Pressors/Inotropes Flashcards
Vasopressin.
Arginine Vasopressin
class: Exogenous antidiuretic peptide and vasopressor
MOA: binds to GPCR and increases cAMP and increases calcium influx to result in the following at each receptor:
- V1: Will induce vasoconstriction in vascular smooth muscle and efferent arterioles - increase BP
- V2: Will act as ADH and stimulate water reabsorption from collecting ducts
- V3: Will increase VWBf release
Pk:
onset: immediate
E1/2: 10-20 minutes
Dose:
- 20 units IVP - varicies
- 40 units IVP - ACLS arrest
- 0.04 units/min gtt for septic shock
metabolized by tissue peptidsases and urinary excretion
SE:
Increase BP, angina, arrthymias, CA spasm
increase peristalsis -> increase N/V/adominal pain
bronchoconstriction
C/I:
- HTN,
- CAD
- Asthma
- renal disease
- GI obstruction
- will increase the effect of NSAIDs
Dobutamine
Dobutamine
class:
synthetic catecholamine,
beta selective adrenergic agonist with greater affinity at B1 than beta 2.
MOA:
Binds to B adrenergic receptors, increases cAMP, increase calcium influx results in increase intropy, dobutamine results in increased inotropy with minimal increase in HR.
At higher doses can also lead to B2 agonism and mediate bronchodilation and some decrease in SVR r/t skeletal muscle vascular dilation .
Uses:
intropic agent!
Increase CO with minimal changes to HR/BP
used in cardiogenic shock.
Pk:
onset: immediate
DOA: 5-10 minutes
E1/2T: 2 minutes
Metabolized by MAO, COMT
Dose:
2-10 mcg/kg/min
<5 mcg/kg/min :: B1 effects
>5 mcg/kg/min :: B1 + B2 effects
not advised in doses greater than 10mcg/kg/min r/t risk for arrthymias
SE:
- Arrthymias , increased ventricular ectopy
- tachycardia - more common in peds or after 72 hours of gtt
- after 72 hrs, can also see down regulation of beta receptors
- HTN
- ANGINA
- Coronary and pulmonary artery vasodilation
- palpitations
- hypokalemia
- Synergitisc effect when used with dopamine, increases renal blood flow.
C/I:
CAD, hx of MI, HT
C/I in IHSS - hypertrophic cardiomyopathy
caution with MAO-Is, TCAs,
Dopamine
Dopamine
Endogenous catecholamine with equal action at D1 and D2 and lesser affinity for B1 and B2 and even less affinity for a1 and a2.
MOA
binds to adrenergic receptors D1, D2 and increases cAMP to vasodilate renal, mesenteric vascular beds and incresae Calcium influx leading to increase inotropy, chronotropy, and peripheral vasoconstriction.
At low doses active at D1, D2 = vasodilates coronary, mesenteric, renal vascular beds, decreases afterload.
At medium doses it also acts at B1, B2 to increase HR and contractility
at highest doses it also acts at alpha 1receptors to vasoconstrict and increases SVR,also at highest doses it induces release of norepinpehrine
Uses:
theoretically the most vasoprotective pressor becuase of its dilation of renal vascular beds
Also is used with dobutamine for CHF patients, cardiogenic shock.
Pk:
Onset: immediate
DOA: 5-10 minutes
E1/2T: 2 minutes
Metabolized by COMT and MAO-I in liver, kidneys, blood. Metabolized 75% to inactive metabolite and 25% to NOREPINEPHRINE.
Dose:
D = 1-3 mcg/kg/min
D+B: 3-10 mcg/kg/min
D+B+A: >10 mcg/kg/min
SE:
Tachycardia, angina, ARRTHYMIAS
NAUSEA/VOMITTING
Increase GFR, increase HBF, increase UOP
Synergistic with dobutamine to decrease SVR but increase CO
INHIBITS CAROTID BODIES, ALTERED REPONSE TO HYPOXIA
Tachyphylaxis r/t indirect NE release.
C/I:
Pheochromacytoma
Hyperthyroidism
caution wtih concurrent use of MAO-Is, TCA, methyldopa
Caution in HTN, CAD
Ephedrine
Ephedrine
synthetic non-catecholamine, primarily indirect acting but also has direct effect. Active at a and beta adrenergic receptors.
MOA:
Ephedrine primarily stimultes the release of norepinephrine which then binds to alpha 1, alpha 2, and bet 1 receptors. It has some direct effects at beta 2. Binding to adrenergic receptors leads to either increased/decrease cAMP and influx of calcium or increased conduciton of potassium that leads to effects.
Over all result is in an increase in SBP, DBP, HR, and CO from sympathomimetic effects.
Uses:
Increase HR and BP
Pk:
onset: immediate
DOA: 1 - 1.5 hours
E1/2: 2-3 hours
Metabolized by MAO, significantly slower metabolism than catecholamines/phenyleprhine so longer DOA.
40% excreted in the kidney unchanged.
Dose:
5-25 mg IV
25 - 50 mg IM
SE:
Arrthymias!
HTN!
Tachycardia!
MI!!
CNS stimulation !
Can cause tachyphylaxis r/t indirect effect and depletion of NE.
decrease uterine activity
C/I:
CAD - can increase myocardial oxygen consumption
Not the drug of choice in trauma r/t tachyphylaxis
Avoid in pts taking MAO-Is, reserpine, TCAs, ephedra, cocaine,
caution in HTN
Epinephrine
Epinephrine
class: endogenous catecholamine,
equal action at B1 and B2 and alpha 1 and alpha 2. most potent at alpha 1.
MOA.
Epinephrine binds to adrenergic receptors in the body that are either Gq, Gi, Gs coupled and either increases or decreases cAMP and increases Ca++ or increases potassium conductance leading to the ultimate effectsl
At lowest doses it works primarily at B2 and leads to dilation of skeletal muscle and decrease SVR and bronchodilation.
At moderate doses it works at B1 as well and leads to increased chronotropy and inotropy.
At higher doses it also works at alpha 1 and alpha 2 leading to vasoconstriction and increased SVR
USES:
anaphylaxis, shock, bronchodilation, CARDIAC ARREST, used with LA to prolong local anesthetic blocks
Pk :
Onset: immediate
DOA: 5-10 minutes
E1/2T: 30 seconds
Metabolized by COMT and MAO in the blood, liver, and kidneys
Effect terminated by diffusion and reuptake.
Dose:
B2: 1-2 mcg/min
B1: 4-5 mcg/min
A+B: 10-20 mcg/min
1 mg q 3-5 min in cardiac arrest as per ACLS
10 mcg/kg q 2 min during suspected anaphylaxis.
SE:
- Tachycardia, HTN, angina, ARRTHYMIAS
- Hyperglycemia
- Vasoconstriction of skin, GI tract, liver, kidneys
- Peripheral vascular insuffiency, gangrene possible in digits,
- Mydriasis, increase humoral outflow.
C/I
- Caution in CAD, HTN, DMII, renal insuffiency
- Pheochromocytoma
- Hypethyroidism
- Glaucoma
- pregnancy
- used with MAO-Is
- avoid in LA in peripheral nerve blocks to fingers, toes, genitals, nose
Isoproterenol
Isoproterenol
Synthetic catecholamine, beta adrenergic selective agonist, equal activity at beta 1 and beta 2.
MOA: Binds to beta adrenergic receptors (GaS coupled) and leads to increase in cAMP and increase in calcium, resulting in increased HR, increased contractility, increased SBP, and decrease DBP.
Uses:
- “chemical pacemaker” drug,
- used after cardiac transplant surgery, or in refractory bradycardia or heart block
- also in beta blocker ovder dose.
Pk:
onset: immediate
DOA: 5-10 minutes
E1/2T: 2-5 minutes
rapidly metabolized by MAO and COMT,
40-50% excreted unchanged by the kidneys
DOSE:
0.5 to 10 mcg/min
SE:
- Tachycardia, ANGINA, arrthymias
- Increase SBP, decrease DBP,
- INCREASE MYOCARDIAL OXYGEN DEMAND
- Decreased coronary blood flow r/t decreased DBP
- Bronchodilation r/t b2 affects
C/I:
- CAD, angina, hx of MI
- digitalis toxicity
- Hypertrophic cardiomyopathy - IIHS
- HTN
- pheochromacytoma
Milrinone
Milrinone
phosphodiesterase-3 inhibitor.
Blocks the degradatoin of cAMP in cardiac muscle by inhibiting phosphodiesterase subtype 3, also prevents degradation of gCMP which potentiates PKG and leads to increased contractility, HR, vasodilation in veins and arteries. Also mediates increased calcicum removal from cardiac cells and improves diastolic relaxation.
Used
immediately post cardiopulmonary bypass, in acute HF
Can help in pulmonary HTN.
Decreased afterload, preload. coronary artery vasodilation, improved diastolic relaxation.
decreased PCWP.
Pk:
onset: 5-20 minutes
E1/2T: 3 hours
Excreted 80% unchanged in kidneys
Dose:
50mcg/kg over 10 minutes then gtt of 0.5 mcg/kg/min
SE:
- arrthymias!
- mild tachycardia
- hypotension,
- hypokalemia
- thrombocytopenia
C/I:
- aortic or pulmonic valve disease
- Acute MI
- Concomittant use with digoxin (too much of the same effect)
- Dose dose in renal failure
- long term use has not been shown to improve M&M and may actually worsen it. Used in acute management.
Norepinephrine
Norepinephrine
Endogenous Catecholamine, action at a1, a2, and b1. No action at beta 2.
MOA:
Binds to adrenergic receptors a1, a,2 and b1 which are GPCR that are wither Ga,GI,Gs coupled and will increase/decrease cAMP and increase calcium flux into cell or increase potassium conductance and lead to ultimate effects. Norpeinephrine leads to vasoconstriction and increases blood pressure, SVR, and MAP. The vasoconstriction activates the baroreceptors and can lead to a decreased HR and therefore overall can decrease cardiac output.
Use:
First line pressor for septic shock.
Pk:
onset immediate
DOA: 5-10 minutes
E1/2: 2 minutes
metabolized by COMT/MAO in liver, kidneys, blood. Action is terminated by diffusion away from recpetor and reuptake.
Dose:
4-16 mcg/min IV gtt
0.01 to 0.1 mcg/kg/min IV gtt
SE:
Increases SBP, DBP, SVR, MAP, decrease HR - decrease CO
Decrease RBF, HBF, and splanchnic BF.
Oliguria, transient anxiety, transient HA
Organ ischemia and metabolic acidosis at high doses
Necrosis with extravasation
C/I:
Hypovolemic shock, cardiogenic shock
Pheochromacytoma, hyperthyroidism
Renal insuffiency
Pts with mesenteric or peripehral vascular thrombosis
caution with MAO-Is
Phenylephrine
Phenylephrine
synthetic non-catecholamine, direct alpha agonist, more potent at alpha 1 than alpha 2.
Binds to alpha receptors (Gaq) receptors, increased calicum influx into cells, contraction, and vasoconstriction of the smooth muscle. Affects VEINS more than arteries. Increase SVP, SBP, DBP, MAP. Activates baroceptors, may have baroceptor mediated bradycardia and decrease in HR and cardiac output.
Uses;
systemic hypotension, increase BP in pts with adequate HR and CO.
Vasodilation associated with general anesthesia.
Pk:
Onset: immediate
DOA: 5-20 minutes
E1/2L: 2-3 hours
Metabolized by MAO in liver and broken down to phenolic conjugates, 90% is excrted UNCHANGED via kidneys.
Dose:
50-200 mcg IVP
20-50 mcg/min gtt
SE:
- Hypertension!
- Bradycardia!
- Arrthmyias!
- Decreased renal blood flow, decrease urine output,
- metabolic acidosis - decrease perfusion
- rebound nasal congestion
C/I:
- HTN, CHF, bradycardia, HB
- glaucoma
- caution with:
- Cocaine/MAO-Is, TCAs
- renal impairment
