Module C-1 IV Anesthetics Flashcards
Differences in Propofol storage
Diprivan- EDTA (preservative)-no problems
Generic- metabisulfate- bronchospasm?
GABA
Primary inhibitory neurotransmitter in brain
Binds GABA receptors on ligand-gated ion channel- causing chloride to flow into the cell and hyper polarizing the postsynaptic cell membrane
Metabolism and clearance propofol
Clearance exceeds hepatic blood flow
Hepatic oxidative (CYP) metabolism is rapid
Extrahepatic elimination via lungs
Elimination halftime 0.5-1.5 (4-5 half-lives to eliminate)
Propofol induction
Adults 1.5-2.5 mg/kg
Pediatric higher doses per kg of body weight
Elderly 25-50% decrease in dose- decreased clearance and smaller central compartment
Propofol maintenance (TIVA)
Adults 100-300 mcg/kg/min
Significant antiemetic effect
Propofol dosing Conscious Sedation
Antiemetic/antipuritic dosing
Adult 25-100 mcg/kg/min. (This is ICU dosing lol)
10-15mg IV
Propofol CNS impact
Decreases CMRO2, CBF and ICP-maintains auto regulation
Minimal impact on evoked potentials
Propofol Cardiovascular response
Relaxation of vascular smooth muscle due to sympatholytic effect (not direct action on vasculature)
Negative inotropy
Exaggerated in hypovolemia, older adults, impaired left ventricle
Propofol lungs and kidneys
Apnea, decreased response to arterial hypoxemia
Little impact on liver/kidneys
Propofol. Allergies
Most people are allergic to egg whites
Lipid is egg yolk- if hx of anaphylaxis there is a theoretical risk
No documented rxns to soy-highly refined lipid emulsion with proteins removed
Current recommendation is that this is not a contraindication
Propofol infusion syndrome
Impaired fatty acid metabolism and mitochondria-rhabdo
Infusions greater than 24-48 hrs (high dose)
Etomidate- receptor and clinical use
Dosing
GABA receptor modulation (highest selectivity of all agents)
High lipid solubility and Vd like propofol
Cardiovascular instability- LV dysfunction or shock
Pt we want to avoid hypotension- impacts on cerebral pp/ ESRD
Induction- 0.2-0.4 mg/kg IV bolus
Etomidate downsides (four)
Myoclonus- common, pretreat with like any drug
Inhibits 11 B-hydroxylase (required for adrenal hormone synthesis)
-cortisol levels suppressed for 8-24 hrs
PONV
Contraindicated in AIP
Etomidate CNS and Cardiac effects
Decreases CBF, CMRO2, ICP
-small sympatholytic effect preserves BP
Unmasking effect- Pts with exaggerated sympathetic tone (severe hypovolemia) may see worsened hypotension
Acute intermittent porphyria
Alterations in heme biosynthesis resulting in accumulation of heme precursors in tissue
ALA-synthetase induction accelerates precursor synthesis-Etomidate induces this enzyme
Symptoms- abd pain, vomiting, seizures, AMS, HTN tachy
-Propofol and all inhaled anesthetics are safe
Ketamine- in general
Dissociative Anesthesia-catatonic state
Minimal cardiac/pulmonary effects
Airway reflexes preserved
Ketamine MOA
NMDA receptor Antagonist- antagonizes an excitatory pathway
Normally NMDA or glutamate displace Mg in ion pore making it permeable to Ca or Na
Ketamine- Cardiac/Pulmonary and analgesia
Preservation of CO (B1 agonism) and BP
-maintenance/increase of sympathetic tone in patients with normal catecholamine stores
Bronchodilation (B-2 agonism)
affects opioid receptors (mu and kappa)
Ketamine dosing
IV Induction 2-2.5 mg/kg (3-5 min for full effect)
IM 4-6mg/kg 5-15 min for onset of anesthesia
Oral- high first pass in Liver 10 mg/kg
Ketamine Elimination
Elimination half life is 2-3 hours- dependent on hepatic blood flow (high extraction) with an active metabolite
Ketamine Clinical uses
Shock/ LV dysfunction
Bronchospasm
Maintenance of spontaneous ventilation
Opioid sparing- multimodal
Analgesia in chronic pain 5-120 mcg/kg/min
Ketamine CNS
CBF, CMRO2, ICP increased- most likely safe if controlling paCO2 with ventilation
No impact on evoked potentials
Emergence delirium- co-administer benzos/prop. Less likely with a lose dose infusion
Ketamine Eye sx
Increased IOP and nystagmus (increased muscle tone)
Methohexital
Currently used in ECT due to lowering of the seizure threshold
Barbituate MOA & and organ impact
GABA receptors modulation
Antagonism of glutamate at AMPA receptors (excitatory pathway)
CNS depression
Venodilation-decreased CO
Suppresses ventilation
Contraindicated in AIP
Benzodiazepines MOA
Subset of GABAa receptors (alpha subunits)
Enhances GABA with ceiling effect
Not induction agent
Benzo kinetics
This is how they are classified (elimination half lives)
Long onset- 10 minutes (stacking doses will lead to oversedation)
Diazepam
Longest actin (t1/2>24hrs)
Large Vd and stays in peripheral tissues
Many active metabolites
Almost entirely hepatic metabolism
Linear relationship with age- as you age the half-life gets longer
Lorazepam
Moderate acting (T 1/2= 6-24 hrs)
Less dependent on hepatic cytochrome enzymes than diazepam
Midazolam
Short Acting (<6hrs)
More rapid metabolism via hepatic cytochrome enzymes
Benzo clinical uses
Oral use in pediatrics-20-30min peak effect
Anterograde amnesia!! Don’t form NEW memories- not reliable at the lower doses
Anxiolysis
Pre-induction agent
Muscle spasms
restless leg- clonazepam
Benzo reversal
Flumazenil- can precipitate seizures in Benzo dependent patients
Half life <1 hr and should be monitored for re-sedation
0.2mg, titrate slowly- don’t exceed 1mg
Dexmedetomidine MOA
Alpha2 agonists in CNS- these receptors are GPCRs- when activated inhibit Ca channels and activate K channels- hyperpolarizes the cell and causes reduced NE release
Dex Kinetics
Elimination half-life 2 hours
Context sensitive halftime- 25-120 min after 1 hour infusion and 87-120 min for >6hrs
Dex clinical uses
Maintaining respiratory drive/easily arousable
No Amnesia!!
Concomitant with volatile anesthetics
decreases MAC and dose requirements in TIVA
Decreases emergence delirium
Dex CNS
Mimics natural sleep- UNLIKE GABA agonists
OK in evoked potentials
Decrease in CBF, no change in CMRO2
Antishivering/blunted response to surgical stress
Analgesic effects
Dex Cardiovascular
Hypotension due to vasodilation- pronounced in pts with high sympathetic tone (hypovolemia)
Bradycardia- dangerous in AV II or III blocks
Transient HTN in loading dose- due to direct efffects on peripheral alpha receptors
Dex miscellaneous lol
Antisialagogue
Mild diuretic effect
Pharmacokinetic similarities btw IV Anesthetics
Large Vd > 0.7
Highly protein bound (except ketamine)
Elimination half-life=half life
Propofol MOA
GABA Agonist- B2 subunit
Directly activates receptor and potentiates GABA mediated responses
10-15 min for redistribution
Propofol Generic vs Diprivan & Fospropofol
Diprivan- bronchodilation (EDTA)
Generic- Bronchospasm due to preservative metabisulfate- avoid in asthmatics
Fospropofol- not approved as a replacement
-PK is not as good as
Etomidate Metabolism
Hydrolysis via hepatic microsomal enzymes- renal excretion- no active metabolite
Adrenocorticoid Suppression Etomidate
11-B-hydroxylase inhibition prevents conversion of cholesterol to cortisol and aldosterone
Problematic in patients reliant on intrinsic stress response
Barbituate metabolism and elimination
Hepatic
Long elimination half-life (hangover effect) and Long context sensitive halftime due to zero order kinetics at high doses
What causes histamine release??
Thiopental which we don’t fucking use
Leads to bronchoconstriction and hypotension
Subclasses of alpha receptors
Alpha 1- vasoconstriction drug target
-Post synaptic nerve fiber
Alpha 2- CNS and PNS
-Pre and Post synapse Sites
-Presynaptic activation inhibits NE release (negative feedback)
Dex effect site location
Locus Coeruleus- Brain-highest density a2 receptors in the CNS
Activation reduces arousal and sympathetic outflow
Spinal cord- modulates nociceptive input- potentially reduced glutamate release
Dex metabolism/elimination
Hepatic, CYP450
Sensitive to hepatic impairment
VARIABLE context sensitive halftime
Dex dosing
0.5 mcg/kg over 15. Min (probably longer)
0.3-0.7 mcg/kg/hr
Scopolamine
Anti cholinergic
Lipid soluble (BBB)
Acts on Reticular Activating System-sedation and some amnesia
Little hemodynamic impact
0.2mg?
Dex loading and infusion
1mcg/kg over 10-15 min
0.4-0.7 mcg/kg/hr
Which IV anesthetics have active metabolite
Ketamine-norketamine 1/3 potency
Midazolam- 1-hydroxymidazolam 0.5x potency
Drugs to avoid in acute intermittent porphyria
Barbiturates
Etomidate
Ketamine
