sedative/ hypnotics Flashcards

Question 1

Q

Etomidate

Answer

A

IV general anesthetic
ultra short acting non barbiturate hypnotic

MAO;

selectively binds to GABA receptors and
increases the affinity of GABA to GABA receptors
this increases chloride conduction and hyper-polarizes the cell producing hypnosis
GABA is an inhibitory NT
causing increased chloride conductance which hyper- polarizes the cell and casques hypnosis
enhances NMDR activity

Uses

induction and maintenance of anesthesia
used for hemodynamically unstable patients and patients with poor CV function
used in hemodynamically unstable pt with neuro pathology; decreases CRMO2, CBF, ICP, and IOP

**no analgesic properties

Induction dose; 0.3 mg/kg
*loses CV protective properties over 0.3 mg/kg
Maintenance; 5 - 20 mcg/kg/ min
*10 mcg/kg/min with N20 or opioid

Pharmacokinetics;
Onset; rapid 
*penetrates the brain within 1 min
Peak; 1 min
E1/2time; 3 - 5 hours 
DOA; 5 - 10 min
Protein Binding; 75%
Large Vd; 3.5 L/kg 
Redistribution; 30 min
*terminated by redistribution
Highly lipid soluble

Metabolism
-Liver; hydrolysis by hepatic enzymes and plasma esterases
hepatic extraction ration >7
[[decreased liver blood flow will prolong effects]]

Elimination

85% kidney
13% biliary
2% unchanged

Side Effects;

minimal CV effects
ADDRENAL SUPPRESSION
myoclonus
burns on injection (propylene glycol)
N/V
decreases CBF, ICP, CMR02 but increases EEG activity
decrease TV increase RR

Contraindicated;

PORPHYRIA
seizures
Liver disease; decrease dose
caution;
in pt with decreased cortisol levels
pt with hx of PONV

Question 2

Q

Dexmedetomidine

Answer

A

Highly Selective Alpha 2 agonist
sedative/ hypnotic

MOA; selectively binds to central and peripheral alpha 2 adrenergic receptor and activates it;

decreased SNS outflow from brain; sedation, analgesia, anxiolytics
increases K conductance, inhibits release of NE; lowers BP and HR

Dose; 1 mcg/kg over 10 min
then infusion of ; 0.2 - 1 mcg/kg/min

Atipamezole; Antagonist

Uses;

sedation, analgesia, anxiety without Resp. Depression
mimics sleep
sedation of NON-intubated pt
attenuates hemodynamic response with intubation
decreases neuroendocrine respsone
decreases MAC of other anesthetics
prevents shivering
prevents emergence delirium

Pharmacokinetics;

onset; < 5 min
peak; 30 min
E1/2 time; 2 - 3 hours
DOA; 2 hours
Protein Binding; 90%

Metabolism; rapid
conjugated by the liver
-n-methylation
-hydroxylation

Elimination; metabolites cleared in urine

*weakly inhibits CYP450 (interferes with clearance of opioids)

Side Effects;

Heart Block, Bradycardia, A-fib, asystole
Decreased HR, BP and SVR
Decreases SNS response
Decreases CBF
decreases TV; minimal effects on RR
transient increase in BP with bolus dose
masks shivering (decrease in thermoregulation)

Contraindicated;
-potentiates effects of sedatives, opioids, IA, ketamine

-caution with vasodilators r/t CV effects

Question 3

Q

Propofol

Answer

A

2,6 di-iso-propophenyl

induction and maintenance of general anesthesia
IV sedative
antiemetic
anticonvulsant
antipyretic
cerebral protective; decreases ICP

MOA;

decreases dissociation of GABA from GABA receptors
increases chloride conductance, hyper-polarizes the cell; produces sedative/ hypnotic effects

2nd MOA;
-inhibits glutamate action at NMDA receptor

Uses;

GA induction
sedation
antiemetic
anticonvulsant
antipyretic
antioxidant; cerebral protective;
decreases ICP and IOP
attenuante bronchoconstriction

Dose; 
induction; 1 - 2.5mg/kg 
maintenance; 100 - 300 mcg/kg/min
sedation; 25 - 100 mcg/kg/min
Antiemetic; 10 -20 mg

Pharmacokinetics;
onset; 30 seconds 
E1/2 time; 30 - 90 min
DOA; 5-15 min
Highly lipid soluble 
Vd; 4 L/kg

Redistribution; 2 - 8 minutes
*causes wake up

metabolism; conjugated in liver to glucuronide and sulfate by CYP450 to water soluble compounds

*active metabolite;
4-hydroxypropofol; 1/3 the potency

eliminated by kidneys
<3%. excreted unchanged

Side Effects;

bradycardia
decreased BP (BP decreased by 25 -40%)
decreased SVR
decrease SV
dose dependent myocardial depression
bronchodilation (diprivan version)
HPV (hypoxic pulmonary vasoconstriction) remains intact
decreased ventilatory response to increased C02 & decreased 02
apnea
cerebral. protection; decreased ICP, CMR02, CBF, IOP, isoelectric EEG
myoclonus
pain on injection (propylene glycol)

sodium bisulfate version can cause bronchospasm

Contraindication

allergy to soy or egg
hypovolemic
decrease dose in elderly
caution and decrease dose in myocardial dysfunction

caution in hypotension and bradycardia

Question 4

Q

Ketamine

Answer

A

induction agent
phencyclidine derivative (like PCP)
provides sedative and analgesia

MOA; NMDA receptor blocker
-decreases influx of Na, Ca and glutamate

antimuscarinic side effects
analgesia and amnesia effects from Mu, Delta, Kappa and Sigma @ sub anesthetic doses
dissociative effect; (thalamocort/limbic)
inhibits neuronal Na channels (LA action) and Ca channels (cerebral vasodilation)

Dose;
sedation; 0.2 - 0.5 mg/kg
induction; 0.5 - 2 mg/kg
infusion; 1 - 2 mg/kg/hr

Question 5

Q

Ketamine

Answer

A

induction agent
phencyclidine derivative (like PCP)
provides sedative and analgesia

MOA; NMDA receptor blocker

decreases influx of Na, Ca and glutamate
SNS stim; inhibits reuptake of NE
antimuscarinic side effects
analgesia and amnesia effects from Mu, Delta, Kappa and Sigma @ sub anesthetic doses
dissociative effect; (thalamocort/limbic)
inhibits neuronal Na channels (LA action) and Ca channels (cerebral vasodilation)

Uses;

IV induction agent
sedation, analgesia, amnesia
asthma

Dose;
sedation; 0.2 - 0.5 mg/kg
induction; 0.5 - 2 mg/kg
infusion; 1 - 2 mg/kg/hr

pharmacokinetics;
onset; <1 min
peak; 1 min
E1/2t; 2 - 3 hrs 
DOA; 15 min
Protein Binding; 12%
Vd;  3L/kg

Highly lipid soluble; crosses BBB

metabolism; in liver by CYP450 to norketamaine

hydroxylation of norketamine; excreted in urine
1st pass effect with PO and Intranasal
metabolism changed by hepatic blood flow
active metabolite norketamine (30% as potent)

Side Effects;

direct myocardial depressant
inhibits reuptake of NE; causing intense SNS stim (increased HR and BP)
increased ICP, IOP, CMR02, and seizure like activity
hallucinations
emergence delirium (out of body experience)
increases salivation –> laryngospasm
bronchodilation from SNS stim
myoclonus
nystagmus

Contraindications;

head injury (ketamines causes increased ICP)
psych drugs and PTSD
MAOI and TCAs
phenochromocytoma

caution; in CAD

enhances effects of NMBD
apnea time after Succinylcholine can be prolonged

Question 6

Q

Clonidine

Answer

A

partial central alpha 2 agonist

Uses;

HTN
Tx of drug withdrawal symptoms
Analgesia
anesthesia pre-med (blunts SNS response, decreases catecholamine release, decreases anesthetic requirements)
prolongs anesthesia action of LA
post-op shivering

MOA:

selective alpha 2 agonist; blocks SNS outflow from the brain (sedation) and increases K conductance hyper polarizing the cell blocking release of NE and causing a decrease HR, contractility and decrees vasomotor tone
anti-nociceptive by blocking release of substance P in the spinal cord
treats drug withdrawal by blocks excessive SNS activity (block release of NE)
stop shivering by increases shivering threshold by blocking central thermoregulatory control

Dose; 0.2 - 0.3 mg/day

Pharmacokinetics;
PO clonidine 
-onset; 30 - 60 min
-Peak; 60 - 90 min 
-E1/2t; 9 - 12 hrs
-DOA; 8 hrs
-Vd; 2L/kg
-Pb; 20 - 40%

50 % Metabolized by the liver and 50% excreted unchanged in urine

Side Effects;

postural hypotension
bradycardia
heart failure
sedation
dry mouth
rebound hypertension with abrupt withdrawal

Contraindications

hypersensitivity
Do NOT hold clonidine before surgery
Do decease anesthetics dosing (50%)

Risk of Rebound HTN;
dose > 1.2 mg/day
seen within 18 hrs of last dose 
lasts 24 - 72 hrs 
give clonidine
tx HTN crisis with hydralazine or SNP

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sedative/ hypnotics Flashcards

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