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Pharmacology #1 > Module C-1 IV Anesthetics > Flashcards

Module C-1 IV Anesthetics Flashcards

1
Q

Differences in Propofol storage

A

Diprivan- EDTA (preservative)-no problems

Generic- metabisulfate- bronchospasm?

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2
Q

GABA

A

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

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3
Q

Metabolism and clearance propofol

A

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)

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4
Q

Propofol induction

A

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

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5
Q

Propofol maintenance (TIVA)

A

Adults 100-300 mcg/kg/min

Significant antiemetic effect

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6
Q

Propofol dosing Conscious Sedation

Antiemetic/antipuritic dosing

A

Adult 25-100 mcg/kg/min. (This is ICU dosing lol)

10-15mg IV

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7
Q

Propofol CNS impact

A

Decreases CMRO2, CBF and ICP-maintains auto regulation

Minimal impact on evoked potentials

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8
Q

Propofol Cardiovascular response

A

Relaxation of vascular smooth muscle due to sympatholytic effect (not direct action on vasculature)

Negative inotropy

Exaggerated in hypovolemia, older adults, impaired left ventricle

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9
Q

Propofol lungs and kidneys

A

Apnea, decreased response to arterial hypoxemia

Little impact on liver/kidneys

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10
Q

Propofol. Allergies

A

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

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11
Q

Propofol infusion syndrome

A

Impaired fatty acid metabolism and mitochondria-rhabdo

Infusions greater than 24-48 hrs (high dose)

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12
Q

Etomidate- receptor and clinical use

Dosing

A

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

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13
Q

Etomidate downsides (four)

A

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

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14
Q

Etomidate CNS and Cardiac effects

A

Decreases CBF, CMRO2, ICP

-small sympatholytic effect preserves BP
Unmasking effect- Pts with exaggerated sympathetic tone (severe hypovolemia) may see worsened hypotension

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15
Q

Acute intermittent porphyria

A

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

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16
Q

Ketamine- in general

A

Dissociative Anesthesia-catatonic state

Minimal cardiac/pulmonary effects

Airway reflexes preserved

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17
Q

Ketamine MOA

A

NMDA receptor Antagonist- antagonizes an excitatory pathway

Normally NMDA or glutamate displace Mg in ion pore making it permeable to Ca or Na

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18
Q

Ketamine- Cardiac/Pulmonary and analgesia

A

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)

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19
Q

Ketamine dosing

A

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

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20
Q

Ketamine Elimination

A

Elimination half life is 2-3 hours- dependent on hepatic blood flow (high extraction) with an active metabolite

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21
Q

Ketamine Clinical uses

A

Shock/ LV dysfunction

Bronchospasm

Maintenance of spontaneous ventilation

Opioid sparing- multimodal

Analgesia in chronic pain 5-120 mcg/kg/min

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22
Q

Ketamine CNS

A

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

23
Q

Ketamine Eye sx

A

Increased IOP and nystagmus (increased muscle tone)

24
Q

Methohexital

A

Currently used in ECT due to lowering of the seizure threshold

25
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
26
Benzodiazepines MOA
Subset of GABAa receptors (alpha subunits) Enhances GABA with ceiling effect Not induction agent
27
Benzo kinetics
This is how they are classified (elimination half lives) Long onset- 10 minutes (stacking doses will lead to oversedation)
28
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
29
Lorazepam
Moderate acting (T 1/2= 6-24 hrs) Less dependent on hepatic cytochrome enzymes than diazepam
30
Midazolam
Short Acting (<6hrs) More rapid metabolism via hepatic cytochrome enzymes
31
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
32
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
33
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
34
Dex Kinetics
Elimination half-life 2 hours Context sensitive halftime- 25-120 min after 1 hour infusion and 87-120 min for >6hrs
35
Dex clinical uses
Maintaining respiratory drive/easily arousable No Amnesia!! Concomitant with volatile anesthetics decreases MAC and dose requirements in TIVA Decreases emergence delirium
36
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
37
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
38
Dex miscellaneous lol
Antisialagogue Mild diuretic effect
39
Pharmacokinetic similarities btw IV Anesthetics
Large Vd > 0.7 Highly protein bound (except ketamine) Elimination half-life=half life
40
Propofol MOA
GABA Agonist- B2 subunit Directly activates receptor and potentiates GABA mediated responses 10-15 min for redistribution
41
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
42
Etomidate Metabolism
Hydrolysis via hepatic microsomal enzymes- renal excretion- no active metabolite
43
Adrenocorticoid Suppression Etomidate
11-B-hydroxylase inhibition prevents conversion of cholesterol to cortisol and aldosterone Problematic in patients reliant on intrinsic stress response
44
Barbituate metabolism and elimination
Hepatic Long elimination half-life (hangover effect) and Long context sensitive halftime due to zero order kinetics at high doses
45
What causes histamine release??
Thiopental which we don’t fucking use Leads to bronchoconstriction and hypotension
46
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)
47
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
48
Dex metabolism/elimination
Hepatic, CYP450 Sensitive to hepatic impairment VARIABLE context sensitive halftime
49
Dex dosing
0.5 mcg/kg over 15. Min (probably longer) 0.3-0.7 mcg/kg/hr
50
Scopolamine
Anti cholinergic Lipid soluble (BBB) Acts on Reticular Activating System-sedation and some amnesia Little hemodynamic impact 0.2mg?
51
Dex loading and infusion
1mcg/kg over 10-15 min 0.4-0.7 mcg/kg/hr
52
Which IV anesthetics have active metabolite
Ketamine-norketamine 1/3 potency Midazolam- 1-hydroxymidazolam 0.5x potency
53
Drugs to avoid in acute intermittent porphyria
Barbiturates Etomidate Ketamine

Pharmacology #1 (15 decks)

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