powerful vasodilator and a potent, rapidly acting antihypertensive agent. The drug is administered by intravenous infusion but is then converted to thiocyanate in plasma. Thiocyanate toxicity can occur with continued use consequently, sodium nitroprusside can be used only for short-term treatment. 

VASODILATOR ANTIHYPERTENSIVES BETA-BLOCKERS t hypotensive effect Additive hypotensive effect with diazoxide, hydralazine, minoxidil and sodium nitroprusside. In addition, hydralazine may T the bioavailability of beta-blockers with a high first-pass metabolism (e.g. propanolol and metoprolol), possibly due to alterations in hepatic blood flow or inhibited hepatic metabolism Monitor BP closely... 

Wagenknecht DM, Baaske DM, Alam AS, Carter JE, ShahJ. Stability of nitroglycerin solutions in polyolefin and glass containers. Am J Hosp Pharm 1984 41 1807-1811. Leeuwenkamp OR, van Bennekom WP, van der Mark EJ, Bult A. Nitroprusside, antihypertensive drug and analytical reagent. Review of (photo)stability, pharmacology, and analytical procedures. Pharm Weekbl Sci 1984 6 129-140. 

Careful monitoring of the heart and hemodynamic status should be performed. Hypertension and symptoms of CNS stimulation usually resolve spontaneously with only supportive measures. Antiarrhythmic and antihypertensive agents may be necessary in severe exposures. If treatment of hypertension is necessary, a direct vasodilator such as nitroprusside or nifedipine should be utilized. Treat agitation and seizures as necessary with benzodiazepines. Management of concurrently ingested drugs should be appropriate to the agent involved. 

Patients with normal left ventricular function will not have an increase in stroke volume when SVR falls because the normal ventricle is fairly insensitive to small changes in afterload. Consequently, these patients experience a significant decrease in blood pressure after administration of arterial vasodilators. This explains why nitroprusside is a potent antihypertensive agent in patients without heart failure but causes less hypotension and reflex tachycardia in patients with left ventricular dysfunction. Nonetheless, even a modest increase in heart rate could have adverse consequences in patients with underlying ischemic heart disease and/or resting tachycardia, and close monitoring is necessary during therapy. 

Leeuwenkamp, O.R., van Bennekom, W.P., van der Mark, E.J., and Bult, A. (1984) Nitroprusside, antihypertensive drug and analytical reagent. Review of (photo) stability, pharmacology and analytical properties, Pharm. Weekbl., Sci. Ed., 6, 129-140. 

The antihypertensive properties of nitroprusside have been known since the late 1920s but they were not clinically used until the 1950s.10 It can be easily synthesized from sodium ferrocyanide and strong nitric acid by heating. 

At first the drug was used orally as an antihypertensive, but it was phased out with the advent of the ganglionic blockers and reserpines. Sodium nitroprusside was subsequently resurrected as a parenteral emergency drug. It is now a most powerful vasodilator, given by IV infusion to obtain almost immediate reduction in pressure in hypertensive crises. By regulating the rate of administration minute by minute, blood pressure control becomes possible. 

This reaction normally represents hepatic detoxification of cyanide ions produced from nitroprusside in erythrocytes. The SCN- is 99% less toxic than CN-. NaSCN was also still official in the NF X (1960) as an antihypertensive drug. A nitroprusside mechanism on vascular smooth muscle by interference with the role of Ca2+ in the muscle contraction process has also been suggested. 

Diazoxide is a parenteral, rapid, and direct-acting vasodilating antihypertensive used in hypertensive emergencies. An IV injection can drop blood pressure by as much as 80 mmHg in 5 minutes. Unlike sodium nitroprusside, however, venous dilation is not part of its mechanism. Chemically it is a benzothiadiazide without the sulfamoyl function at the 7 position (see diuretics). In fact, diazoxide is not a diuretic. Chronic use of diazoxide reflexly increases renin release, which actually counteracts the antihypertensive effect of the drug by expanding the volume of circulating fluid. 

The drug must be administered as a controlled continuous infusion, and the patient must be closely observed. Most hypertensive patients respond to an infusion of 0.25-1.5 flg/kg/min. Higher infusion rates are needed to produce controlled hypotension in normotensive patients under surgical anesthesia. Infusion of nitroprusside at rates >5 flg/kg/min over a prolonged period can cause cyanide and/or thiocyanate poisoning. Patients receiving other antihypertensive medications usually require less nitroprusside to lower blood pressure. If infusion rates of 10 pg/kg/min do not produce adequate reduction of blood pressure within 10 minutes, the rate of administration of nitroprusside should be reduced to minimize potential toxicity. 

Compound (37) (Table 4) has been screened for antibacterial and antifungal activities. ( + )-Bis(trimethaphan)nitroprusside (238) was found to be a very effective antihypertensive agent and vasodilator <83GEP(O)330ll34>. 

Smaller doses of sodium nitroprusside might be required in patients receiving antihypertensive drugs. There is a risk of severe hypotension if phosphodiesterase inhibitors (e.g. sildenafil, tadaiafil and vardenafil) are used with sodium nitroprusside. 

The use of phosphodiesterase inhibitors (e.g. sildenafil, tadaiafil and var-denafil) with sodium nitroprusside is contraindicated by the manufacturers, due to the risk of severe hypotension. See also Phosphodiesterase type-5 inhihitors +Nitrates , p.l272. A case report describes the therapeutic use of sildenafil to enhance the hypotensive effect of sodium nitroprusside and other antihypertensives in a patient with a hypertensive crisis. ... 

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