S241, 2 Beep «is central alpht-adrenaceptor ago So appears to act trough stimulation of hulne receptors thas general proper- to those of clonidine (ace p43), buts Cause less sedition and central adverse the management of hypertension it has ‘the phosphate, in doves equivalent 10 ise daly as single dose by mouth his teased if nocestary, after 1 month, 10 | individ doses ssson of the treatment of hypertension, sin Acetate pa Se a ave Pose [L(N by | cea gon heme acca competitive antagonist of angi fe tho blocks presor ston Itsalso gonist and eausesatansient inal risen Sure, Surlasin has a short halF-ife and ted inthe differential diagnosis of reno hypertension; following intravenous ad- fn saralasin commonly causes a fall in Sse in patients ith renovascular hyper. Sheveas patients with low-renin esential Sion may have a sustained pressor re The reaction is affected by sodium balance sare normally mildly depleted of sodiom test False postive and false native re | Squmerous, and the use of saraasin has cen superseded by the ACE inhibitors. ations treater slase Recontnare Hunan Srde ha 4 Effects, Treatment, and Precat- nepokinase,p 948. nd Administration fis ethombolytic agent. tis» urokinase Esininogen activator with single chain [prepared via recombinant DNA technolo [aconverted to urokinase inthe boy by plas Faso has some intrinsic plasminogen Da properties and is reported to have greater Jip for fbin-bound plasminogen than for Plasminogen, Sarupace is under investi tion in the thrombolytic therapy of acute myocardial fnfarton Sodium Apolate (21 Camco. Sodium spot sa synthetic hepsrnoid antic Tant tis employed in the topical treatment of ae Imatomas and superficial thromboses and for 0 Folie of spins and contusions. Preparations Sodium Nitroprusside Sodium nitroprusside fsa direct and rapidly acting peripheral isodllator which reduces blood pres: ‘re within a fe seconds of intravenous infusion Ttis given intravenous Inthe treatment of hyper tensive criss, and (o produce contrlled hypoten- Som frsunger, ts effects last ony afew minutes, permitting rapid and accurate adjustment of Brood pressure, It has also been used in severe hear allure Its metaboised to cyanide ad hi cyanate, and some of savers effects are det these meiaboites; others can be contre by re {ducing the infusion rate, Ide unstable igh and {nfosions must be protected accordingly. roaibenasancter( yee. {3755-989 (sium nitroprusside hpérte Poe a US see der Serf Sedum erp Seabiey in solution. Te inabity 943. Reserpine/Sodium Ni troprusside Adverse Effects Sodium nitroprusside rapidly reduces blood Sure and iseonverted in the bod) 1 cyanide und then {Diocyanate, Is adverse effects can be attibuted mainly to excessive hypotension and excessive cya ride accumulation; thiocyanate toxicity may als tocur especialy in patcnts wih renal impairment. Intravenous infusion of som nivopeussie may produce nausea and vomiting, apprehension, head Uche, dizziness, retlessnes, perspirati,palpit tions, retrosteraldiscomfor, abdominal pain and tmuscle twitching but these eifets may be reduced by slowing the rate of iafuson. ‘An excessive amount of cyanide in plasma (more than 008 ug per mL}, because of overdosage or de Dletion of endogenous hisulphate (which conver yanide to thioeyanate in vivo), may esl in tachy ‘ara, sweating, hyperventilation, aythmias, and profound metabolic acidosis. Metaboli acidosis nay be the fis sign of cyanide toxicity, Metharto: lobinaemia may also ecu Adverse effects tributed o thiocyanate include tn mits, msi, and hypereflexia: confusion, hall rion, and convulsions have also been reported Other adverse effet inlude thrombocytopenia and phlebitis “Treatment of Adverse Effects Sideeffets due to excessive hypotension may be {tented by slowing or discontinuing the infusion. For details of the treatment of eyanide poisoning see Hydrocyanic Acid, p1837. Thioeyanate can be re ‘moved by dialysis, Hydroxocobalain canbe given944 Cardio ‘Treatment of Adverse Effects continued ascular Agents to reduce eyanide concentrations, buts of ite tn aeate poisoning because of he large quantities required, Precautions Sruhom niropruside shoul not be use in the pres noe of compensitory hypertension. Tt should be ‘nod with caution in tients with impalred hepatic function, inpatients sith Tow plasma-cobalamin ‘Concentrating of Lebe's optic soph. Some a Ahortes consider that its comra-indicated in such Patents ifthe impairments severe Itshould also be teed with caution inpatients with impaired renal or atmonary function and sith particular cation in faliens wih impaired cerebrovascular circulation. The use of hydrexocobalamin before and during a Iristraton of sodium nitroprusside has been a Mocated. Thioeyanate, 4 metabolite of sodivm iropruside, ibs iodine binding and uptake A Batam eitroprusside shouldbe used wih cat tion in patients with hypayroidism. The pase fhecyanate concentration should be monitored if {Teatinent continues Tor several days and should not (Reeo0 100 ug per mL alhough toxiity may be ap parent at lower thioeyanate concentrations. Thiocy nate concentrations do not elect cyanide toxicity inl cyanide concentrations should also be moni- tne ihe hood concetation of eyanide should not exceed Tus pet mi. and the plsma concentration Should po exceed 08 yg per mL, The acid-base butane should also be monitored. Care should be kent ensue that extravasation does no out este “achyphyans Taio a Pharmacokinetics Sodium nitrprassde i converte jn the erythro ytes to eyanide. Nitsie oxide is also released in hos Cyanide is metabolised jn the lve they hate by the enzyme thodanase in the presence of {Hiosalpate and slowly excreted inthe urine. The Plsmng halflife of thoeyanate is reported to be Trout 3 days, but nay Be much longer in patients ‘with renal impairment Uses and Administration Soaditm nivoprussie i short-acting hypotensive ‘eeot witha duration of ction of It 10 mints. Ki Foduces peripheral vasoiltation and reduces Fiperl resistance by a diect ation on both veins a arteoles. thas been fenmed a mrovasoiator ‘Because it releases ire oxide no. effets ap peat within afew seconds of ineavenousinfsion, odio nttopresside i sed in the treatment of y= pestconve eres ad o proce contolled hypote Ti during general anaeathesia Tt has also been the fo reduce preload and fra in severe heart ale inclding tha associated with myocar farction. For discussions ofthe management of by pertenson, hea fale, and year infarcin, e796, p79, and 799, respectively. This given by continuous inravenous infusion of @ totuon containing 504 200 jg pet mi, The sole fiom should e prepared immediately before use by Uinsolving slum nitroprssie in 8% glucose in fection and then diluting with 5% glucose or other ‘ital iniavenous infusion Md; the solution mast be prected from ight during administration, Blood Prewure should be monitored closely daring amin Ffration and care should e taken to prevent ex tavasation. In genera, Weatment should not ntnue for more than 72 hows requ {fal days blood and plasma concentrations of ey de should be monitored and should not exceed Tug per mL and 0.08 yg per ml respectively: thio yannte concentations i serum should also be rasured if infusion continues for more than 72 fours and should not exceed 100 Hg perm Since rehound Byperension has been reported when so tim nitoprusside is withdawa, the inflson should be ile ff gradually over 10 30 minutes. For hypertensive rises in patients nt receiving Einypertensive agents, the initial dose is 0:3 per guy weight per minut increasing gradually Uo ‘rctose supervision until th desired reduction in food pressure i achieved, The average dose re ‘ihre to maintain te blood presse 30 t0 40% be ‘Bar the pretreatment dastoli blood pressures 315 perkg per minute and the usual dose range is 0.5 Bug por hyper minute, Lower doses should be wed ie paents already receiving other antihyperten ‘ives. The maximum recommended rate is about ‘Ss perk per minut in the UK, and 10 pe Per minute in the US, and infusions should be repped afer 10 minutes there is no response. If theresa esponse sodium nitroprusside shoud ide tly be given for only few ours to avoid the sk of cyanide toxicity. An alterative antihypertensive ca that can be given BY mouth shouldbe into ‘doced a soon as possible Fore induction of hypotension during anaesthesia t nanimum dose of 1-3 pet kz bodyweight per minute ts recommended, Tn hear failure an initial dose of 10 t 15 ne pet Minus has been recorimended increasing by incre ‘Bans of 10 to 13 upper inate every 5 10 10 min Ties until the Inia response is seen. The usual ange range s 10 200 per minute andthe dose Shouid not exceed 280 yg per minute or 4 ug per tody-seight per minute Sodium nitroprusside is also used asa reagent for ; ‘eteting ketones in une soared ein 24 oat oe oa |Misra ge ned in he mange of were nyc we dscosedon po Petphoral vascular disease Many dup tae ee ed fate Ther na ers : eee ted Reals yao, ora Fetancson fh trament of Rayna’ sone nd Preparations ial reparane Proprietary reparations feeb: Nn Ni esti rae Sotalol Hydrochloride o» etl Hynde ANN, USA, NH Be, (Hydro 2 ucpr IeataNio,scl = 3038 FES — 2930-20-9cle; 959-240 (ota Freres Pay sn seal tly we cher ‘Adverse Effects, Treatment, and Precau- Afr ta blockers in general, 830. Mixed pointes has bee reported in pation 5 aol, usally due to prolongation ofthe OT in Teal The OT interval shouldbe monitored and the tose of sotalol reduced if the QT interval exceeds 1S seconds. Ax hypokalaemia may predispose pe Hans to ariythmuss, serum-cleerolte concent Hidns should be monitored before and during Heater with sotto here may bean increased risk of aehythmiss when Soto s given concuerently with other arthyt hipgshi drvgs such asthe anhistamines aster le nd terfenane, the animal halfantine, fn phenotiazincs lacs onthe gasro-inteatinal rat rear of 00 sab ta ay be tec! wah ple ‘he OT ly wit esis spas Gy nears tan Pharmacokinetics Sotalol is virtually completely absorbed from the usrovintetinal tract and poak plasma concent fons are obtained about 2 3 hous after a dose The plasma elimination half-life i about 10 to 15 owes, Sotaol has low lipid solubility. Vey ite is Iclabolised and i x eXereted unchanged in the tine Binding t plsma proteins is reported tobe Tow Iterosses the placenta and is excreted in breast mnilk where higher concentrations have been tchieved than in maternal serum. Only smal [mounts are reported to ross the Blgod- rain barrier fin enter the CSF. Sotalol removed by dialysis Uses and Administration Sotalol is a nomcardoselective beta blocker (see $2830) is eported olck both ininsi sympstho hhimetic and membrane stabilising properties. In dition tothe class I antarctic activity of ets blockers in general, sotalol lengtens the drs tion ofthe action potential resling i class 1 an tiarmhythmic activity, For a classification and {explanation of antiarythmie atv. se p. 785. Sotalol is used asthe hydrochloride inthe man nent of hypertension, angina pectoris, cardiac a Thythmias, and myocardial infarction. For Wiscussions of the treatment ofthese cardiovascular fisorder, se 9.796, 788, p.791, and p.799, re Spontively. It iy also used in the management of Rypertiytoidism and this discussed on p.1597 Infypertension staal hydrochloride is usually gv fn nan intl dose of 160 me daly by mouth a Single or divided dose increased at fori inter vals according tothe response ofthe patient, (0 00 mg or more daly i daly by mouth sa sing ts necessary to 600 m8 daly. ina pectoris the asin dose is 160 mg or divided dose, increased For cardiac arhythmias sotalol hydrochloride is fiven in usual doses of 120 to 240 mg daly. Some Fuients may require doses of up (0 640 mg daily Forte emengeny treatment of cardige anthyshmias Abe symbo + dene proprton no loge actively mated Sodium Nitroprusside/Sotalol Hydrochloride 9: sotalol hydrochloride maybe given by slow intave ous injection in dose of 20 0 60mg over 210 3 mimes; ge doses of upto 100 mg shoul be tnover 3 minutes or longer, Doses may be repeated ‘fnccessary after 10 minis Tn the management of myocardial infarction a dose 1 320 mg is given daily starting 5 o 14 days after Doses of 120 0 240:mg daily may be given re fluce symptoms of sympathetic overactivity in hiypentiyoidim Reduced doses maybe require in renal impairment Sotalol is used as the racemic mixture; soll is ion a an atarehythmie agen (See tnder Action, p.945) —sbgon te OT iver wach cosine! wi Pe Preparations