Anesthetics (Khan)

Based on Study Guide

What is MAC

What is Potency

Minimum Alveolar Concentration

• measures the potency of an inhaled anesthetic

• Lower MAC → more potent

Potency = 1/MAC

What is blood/gas coefficient

meaure of how soluble an inhaled anesthetic is in blood compared w/ alveolar gas phase

• how quickly an inhaled anesthetic induces anesthesia and how quickly a pt recovers

• Low b/g = anesthetic stays in lungs rather than dissolving in blood

  • Faster induction and recovery

• High b/g = anesthetic dissolves extensively in blood

  • Slower induction and recovery

What are the inhaled anesthetics

Which is non-halogenated

Nitrous Oxide (non-halogenated)

Halothane

Methoxyflurane

Enflurane

Isoflurane

Desflurane

Sevoflurane

General MOA of Anesthetics

Potentiate inhibitory synaptic activity

• Enhance GABA-A and glycine receptors

• Increases Cl influx, activate K channels → neuronal hyperpolarization

Diminish excitatory synaptic activity

• Inhibit ACh and NMDA receptors

• Decreases Na and Ca influx

Net Effect: decreased CNS excitation + increased inhibition

Nitrous Oxide

• MOA

Activates opioid neurons in the periaqueductal grey matter

Produces strong analgesia

Nitrous Oxide

• Pharmacological Properties

• Least potent inhaled anesthetic

• Very rapid induction/recovery (low blood/gas)

• Strong analgesic effect

Isoflurane

• Pharmacological Properties

• Volatile liquid at room temp w/ pungent odor

  • Used mainly for maintenance anesthesia

• Relatively slow onset and delivery

• Good safety profile (commonly used)

Desflurane

• Pharmacological Properties

• Rapid onset and recovery (low blood/gas)

• Commonly used for outpatient surgery

Desflurane

• ADRs

• Pungent odor

• Airway irritation/cough

Sevoflurane

• Pharmacological Properties

• Rapid onset and recovery

• Drug of choice for pediatric anesthetic induction

Sevoflurane

• ADRs

• Volatile at room temp (not pungent)

• Metabolized to fluoride ions

• Potential nephrotoxicity

Name IV anesthetics

Propofol

Dexmedetomidine

Lorazepam

Midazolam

Ketamine

Etomidate

Propofol

• MOA

• Pharm Properties

MOA

• Potentiates GABA-A receptors

Pharm Properties

• Short acting sedative-hypnotic

• Poor water solubility, formulated as an IV emulsion (pain on injection)

• Causes sedation and hypnosis

• Lowers BP

• Respiratory depression

• No analgesic effect

Propofol

• ADRs

• BW

ADRs

• Hypotension

• Apnea

• Hypertriglyceridemia

• Green urine/hair/nailbeds

• Propofol Infusion Syndrome (PRIS); rare but fatal

BW

• Risk of bacterial contamination; discard tubing and vial within 12 hours

• C/I to egg or soy allergy

Dexmedetomidine

• MOA

• Pharm Properties

• ADRs

MOA

• Selective α2-adrenergic agonist

Pharm Properties

• Sedation and analgesia

• Minimal respiratory depression

• Lowers HR and BP

• High doses may cause HTN

ADRs

• Hypo/Hypertension

• Bradycardia

Benzo (Lorazepam & Midazolam)

• MOA

• Pharm Properties

• ADRs

MOA

• Positive allosteric modulators fo GABA-A

• Increase frequency of Cl channel opening

Pharm Properties

• Sedation, anxiolysis, amnesia

• CNS depression limited by endogenous GABA

• Respiratory depression increased when combined with opioids

ADRs

• Respiratory depression

• Dependence and withdrawal

• Abuse potential

Midazolam Box Warning

Respiratory depression, respiratory arrest

• Use lower end of dosing range in debilitated and geriatric population

• Not to administer by rapid IV injection in neonates

What can happen if you take a Benzo + Opioid

• Sedation

• Respiratory depression

• Coma

• Death

Use flumazenil BZD respiratory antagonist for OD

Ketamine

• MOA

• Pharm Properties

• ADRs

MOA

• NMDA receptor antagonist

Pharm Properties

• Produces anesthesia and significant analgesia

• Sympathetic stimulation; Increases HR, BP, and cardiac output

ADRs

• Emergence Reactions

  • Vivid dreams

  • Hallucinations

  • Delirium

• BZDs reduce incidence of emergence reactions

Etomidate

• MOA

• Pharm Properties

• ADRs

MOA

• Produces hypnosis (no analgesia)

Pharm Properties

• Ultra short acting

• Minimal effects on cardiac output and peripheral resistance

• Less respiratory depression

ADRs

• N/V

• Adrenal suppression (less cortisol production)

  • Monitor Hypotension and Hyperkalemia

Therapeutic uses of Local Analgesics

• Abolish pain sensation in limited area of the body without producing unconciousness

• Uses

  • Topically in burns and small cuts

  • Injection during dental procedure

  • Epidural blocks during obstetric procedure and surgery

Are LAs specific for pain fibers?

If not then what muscles and fibers are blocked

Not specific for pain fibers; can block other sensory motor and autonomic fibers

Cardiac and skeletal muscles action potential

List ester and amide LA

Ester

• Tetracaine

• Procaine

• Benzocaine

Amide

• Lidocaine

• Mepivacaine

• Bupivacaine & Levobupivacaine

• Ropivacaine

• Prilocaine

What is the importance of ionic form of LA

Most active at the receptor site because it cannot exit from closed channels

Importance of nonionic form of LA

Uncharged form is important for rapid penetration of membranes

SAR Properties

Lipophilic Portion

• Essential for local anesthetic activity

• Important binding to the sodium channel receptor

• Di-ortho substitution protects the amide bond from hydrolysis

  • Increases metabolic stability and duration of action

Aliphatic Chain

• Connects aromatic ring and amine

• Usually 1-3 carbons long

• Determines whether drug is ester or amide

  • Amide- more resistant to metabolic inactivation

  • Ester- more susceptible to ester hydrolysis

Alkyl amine Hydrophilic portion

• Most local 3^o alkyl amine

• Increases water solubility

• Protonated form binds to the receptor site inside the Na channel

Which LA lacks a tertiary amine

Benzocaine

• poor water solubility

• mainly used as topical anesthetic

Absorption of LA

• The rate and extent of systemic absorption of LAs is greater

  • From densely perfused tissues (more vascularity)

  • Following multiple administrations (increasing concentration of LA)

• Vasoconstrictor

  • Increases conc. and duration of action of LA at site of injection

  • Decreases the max systemic conc. of LA, and thereby reduces the potentials for systemic toxicity

Distribution of LA

• IV bolus of amide LAs results in wide tissue distribution

• Sequestration occurs in fatty tissue

• Initial rapid distribution-uptake into highly perfused organs (heart, brain, liver, kidney)

Metabolism of LA

• LA are converted in the liver and plasma to more water-soluble metabolites and then excreted in urine

• Ester type drugs are hydrolyzed very rapidly in the blood by butyryl cholinesterase

• Amide drugs are hydrolyzed by liver microsomal CYP 450

  • Toxicity of amide drug is more likely to occur in patients with liver disease

Why is Epinephrine given along LA

Enhances and prolongs LA induced spinal anesthesia by acting on α2 adrenoreceptor, which inhibit release of substance P and reduce sensory neuron firing

Epi-LA combo reduces systemic absorption, and enhances LA uptake

What is the MOA of LA

• Block VG Na channels of the cell membrane

• Prevent membrane depolarization and AP generation

• Receptor is not readily accessible from the external side of the cell membrane

• LA gain access to their receptors from the cytoplasm or the membrane

Cardiovascular Effects of LA

• LAs can depress myocardial contractility and produce arteriolar vasodilation → severe hypotension

• At high concentrations block cardiac Ca channels

Other toxicities of LA

• Prilocaine in high doses causes methemoglobinemia (cyanotic and chocolate colored blood)

• IV administration of reducing agents to convert to Hgb

• Ester type drugs are metabolized to PAPA derivatives

• These metabolites are responsible for allergic reactions in a small percentage of population

Lidocaine properties

• Rapid onset of action due to high lipophilicity

• Longer duration of action

• Also used as Class IB antiarrhythmic agent

• Extensively metabolized in liver by N-dealkylation & aromatic hydroxylation

Lidocaine ADRs

• Drowsiness

• Seizure

• CV depression

Which isomer is responsible for Bupivacaine cardiotoxicity

• R(+) enantiomer responsible for cardiotoxicity → ventricular arrhythmia