Exam 2 Additional Information (Week 3) Flashcards
What is an endogenous hormone
Antidiuretic Hormone
ADH
arginine vasopressin
Where is ADH produced?
hypothalamus
Where is ADH stored?
posterior pituitary
What does ADH control?
osmoregulation
release stimulated by increased osmolality and hypovolemia
Additional role of ADH
potent vasoconstrictor, but dilates renal afferent pulmonary and cerebral arterioles
What are the three type of vasopressin receptors?
V1 -V3
V1
mediates vasoconstriction
V2
mediates water reabsorption in the renal collecting ductts
V3
found in the CNS and stimulate modulation of corticotrophin secretion
Multiple Uses of Vasopressin are
post cardiopulmonary bypass shock refractory hypotension reduce bleeding in von willebrand's disease anti-diuresis in diabetes insipidus treatment of enuresis
Dosages of Vasopressin
low dose gtt 0.03-0.04unit/min up to 0.1unit/min
1-2units bolus
Onset of vasopressin
1-5 minutes
Peak of vasopressin
5 minutes
DOA of vasopressin
10-30mins
Complications of vasopressin are seen at
> 0.04units/min
What are the complications of vasopressin?
GI ischemia
decreased CO
skin or digital necrosis
Sodium nitroprusside is
a direct acting, nonselective peripheral vasodilator
relaxation of arterial and venous smooth muscle
lacks significant effects on nonvascular smooth muscle and cardiac muscle
MOA of Sodium Nitroprusside
interacts with oxyhemoglobin and dissociates to form methemoglobin which releases NO and cyanide
NO activates guanylate cyclase (in the vascular muscle) thus increasing cGMP
cGMP inhibits calcium entry into vascular smooth muscle but increases uptake of Ca into SR
results in vasodilation via NO
Metabolism of Sodium Nitroprusside
transfer of electron from the iron (Fe) of oxyhemoglobin to SNP yields metHgb and an unstable SNP radical
unstable SNP radical breaks down all 5 cyanide ions are released
one of these cyanide ions reacts with methgb to form cyanomethemoglobin (nontoxic)
remainder are metabolized in the liver and kidney-> converted to thiocynate
SNP Toxicity
occurs d/t effects of high plasma concentrations of thiocyanate
Cyanide toxicity
can occur at rates >2ug/kg/min for long periods
suspect when patient starts demonstrating resistance to hypotensive effects or previous responsive patient who is unresponsive (tachyphylaxis) at rates >2-10ug/kg/min
may precipate tissue anoxia, anaerobic metabolism and lactic acidosis
Treatment of cyanide toxicity
immediate d/c of SNP
100% O2 administration despite normal oxygen saturation
sodium bicarbonate to correct metabolic acidosis
sodium thiosulfate 150mg/kg over 15 mins
sodium nitrate 5mg/kg if severe toxicity
sodium thiosulfate acts
as a sulfur donor to convert cynaide to thiocyanate
What does sodium nitrate do
converts hemoglobin to methgb which converts cyanide to cyanomethemoglobin
Thiocyanate toxicity
rare as thiocyanate is cleared by kidney in 3-7 days
less toxic then cyanide
Symptoms of thiocyanate toxicity
N/V tinnitus, fatigue, CNS hyperreflexia, confusion, psychosis, miosis seizure and coma
Methemoglobemia
rare
should be considered as differential diagnosis in patients with impaired oxygenation despite adequate cardiac output and arterial oxygenation
Dosages of SNP
0.3ug/kg/min - 10ug/kg/min
max dose: should not be infused for greater that 10 mintues
immediate onset
short duration of action
requires continous IV adminstration to maintain therapeutic effect
extremely potent- use of A-line
SNP effects (CV)
direct venous and arterial vasodilation, decreased venous capacitance due to venous return
baroreceptor mediated reflex responses increase HR
decrease SBP, decrease PVR, increase contractility, causes intracoronary steal in areas of damage associated with MI, decreased diastolic BP -> decreased coronary perfusion
SNP Effects (CNS)
increase CBF and ICP with modest decrease in MAP or with greater decrease in MAP can reduce cerebral BF (caution with carotid disease)
SNP Effects (Pulmonary)
attenuation of hypoxic vasoconstrction
SNP Effects (blood)
increase in intracellular GMP inhibit platelet aggregation and increase bleeding time
Clinical Uses of SNP
controlled HTN (0.3-0.5 ug/kg/min do no exceed 2ug/kg/min)
HTN crisis- 1-2ug/kg gtt IV can be adminstered as bolus
Cardiac Disease- decreases LV afterload, benefits management of MR or AR, CHF and HF
consider coronary steal
Pharmacokinetics of Enalapril (Prodrug and Duration of BP lowering effects
yes to prodrug (enalaprilat)
12-24 hours of lowered BP
enalaprilat- 6hrs
Pharmacokinetics of Lisinopril
Prodrug and Duration of BP lowering effects
No prodrug
24 hours
Pharmacokinetics of Ramipril
Prodrug and Duration of BP lowering effects
Yes, ramiprilat
24 hours
Pharamcokinetics of Captopril
Prodrug and Duration of BP lowering effects
no
about 6 hours
Pharmacokinetics of Benazepril
Prodrug and Duration of BP lowering effects
yes, benazeprilat
24 hours
Pharmacokinetics of ARBS
highly protein bound
Majority not effected by renal dysfunction
Majority effected by hepatic dysfunction
Peaks in various hours after administration
Variable elimination 1/2 times
