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N926 Pharmacology > Induction Agents > Flashcards

Induction Agents Flashcards

1
Q

Ideal Anesthetic Properties

A 
Water-soluble
Minimal cardiovascular or respiratory depression
Lack toxicity or histamine release (hypersensitivity reactions)
Rapid & smooth onset
Rapid & smooth recovery
Quick return to baseline mental status
Rapid metabolism
Steep dose-response curve
Analgesia
Anti-emetic action
Bronchodilation
Advantageous PK & PD
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2
Q

Propofol

A

Insoluble - requires lipid vehicle to emulsify
Supports bacterial growth
Not chiral
Pain on injection d/t phenol
No antagonist (married to the effects)
Rapid return to consciousness w/ minimal residual SE

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3
Q

Diprivan

A

pH 7-8.5
pKa 11
0.05% EDTA (ethylenediaminetetraacetic acid)

Propofol pH 4.5-6.4
pKa 11
0.025% sodium metabisulfite or benzyl alcohol

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4
Q

Propofol MOA

A

Selective GABA receptor modulator
GABA = inhibitory transmitter in CNS
Influx Cl¯ ions into cell resulting in cell hyperpolarization
Spinal motor neuron excitability not altered

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5
Q

Propofol PK

A

Clearances exceeds hepatic blood flow
1st pass pulmonary uptake
Extensive hepatic metabolism CYP450
Active metabolite 4-hydroxypropofol
Context sensitive half-time infusion <40min
NOT influenced by hepatic or renal dysfunction
↓ plasma clearance rate in patients older than 60
Binds reversibly to erythrocytes & plasma proteins, plasma albumin, free
Increase free fraction seen in severe hepatic/renal disease & pregnancy

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6
Q

Propofol PD

A

Rapid & pleasant loss & return to consciousness
Myoclonus induced secondary to disinhibition subcortical centers (less than etomidate)
Neuro protectant
Mild to moderate ↓ BP secondary to ↓ sympathetic tone & vasodilation & CNS, cardiac, & baroreceptor depression
Respiratory depression common in induction doses
Minimal bronchodilation

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7
Q

Propofol Induction

A

1.5-2.5mg/kg
Effects exaggerated w/ CV disease
↓ dose in elderly
↑ dose in pediatrics

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8
Q

Propofol Infusion

A

IV sedation 25-100mcg/kg/min
Prompt recovery w/out residual sedation (endoscopy)
Minimal/no analgesic properties
Used in conjunction w/ anxiolytic & opioid

Anesthesia maintenance
100-300mcg/kg/min
Associated w/ minimal post-op N/V
Used in conjunction w/ short-acting opioid

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9
Q

Propofol Other Doses

A

Antiemetic 10-15mg followed by 10mcg/kg/min infusion
Antipruritic 10mg
Anticonvulsant 1mg/kg

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10
Q

Propofol Contraindications

A

Hypersensitivity
Lipid metabolism disorder
Sulfate allergy (common in patients w/ asthma)
Caution in elderly, debilitated, & cardiac-compromised patients

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11
Q

PRIS

A

Long-term, high dose infusions
Associated w/ significant morbidity & mortality
MOA unknown
Seen in acute inflammatory disease - infection, sepsis, acute neurologic disease
Propofol triggering agent (catechol/steroids) administered

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12
Q

PRIS Risk Factors

A 
> 4mg/kg/hr
> 48hrs
Critical illness
High fat-low carb intake
Concomitant catecholamine infusion
Steroid administration
Inborn mitochondrial fatty acid oxidation errors (creates oxygen supply-demand mismatch causing tissue necrosis)
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13
Q

Propofol S/S

A

Hypotension, bradycardia, widening QRS, Vtach or Vfib, asystole, ischemic EKG, arrhythmia, heart failure
Hypoxia & pulmonary edema
Acute kidney injury & hyperkalemia
Rhabdomyolysis
Hyperthermia, high anion gap metabolic acidosis, urine discoloration
Hepatomegaly, abnormal LFTs, steatosis, lipidemia, hypertriglyceridemia

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14
Q

Propofol Abuse

A

Addictive properties - develop tolerance & well-being on emergence
Incidence markedly increased over past 10yrs
Not controlled substance (facility dependent)

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15
Q

Etomidate

A

pH 8.1 pKa 4.2
Weak base
Water soluble in acidic pH; lipid soluble in physiologic
Preferable induction agent in unstable cardiac patient
Chemically unrelated to any other induction drug

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16
Q

Etomidate MOA

A

Administered as single isomer
R+ isomer 5x more potent
Selective GABA receptor modulator

17
Q

Etomidate PK

A

Large Vd
Significant tissue uptake
Moderate lipid solubility
75% bound to plasma albumin
↓ albumin ↑ active fraction
Prompt emergence 2nd to redistribution to tissues & rapid metabolism
Metabolized by hydrolysis - plasma esterases & microsomal enzymes in the liver

18
Q

Etomidate PD

A

Rapid onset w/in one arm-to-brain circulation
Return to consciousness in 5-15min
↓ CBF ↓ CMRO2
↓ ICP while maintain CPP
Involuntary myoclonic movements common - mistaken as seizures secondary to distribution to deep cerebral & brainstem
↓ amplitude ↑ latency
Maintain hemodynamic stability (acts on alpha 2 adrenergic receptors - mediated ↑ BP)
↓ minute volume
↑ RR

19
Q

Etomidate Clinical Uses

A 
Cardiac depressive effects minimal
No longer used as infusion
Induction doses up to 0.3mg/kg result in minimal changes 
- HR, SV, CO
- MAP decrease secondary to SVR
- Doses > 0.45mg/kg result in ↓ BP & CO
- Apnea w/ rapid injection
20
Q

Etomidate Dose

A

Induction 0.2-0.4mg/kg

NO analgesic properties

21
Q

Etomidate SE

A

Spontaneous myoclonus (involuntary movements common)
Adrenocortical suppression
Increased post-op N/V incidence
Low allergic reaction incidence
Minimal pain on injection
Contraindicated in patients w/ porphyrias

22
Q

Ketamine

A

pH 3.5-5.5 pKa 7.5
Dissociative anesthesia
EEG dissociation b/w thalamocortical & limbic systems
Cataleptic state where eyes remain open w/ slow nystagmus gaze
Potent amnestic & analgesic
No significant respiratory depression
Racemic mixture

23
Q

Ketamine MOA

A 
Binds non-competitively to phenylcyclindine site
N-methyl-D-apartate receptors
Glutamate antagonist
Direct cytokines inhibition
Limbic system activated
Weak action on GABA receptors
24
Q

Ketamine PK

A

Rapid distribution to tissues
Highly lipid soluble; rapid transfer blood-brain barrier
Not significantly bound to plasma proteins
Demethylation by CYP450 microenzymes
Metabolism dependent on hepatic flow
Active metabolite - Norketamine (broken down to form water-soluble and inactive metabolites)
Elimination half-life 2-3hrs

25
Q

Ketamine PD

A

Cataleptic dissociative state - eyes open, pupils reactive, corneal reflex intact, nystagmus present, lacrimation & blinking continue
Airway reflexes intact
Maintain spontaneous respirations
Bronchodilator
↑ salivary secretions
↑ skeletal muscle tone
↑ CBF/CMRO2/ICP attenuated w/ opioid & benzodiazepine
↑ IOP (contraindicated in eye procedures)
SNS activation ↑ HR/BP/SVR

26
Q

Ketamine Dose

A

IV 1-2.5mg/kg onset 2-3min
IM 4-8mg/kg <10min
PO 10mg/kg 10-20min
Analgesic effects at sub-anesthetic doses 0.2-0.5mg/kg (somatic > visceral)
Acts in thalamic & limbic systems
NMDA receptors responsible for spinal cord sensitization

27
Q

Ketamine Clinical Uses

A

Hypovolemic patients (trauma) favorable CV effects
Bronchodilation useful for patients w/ asthma
Induction complicated in patients w/ CAD
OB anesthesia w/out neonatal depression - does not compromise uterine tone, blood flow, or neonatal status
Chronic pain syndromes
Management in preventing hyperalgesia CRPS treatment & cancer pain
Burn patients - extensive dressing changes & skin grafting procedures
Ketamine “dart” pediatric patients
+ Propofol TIVA = more stable hemodynamic effects w/out unwanted emergence reactions

28
Q

Ketamine SE

A

Effects similar to SNS stimulation
Potent cerebral dilator
Intracranial pathology patients vulnerable to sustained increases in ICP
↑ pulmonary arterial BP, HR, CO, cardiac work, & myocardial O2 requirements
Apnea after Succinylcholine prolonged
Enhancement non-depolarizing neuromuscular blocking agents

29
Q

Emergence Delirium r/t Ketamine

A

5-30% incidence
Partially dose dependent
Visual, auditory, proprioceptive, & confusional illusions (up to 24hrs after admin)
Morbid content & vivid color
Floating sensation d/t loss skin & musculoskeletal sensation
Transient cortical blindness
Factors: >15yo female, personality problem history, frequent dreams
Occurs less frequently w/ repeated doses
Admin benzo 5min prior to surgery ↓ incidence (Midazolam > Diazepam)
Atropine ↑ incidence

30
Q

Dextromethorphan

A

D-isomer opioid agonist Levomethorphan
Low affinity NMDA antagonist
Antitussive effects in cough medicines
Psychoactive effects ↑ abuse potential
Lack analgesic or physical dependence properties
Excessive intake = hypertension, tachycardia, somnolence, agitation, slurred speech, ataxia, diaphoresis, skeletal muscle rigidity, seizures, coma
Hepatic toxicity w/ acetaminophen ingestion

31
Q

Dexmedetomidine (Precedex)

A 
Alpha 2 adrenergic agonist
Locus coeruleus
Vigilance, memory, analgesia, arousal
Produces sedation by ↓ SNS activity
Inhibits NE release
Reversal agent - Atipamezole (specific & selective)
32
Q

Dexmedetomidine PK

A

Highly protein bound
Extensive hepatic metabolism
Inhibit CYP450 increasing plasma opioid concentrations
Half-life 2-3hrs

33
Q

Dexmedetomidine Clinical Uses

A

Attenuates hemodynamic response to tracheal intubation
↓ MAC & opioid requirements
↑ hypotension
Severe bradycardia/asystole
Intranasal pre-op anxiolysis in pediatric patients

34
Q

Dexmedetomidine TIVA

A

IV anesthesia w/out ventilation depression
0.5-1mcg/kg bolus over 15min
Infusion 0.2-0.7mcg/kg/hr (up to 24hrs)

35
Q

Scopolamine

A

Anticholinergic
Only anticholinergic used for sedation
↓ reticular activating system activity
Effects enhanced w/ concomitant opioid & benzo administration
Strong antisialagogue effect (inhibits saliva)
Less likely to produce cardiac effects
Commonly admin transdermal for N/V

36
Q

Scopolamine SE

A

Mydriasis (Bella Donna) - block normal aqueous humor drainage
Cycloplegia - inability to focus near vision
Central anticholinergic symptom - restlessness & hallucinations to somnolence & unconsciousness
Overdose (muscarinic cholinergic blockade characteristics) - dry mouth, difficulty swallowing, blurred vision, photophobia, tachycardia, skin dry & flushed, ↑ body temp (inability to sweat)

37
Q

Scopolamine Dose

A

Pre-op sedation

IV/IM 0.3-0.5mg

38
Q

Physostigmine

A

Anticholinesterase
Scopolamine reversal
IV 15-60mcg/kg
Repeat doses as required

N926 Pharmacology (17 decks)

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