Vasodilators Flashcards
Most frequent clinical uses of Peripheral Vasodilator?
1) Tx of hypertensive crisis and pulmonary HTN
2) Produce controlled hypotension spring anesthesia to reduce blood loss
3) Fascilatation of vessel surgery
4) Acute decompensated HF mgmt
5) Ichemic heart disease i.e. ACS and chest pain
*Hows is NO produced in our bodies
1) NO is produced by vascular endothelial cells and various other tissues of the body
2) Endogenous NO is synthesized from L-Argenine by the enzyme Nitric Oxide Synthase (NOS)
3) NOS enzyme catalyzes the oxidation of L-Argenine to produce L-citruline and NO
*Nitric Oxide is also known by what other name?
Endothelium-derived Relaxing Factor (EDRF)
Explain the steps of how NO moves from Endothelial cells to Smooth muscle cells and cause dilation?
1) NO produced by endothelial cells»_space;> diffuses into smooth muscle cells»_space;> NO binds and activates soluble guanylate cyclase»_space;> Guanylate cyclase dephosphorylates into GTP and cGMP»_space;> cGMP (2nd Msgr) induces smooth muscle relaxation
How is cGMP metabolized
It is broken down by phosphodiesterase, which convert cGMP to guanosine monophosphate (GMP)
Cardiovascular Effects of NO
1) Vasodilation
2) ↓ pulmonary vascular resistance
Pulmonary Effects of NO
- Bronchodilation, improves ventilation-perfusion matching
Effects of NO on Platelets
1) Inhibits platelets activation, aggregation, and adhesion to the vascular endothelium
Does NO prolong bleeding time
No
Anti-inflammatory Effects of NO
1) NO has a role in modulation of inflammation, host defenses and immunologic function
2) Inhibits leukocyte adhesion to vascular endothelium
Anti-Proliferative Effects of NO
Inhibits smooth muscle hyperplasia
Nervous System Effects of NO
1) Endogenous NO is a neurotransmitter in the brain, spinal cord, and PNS
2) NO released in response to stimulation of excitatory (NMDA) glutamate receptor
3) NO is involved in anti-nociceptive and in modulating anesthetics effects
4) Various peripheral nerves are known to synthesize and release NO i.e. nerves to myenteric plexus and penile tissue
What is the main use for NO in Anesthesia?
As a vasodilator
Sodium Nitroprusside (Nipride) MOA
- Direct-acting non-selective mixed arterial and venous smooth muscle dilator
- 44% cyanide by weight
Sodium Nitroprusside (Nipride) onset duration and 1 1/2
1) Onset - immediate (seconds)
2) Duration - 1 to 2 mins
3) T 1/2 - ~ 2mins
Which 2 equipment is needed when administering Sodium Nitroprusside (Nipride)?
1) IV Pump
2) A-line
*Sodium Nitroprusside (Nipride) MOA
1) SNP is a vasodilator that releases NO when broken down (* known as a “direct NO donor)
2) NO then follows its normal pathway to producing smooth muscle vasodilation
Sodium Nitroprusside (Nipride) Metabolism
1) SNP interacts with oxyhemoglobin to form methemoglobin and an unstable nitroprusside radical
* 2) This unstable radical then dissociates rapidly to release 5 cyanide ions AND NO /? (which occurs via a non-enzymatic process)
3) The amount of cyanide and NO generated depends on the dose of SNP administered
What is the effect of light on SNP
SNP decomposes when exposed to light
What does it indicate if a solution of SNP is bluish in color
It indicated almost complete degradation and breakdown to cyanide
What are the products of Nitroprusside/hemoglobin reaction?
1) 1 Cyanide ion - reacts with methemoglobin to form cyanmethemoglon which is non-toxic.
2) 4 cyanide ions - converted in the liver to thiocyanate by rhodanse, which uses thiosulfate to do so.
3) Thiocyanate is then excreted by the kidneys
What happens if cyanide is not removed by either binding to methemoglobin or by being converted to thiocyanate?
Free cyanide ions that are not removed can bind to cytochrome complex in cell walls and cause toxicity.
Effect of hypothermia on cyanide metabolism?
1) Nonezymatic release - not inhibited by hypothermia except during cardiopulmonary bypass
2) Enzymatic conversion to thiocynate - delayed by hypothermia
3 Toxicities the could result from SNP
1) Methemoglobinemia
2) Thiocynate toxicity
3) Cyanide toxicity (most toxic
Sodium Nitroprusside (Nipride) Cyanide toxicity levels
1) SNP infusions up to 2mcg/kg/min eliminated by liver without causing cyanide toxicity
2) SNP infusions > 2mcg/kg/min result in does-dependent accumulation of cyanide and ↑ risk of toxicity
What happens if free cyanide radicals bind to and inactivate cytochrome oxidase?
This leads to anoxia, aerobic metabolism and lactic acidosis
*The removal of cyanide ion depends on which 3 physiological requirements?
1) Adequate liver function
2) Adequaterenal function
3) Adequate bioavailability of thiosulfate
Signs and Symptoms of Cyanide toxicity
1) Headache, dizziness, tachypnea/hyperapnea 1)early, tachycardia, N/V, mydriasis, bradypnea/apnea (late)
2) ↑ mixed venous PO2 = PaO2 due to paralysis of cytochrome oxidase and the inability to tissues to use O2
3) Venous hyperemia with bright red blood
4) Smell of almonds on breath
5) Metabolic acidosis due to anaerobic metabolism
6) Cardiovascular collapse
7) CNS dysfunction
CNS dysfunction due to cyanide toxicity sysmptoms
1) Mental status changes i.e. confusion and disorientation
2) seizures
3) encephalopathy
4) coma
5) irreversible focal neurological damage
Sodium Nitroprusside (Nipride) Cyanide toxicity Tx
1) 100% O2, hydration, CV support and seizure mgmt
2) Amyl nitrate
3) Sodium nitrate (5mg/kg IV over 2 to 4 mins)
4) Sodium thiosulfate (150 to 200 mg/kg IV over 15 mins
5) Hydroxocobalamin (aka Cyanokit)
What is the MOA of the following SNP cyanide toxicity Tx:
1) Amyl nitrate
2) Sodium nitrate (5mg/kg IV over 2 to 4 mins)
3) Sodium thiosulfate (150 to 200 mg/kg IV over 15 mins
4) Hydroxocobalamin (aka CYANOKIT)
1) Amyl nitrate - converts Hgb to methemoglobin, which reacts with cyanide to form cyanomethemoglobin
2) Sodium nitrate - Converts Hgb to methemoglobin, which reacts with cyanide to
form cyanmethemoglobin
3) Sodium thiosulfate - acts as a source of sulfur groups, which are needed for the conversion of cyanide to thiocyanate
4) Hydroxocobalamin - Binds to cyanide to form nontoxic cyanocobalamin which is
eliminated by the kidneys and allows the body to use O2 again
Thiocyanate Toxicity Characteristics
1) Cleared via the kidneys
2) 100x less toxic than cyanide
3) Is dialyzable
4) Thiocyanate toxicity onset is slower than cyanide toxicity
Cardiovascular Clinical Effects of Sodium Nitroprusside
1) Hypotension (⇓ SVR)
2) ⇓ preload and ⇓ afterload
3) Dilation of coronary arteries
4) Baroreceptor-mediated reflex responses to the SNP-induced decreases in systemic BP manifest as tachycardia and increased myocardial contractility
5) Reduces cardiac filling pressures (⇓ right atrial and ventricular pressures)
6) May cause coronary steal!
7) ⇑ plasma renin
8) ⇑ plasma concentrations of of catecholamines can occur
Sodium Nitroprusside (Nipride®) Coronary Steal Phenomenon
- SNP ↑ the area of damage associated with a MI due to coronary steal
- Coronary steal due to coronary perfusion pressure and associate coronary blood flow leading to possible myocardial ischemia