Anesthesia Flashcards
zero order
not constant and dependent upon plasma (constant mg/hr)
Clearance of drugs with first order kinetics
constant regardless of plasma concentration (%)
Phase 1 metabolism
Converts parent drug to more polar
water soluble
Phase II metabolism
Conjugate drug with polar moiety
making it more water soluble
Distribution of Cardiac Output
VRG= 10% body mass but 75% CO Muscle = 40% body mass but 19% CO Fat = 30% body mass but 6% CO VPG = 20% body mass but 0.5% CO
Albumin binds _____ drugs?
Acidic I.e. Barbiturates
A1AG bind to _____ drugs?
Basic I.e. Local anesthetics
Which diseases decrease Albumin available to bind to drugs?
liver, kidney, CHF, Cancer which increase available drug
Which diseases decrease A1AG available to bind to drugs?
trauma, infection, MI, chronic pain
Volume of Distribution
total amount of drug in the body/drug blood concentration
– VD 0.7=total body water
Propofol Mech. of action?
Presumed interaction with GABA
– Delays the dissociation of GABA from receptors
• Increasing GABA activated opening of chloride ion channels
• Also acts as a sodium channel blocker
– Hyperpolarization of cell membranes.
Propofol Pharmacokinetics?
- 95-99% protein binding
- Metabolized via glucoronidation in the liver (up to 30% possibly in lungs
- Renal excretion
Dosing Propofol?
Induction - 1.5-2.5 mg/kg (adults) - decrease in elderly
- 2.5-3.5 mg/kg (kids)
Sedation (MAC) - 25-100mcg/kg/min
TIVA - 100-300 mcg/kg/min
Propofol effects on Cardio?
SBP ⇓d; MAP ⇓d; SVR ⇓d; HR ⇔
– Profound arterial and venous vasodilation ⇓s both preload and afterload.
Propofol effects on RESP and CNS?
RR depressed dose dependent—apnea after bolus
– Reduces airway reflexes
CBF ⇓d; ICP ⇓d; CMRO2 ⇓d; ⇓d IOP
What is Propofol infusion syndrome?
Acute refractory bradycardia (kids)
– RBBB is an early sign
– May lead to asystole if one or more:
• Metabolic acidosis
• Rhabdomyolisis
• Hyperlipidemia
• Enlarged or fatty liver
– Associated with propofol infusion >4mg/kg
for long duration (> 48 hours)Fospropofol
Prodrug of Propofol
Longer onset
6.5 mg/kg (60-90kg)
Perianal paresthesia in 74%
Prop key points? - take home?
Awaken due to redistribution • CV depression slightly > than NaP • Resp effects similar to NaP but good bronchodilator • Does NOT cause hyperalgesia • Reduces PONV and PDNV • Good hypnotic • Burns upon rapid injection in small vein • Contraindicated with Egg Allergy
Etomidate Mech of action and Pharm?
Mechanism of Action – Rapid onset of sleep--30-60 seconds – Assumed to enhance the effects of GABA – Rapid awakening – 75% protein bound – Hydrolyzed to inactive metabolites via ester hydrolysis – Elimination half life is 75 minutes – Clearance is 5X faster than Sodium pentothal – Excretion 85% renal, 15% biliary
Etomidate S/E Card, Pulm, CNS
CV effects – SBP ⇔⇓d; HR ⇔⇑d ; SVR ⇔⇓d • Pulmonary effects – Minimal respiratory depression; increased with opioids. • CNS effects – CBF ⇓d, ICP ⇓d, CMRO2 ⇓d
Etomidate Induction and maintenance dose?
.2-.4 mg/kg
NO REDOSING!!! Suppresses Adrenals!!!
- Inhibits 11β-hydroxylase and to a lesser extent 17α
hydroxylase
What to think about when giving Etomidate?
Beware of – Myoclunus (spontaneous jerking) – Adrenal Suppression • Inhibits 11β-hydroxylase and to a lesser extent 17α hydroxylase. – ⇑d PONV versus NaP or Propofol – No Analgesia
_______________ states that the potency of an anesthetic is proportional to its lipid solubility. This suggests a lipophilic site of action.
The Meyer-Overton rule
Ketamine works on which receptors?
NMDA; Opioid; Monoaminergic; muscarinic
receptors; & voltage gated Ca+ channels
Ketamine Pharmacokinetics?
Extremely lipid soluble (5-10X NaP)
– Metabolized in liver to norketamine
• 1/3 to 1/5 potency Ketamine
– Norketamine is hydroxylated and conjugated to
H2O soluble and excreted.
– Elimination half-life 2-3 hours
– Excretion >90% renalKetamine CV, Pulm, & CNS effects?
• CV effects
– SBP ⇑d; HR ⇑d ; SVR ⇑d
• Pulmonary effects
– No respiratory depression; increased with
opioids.
• CNS effects
– CBF ⇑d, ICP ⇑d, CMRO2 ⇑d (probably not good for neuro cases)
Ketamine induction dose IV & IM?
Induction of Anesthesia
– 1-3mg/kg IV or 4-8mg/kg IM
• Adjunctive Analgesic
– 0.2-0.5 mg/kg can provide profound analgesia
BEWARE OF:
– Emergence Delirium
• Visual, auditory, proprioceptive, and confusion
• Premedicating with Midazolam seems to help
Barbiturates Mech. of Action? (what receptors?)
Interact with GABAA (α subunit) receptor
• Different from the GABA or the BZD site
• Directly activate Cl-
ion channels, increase their duration
of opening.
– Increases the efficacy of GABA
• Hyperpolarize postsynaptic cell membranes.
– Also block the AMPA receptors (excitatory receptor)
Barbiturates elimination and protein bound?
NaP 83% protein bound (Albumin) – Highly lipid soluble=rapidly into CNS – Achieve CNS uptake in 30 seconds – Prompt awakening after a single dose – Hepatic metabolism (inactive) and eliminated by kidneys
Barbiturates CV, Pulm, & CNS effects?
CV effects
– SBP ⇓d; HR ⇑d (reflexive) ; SVR ⇓d
• Pulmonary effects
– Respiratory depression, APNEA, return with slow
respers and ⇓d tidal volumes.
• CNS effects
– CBF ⇓d, ICP ⇓d, CMRO2 ⇓d - neuro protective
Barbiturates effect on Renal & pH?
Modest decrease in GFR
– Metabolic acidosis ⇑s the effect of barbiturates
– Metabolic alkalosis ⇓s the effect of barbiturates
– Respiratory acidosis has much less effect
Barbiturates Key Points?
Awakening due to redistribution • NaP causes dose dependent ⇓ SBP, SVR, CO due to myocardial depression and increased venous capacitance • Potent respiratory depressants • Poor analgesics-may cause hyperalgesia • Contraindicated in Acute Intermittent Porphyria • Can cause histamine release • Avoid SubQ and Intra-arterial injection
