Peripheral Vasodilators Flashcards
List the five uses of peripheral vasodilators
manage hypertensive crises induce controlled hypotension facilitate LV forward SV tx pulmonary HTN mangange angina/myocardial ischemia
What are the three general mechanism by which peripheral vasodilators exert their effects
arterial vasodilation to decr. SVR (afterload)
venous vasodilation to decr. venous return and ventricular filing (preload)
to decrease both preload and afterload
What is Nitric Oxide (NO) synthesized from
amino acid L-arginine
How does NO gain access to the smooth muscle cells
via diffusion from endothelial cells into vascular smooth muscle cells
What is the MOA of NO once it enters smooth muscle cells
activates guanylate cylase»increase in cGmp»activation of MLC phosphatase»leading to dephosphorylation of MLC and promoting vasorelaxation
What are the five normal physiologic CV effects of NO
regulates SVR/PVR regulates distribution of CO released in vascular autoregulation generated by both art/veins negative inotropic and chronotropic effects
What are the three normal effects of NO on the lungs
bronchodilation
selective dilation of vasculature supplying well-ventilated lung segments
mediator of V/Q matching
What is the normal effect of NO on platelets
inhibits platelet activation, aggregation, and adhesion
What is the normal effect of NO on the nervous system
NT of CNS and PNS
helps with memory
modulates pain and anesthetic effects
What is the normal effect of NO on the immune system
modulates inflamation
Macrophages activate NO synthase»NO
Kills bacteria, fungi, and protozoa in high concentration
How is NO used to tx pulmonary HTN
SELECTIVE pulmonary vasodilator: diffuses from alveoli to PV smooth muscle 3-5x CO and produces only pulmonary vasodilation (not systemic) bc it rapidly binds to and is inactivated by HEMOGLOBIN
*Vasodilates only portions of the lung that is well ventilated
What is the therapeutic concentration range of NO
0.05-80 ppm
What is the onset of action of NO
1-2 minutes with rapid offset
*rapidly binds to heme moiety of hgb and gets metabolized to methemoglobin
What is the half-life of NO in blood
6 seconds
What are the six disadvantages of NO use
corrosive to metal parts
special equipment required
metabolite (nitrogen dioxide»nitric acid)»pulmoonary edema and acid pneumonitis
methemoglobinemia
epithelia hyperplasia and ciliary depletion
rebound HTN
Sodium Nitroprusside Dehydrate (NTP) is a PRODRUG composed of
ferrous (Fe2+) iron center complexed with five cyanide (CN-) moieties and nitrosyl group
- 44% cyanide
In the presence of light, NTP is rapidly converted to
CN-
*must protect from light
What is the MOA of SNP
direct-acting, non-selective art/ven vasodilator
enters RBC and interacts with 02hgb»methemoglobin + unstable SNP radical»5 CN- + NO
What three options does CN- have once produced by toxic NTP radical
bind to methemoglobin»cyano-methgb
react with liver and kidney»thiocyanate (sulfur required)»long term toxicity
bind to P-450»acute cyanide toxicity
Name the three complications associated with NTP administration
Cyanide toxicity
Thiocyanate toxicity
Methemoglobinemia
What are the s/s associated with CN- toxicity
Tachyphylaxis
Elevated SVO2
Mental status change»seizures
Metabolic acidosis
Is there cyanosis associated with CN- toxicity
NO
*Blood arterial saturation high, but cell can’t use it
Name six tx measures for cyanide toxicity
DC NTP give 100% 02 Sodium thiosulfate Sodium Nitrate Sodium Bicarbonate Vitamin B12
What is the clinical indication for NTP
Acute management of HTN
Controlled hypotension
Afterload reduction
What are the two contraindications of NTP
compensatory HTN
inadequate cerebral circulation
Name some CV effects of NTP
decreased afterload/preload increased HR/contractility (reflex) decreased renal perfusion>>increased renin increased catecholamine intracoronary STEAL and decreased DBP
Name some Pulmonary effect of NTP
causes pulmonary vasculature dilation»reduction in pulmonary artery pressure»decreased perfusion of normally ventilated alveoi»increased dead space
prevents normal vasoconstrictive response of pulmonary vasculature to hypoxia»decreased pa02»>V/Q mismatch
*Tx with PEEP
What is the MOA of Nitroglycerin (NGT)
permeates vascular smooth muscle and reacts with tissue thiols to liberate NO
NO»>increased cGMP»activates MLC phosphotase»»dephosphorates MLCK»relaxation
NGT selectively binds to
post-capillary veins
- dilates capacitance vessels»decreased venous return»decreased ventricular wall tension (preload)
- reduced myocardial O2 demand and increased endocardial perfusion
In high doses NTG can cause arterial vasodilation resulting in
decreased SVR (afterload)
decreased ESP»decreased myocardial workload»02 demand
reduced LVEDP»decreased coronary perfusion pressure and reduction of myocardial 02 supply
Does NTG increase TOTAL coronary blood flow in the presence of atherosclerotic CAD
NO
- Selectively dilates large epicardial arteries increasing blood flow to ISCHEMIC areas of subendocardium
- RobinHood effect
What is the difference b/t NTG and NTP
NTG may decrease the area of myocardial ischemia
NTP may increase the area of myocardial ischemia
IV NTG has a half-time of
- 5 minutes
* making it useful for when short decreases in BP is needed. eg. mayfield pin insertion
Can NTG produce methemoglobinemia
Yes
doses> 5 mg/kg
SPO2 will read 85% regardless of Pa02
Tx with methylene blue
What are the six indications for NTG
periop HTN CHF Pulmonary HTN Angina pectoris Controlled Hypotension Sphincter of Oddi spasm
What are the three contraindications of NTG
constrictive pericarditis or pericardial tamponade
Hypotension
Increased intracranial pressure
Does NTG effect platelet function and is bleeding time prolonged
No
yes,bleeding time is prolonged d/t vasodilation/venous pooling
Nicardipine is a calcium channel blocker that
binds to L-type calcium channels and impairs calcium entry into smooth muscles.
- selective for arterial smooth muscle instead of cardiac muscles like verapamil
What are main cardiovascular effects of nicardipine
Significant SVR decrease (afterload goes down)
dilation of coronary arteries 1000x nifedipine
What is the main effect that nicardipine has on the heart
Indirect increase in HR d/t compesatory response to vasodilation
Nicardipine is indicated for what two reasons
short term tx of hypotension
periop control of bp during CV surgery
Nicardipine is not comptible with what solutions
LR or NaHCO3
Nicardipine is compatible with what solutions
Dextrose and saline
What are the three main AE of nicardipine
H/A»>hypotension»N/V
What are the two treatment medications for overdose of nicardipine
vasopressors
calcium GLUCONATE
What is the single most important contraindication of nicardipine
Aortic stenosis
Nicardipine should be used with caution in which heart patient
CHF
*may have negative inotropic effects
Clevidipine is a dihydropyridine CCB similar to nicardipine, but what is different about it’s preparation
milky white injectable emulsion
Clevidipine is contraindicated in what three patient populations
allergies to soybeans, eggs
hyperlipemia, acute pancreatitis
Severe aortic stenosis
What is the onset, half-life and context-specific half-life of clevidipine
onset= 60 seconds
half-life= 15 minutes
context-specific half-life at 12 hour= < 2 minutes
What is the MOA of Hydralazine
relaxes ARTERIAL smooth muscle via:
inhibits release of calcium store from SR
stimulates NO formation
hyperpolarizes vascular smooth muscles
increase cGMP
What is the onset of action of hydralazine
10-20 minutes
What is the effective half-life of hydralazine
2-4 hours
What is the elimination half-time of hydralazine
3 hours
*effects last long, must be committed when using
What is a major SE of hydralazine
produces a drug-induced LUPUS syndrome
*fever, arthralgia, arthritis, anemia, vasculitis
What is hydralazine used to treat
essential HTN
pregnancy-induced HTN
What are the three contraindications of hydralazine
coronary artery disease (decreased afterload, but increased HR)
mitral valve heart disease
critical aortic stenosis
What is the negative effect of decreasing afterload with hydralazine with use in heart patients
greater diastolic decrease in BP»decreased coronary perfusion
decrease afterload»>increase HR, contractility, SV»>CO= WORKLOAD»>angina pectoris and MI
*increase demand with decrease supply
Fenoldapam is a dopamine agonist that agonizes what two receptor types
D1
A2
What is the effects of fenoldopam
rapid-acting vasodilator in coronary, renal, mesenteric, and peripheral arteries
Can fenoldapam be used in glaucoma patients
NO
*increases intraocular pressure
What are the effects of B-type NAtriuretic Peptide (BNP)
increase in intracellular cGMP»vascular smooth muscle relaxation
counters angiotensin/NE in setting of HF
decrease PAOP and SVR in HF patients
What drug is used as a short term tx for pheochromocytoma
Phentolamine
*increase in HR (reflex), increased release of NE (paradoxical)
