Common Drugs Flashcards
I pulled what I thought were most common drugs/most likely to appear on the oral and placed them in a deck. Trying to narrow down my studying!
Epinephrine
Class? MOA? Pharmacokinetics? SE? Contraindications? Doses?
CLASS= endogenous catecholamine & nonselective adrenergic agonist w/ a1=a2=ß1=ß2 affinity; MOST potent at alpha 1
MOA= .
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Low doses (B2) (1-2 mcg/minute) = vasodilation of skeletal muscle & decrease SVR, bronchodilation, & decrease histamine release;
- MOA- B2 receptors coupled w/ G-alpha-s proteins which increase cAMP causing an influx intracellular Ca2+ causing agonist effects
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Moderate Doses (B1) (4-5mcg/min)= increase HR & contractility;
- MOA B1- receptors coupled w/ G-alpha-s proteins which increase cAMP causing an influx intracellular Ca2+ causing agonist effects
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High doses (A1&B) (10-20 mcg/min)= increase vasoconstriction= increase SBP, increase cardiac work; A2 = negative feedback & decrease BP
- Binds to Alpha 1 (G=alpha-q) which increase PLC–> increase IP3/DAG–> increase PKC–> incrase Ca.
- Binds to Alpha2 (G-alpha-i) inhibits adenylate cyclaSe–> decrease cAMP–> Increase K conductance causing hyperpolarization, relaxation,
- Pre- Vascular- dilate, adrenergic- inhibit NT release, GI-relax
- post- Cns- sedation, vascular- contraction, PLT- aggregation
Pharmacokinetics= poorly lipid soluble (little CNS effect);
- onset- 1-2 min;
- DOA- 5-10 min;
- E1/2- 30 seconds;
- metabolized & eliminated by MAO, COMT in the blood, liver & kidneys- reuptake & diffusion away
SE= tachycardia, HTN, angina, arrhythmias, hyperglycemia, decrease LA absorption, vasoconstriction of skin, GI tract, muscle, liver & kidneys; peripheral vascular insufficiency/gangrene in digits
CI= avoid in certain peripheral LA blocks, caution in DM, CAD, MI HTN, renal insufficiency, pheochromocytoma, hyperthyroidism, glaucoma, pregnancy
Dose= 1-2 mcg/min ß2; 4-5 mcg/min ß1; 10-20 mcg/min alpha & ß;
1 mg q 3-5 min for CV arrest ACLS;
2-8mcg/min infusion
Norepinephrine
Class? MOA? Pharmacokinetics? SE? CI? Dose?
CLASS= endogenous catecholamine & adrenergic agonist w/ potent alpha 1 & 2 minimal ß1 receptor affinity- lacks ß2 effects (a1=a2> B1>>>>>>>>>>>B2)
MOA= -alpha1= GalphaQ (Incrase Ca), Alpha 2= Galphai (decrease cAMP) Beta 1= Galpha-s =binds to receptors coupled w/ G proteins which increase cAMP causing an influx of Ca2+ causing agonist effects increases contractility, intense arterial & venous vasoconstriction (alpha1) of skin skeletal muscles, kidneys, & liver = increase BP, increase MAP, increase SVR; baroreceptor activation= decrease HR; decrease venous return- CO
Pharmacokinetics= onset- rapid; DOA- 5-10 min; E1/2- 2 min; metabolized & eliminated by MAO & COMT in blood, liver, kidneys, & lungs- reuptake or diffusion away
SE= increase SBP, DBP, MAP, SVR; decrease HR- d/t baroreceptors; decrease RBF, HBF & splanchnic BF; organ ischemia, metabolic acidosis & extravasation & necrosis of extremities & digits (do not administer in peripheral IV)
CI= thrombosis, cardiogenic & hypovolemic shock, MAOIs & TCAs (HTN crisis), caution in liver & renal disease (exacerbate damage d/t decrease BF) hyperthyroidism, pheochromocytoma
Dose= 4-16 mcg/min IV
Isoproterenol
Class? MOA? Pharmacokinetics? SE? CI? Dose?
CLASS = synthetic catecholamine & adrenergic agonist w/ ß1=ß2 affinity; minimal alpha (cardiac pacemaker)
MOA= binds to receptors coupled w/ G proteins to increase cAMP causing an influx of Ca2+ causing increase HR (greater) & contractility; increase SBP, decrease DBP; B2 = bronchodilation & peripheral vasodilation
Pharmacokinetics= onset- rapid; DOA- 5-10 min; E1/2- 3-5 min; rapidly metabolized & eliminated by COMT in the liver & pulmonary with 50% eliminated unchanged in the urine (need continuous infusion)
SE= tachycardia, angina, arrhythmias, increase SBP, decrease DBP, decrease CA BF ß1- increase contractility & increase O2 demand
CI= HTN, CAD (increased O2 demand), MI, pheochromocytoma, hypertrophic cardiomyopathy, tachycardia, caution dig toxicity
Dose= 0.5-10 mcg/min
Dopamine
CLASS= endogenous catecholamine/precursor of NE & adrenergic agonist that stimulates all adrenergic receptors including DA receptors
MOA= Low doses (D1 1-3 mcg/kg/min)= vasodilates coronary, mesenteric, & renal vascular beds (ê afterload); Medium doses (B1 3-10mcg/kg/min)= é contractility, HR, & CO; High doses (A1 10mcg/kg/min)= vasoconstriction of all vascular beds including renal thereby increasing BP, SVR; also increase endogenous NE release
Pharmacokinetics= onset- rapid; DOA- 5-10 min; E1/2- 2 min; metabolized & eliminated by MAO & COMT in liver kidney, blood to 75% inactive & 25% NE
SE= tachycardia, arrhythmias, angina, extravasation, N/V, increase GFR, increase RBF, increase UOP; synergistic with Dobutamine to decrease SVR & increase CO (DA dilates renal & mesenteric vascular beds while Dobutamine dilates skin & skel muscle vascular beds)
CI= pheochromocytoma, hyperthyroidism, MAOIs, caution in HTN, CAD, sulfa allergy
Dose= DA1- low dose- 1-3 mcg/kg/min (ß1 medium dose- 3-10 mcg/kg/min; alpha- large dose- 10 mcg/kg/min
Dobutamine
CLASS= synthetic catecholamine & adrenergic agonist w/ ß1>B2 affinity & also weak alpha 1 stimulation; synthetic analog of isoproterenol
MOA= B1 stimulation <5 mcg/kg/min, weak Alpha 1 stimulation at >5 mcg/kg/min; binds to receptors coupled w/ G proteins to increase cAMP causing an influx of Ca2+= B1 increases contractility & CO WITHOUT increase HR or BP too much; some ß2 bronchodilation & skin & skeletal muscle peripheral vasodilation= decrease SVR; minimal alpha 1 antagonism to further decrease afterload = good in CHF
Pharmacokinetics= onset- rapid; DOA- 5-10 min; E1/2- 2 min; metabolized & eliminated by MAO & COMT; reuptake or diffusion away from active site
SE= arrhythmias, SVT, angina, HTN, tachycardia; platelet inhibition, thrombocytopenia, coronary artery & pulmonary vasodilation, increase renal perfusion especially when used with DA (synergistic)
CI= avoid in hypertrophic cardiomyopathy, MAOIs, TCAs, caution in CAD & MI (ok for CHF)
Dose= 2-10 mcg/kg/min
Ephedrine
Class? MOA? Pharmacokinetcis? SE? CI? Dose?
CLASS= synthetic NON-catecholamine; direct & indirect (primarily) adrenergic agonist
MOA= indirectly activates alpha & ß receptors by stimulating NE release from post ganglionic SNS nerves; directly acts ß1 —- increase contractility & increase HR, increase BP, increase CO; increase CA & skeletal muscle vasodilation (B2); decrease RBF & splanchnic BF
Pharmacokinetics= onset- rapid; DOA- 1 hr; E1/2- 3 hrs; slower MAO metabolism & excreted 40% unchanged in the urine
SE= arrhythmias, HTN, tachycardia, MI, CNS stimulation, can cause Tachyphylaxis, decrease uterine activity;
CI= HTN, CAD, MAOIs, TCAs, ephedra, caution in trauma (depleted stores)
Dose= 5-25mg IV
Phenyhlephrine?
Class? MOA? Pharmacokinetcis? SE? CI? Dose?
CLASS= synthetic NON-catecholamine; direct acting selective alpha 1 agonist
MOA= direct stimulation of alpha 1 receptors causing venous> arterial constriction; increase MAP, SBP, DBP, SVR; decrease HR & CO (strong activation of baroreceptors); can be used for hypotension & nasal decongestion
Pharmacokinetics= 90% PB; onset- rapid; DOA- 5-20 min; E1/2= 2-3 hrs; metabolized by MAO to phenolic conjugates & excreted in the urine 90%
SE= rebound nasal congestion, Bradycardia, HTN, arrhythmias, decrease RBF & splanchnic BF= decrease UOP; metabolic acidosis
CI= HTN, bradycardia, arrhythmias, CHF, glaucoma, cocaine, MAOI’s, TCA’s, renal impairment
Dose= 50-200 mcg IVP; 20-50 mcg/min gtt
Clonidine (unsure if for oral….)
CLASS= centrally acting alpha 2 adrenergic agonist
MOA= selectively activates alpha-2 adrenergic receptors in CNS, decreases sympathetic outflow from the medulla which decrease HR, contractility & decrease BP; has analgesia properties b/c alpha 2 receptors found in the dorsal horn of the SC inhibiting the release of substance P & decrease neuronal firing; used for HTN, induced sedation, analgesia
Pharmacokinetics= Vd 2.1 L/kg ; 20-40% PB; Onset 0.5-1 hour; DOA- 8 hrs; E1/2- 9-12 hrs; 50% metabolized in the liver & 50% excreted unchanged in the urine
SE= Bradycardia, hepatotoxicity, sedation, rebound HTN with abrupt w/d, Na+ & H2O retention,
CI= hypersensitivity, pregnancy, clonidine potentiates the effects of VA or other anesthetics
Dose= 0.2-0.3 mg/day
Phentolamine
CLASS=nonselectivecompetitive alpha adrenergic antagonist; a1=a2 affinity
MOA= binds to alpha-receptors to block the effects of catecholamines & inhibit G-protein coupled signaling cascade; peripheral vasodilation (arterial > venous) decrease BP; may have some antihistamine and cholinomimetic activity
used to treat hypertensive emergencies especially those with pheochromocytoma, or as LA infiltration for tx. of sympathomimetic extravasation
Pharmacokinetics= onset- 2 min; DOA- 10-15 min; E1/2- 19 min; liver metabolism & excreted 10% unchanged in urine
SE= HA, arrhythmias, angina, MI, reflex tachy (baroreceptors activated from decrease BP), cramping, diarrhea (from cholinomimetic activity)
CI= CAD, MI, angina, PUD, treat hypotension after admin of phentolamine with NE over Epi
Dose= 1-5 mg IV bolus q 5 min, max 20 mg
for treatment of extravasation of norepinephrine- 5-10 mg in 10 mL of saline injected into affected area within 12 hours
Phenoxybenazmine
CLASS=nonselectivecovalent alpha adrenergic antagonist; a1>a2
MOA= covalently binds with alpha receptors to block the effects of catecholamines & inhibit G-protein coupled signaling cascade; peripheral vasodilation (arterial > venous) & decrease SVR & BP; given preop for patients with pheochromocytoma, or Raynaud’s disease>>- irreversible and long-acting
Pharmacokinetics= prodrug; onset- 1 hr; E1/2- 24 hrs; hepatic metabolism with renal/biliary excretion
SE= orthostatic hypotension, reflex tachy (baroreceptors- also increase HR/CO d/t NE having increaes effects at beta receptors), nasal congestion, impotence
CI= severe hypotension or hypovolemia; treat hypotension with NE over Epi
Dose= 10-120 mg/day PO
Prazosin
CLASS= alpha 1 adrenergic antagonist
MOA= blocks alpha 1 receptors antagonizing Epi & NE vasodilation/ decrease SVR & minimal reflex tachycardia; used to treat HTN especially those with BPH (decrease prostate size), used preop for pheochromocytoma, & decrease vasospasm in Raynaud’s disease
Pharmacokinetics= highly PB; onset- 1 hr; DOA- 6-10 hrs; E1/2- 4 hrs; metabolism & conjugation in the liver & excreted in the bile & feces
SE= dizziness, HA, orthostatic hypotension, edema, anticholinergic effects- dry mouth, urinary frequency; hepatotoxicity, SLE
CI= caution with regional- decrease BP exaggerated, caution with ßB & other drugs that decrease P, pregnancy
Dose= 1mg PO bedtime
Labetalol
CLASS= competitive ß1, ß2 & alpha 1 antagonist
MOA= blocks ß1, ß2 & alpha 1 receptors to block the effects of catecholamines & inhibit G-protein coupled signaling cascade (beta: alpha 7:1) thereby decrease BP, SVR, HR; CO unaffected (no alpha 2, so negative feedback not blocked). Also, decreases stage 4 depolarization in SA & AV node
Pharmacokinetics= 50% PB; onset- 5 min; DOA- 4 hrs; E1/2- 5-8 hrs; conjugation to glucuronic acid & eliminated via liver by CYP2D6 & kidneys. LIpid soluble
SE= hypotension, bradycardia, angina, bronchospasm, mask hypoglycemia, exercise intolerance, exacerbate PVD
CI= hypotension, bradycardia, HB, caution: asthma, COPD, CHF, cardiogenic shock, DM; avoid concurrent use with CCBs; effect decreased by salicylates & NSAIDs (decreases antiHTN effect)
Dose= 5-20 mg IV q 5-10 min (max 300mg)
Esmolol
CLASS= ß1 selective adrenergic antagonist & class II anti-arrhythmic
MOA= selective blockade of ß1 receptors to block the effects of catecholamines & inhibit G-protein coupled signaling cascade to decrease HR without decrease BP significantly; class II antiarrhythmic- decrease rate of spontaneous phase 4 depolarization, decrease SA node discharge, decrease ANS activity and conduction velocity AV node. DECREASE automaticity
Pharmacokinetics= 55% PB; onset- 2min; DOA- 10-15 min; E1/2- 9 min; rapidly hydrolyzed by plasma esterases and excreted in urines
SE= CNS sedation (lipid soluble); hypotension, bradycardia, HB, bronchoconstriction, can mask hypoglycemia
CI= hypotension, bradycardia, HB, caution: asthma, CHF, DM; avoid concurrent use with CCBs; effect decreased by salicylates & NSAIDs. 2nd and 3rd trimester
Dose= 5-10 mg IV q 3 min max 80 mg; infusion- 50-300 mcg/kg/min
Propranolol
CLASS= nonselective beta antagonist; ß1=ß2
MOA= antagonizes the ß1 & ß2 receptors equally to block the effects of catecholamines & inhibit G-protein coupled signaling cascade; ß1- decrease contractility, HR, CO & O2 demands; ß2 blockade= increase PVR & increase CA vascular resistance (offset by decrease demand on the heart with the ß1)
Pharmacokinetics= 90% PB; high lipid solubility; large first pass effect; onset- 5 min; DOA- 4 hrs; E1/2- 2-3 hrs; extensive pulmonary uptake; liver metabolism by CYP450 which relies on HBF & excreted in the urine (can decrease clearance of other drugs metabolized by CYP 450- LA, benzos, warfarin, etc.)
SE= hypotension, bradycardia, bronchospasm, Na+ retention d/t renal response from decrease CO, mask hypoglycemia, exacerbate PVD
CI= HB, bradycardia, hypotension, asthma/bronchospasm, CHF, DM, decrease clearance of LA; decrease pulmonary 1st pass effect of fentanyl
Dose= 0.05 mg/kg IV or 1-10 mg (slowly 1mg q 5 min)
Metoprolol
CLASS= ß1 selective antagonist
MOA= selective blockade of ß1 receptors to block the effects of catecholamines & inhibit G-protein coupled signaling cascade causing decrease HR & BP
Pharmacokinetics= 10% PB; onset- 5 min; DOA- 3-4 hrs; E1/2- 7 hrs; liver metabolism by CYP2D6 & renal excretion; 50% first pass metabolism
SE= hypotension, bradycardia, angina, exercise intolerance; In high doses= bronchoconstriction, mask hypoglycemia, exacerbate PVD
CI= hypotension, bradycardia, HB, caution: asthma, CHF, DM; avoid concurrent use with CCBs; effect decreased by salicylates & NSAIDs
Dose= 1-5 mg IV q 2-5 min up to 15mg
Method of Action of all anti-cholinergics?
Competitively inhibit ACh at the muscarinic receptors & decrease PNS activity (preventing decrease cAMP & cGMP);
causes sedation by blocking Ach effects @ M1;
increase HR by blocking the ACh effects @ M2;
relaxes bronchial smooth muscle & decrease secretions by blocking Ach effects @ M2 & M3; also decrease GI secretions;
used to tx. Bradycardia, secretions, nausea, biliary spasm r/t opioids; bronchodilation, mydriasis for eye procedures; w/ anticholinesterases
Atropine
CLASS= tertiary amine anticholinergic- crosses BBB
(Most potent increase in HR)
MOA- Competitively inhibits muscariniac receptors at M1, M2, M3 with most predominant at M2, allowing SNS to dominate, raising the HR.
Pharmacokinetics= 40% PB; onset- 1 min; peak- 1-2 min; DOA- 30-60 min; E1/2- 2 hrs; hydrolyzed in the liver to tropine & tropic acid & excreted 18% unchanged in the urine. VD 1.6 L/kg
SE= increase IOP, sedation, post-op delerium- crosses BBB, increases HR, CO, arrhythmias, IOP, blurry vision; decreases secretions & GI motility, bronchodilation, urinary retention; inhibits diaphoresis; central anti-cholinergic syndrome
CI= glaucoma, renal disease, CAD, caution elderly
Dose= 0.01 mg/kg for reversal; 0.4-1 mg for brady; 1 mg q 3-5 min for asystole, PEA
Glycopyrrolate
CLASS= synthetic quaternary ammonia anticholinergic that does not cross the BBB; best for elderly
MOA:
Competitively inhibit ACh at the muscarinic receptors & decrease PNS activity (preventing decrease cAMP & cGMP);
increase HR by blocking the ACh effects @ M2;
relaxes bronchial smooth muscle & decrease secretions by blocking Ach effects @ M2 & M3; also decrease GI secretions;
Pharmacokinetics= onset-2-3 min; DOA- 2-4 hrs; E1/2- 1 hr; liver metabolism & 85% excreted unchanged in the urine; poorly lipid soluble
SE= inrease HR (++), CO, IOP; arrhythmias; blurry vision; decrease secretions(++) & GI motility, bronchodilation (++)
CI= neonates, CAD, HTN, CHF, glaucoma, renal
Dose= 0.01-0.02 mg/kg IV reversal with neostigmine; 0.1-0.2 mg anti-sialagogue & bradycardia
Scopolamine
CLASS= tertiary amine anticholinergic that crosses BBB; used for motion sickness, PONV, sedation, bronchodilation; biliary & ureteral SM relaxation; NOT used for reversal of NMB
(Most potent anti-sialagogue (+++) & sedative anti-cholinergic) (+++)
MOA:
Competitively inhibit ACh at the muscarinic receptors & decrease PNS activity (preventing decrease cAMP & cGMP);
causes sedation by blocking Ach effects @ M1;
increase HR by blocking the ACh effects @ M2;
relaxes bronchial smooth muscle & decrease secretions by blocking Ach effects @ M2 & M3; also decrease GI secretions;
Pharmacokinetics= lipid soluble; onset- 10 min; DOA- 2 hrs; E1/2- 4 hrs- may last 3-7 days; metabolized by the liver with <1% excreted unchanged in urine
SE= sedation, post-op delerium; increase HR (+), CO, IOP; OH; arrhythmias; blurry vision; decrease secretions (+++) & GI motility; urinary retention; central anti-cholinergic syndrome, bronchodilation (+)
CI= glaucoma, GI/GU obstruction; caution elderly
Dose= 0.3-0.6 mg IV q 4-6 hrs
MOA Benzodiazpines? 5 uses? Specific antagonist?
CLASS= benzodiazepine
MOA= potentiates binding of GABA to the GABA-A receptor facilitating the action of GABA- opens Cl- channels & increases Cl- conductance, hyperpolarizing the cell, decreasing neuronal transmission & making it more resistant to excitation
5 uses- anxiolysis, sedation, anterograde amnesia, muscle relaxation at the spinal level, anticonvulsants (no analgesia properties)
Specific antagonist- flumenazil
Midazolam
CLASS= benzodiazepine
MOA= potentiates binding of GABA to the GABA-A receptor facilitating the action of GABA- opens Cl- channels & increases Cl- conductance, hyperpolarizing the cell, decreasing neuronal transmission & making it more resistant to excitation
Pharmacokinetics= 94% (highly) PB, highly lipid soluble, large Vd (1-1.5L/kg); rapidly crosses BBB; comes as water soluble Imidazole ring- lipid soluble when injected; ONSET- 60-90 second, PEAK 3-5 min; DOA 15-80 min; hepatic metabolism by CYP450- excreted in urine; 1 active metabolite- 1-hydroxy-midazolam (1/2 as potent); E1/2= 1-4 hrs; redose in 5 min
SE= decrease CBF & CMRO2; does not produce isoelectric EEG; preserves cerebral response to CO2; CO2 response curve flattens; anticonvulsant and amnestic; decrease SVR & BP @ induction doses but no change in CO; CV stable; Depresses ventilation with induction dose or with opioids; depresses deglutition reflex; does not attenuate SNS response to DVL
CI= early pregnancy, glaucoma; decrease dose in hepatic impairment; increase sensitivity in old people; synergistic effect with opioids in respiratory depression; paradoxical excitement- rare
Dose= premed-1-2.5 mg IV (max 5mg); induction- 0.1-0.2mg/kg over 30-60 sec
Diazepam
CLASS= benzodiazepine
MOA= potentiates binding of GABA to the GABA-A receptor facilitating the action of GABA- opens Cl- channels & increases Cl- conductance, hyperpolarizing the cell, decreasing neuronal transmission & making it more resistant to excitation
Pharmacokinetics- highly PB, highly lipid soluble, large Vd; rapidly crosses BBB & placenta; hepatic conjugation by CYP450 & excreted in urine; rapidly absorbed in GI tract & rapid IV onset; 3 active metabolites- most active is desmethyldiazepam which lasts 48-96 hrs (hangover effect); E1/2= 21-37 hours; least potent of the benzos; pain on injection- propylene glycol
SE= DECREASE CBF, CMRO2, DOES NOT cause isoelectric EEG; preserves cerebral response to CO2; CO2 response curve flattens; DECREASE SVR, BP with induction dose but no change in CO; CV stable; Depresses ventilation with induction dose or with opioids; depresses deglutition reflex; does not attenuate SNS response to DVL
CI= pregnancy, glaucoma; decrease dose in renal/hepatic impairment; increase sensitivity in old people; synergistic effect with opioids in respiratory depression; paradoxical excitement-rare; Cimetidine prolongs clearance
Dose= premed- 0.2 mg/kg IV; 10-15 mg PO; induction- 0.5-1 mg/kg IV; anticonvulsant- 0.1mg/kg IV
Lorazepam
CLASS= benzodiazepine
MOA= potentiates binding of GABA to the GABA-A receptor facilitating the action of GABA- opens Cl- channels & increases Cl- conductance, hyperpolarizing the cell, decreasing neuronal transmission & making it more resistant to excitation
Pharmacokinetics= 80% (highly) PB, highly lipid soluble, large Vd; hepatic metabolism by CYP450 & 80% excreted unchanged in urine; 6 hours amnesia without sedation; most potent benzo; no active metabolites; lipid soluble- pain on injection- propylene glycol; does not alter NMB dose; SLOWER onset = 2 hours (limits usefulness); E1/2= 10-20 hours
SE= decrease CBF & CMRO2; DOES NOT produce isoelectric EEG; preserves cerebral response to CO2; does not flatten CO2 curve; decrease SVR, BP @ induction doses w/ no change in CO; Depresses ventilation with induction dose or with opioids; depresses deglutition reflex; does not attenuate SNS response to DVL
CI= glaucoma; increase sensitivity in old people; decrease dose in hepatic/renal impairment; synergistic effect with opioids in respiratory depression; paradoxical excitement- rare
Dose= premed- 1-4 mg IV; 50 mcg/kg PO
Propofol
Class? MOA? Pharmacokinetics? SE? CI? Dose?
CLASS=non-barbiturate induction agent; 2,6 di-isopropophenol
MOA= (1) discourages the dissociation of GABA from the GABA A receptor, prolonging the action- causing increase Cl- conductance- hyperpolarizing the cell & decreasing neuronal transmission; (2) ALSO inhibits glutamate at the NMDA receptor – both producing sedation & hypnosis
Pharmacokinetics= 90% PB; highly lipid soluble onset- rapid 30-60sec; DOA- short-2-8 min(terminated by rapid redistribution); Vd- 4L/kg; E1/2- 0.5-1.5 hrs; prepared with egg, soy & glycerol & has preservatives; conjugated in liver by CYP450 & excreted in the urine (<0.3% unchanged)- also extrahepatic metabolism (kidneys, lungs, intestinal mucosa); clearance exceeds HBF (not dependent on blood flow but enzymes); antiemetic & anti-pruritic @ low doses. Context sensitive 1/2 life infusion up to 8 hours is 40 minutes
SE= decreases CBF, CMRO2, ICP, & IOP- isoelectric EEG; myoclonus; Dose-dependent CV depression; decrease BP (25-40%), SVR, NO change in HR; apnea w/ induction dose- decrease RR & decrease ventilatory response to CO2; bronchodilation; pain on injection
CI= soy, egg allergy; decrease dose in elderly; caution in hypotension & hypovolemia (CV instability); caution in asthma & COPD w/ Na metabisulflate preservative (bronchoconstriction)
Dose= induction- 1-2.5 mg/kg IV; sedation- 25-100 mcg/kg/min IV; maintenance- 100-300 mcg/kg/min IV; (Anti-emetic-10-20mg IV)
Etomidate?
Class? MOA? Pharmacokinetics? SE? CI? Dose?
CLASS= carboxylated imidazole derivative
MOA= binds to GABA-A receptors & (1) increases affinity of GABA & also (2) mimics GABA at the GABA-A receptor site = increases Cl- conduction= hyperpolarizes cell= decreases neuronal transmission - producing sedation & hypnosis
Pharmacokinetics= 75% PB; lipid soluble; onset- rapid 30-60sec; DOA- short 5-15 min (terminated by rapid redistribution); Vd- 3L/kg; E1/2= 3-5 hrs; water soluble in solution & mixed w/ propylene glycol (burning on injection); liver hydrolysis & metabolism by plasmaesterases & excreted in urine (2%) & bile; _clearance dependent on HBF (_need HBF to clear drug, will be decreased clearance in time of decreased blood flow)
SE= decrease CBF, CMRO2, ICP, & CMRO2- can increase EEG- causing seizures;; NO change in BP, HR, SVR, CO- very cardiac stable; Potentiates NMB; 30-40% N/V; myoclonus; hiccups; adrenocorticoid suppression - may need cortisol replacement; pain on injection (reversible inhibition of 11- b-hydroxlyase and 11-a-hydroxylase)
CI= seizures, porphyria, Addison’s disease/adrenal insufficiency
Dose= induction- 0.3mg/kg; sedation- 5-8 mcg/kg/min; maintenance- 10 mcg/kg/min
Ketamine
Class? MOA? Pharmacokinetics? SE? CI? Dose?
CLASS=non-barbiturate induction agent; phencyclidine derivative
MOA= (1) blocks NMDA receptors to inhibit influx of Na+, Ca2+- inhibits the excitatory response of glutamate & produces a “dissociative state anesthesia” via depression of association areas of the brain (depresses cerebral cortex and thalamaus while increasing hippocampus); (1) analgesia effects by interacting with mu, kappa, delta & sigma receptors- (3) works on monoaminergic descending pain pathways & substance P in SC; (4) muscarinic (antagonist?) & (5) Ca++ channel antagonist
Pharmacokinetics= 12% (poor) PB; highly lipid soluble; onset- rapid 30-60sec; DOA= short 5-15min (short d/t redistribution); Vd- 3L/kg; E1/2- 2-3 hrs; acidic soluble & racemic mixture; metabolized by CYP450 to norketamine (active metabolite) then excreted in urine; clearance dependent on HBF
SE= increase CBF, ICP & CMRO2 & IOP; myoclonus, hallucinations & emergence delirium (can prevent with benzos); increase SNS stimulation = increase HR, SVR, BP; direct myocardial depressant (especially in critically ill patients that cannot surmount a SNS response); BRONCHODILATION (SNS); increase PVR; increase saliva production (laryngospasm risk), potentiates NMB’s
CI= psych disorders, head injury (increase ICP), eye injury, CAD, IHD, Systemic or pulmonary HTN
Dose= induction- 0.5-2 mg/kg IV; sedation 0.2-0.5 mg/kg IV; maintenance- 1-2 mg/kg/hr IV; 5-10 mg/kg IM/PR
Dexmedetomidine?
Class? MOA? Pharmacokinetics? SE? CI? Dose?
CLASS= highly selective central-acting alpha 2 adrenergic agonist; GA/TIVA adjunct (a2/a1 1620:1)
MOA= activates alpha 2 receptors- decrease SNS outflow & NE release causing sedation, anxiolysis, decrease neuroendocrine response; closely mimics sleep & causes analgesia by inhibiting substance P in SC (also locus ceruleus (hypnosis))
Pharmacokinetics= 90% PB; water soluble; Vd- 3L/kg; redistributes in 6 min; E1/2- 2-3 hrs- can build tolerance & dependence & has context sensitive ½ time- longer gtt on- longer it takes to metabolize; metabolized in the liver (rapid metabolism in liver by conjugaiton, n-methylation, hydroxylation) & excreted in urine & bile; antagonist- atipamezole
SE= decrease CBF but no change in CMRO2 & ICP; decrease BP, HR (most significant), SVR; minimal change in RR & small decrease in TV; depresses thermoregulation; decreases MAC/doses of other anesthetic agents. Attenuates CV resposne to noxious stimuli, no change in CO2 response
CI= Afib, HB, severe bradycardia, pts that cannot tolerate lower BP or HR
Dose= 1 mcg/kg over 15 min bolus then 0.2-1 mcg/kg/hr
Succinylcholine
CLASS= Depolarizing NMB; benzylisoquinolone
MOA= PARTIAL AGONIST- Binds to alpha subunits of nicotinic Ach receptors mimicking the action of ACh at the NMJ opening Ca++ channels & depolarizing the motor endplate; fasciculations then flaccid paralysis occurs; Channels stay open & membrane cannot respond to subsequent ACh; effect terminated when SCh diffuses away from the NMJ
Pharmacokinetics= water soluble; small Vd (0.2L/kg) & PB; onset- 30-60 sec; DOA- 8-15 min; E1/2- 2-4 min; rapidly hydrolyzed by plasmaesterases when diffuses away from the NMJ & excreted in the urine
SE= increase ICP, IOP, IGP; histamine release - decrease HR & BP, HYPERK+ (increae 0.5-1 mEq/L) (dysrhythmias); masseter spasm, myalgias, fasciculations, rhabdomyolysis, myoglobinuria, MH
CI= MH, renal patient with high K+, high K, peds unless emergency, caution asthma & COPD; atypical plasma esterase deficiency; muscles weakness like muscular dystrophy; sepsis, burn patients
Dose= laryngospasm-10-20 mg IV; RSI/intubation- 1-1.5 mg/kg; infusion- 2-4mg/min
NDMR MOA?
COMPETITIVE ANTAGNOIST- Competitively inhibit ACh binding at the post-junctional nicotinic receptors thereby preventing Ca++ channels from opening, thus no depolarization of the muscle cell membrane & no contraction
Atracurium
CLASS= intermediate acting benzyllisoquinoline NDMR (-curium)
pre and post NMJ AcH inhibition
MOA: Competitively inhibit ACh binding at the post-junctional nicotinic receptors thereby preventing Ca++ channels from opening, thus no depolarization of the muscle cell membrane & no contraction
Pharmacokinetics= water soluble; 80% PB; Vd: 0.2L/kg; onset- 2-3 min; DOA- 30-60 min; E1/2- 20 min; metabolized by ester hydrolysis 2/3 & Hofmann elimination 1/3 (temp & pH dependent) & excreted in the urine; has metabolite Laudanosine (can accumulate in RF & cause CNS problems like seizures- is a tertiary amine and can cross BBB)
SE= Histamine release; decrease BP (minimal) & increase HR; skin flushing (all related to histamine release); muscle weakness; NMB can be potentiated with IA’s, ketamine, some abx, lithium, LA’s, antiarrhythmics, Mg++
CI= conscious patient, hypersensitivity; caution with asthma, COPD, CAD, seizure hx, muscle weakness, myasthenia gravis (increase sensitivity); metabolite can accumulate with renal problems; prolonged action in acidosis & hypothermia
Dose= initial- 0.5 mg/kg IV; maintenance- 0.08 - 0.1 mg/kg q 20-45 min
Cisatracurium
CLASS= intermediate acting benzyllisoquinoline NDMR; (-curium) stereoisomer of Atracurium (A/C)
MOA: Competitively inhibit ACh binding at the post-junctional nicotinic receptors thereby preventing Ca++ channels from opening, thus no depolarization of the muscle cell membrane & no contraction
Pharmacokinetics= water soluble; Vd: 0.2L/kg; onset- 3-5 min; DOA- 30-60 min; E1/2- 30 min; metabolized 80% by Hofmann elimination (temp & pH dependent) & excreted in the urine; has metabolite Laudanosine 1/5 that of Atracurium (can accumulate in RF & cause CNS problems like seizures)
SE= NO histamine & CV stable; good choice if CV instability or severe renal dysfunction, asthma or COPD or peds (immature liver); muscle weakness; potentiated NMB with IA’s, ketamine, some abx (such as aminoglycosides), lithium, LA’s, antiarrhythmics, Mg++
CI= conscious patient, hypersensitivity; muscle weakness, myasthenia gravis (give 1/10th of dose), seizure hx; metabolite can accumulate with renal problems; prolonged action in acidosis & hypothermia
Dose= initial- 0.1-0.2 mg/kg IV; maintenance- 0.02 mg/kg IV q 40-60 min
Rocuronium
CLASS= short-intermediate acting steroid derivative NDMR
MOA: Competitively inhibit ACh binding at the post-junctional nicotinic receptors thereby preventing Ca++ channels from opening, thus no depolarization of the muscle cell membrane & no contraction
Pharmacokinetics= water soluble; Vd: 0.2L.kg; onset-30-60sec ; DOA- 30-90 min; E1/2- 2 hrs; hepatic metabolism with renal (30% unchanged) & biliary (50%) elimination (Prolonged effects in hepatic, renal, & biliary disease)
SE= NO histamine & CV stable; bronchospasm; muscle weakness; effects potentiated IA’s, ketamine, some abx, lithium, LA’s, antiarrhythmics, Mg++
CI= conscious patient, hypersensitivity, myasthenia gravis, caution muscle weakness; caution hepatic, renal, & biliary disease; hypothermia prolongs action
Dose= initial- 0.6-1.2 mg/kg (low = intubation; high = RSI); defasiculating- 0.06-0.1mg/kg (5-10 mg per lecture); maintenance- 0.1-0.2 mg/kg
Vecuronium
CLASS= intermediate acting steroid derivative NDMR
MOA: Competitively inhibit ACh binding at the post-junctional nicotinic receptors thereby preventing Ca++ channels from opening, thus no depolarization of the muscle cell membrane & no contraction
Pharmacokinetics= 80% PB; Vd: 0.2L/kg; onset-3-5 min; DOA- 30-60 min; E1/2- 1hr; hepatic metabolism with renal (30% unchanged) & biliary (50%) excretion (prolonged effects in hepatic, renal, & biliary disease); active metabolite= 3-desacetyl vecuronium (was called 3-OH in lecture) (50% as potent as parent)
SE= NO histamine & CV stable; bronchospasm; muscle weakness, can cause SA node exit block; NMB potentiated with IA’s, ketamine, some abx, lithium, LA’s, antiarrhythmics, Mg++
CI= conscious patient; hypersensitivity; myasthenia gravis, caution muscle weakness; caution hepatic, renal, & biliary disease; hypothermia prolongs action
Dose= initial- 0.1 mg/kg; defasiculating 0.01mg/kg IV; maintenance- 0.01-0.02mg/kg q 25-45 min
Pancuronium
CLASS= long acting steroid derivative NDMR
MOA: Competitively inhibit ACh binding at the post-junctional nicotinic receptors thereby preventing Ca++ channels from opening, thus no depolarization of the muscle cell membrane & no contraction
Pharmacokinetics= small PB; Vd: 0.2L/kg; onset- 3-5 min; DOA- 2-3 hours; E1/2- 2 hrs; 10-20% hepatic metabolism with renal excretion (80% unchanged); 3 active metabolites- most is the 3-desacetyl pancurounium (50% as potent as parent)- (aka 3-OH in lecture) prolonged excretion in renal, hepatic disease, elderly & obese
SE= SNS stimulation = increase HR, BP; bronchospasm; no histamine; muscle weakness, NMB potentiated with IA’s, ketamine, some abx, lithium, LA’s, antiarrhythmics, Mg++
CI= conscious patient, hypersensitivity, renal dysfunction; CAD, HF or HD, myasthenia gravis, caution muscle weakness
Dose= initial- 0.1 mg/kg; maintenance- 0.01-0.02 mg/kg q 40-60 min
Mivacurium
CLASS= short acting benzyllisoquinoline NDMR
MOA: : Competitively inhibit ACh binding at the post-junctional nicotinic receptors thereby preventing Ca++ channels from opening, thus no depolarization of the muscle cell membrane & no contraction
Pharmacokinetics= Vd: 0.2L/kg; onset- 1-2 min; DOA- 10-20 min; E1/2- 1hr; metabolized by plasma esterases & excreted (7% unchanged in the urine)- good for liver or renal failure
SE= HISTAMINE release, increase HR & DECREASE BP, bronchospasm, flushing; muscle weakness
CI= conscious patients, hypersensitivity, atypical plasma esterase deficiency, asthma, COPD; caution myasthenia gravis & muscle weakness; NMB potentiated with IA’s, ketamine, some abx, lithium, LA’s, antiarrhythmics, Mg++
Dose= initial- 0.2 mg/kg; maintenance- 0.01-0.1 mg/kg
Neostigmine
CLASS= quaternary ammonia acetylcholinesterase inhibitor (does not cross the BBB)
MOA= Covalently. binds to the carbamyl group at the esteric site on acetylcholinesterases inhibiting it, thus inhibiting the breakdown of ACh & increasing its availability at the motor end plate; used to antagonize the effects of the NMB; most reliable with a deep block
Pharmacokinetics= water soluble; Vd: 1L/kg; onset- 5-15 min; peak 7-10 min; DOA- 1 hr; E1/2- 70 min; metabolized by plasma & liver esterases 50% & excreted unchanged in the urine (50%)
SE= increase salivation, bronchoconstriction, decrease HR, BP, SVR; N/V; increase gastric secretions; seizures
CI= renal failure prolongs clearance, GI/GU obstruction, asthma, caution in CAD, prolongs effect os SUCCINYLCHOLINE d/t inhibiton of plasma esterases
Dose= 0.04-0.07 mg/kg with Glyco 0.01 mg/kg
Erdophonium
CLASS= quaternary ammonia acetylcholinesterase inhibitor (does not cross the BBB)
MOA= reversibe H+ binding to the acetylcholinesterases through an electrostatic attachment thereby inhibiting the breakdown of ACh & increasing its availability at the motor end plate; has less severe muscarinic effects. Fast onset than neostigmine and less effectiv ethan neostigmine. Not effective for deep block (need TOF 4/4 to work)
Pharmacokinetics= water soluble; Vd: 1L/kg; onset- fast; peak- 1-2 min; DOA- short @ 1 receptor, but leaves that receptor & occupies another until eliminated which prolongs the DOA (1hr); 25% hepatic metabolism & renal excretion 75% unchanged
SE= increases salivation, bronchoconstriction, decreases HR, BP, SVR; N/V; increase gastric secretions; seizures
CI= renal failure prolongs clearance, GI/GU obstruction, asthma, caution in CAD
Dose= 0.5-1 mg/kg; given with atropine (0.01 mg/kg)
Physostigmine
CLASS= tertiary amine (crosses BBB) acetylcholinesterase inhibitor;
MOA= Reversibly binds to the carbamyl group at the esteric site on acetylcholinesterases inhibiting it, thus inhibiting the breakdown of ACh & increases its availability at the motor end plate; can be used reversal of central anticholinergic syndrome. Not used for NMB reversal but used with central anticholinergic syndrome
Pharmacokinetics= lipid soluble & crosses BBB; onset- 5 min; DOA- 1-5 hrs; E1/2- 30 min; hydrolyzed by cholinesterases & minimal renal excretion
SE= increase salivation, bronchoconstriction, decrease HR, BP, SVR; N/V; increase gastric secretions; seizures; inhibits somnolent effects of benzos, ketamine, IA & opioids
CI= GI/GU obstruction, asthma, caution in CAD
Dose= 15-60 mcg/kg IV
Pyridostigmine
CLASS= quaternary ammonia acetylcholinesterase inhibitor (does not cross the BBB)
MOA= REVERSIBLY binds to the carbamyl group at the esteric site on acetylcholinesterases, inhibiting the breakdown of ACh & increase availability at the motor end plate; used to antagonize the effects of the NMB; can be given orally for myasthenia gravis. Not used for reversal of NMB because of long onset of action also a very weak anticholinesterase inhibior.
Pharmacokinetics= water soluble; Vd: 1L/kg; onset- 10 min; peak- 12 min; DOA- 1 hr; 25% hepatic metabolism & excreted in the urine 75% unchanged; not used often as reversal d/t its slow onset and low potency
SE= increase salivation, bronchoconstriction, decrease HR, BP, SVR; N/V; increase gastric secretions; seizures
CI= renal failure prolongs clearance, GI/GU obstruction, asthma, caution in CAD
Dose= 0.14-0.25 mg/kg; given with glyco (0.01 mg/kg)
Opioid MOA?
Activates Mu, Kappa & delta G protein coupled opioid receptors in the brain, spinal cord, & peripheral afferent neurons causing Ca2+ channel inactivation presynaptically to inhibit the release of excitatory NT’s such as Epi, NE & Substance P or post synapatically increase K+ conductance to hyperpolarize the cell & directly decrease neurotransmission; this increasing the pain threshold, alters pain perception & inhibits ascending pain pathways
Morphine
CLASS= Natural opioid agonist
MOA: Activates Mu, Kappa & delta G protein coupled opioid receptors in the brain, spinal cord, & peripheral afferent neurons causing Ca2+ channel inactivation presynaptically to inhibit the release of excitatory NT’s such as Epi, NE & Substance P or post synapatically increase K+ conductance to hyperpolarize the cell & directly decrease neurotransmission; this increasing the pain threshold, alters pain perception & inhibits ascending pain pathways
Pharmacokinetics= 30% PB; 23% non-ionized (pKa= 7.9); low lipid solubility; Vd: 3L/kg
- IV peak- 15-30 min; DOA- 3 hrs; E1/2- 3-4 hrs
- Hepatic & renal metabolism to morphine-3 glucoronide (less active) & morphine-6-glucoronide (active metabolite which is 650x more potent) & excreted in the urine (1-12% unchanged) & feces
SE= analgesia, euphoria, sedation, N/V/C, pruritus, dry mouth, urinary retention; SOO spasm; dose-dependent respiratory depression (decrease RR & increase TV), dose dependent decrease HR, BP, SVR more profound w/ HISTAMINE release; inhibits SA/AV node; delayed respiratory depression in epidural & spinals b/c not as lipid soluble
CI= allergy, respiratory depression, asthma, COPD; renal disease (metabolites can accumulate); synergistic hypnosis & respiratory depression w/ Benzo’s & other CNS depressants; decrease dose in peds & elderly
Dose= 0.01-0.2mg/kg – usually 2.5-15mg IV (in divided 1-4 mg doses q 5 min) Q 3-4 hours; infusion 0.8-10mg/hr
Meperidine
CLASS= phenyl-piperidine synthetic opioid agonist
MOA: Activates Mu, Kappa & delta G protein coupled opioid receptors in the brain, spinal cord, & peripheral afferent neurons causing Ca2+ channel inactivation presynaptically to inhibit the release of excitatory NT’s such as Epi, NE & Substance P or post synapatically increase K+ conductance to hyperpolarize the cell & directly decrease neurotransmission; this increasing the pain threshold, alters pain perception & inhibits ascending pain pathways
MOA cont.: anti-cholinergic effects (atropine-like structure), Alpha-2 agonist, blocks Na channels
Pharmacokinetics= 1/10th as potent as morphine. 60% PB; nonionized- 10% (pKa: 8.5); low lipid solubility; Vd: 4L/kg;
- Onset fast; peak 5-10min; DOA- 3 hrs; E1/2: 3-4hrs
- Liver metabolism to normeperdine (½ as potent as parent & can cause seizures & myoclonus) & excreted in the urine
- 65% pulmonary 1st pass effect
SE= analgesia, euphoria, sedation; N/V/C, pruritus, dry mouth, urinary retention; SOO spasm; dose dependent respiratory depression (increase RR & decrease__TV); dose dependent decrease BP & SVR more profound w/ HISTAMINE release, decrease shivering; sympathomimetic - increase HR & direct cardiac depressant
CI= allergy, respiratory depression, asthma, COPD; caution seizure hx, CAD; fatal interaction with MAOIs; decrease dose in renal disease (metabolites can accumulate); decrease dose in peds & elderly
Dose= 50-100 mg IV; 12.5mg for shivering (total dose should not exceed 1 gram/24 hrs)
Hydromorphone
CLASS= semi-synthetic opioid agonist that is derivative of morphine & 5x more potent than morphine
MOA: Activates Mu G protein coupled opioid receptors in the brain, spinal cord, & peripheral afferent neurons causing Ca2+ channel inactivation presynaptically to inhibit the release of excitatory NT’s such as Epi, NE & Substance P or post synapatically increase K+ conductance to hyperpolarize the cell & directly decrease neurotransmission; this increasing the pain threshold, alters pain perception & inhibits ascending pain pathways
Pharmacokinetics= 8-19% PB; onset <30 minutes ; peak- 5-10 min; DOA-2-4 hrs (longer); E1/2- 1-3 hrs; significant 1st pass metabolism in liver with 95% metabolized to Hydromorphone-3- glucuronide (inactive) & excreted in the urine
SE= analgesia, more sedation & less euphoria than Morphine; N/V/C, pruritus, dry mouth, urinary retention, SOO spasm; dose dependent respiratory depression (decrease RR & increase__TV); Dose dependent decrease HR, BP, SVR
CI= allergy, respiratory depression; synergistic hypnosis & respiratory depression w/ Benzo’s & other CNS depressants; decrease dose in peds & elderly; increased ICP without controlled ventilation
Dose= 1-4 mg IV q 4-6 hrs
Fentanyl
CLASS= Phenyl piperidine synthetic opioid agonist
MOA: Activates Mu G protein coupled opioid receptors in the brain, spinal cord, & peripheral afferent neurons causing Ca2+ channel inactivation presynaptically to inhibit the release of excitatory NT’s such as Epi, NE & Substance P or post synapatically increase K+ conductance to hyperpolarize the cell & directly decrease neurotransmission; this increasing the pain threshold, alters pain perception & inhibits ascending pain pathways
Pharmacokinetics= 100x more potent than MSO4 (morphine)
- 80% PB; non-ionized- <10% (pKa= 8.4); high lipid solubility; Vd-4L/kg
- Fast onset; peak- 6.4 min; short DOA- 1 hr; E1/2- 3-6 hrs;
- Liver metabolism (n-dealkylation & hydroxylation) that is dependent on HBF & excreted in the urine
- Weak active metabolite norfentanil
- 75% pulmonary 1st pass effect & Secondary peak
- Longer context sensitive ½ time with infusions
SE= analgesia, euphoria, sedation, N/V/C, pruritus, dry mouth, urinary retention; SOO spasm; dose-dependent respiratory depression (decrease RR & increase__TV), dose dependent decrease HR, BP, SVR; seizure like activity, muscle rigidity & wooden chest syndrome; blunts SNS response to DVL
CI= allergy, respiratory depression, caution in hepatic/renal disease, head trauma (increase ICP), gallbladder disease, bradyarrhythmias; synergistic hypnosis & respiratory depression w/ Benzo’s & other CNS depressants; decrease dose in peds & elderly
Dose= bolus- 1-2 mcg/kg (analgesia); 25-100mcg (pre-med); infusion- 0.01-0.05 mcg/kg/min
Sufentanil
Sufentanil- Phenyl-piperidine synthetic opioid agonist; most potent opioid
MOA: Activates Mu G protein coupled opioid receptors in the brain, spinal cord, & peripheral afferent neurons causing Ca2+ channel inactivation presynaptically to inhibit the release of excitatory NT’s such as Epi, NE & Substance P or post synapatically increase K+ conductance to hyperpolarize the cell & directly decrease neurotransmission; this increasing the pain threshold, alters pain perception & inhibits ascending pain pathways
Pharmacokinetics= 1000x more potent than morphine
- 90% PB; 20% non-ionized (pKa= 8.0) ; highest lipid solubility; Vd-3L/kg
- Fast onset; peak – 6.2 min; short DOA- 30 min; E1/2- 2.5 hr
- Liver & SI metabolism & excreted in urine
- Active metabolite desmethylsufentanil
- 75% pulmonary 1st pass effect & Secondary peak
SE= analgesia, euphoria, sedation, N/V/C, pruritus, dry mouth, urinary retention; SOO spasm; dose-dependent respiratory depression (decrease R__R & increase__TV), dose dependent decrease HR, BP, SVR; bronchospasm; seizure like activity, muscle rigidity & wooden chest syndrome; blunts SNS response to DVL
cyp 3a inhibitors may increase levels of sufentanil
CI= allergy, asthma, airway obstruction; caution in hepatic & renal dysfunction; synergistic hypnosis & respiratory depression w/ Benzos & other CNS depressants; decrease dose in peds & elderly
Dose= analgesia -0.1-1 mcg/kg; infusion- 0.0015-0.01mcg/kg/min
Alfentanil
CLASS= tetrazole fentanyl derivative; synthetic opioid agonist
MOA: Activates Mu G protein coupled opioid receptors in the brain, spinal cord, & peripheral afferent neurons causing Ca2+ channel inactivation presynaptically to inhibit the release of excitatory NT’s such as Epi, NE & Substance P or post synapatically increase K+ conductance to hyperpolarize the cell & directly decrease neurotransmission; this increasing the pain threshold, alters pain perception & inhibits ascending pain pathways
Pharmacokinetics= 90% PB; 90% non-ionized (pka 6.5); high lipid solubility; Vd- 0.4L/kg
- Onset- fastest; peak- 1.4 min; short DOA- 30-60 min; E1/2- 1.5hr
- Metabolized in the liver & SI & excreted in the urine
- Active metabolite norfentanil
- Context sensitive half time is 60 min for infusion up 8 hours (longer than sufentanil despite similar DOA)
SE= analgesia, euphoria, sedation, N/V/C, pruritus, dry mouth, urinary retention; SOO spasm; dose-dependent respiratory depression (decrease RR & increase TV), MINIMAL CHANGE in HR, BP, SVR; skeletal muscle rigidity, blunts SNS response to DVL
CI= allergy, respiratory depression, untreated Parkinson’s, increase ICP; synergistic hypnosis & respiratory depression w/ Benzo’s & other CNS depressants; decrease dose in peds & elderly
Dose= initial- 10-20 mcg/kg; infusion- 0.25-0.75 mcg/kg/min
Remifentanil
CLASS= phenyl-piperidine synthetic opioid agonist with ester link
MOA: Activates Mu G protein coupled opioid receptors in the brain, spinal cord, & peripheral afferent neurons causing Ca2+ channel inactivation presynaptically to inhibit the release of excitatory NT’s such as Epi, NE & Substance P or post synapatically increase K+ conductance to hyperpolarize the cell & directly decrease neurotransmission; this increasing the pain threshold, alters pain perception & inhibits ascending pain pathways
Pharmacokinetics= 80% PB; 65% non-ionized (pKa= 7.3); high lipid solubility; Vd- 0.4L/kg
- Onset 1-3 min; peak- 2 min; DOA- shortest 10 min; rapidly metabolized by tissue & plasma esterases
SE= analgesia, euphoria, sedation, N/V/C, pruritus, dry mouth, urinary retention; SOO spasm; dose-dependent respiratory depression (decrease RR & increase TV), dose dependent decrease HR, BP, SVR; skeletal muscle rigidity, blunts SNS to DVL
CI= allergy, respiratory depression; do not use in epidural/spinals (d/t glycine prep); need plan for post-op pain; synergistic hypnosis & respiratory depression w/ Benzo’s & other CNS depressants; decrease dose in peds & elderly
Dose= initial- 1-2 mcg/kg; infusion- 0.05-0.25 mcg/kg/min
Theory of MOA of IA?
- Unsure of MOA- myer-overton theory that states anesthetic molecules caused hydrophiobic region to expand beyond critical amount and distorting channels has been debunked. Current theories are:
- Presynaptic voltage gated Na channels
- 2-pore potassium chennels
- TREK and TASK channels
- Ionotropic and metabotropic receptors
- GABA, Glycine
- Glutamate (NMDA, AMPA, Kainate)
N2O
CLASS= inorganic gas with double bond b/t 2 N atoms
Pharmacokinetics= eliminated by exhalation, biotransformation with 0.004% hepatic metabolism;
- fast on & off b/c low BG coefficient;
- can be used for 2nd gas effect - increases concentration & uptake of other gases;
- potentiates NMB’s;
- DECREASES MAC of other gases;
- 34x more soluble than N2–> diffuses into hollow cavitiies
SE= odorless, sweet smell
- increase CBF, ICP, CMRO2 (couples!)
- SNS stimulation; direct myocardial depression; NO CHANGE/minimal increase in HR, BP, CO, SVR; increase PVR
- increase RR & decrease TV; no change in resting PaCO2; diffusion hypoxia (need O2 when d/c N2O!)
- decrease HBF; decrease RBF, GFR & UOP; post op N/V; bowel distention
- Inhibits B12 dependent enzymes responsible for myelin formation & DNA synthesis; BM suppression; can impair immune response to infection
- Analgesic properties
CI= PTX, air embolism, tympanic membrane surgery, eye surgery, intestinal obstruction/bowel surgery, intracranial air, pulmonary HTN, immunosuppressed pts, caution CAD, sepsis, epinephrine use (dysrhythmias)
Dose= VP- 39,000, BG- 0.47, MAC- 104, cannot be used as sole anesthetic
Isoflurane
CLASS= halogenated methyl ethyl ether; isomer of enf
Pharmacokinetics= pungent odor; eliminated by exhalation & biotransformation; hepatic metabolism <0.2-2%; potentiates NM blockade
SE=
- increase CBF, ICP, decrease CMRO2;(mainly mac>1)- effects reversed by hyperventilation; electrically silent EEg at 2 MAC; enhances CSF reabsorption
- decrease SVR, BP but CO maintained; increase HR (mild Beta stimulation); CA vasodilator- coronary steal (Not for CAD); BEST for patients going on bypass.
Anesthetic preconditioning- brief exposure to VA can activate K-ATP channels- hyperpolarizing effect which proects tissue to subsequent ischemic episodes. (hyperpolarizing decreases O2 requirement and makes cell tolerate lack of perf/reperfusion better)
- increase RR & decrease TV, bronchodilator; tachypnea less pronounced at 1 MAC compared to other agents; blunted response to hypoxia and hypercarbia; >1 MAC, decreases hypoxic vasoconstriction, which can be detrimental in single lung ventialtion
- decrease RBF, GFR & UOP; maintains HBF
CI= peds- pungent causing coughing, laryngospasm; MH; ½ MAC in CAD & Neuro anesthesia; caution transient increase HR & BP w/ rapid increase concentration
Dose= VP- 240, BG- 1.4, MAC- 1.2
Desflurane
CLASS= fluorinated methyl ethyl ether; structure similar to iso
Pharmacokinetics= pungent odor; uses Tec 6 vaporizer b/c VP is so close to atmospheric pressure; fast on & off; eliminated by exhalation & biotransformation; hepatic metabolism <0.1%; highest risk of CO formation from degradation by dried out CO2 absorbent
SE=
- increase CBF, ICP, decrease CMRO2;
- decrease BP, SVR, increase HR (SNS stimulation when [] increase rapidly); CO maintained
- increase RR & decrease TV; irritating to the AW can cause coughing, bucking & laryngospasm
- decrease RBF, GFR, UOP, decrease HBF
- Potentiates NMB’s
CI= MH, peds for inhalational induction, asthma, increase ICP, caution CAD; caution transient increase HR & BP w/ rapid increase concentration
Dose= VP- 669, BG- 0.42, MAC- 6
Sevoflurane
CLASS= fluorinated methyl isopropyl ether
Pharmacokinetics= ideal for peds- sweet & non-pungent with minimal AW irritation; expensive; fast on & of; eliminated via exhalation & biotransformation; hepatic metabolism 3-5%
SE=
- increase CBF, ICP, decrease CMRO2;
- SLIGHT decrease SVR, BP, CO, no change HR; no change in CVP
- increase RR & decrease TV; Bronchodilation
- decrease RBF, GFR, UOP; HBF maintained
- Compound A can form causing renal toxicity with low flows (keep flows at >2L)
- Potentiates NMB’s
CI= MH, severe renal disease
Dose= VP- 160, BG- 0.69, MAC- 2
Lidocaine
CLASS=amide LA (& Class IB antiarrhythmic – its active metabolite monoethyglycinexylidide blocks Na+ channels in cardiomyocytes,decrease AP duration & refractory period)
- LA MOA- bind to H-gate of Na channel and physically obstruct the channel
- keeps Na channel in closed/inactivated state and prevents further transmission AP (unionized portion diffuses across membrane, ionized portion blocks channel)
Pharmacokinetics=
- pKa- 7.9; non-ionized- 24%, PB- 70% (PB 50% for antiarrhythmic); low potency & low lipid solubility
- Fast onset & moderate DOA (1-2hr); E1/2- 1.5hr (antiarrhythmic- 1-8 hrs)
- Intrinsic vasodilator activity; uptake into the lungs
- CYP450 liver metabolism that depends on HBF & excreted in urine
- 2 active metabolites- xylidide & monoethylglycinexylidide
SE= TNS, high incidence of cauda equina syndrome (specfiically high concentraiton lidocaine); BLUNT SNS TO DVL
LA toxicity
5-10 mcg/ml: circumoral numbness, lightheadedness, tinnitus, skeletal muscle twitching, visual disturbances, systemic hypotension, myocardial depression, & tachycardia, decreased SVR & cardiac output.
10-15 mcg/ml: seizures, unconsciousness
15-25 mcg/ml: apnea, coma
>25 mcg/ml: cardiovascular depression/collapse
CI= methemoglobinemia
LA hypersensitivity to amide LA, coagulopathies, infection, hypovolemia, refusal, inability to cooperate inexperience of provider
Antiarrhythmic hypersensitivity; WPW syndrome, HB, hepatic disease; CYP450 inhibitors such as Cimetidine & Propranolol decrease metabolism
Dose=
MAX: 4mg/kg & with epi 7mg/kg;
Spinal MAX- 30-100mg (1-2mL) (1.5-5%)
Epidural: 15-30 ml of 1-2%
PNB- volume depends on location- 1-2%
Intubation to blunt DVL & antiarrhythmic- 1-2 mg/kg (max antiarrhythmic: 3mg/kg)
Bupivicaine
CLASS= amide LA
Pharmacokinetics=
- pKa- 8.1; non-ionized- 17%, PB- 95%; very potent & highly lipid soluble
- Moderate onset & long DOA (4-8hr); E1/2- 3.5hr
- CYP450 liver metabolism that depends on HBF
SE= differential blockade; TNS, “very low risk for neuro complications with spinal” (CB) ; highly CV toxic hypotension, myocardial depression, AV block, arrhythmias; local anesthestic toxicity (cirucmoral numbness, tinnitus, vision changes, dizziness, restlessness, muscle twitching in face/extremities–> seizures)–> CNS depression, apnea, hypotension).
CI= refusal, inability to cooperate, coagulopathies, hypovolemia, infection @ site; inexperience of clinician; extreme caution in poor CV function & HB
Dose=
- MAX- 2.5mg/kg
- Spinal MAX - spinal-15-20mg (0.5, 0.75%, 3-4 mL)
- Epidural- 15-30 ml of 0.125-0.5%
- PNB- amount depends on location- 0.25-0.5%
Ketorolac? Toradol?
CLASS= non-steroidal anti-inflammatory drug
MOA= blocks cyclooxygenase 1 & 2; inhibits prostaglandin synthesis causing anti-inflammatory effects & analgesia effects; also blocks synthesis of thromboxane A2 causing REVERSIBLE inhibition of platelet aggregation
Pharmacokinetics=99% PB; onset- 10 min; peak- 2-3 hrs; DOA 6-8 hours; E1/2- 5 hrs (prolonged to 6-8 hrs in elderly); liver conjugation &60% excreted unchanged in urine
SE=no respiratory or CV depression; impaired bone healing,increasebleeding time,GIB/ulcerations; bronchospasm (increaseleukotrienes), renal toxicity/ARF; black box- do not use peri-op in CABG, can causeincrease CV effects like MI & stroke; can inhibit platelet function
DDI’s= reduces effect of diuretics, beta blockers, & ACEI’s; increased risk of bleeding when combined with other anticoagulants; increases levels of other protein bound drugs such as Warfarin; AVOID with Probenecid =increases levels/prolongs action of Ketorolac
CI=asthma–> bronchospasm, ASA allergy, RF, liver failure, GIB, coagulation problems, 3rd trimester; NO post-CABG
Dose= 30 mg IV x 1 or q 6 hrs (max daily is 120mg)- do not give longer than 5 days; decrease dose in elderly to 15mg
Metoclopramide
CLASS= central dopamine receptor antagonist & serotonin-4 receptor agonist
MOA= blocks the DA2 receptors centrally in the CRTZ of the medulla preventing N/V; stimulates serotonin-4 receptors causing increase gastric motility & peristalsis; this is also accomplished by increase ACh @ the muscarinic post-synaptic receptors; increase LES tone & relaxation of pylorus & duodenum
Pharmacokinetics= 30-40% PB;; Vd 2-4L/kg; onset- 1-3 min; DOA- 1-2 hrs; E1/2- 2-4 hrs; metabolized in the liver & 40% excreted unchanged in the urine
SE= increase gastric motility, LES tone; decrease N/V; extrapyramidal SE, abdominal cramping (w/ rapid administration), sedation, prolactin secretion, dry mouth
DDI’s= potentiates sedation of CNS depressants; inhibits plasma cholinesterases thus may prolong Succinylcholine & Mivacurium , MAOIS, TCA, pt with EPS
CI= Parkinson’s, bowel obstruction, GI hemorrhage, seizure disorders, arrhythmias with Zofran; do not give with phenothiazines, MAOI, TCA, pt c EPS; pheochromocytoma
Dose= 10-20 mg IV over 3-5 min 15 min before induction
Ondansetron
CLASS= serotonin-3 receptor antagonist
MOA= blocks serotonin receptors peripherally on vagal nerve terminals in GI tract & centrally in the CRTZ
Pharmacokinetics= 70% PB; Vd 2-2.5 L/kg; onset- 30 min; DOA- 4-8 hrs; E1/2- 3-4 hrs; metabolized in the liver with renal excretion (5% unchanged)
SE= HA with rapid administration, fatigue, arrhythmias (w/ Reglan), constipation, diarrhea
CI= hypersensitivity, liver disease (decrease dose), SSRIs, Generally not recommended for treatment of existing chemotherapy-induced emesis or
for prophylaxis of nausea from agents with little potential to cause nausea
Dose= 4-8mg IV over 2-5 min
Famotidine
CLASS= selective competitive H2 receptor antagonist (MOST potent)
MOA: Competitively bind to H2 receptors, inhibiting the binding of histamine to gastric parietal cells, decrease cAMP & secretion of H+ ions, decrease gastric acid secretion from the parietal cells; can prevent Mendelsson syndrome or to treat GERD or ulcers; crosses BBB
Pharmacokinetics= 20% PB; onset- 30 min; DOA- 8 hrs; E1/2- 3 hrs; liver metabolism with 75% excreted unchanged in the kidneys; must be given IV d/t extensive first pass effect
SE= dMultisystem disease and advanced age increase severity of side effects. Diarrhea, HA, fatigue, skeletal muscle pain, confusion (crosses BBB), arrhythmias; rapid IV administration may cause bradycardia & hypotension (Give over 2 minutes for famotidine)
CI= caution liver/renal disease, hypersensitivity; may alter absorption of some drugs by increasing gastric pH
Dose= 20 mg IV over 2 min
Ranintadine?
CLASS= selective competitive H2 receptor antagonist
moa: Competitively bind to H2 receptors, inhibiting the binding of histamine to gastric parietal cells, decrease cAMP & secretion of H+ ions, decrease gastric acid secretion from the parietal cells; can prevent Mendelsson syndrome or to treat GERD or ulcers; crosses BBB
Pharmacokinetics= 15% PB, onset- 1 hr; E1/2- 2 hrs; 50% metabolized in the liver & 50% excreted unchanged in the kidneys; must be given IV d/t extensive first pass effect
SE= The frequency of severe side effects is low, and the risk of experiencing adverse side effects is increased by presence multiple medical illnesses, hepatic or renal dysfunction and advanced age..
HA, fatigue, dizziness, confusion, skeletal muscle pain, arrhythmias; rapid IV administration may cause bradycardia & hypotension
CI= caution in RF & liver disease; hypersensitivity; may alter absorption of some drugs by increasing gastric pH
Dose= 50 mg IV over 15-30 min preop; decreasein RF
Cimetidine?
CLASS= selective competitive H2 receptor antagonist (least potent)
MOA: Competitively bind to H2 receptors, inhibiting the binding of histamine to gastric parietal cells, DECREASE cAMP & secretion of H+ ions, decrease gastric acid secretion from the parietal cells; can prevent Mendelsson syndrome or to treat GERD or ulcers; crosses BBB
Pharmacokinetics= 20% PB; onset- 1 hr; DOA- 4 hrs; E1/2- 2 hrs; liver metabolism with CYP450 & 75% excreted unchanged in urine; must be given IV d/t large oral first pass effect
SE= delays awakening from GA in RF; decrease HBF- transient increase liver enzymes; HA, fatigue, dizziness, confusion, skeletal muscle pain, arrhythmias; rapid IV administration may cause bradycardia & hypotension
CI= caution in RF & liver disease, caution in asthma (may exacerbate bronchospasm with unopposed H1 bronchoconstriction)
DDI’s= Inhibits CYP450 = prolonged effect of warfarin, diazepam, Lidocaine, Propranolol, morphine, CCB, TCAs, Phenytoin; may alter absorption of some drugs by increasing gastric pH
Dose= 300 mg IV over 15-30 min; 1-2 hrs preop; decrease in RF
FUrosemide?
CLASS= loop diuretic
MOA= inhibits Na/2Cl/K pump in the thick ascending limb of loop of Henle causing excretion of H2O, Na+, Cl-, K+, Mg2+ & Ca2+; evokes renal production of prostaglandin; used for treatment of edema, hypercalcemia & differential diagnosis of oliguira
Pharmacokinetics= 90% PB; onset of diuresis- 5 min; DOA- 2 hours; E1/2- 1 hr; hepatic metabolism with 50% excreted by kidneys (glomerular filtration & renal tubular secretion) & 30% excreted unchanged in the bile
SE= hypotension, hyperglycemia, electrolyte imbalances = especially hypokalemia & hypochloremia, nephrotoxicity, ototoxicity, potentiates NMB, decrease clearance of lithium; possible cross reaction if have sulfa allergy
CI/Caution= fluid & electrolyte abnormalities (hyperK), can increase risk of nephrotoxicity or ototoxicity if administered with aminoglycosides & cephalosporins
Dose= 0.1-1 mg/kg IV; titrate & start with 5-40 mg IV
Mannitol
CLASS= osmotic diuretic (6 carbon hexose sugar)
MOA= increase osmolarity of the plasma drawing fluid into the intravascular space = causing increase UOP & diuresis; used to decrease ICP & IOP & differential diagnosis of oliguria
Pharmacokinetics= onset- 15 min; DOA- 3-6 hrs; E1/2- 1 hr; cleared by the kidney 100% unchanged- none is reabsorbed
SE= HA, convulsions, rash, blurry vision, pulmonary edema, hypovolemia, electrolyte imbalances; hypokalemic hypochloremic alkalosis; decrease ICP & IOP
CI= hypovolemia, severe kidney disease, CV dysfunction, intracranial bleeding
Dose= 0.25-1 g/kg over 30-60 min
Hydrochlorothiazide
CLASS= thiazide diuretic
MOA= inhibits the reabsorption of Na+ & Cl- in the ascending loop of Henle & DCT, thereby enhancing Na+ & H2O excretion; used for treatment of HTN usually in combo with ßB
Pharmacokinetics= 70% PB; onset- 2 hrs; DOA- 6-14 hrs; E1/2- 6-14 hrs; 100% excreted unchanged in the urine
SE= hypotension, rash, hyperglycemia, decrease K+ & Mg2+, electrolyte imbalances, potentiates NMB, nephropathy, increase digoxin toxicity, low ceiling effect
CI= renal failure, pregnancy, Antiarrhythmic agents that prolonged QTI causing torsades, decrease dose in elderly
Dose= 25-100 mg/day PO in 1-2 doses; max 200 mg
Dexamethason
CLASS= corticosteroid with ONLY glucocorticoid properties
MOA= enters the cell & binds to glucocorticoid & receptors in the cytoplasm forming a steroid-receptor complex that enters the nucleus & affects DNA transcription; Metabolically causes an increase nutrient availability by increase BG, amino acids, & Triglycerides; inhibits the inflammatory process by inhibiting phospholipase A2 = decrease arachnidonic acid = decrease inflammatory mediators such as leukotrienes, cytokines, & prostaglandins
ALSO- inhibits COX & Lipoxygenase pathways- may lead to analgesia effects; antiemetic property MOA unknown (poss. decrease prostaglandin, increase endorphins & appetite)
Good: Antiemetic, analgesia, periop airway edema, cerebral edema
Pharmacokinetics=DOA= 72hrs; E1/2- 3 hrs; liver metabolism with 30% excreted unchanged in the urine; antiemetic effect may last 24 hrs
SE= perineal burning, increase BG, HTN, HYPOK+; immunosuppression, HPA axis suppression, delayed wound healing, fat redistribution, muscle & bone wasting
CI= caution in DM, untreated infection, hypersensitivity
Dose= 4-10 mg IV
Hydrocortisone
CLASS=corticosteroid withequal glucocorticoid & mineralcorticoid properties
MOA= enters the cell & binds to glucocorticoid & mineralcorticoid receptors in the cytoplasm forming a steroid-receptor complex that enters the nucleus & affects DNA transcription; Metabolically causes an increase in nutrient availability by increase BG, amino acids, & Triglycerides; inhibits the inflammatory process by inhibiting phospholipase A2 = decrease arachnidonic acid = decrease inflammatory mediators such as leukotrienes, cytokines, & prostaglandins; decrease capillary membrane permeability; causes reflex Na+ & H2O retention with excretion of K+ in DCT
Pharmacokinetics= 90% PB; DOA- 8-36 hrs; E1/2- 1-2 hrs; liver metabolism (conjugated) & 30% excreted unchanged in the urine
SE=increaseBG,increaseNa+ & H2O retention,increase appetite, HTN, HYPOK+; immunosuppression, HPA axis suppression, delayed wound healing, fat redistribution, muscle & bone wasting
CI= caution in DM, untreated infection, hypersensitivity
Dose= Supplementation based on individual need and degree of surgery (multiple different mehodologies)- 100 mg IV q 6-8 hours for stress dose; Dosing depending on severity of surgery 25-150mg; 10-20mg/day average needed
Methylprednisolone
CLASS=corticosteroid withMORE glucocorticoid properties than mineralcorticoid properties
MOA= enters the cell & binds to glucocorticoid & mineralcorticoid receptors in the cytoplasm forming a steroid-receptor complex that enters the nucleus & affects DNA transcription; Metabolically causes an increase nutrient availability by increase BG, amino acids, & Triglycerides; inhibits the inflammatory process by inhibiting phospholipase A2 = decrease arachnidonic acid = decreaseinflammatory mediators such as leukotrienes, cytokines, & prostaglandins; decrease capillary membrane permeability; causes reflex Na+ & H2O retention with excretion of K+ in DCT
GOOD for SC injuries, joint inflammation
Pharmacokinetics= PB- 90%; DOA- 12-36 hrs; E1/2- 2-4 hrs; liver metabolism & 30% excreted unchanged in urine
SE= increase BG, increase Na+ & H2O retention, HTN, HYPOK+; immunosuppression, HPA axis suppression, delayed wound healing, fat redistribution, muscle & bone wasting
CI= caution in DM, untreated infection, hypersensitivity
Dose= 10-250 mg IV
Nitroglycerin
CLASS= organic nitrate
MOA= produces NO, which activates guanylate cyclase, increase cGMP inhibiting Ca2+ entry into cell & increase uptake of Ca2+ into the smooth ER causing peripheral & SM vasodilation; Dilates Venous> arterial to decrease preload with NO change in SVR & HR; increaseCA blood flow to ischemic areas; relaxes SM in GI tract and SOO
Pharmacokinetics= 60% PB; large Vd; onset- immediate; DOA- 5min; E1/2- 5 min; metabolized rapidly with nitrate metabolite that is capable of producing methemoglobin by oxidation of ferrous to ferric ion in Hgb with <1% excreted unchanged in the urine
SE= increase ICP; dizziness, HA, syncope, N/V, MI, decrease venous return, CA vasodilation, decrease hypoxic vasoconstriction; increase bleeding time,; relaxes SM & SOO spasm,; can cause tachyphylaxis (need nitrate free periods);
CI= do not use with PDIs; hypotension, hypertrophic cardiomyopathy, aortic stenosis, increase ICP, anemia, cardiac tamponade, caution in liver failure increase risk of methemoglobinemia,
Dose= initially 5-10 mcg/min & titrate to 5-200 mcg/min; 200 mg at a time for SOO spasm
Nitroprusside
CLASS= direct nonselective peripheral vasodilator
MOA= prodrug that interacts with oxyhemoglobin dissociates to methemoglobin, NO, & cyanide; NO activates guanylate cyclase, increase cGMP inhibiting Ca2+ entry into cell & increase uptake of Ca2+ into the smooth ER causing peripheral & SM vasodilation; equally dilates venous to ê preload & arteries to decrease afterload; reflex increase HR & contractility
Pharmacokinetics= onset- immediate; E1/2- 5 min; metabolism- transfer of an electron from iron to SNP yields methemoglobin & SNP radical- 5 cyanide ions released; 1 reacts with methemoglobin to form cyano-methemoglobin (nontoxic) & the rest are metabolized in the liver & kidney & converted to thiocyanate which is cleared by the kidney (slowly cleared- takes 2-7 days)
keep bag covered- light can conver SNP–> aquapentacyanoferrate and release hydrogen cyanide in the presence of light
SE= methemoglobinemia (higher risk with gtt >2mcg/kg/min), cyanide toxicity (s/s development is tachyphylaxis of drug), thiocyanate toxicity (causing seizures, & mental status changes), hypotension, tachycardia, increase bleeding time (plt inhib), increase ICP, Tachyphylaxis, hypoxia, lactic acidosis, decrease hypoxic vasoconstriction, CORONARY STEAL
CI= renal failure, hypotension, hypertrophic cardiomyopathy, aortic stenosis, increase ICP, caution CAD, don’t use with PDIs
Dose= 0.3-10 mcg/kg/min (maintain <2mcg/kg/min to reduce r/f toxicity) or 1-2 mcg/kg for HTN crisis bolus
Hydralazine
CLASS= vasodilator (vasodilator, more effective arteriole >venous)
MOA=from class—-vasodilation via activation of guanylate cyclae–> increases cGMP, decreases Ca entyr into cell. hyperpolarization–> SM relaxation. Direct vasodilating effect on vascular SM to decrease SVR (arteries> veins)
another way to say it…
activates guanylate cyclase causing increase cGMP directly dilating arterial > venous; membrane hyperpolarizes causing K+ channel activation & inhibition of IP3 & Ca2+ release from SR in vascular SM thereby decrease SVR & BP
Pharmacokinetics= 90% PB; onset- 15 min; DOA- 6 hrs; E1/2- 3 hrs; metabolized by the liver & excreted by the kidneys
SE= increase ICP, HA, reflex tachycardia, angina (decreae in DBP > SBP) ,SLE syndrome, Na&H20 retention, Tachyphylaxis
CI= use with caution in CAD (tachy might increase O2 demand, also DBP decreases > SBP), wait appropriate amount of time before redose or will get hypotensive
Dose= 5-20 mg IV q 4 hrs; 2.5-10 mg IV in OR
Transexamic Acid (TXA )
Class: Antifibrionlytic: lysine analog
MOA: Competitively inhibits plasminogen activation (binds to kringle domain in palce of lysine on plasminogen)
reduces plasmin concentrationa nd fibrinolytic activity; TXA directly inhibits plasmin at high doses
- Still examining exact MOA- Alternative hypothesis is that TXA improves survival via reduciton of proinflammatory plasmin activity
Pharmacokinetcis: 3% PB vd 9-12 L; 95% excreted unchanged (reduce dose in renal pts) Onset 5-15 min; DOA 3 HOURS. E1/2T: 2-11 Hours
S/E: Seizures (gaba blockade), vision changes, ureteral obstructionand bleeding, renal toxicity
C/I: (not given in lecture…) from pfizer website:
- In patients with subarachnoid hemorrhage. Anecdotal experience indicates that cerebral edema and cerebral infarction may be caused by CYKLOKAPRON in such patients.
- In patients with active intravascular clotting.
- In patients with hypersensitivity to tranexamic acid or any of the ingredients
DOSE: 1 gm in 100 cc NS over 10 min then 1 gm in 100 cc NS over 8 hours. Do not admin in same line as blood, VIIa, or PCN. Stored 15-30C
Nicardipine
