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Q. Outline the difference between SNP and GTN
Short answer questionSNPDrug action
y
 
SNP react with oxyhb- heam guanylatecyclase
y
 
O
xyhb dissociate to formmetahaemoglobin , cyanide and N
O
 
y
 
the N
O
then bind to guanylate cyclase toincrease intracellular cGMP
y
 
cGMP cause relaxation of smooth musclePharmacokineticabsorption
y
 
administered as a continuous IV infusionby a calibrated pump,
y
 
with continuous IABP monitoring
y
 
due to the rapid onset of actionmetabolism
y
 
T
he electron is transferred from the Fe++of Hb
O2
to nitroprusside
y
 
T
he reaction produced MetHb andunstable nitroprusside compound
y
 
unstable nitroprusside compoundproduced 5 cyanide molecules
y
 
cyanide then react with methaemoglobinto produced cyanmethaemoglobin
y
 
T
he other 4 cyanide molecules is thenundergo non-enzymatic reactionthese CN-ions have 4 fates,SMHC1. Conversion to thiocyanide
y
 
60
-7
0%
are enzymatically converted tothiocyanate
y
 
R
eaction catalyzed by rhodanese in the liverand kidneys
y
 
requires thiosulphate and B1
2
as cofactors
y
 
rate limiting factor is the availability of endogenous thiosulphate
2
. combination with MetHb to formcyanmethaemoglobin3. combination with hydroxocobalamin to formG
T
NDrug action
y
 
G
T
N---smooth muscle cell smooth musclecell release N
O
 
y
 
N
O
activate gunaylate cyclase
y
 
Guanylate cyclase increase cGMP
y
 
cAMP cause relaxation of smooth muscleabsorption
y
 
administered as a continuous IV infusionby a calibrated pump,
y
 
with continuous IABP monitoring
y
 
due to the rapid onset of actionmetabolism
y
 
O
rganic nitrates undergo reductivehydrolysis in the liver
y
 
reaction catalyzed by glutathione-organicnitrate reductase
y
 
biotransformation converts the lipidsoluble organic esters into more watersoluble denitrated metabolites andinorganic nitritemetabolites
y
 
dinitrated metabolites have ~ 1/1
0
th thepotency as vasodilators
y
 
elimination t½b ~ 4
0
mins
 
cyanocobalamin4. combination with tissue cytochrome oxidaseresult in toxicityfactor cause tachyplaxis
y
 
toxicity with cyanidefactor causes tachyplaxis
y
 
biotransformation is the principaldeterminant of the duration of actionmetabolitesChemical compound
y
 
ferrous iron center complex with fivecyanide moieties and a nitrosyl group(44
%
cyanide by weight)Stability
y
 
SNP is broken down to cyanide ions onexposure to light
y
 
Solution change to dark blue from orangebrown> discard
y
 
W
rapped in aluminum foilPreparation
y
 
0
.
0
1
%
solution in 5
%
dextrose or NS
y
 
Freed dried crystals
y
 
5
0
mg/ampouleChemical compound
y
 
polyol esters characterized by a C-
O
-Nsequence,
y
 
these agents act via nitric oxidenitrovasodilatorsStability
y
 
Must be protected from ultraviolet light
y
 
in the pure form, without an inert carrier suchas lactose, NG is explosiveAdditive
y
 
Contain thio compound, therefore doesn'tgenerate N
O
spontaneously like SNPChemical interaction
y
 
Absorbed by plastic
y
 
Must use in glass container
y
 
the solution is not compatible with PVC tubing
 
CVSBP
y
 
decreased in BP with increase in heart rateHeart rate
y
 
Increased heart rate
y
 
secondary to activation of symphathotoadrenal
y
 
increased myocardial contractility and reninreleaseMechanism for BP reduction
y
 
N
O
> dilates both resistance and capacitancevessels
y
 
> decrease SV
R
> decrease Venous return>decrease BPC
O
 
y
 
the induced hypotension activates thesympathoadrenal system,
y
 
resultant tachycardia, increased myocardialcontractility and renin release
y
 
the usual response is an increase in C
O
 CVSBP
y
 
decrease in blood pressure with unchangedheart rate
y
 
systolic BP decrease more than diastolicHeart rate
y
 
U
nchanged heart rateMechanism of BP reduction
y
 
predominant effect of low doses --------venodilation
y
 
NG and the organic nitrates relax venoussmooth muscle in low doses
y
 
SV
R
usually remains unchangedC
O
 
y
 
L
V pressure , end diastolic pressure ,myocardial oxygen demand ; all reduced
y
 
C
O
 ; decrease minimally
y
 
doesn't causes rebound hypertension
y
 
rebound hypertensionCerebral blood flow
y
 
SNP increases CBF and cerebral volume
y
 
how-----by a direct effect on cerebral vesselsBronchomotor tone
y
 
no rebound hypertension like sodiumnitroprussideCerebral blood flow
y
 
cerebral vasodilation may lead to an increasein ICP in patients with reduced cerebralcomplianceBronchomotor tone
y
 
relaxation on smooth muscle includingbronchi,

SAQ Pharmacology CVS

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