TABULACIÓN

4?

1

Johnson f ir s t described the hypotensive action o f sodium

nitroprusside in 1929, but i t was the mid 1960*s before i t became established as the potent rapid acting vasodilator used in anaesthesia as a treatment for hypertension to lower the blood pressure. More

recen tly i t has found wider use in the treatment of myocardial in farction (heart a t t a c k s c h r o n i c low cardiac output^, and cardiac surgery^'^*^ as i t relaxes the arteries reducing stress on the weakened heart « On infusion o f the nitroprusside anion into the Vascular system an almost instantaneous reduction in blood pressure

resu lts. The compound is metabolised rapidly and consequently a sa fe,

steady, low blood pressure can be established and maintained. Rapid metabolism is said to occur because immediately a fter infusion stops the blood pressure gently r ises to normal and does not overshoot. The compound, being an inorganic complex is extremely water soluble and lip id insolu b le, passes into the blood stream remaining there during action

unlike organic hypotensive agents, which have a problem o f becoming membrane bound. This a ssociation with the membrane causes problems o f achieving rapid s ta b ilisa tio n o f the blood pressure both before and a fter the operation as the organic compounds d iffuse slow ly into and out of the lip id phase.

Chemical comparisons between sodium nitroprusside and sodium

n it r ite have been made^^. Both are good n itrosatin g agents reacting

10 11 10 1? IT i a 15

with amines ' , th io ls ' , sulphite , and activated methylene groups (table 1) except that sodium n itr ite is e ffe c tiv e in a cid ic media and sodium nitroprusside in a basic one. Although th is does not a ffec t the f ir s t three classes o f compound mentioned i t does lim it the

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Reactions o f Sodium Nitroprusside and Sodium N itr ite Product using Sodium Product using Sodium

Reagent Formula Nitroprusside N itrite Product

Primary

Amines NHgE Ng ; ROH Ng ; ROH Alcohols

Secondary

Amines “ ®2 ONNRg ONNRg Nitrosamines

Thiols ES" RSSR RSSR Dimers

Sulphite SOj" ON^SOj)^" onCsOj)!" Frem/s S alt

Activated Methylene Group

q

ECCHgH HON=GRGR9 HON=GR&R0 Oximes (table i)

activatin g group on the methylene group to one which is media s pe c ific . Table 1 shows the carbonyl group which is one exception being a ctiv e in both acid ic and basic medium.

Media S p ecific A ctivating Groups -NOg -G=N -C-R 0 -NO -NO,

Acid media spe c ific Acid media spe c ific

Both acid and basic active Basic media spe c ific

Basic media spe cific (figure 1)

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The f ir s t four reagents (table l) produce exactly the same organic

product (Fremy's s a lt is classed as organic compound for th is argument), but th is is not generally true of activated methylene groups. Since

sodium n it r ite and sodium nitroprusside are sim ilar in their reactions it comes as no surprise that they are both vasodilators , sodium n it r ite being v astly in ferio r (p ossib ly due to the pH of the blood stream) with the nitroprusside anion being reported as 5O-IOOO times more e ff ic ie n t . The action is associated with a n itrosation reaction at the smooth

i6 17

muscle receptors in particular th io l groups * (cysteine residues), but as was discussed in chapter I amines are also reactive and should not be to ta lly dism issed. It was reported that sodium nitroprusside

has toxic side e ffe c ts releasin g cyanide in the presence of erythrocytes (red blood c e lls ) both in vivo^^'^^'^^ and more important in vitro^^'^^. Patients on long term treatment show signs o f cyanide poisoning, the origin of which must be the nitroprusside ion. A number o f f a t a lit ies

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have been reported * and the compound was said to be highly

dangerous and extremely to x ic . The liv er is the s ite o f d eto x ifica tio n converting cyanide to thiocyanate (figure 2 ), but although the liv er is said to be an e ffic ie n t processor, the compound is believed to be so

Method of Detoxification o f Cyanide ^®'2^2°3 S^^j|~^^NaSGN + NaHCO

(figure 2)

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conjunction with sodium nitroprusside during therapy to "soak" up the cyanide ion produced in so lutio n. Quantitative release o f cyanide is

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claimed ’ with the cyanide concentration peaking some 30-45 minutes

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after infusion stops (th is time is dose dependant). This release is said to occur by an interaction with haemoglobin producing

metcyanohaemoglobin (figure 3 ). This was shown by Smith^^ in h is study o f the u .v ,-v is ib le spectra of haemoglobin in the presence of

sodium n itrop russide. The ch aracteristic bands o f haemoglobin being Decomposition o f Sodium Nitroprusside in Blood

Hb + Fe(CN)^NO^ --- MetCNHb + 4CN" + NO^ i (

(figure 3) 24

Fe (iron*sink)

replaced, a fter reaction , with that o f metcyanohaemoglobin. The weight of th is information has led to the manufacturers^’^ and users

giving conservative guidelines to the maximum dosage, which they stress should not be exceeded. The to x ic ity and hypertensive action are thought to be unrelated considering that the to x ic ity is an interaction

with the red blood c e lls and the hypertensive a b ility an interaction

+ (CNlsFeNO"’

Porphurin JX

4(CN")

+ NO'

CN

Metcggnohaemoqlobin