Exam 3 - Lecture 27 & 28 General anesthetics, anxiolytics & sedatives, hypnotic drugs

Can induce a state of systemic anesthesia, lack of feeling

reduce anxiety

CNS depressants that induce calm

Typically psychoactive drugs that induce sleep

Inhalation or injection

MAC - Minimum alveolar concentration, equivalent of potency The lower the MAC, more potent the anesthetic MAC is ~20% higher in red heads, due to mutations in melanocortin-1 receptor

Hypoatraemia (low sodium), increased age, pregnancy, opioid use, benzo, intoxication

Chronic amphetamine, cocaine, ephedrine, chronic alcohol use, decreased age

Simple, diverse structures argues against obvious SAR Suggest physicochemical mechanisms of action; Bilayer thickness, curvature, fluidity

Stereoisomers have similar oil:gas partition coefficients but different MAC Many lipophilic drugs are not anesthetics Change in body temp alter membrane fluidity but is not anesthetic Changes in chain length increase lipophilicity but not MAC

Distinction between anesthesia and sleep If sleeping you can be arousable but if you’re anesthetized then you are unarousable. Nonphysiological Oscillations in anesthesia physiological Oscillations in Sleep

The lower the better it will cross from Alveoli, into blood and then into Brain. For example, drug with MAC 0.47 will cross better than one with a MAC of 2.3

The age and life-style of the patient How fat Other medications Hair color

The lower the blood/gas partition coefficient, the faster the induction of effect and recovery rate

Inhibiting Nav channels in CNS neurons reduces excitability Concentration dependent, decreasing excitability in the brain

Activating K2P channels in CNS neurons reduces excitability Open channel = less excitability, decreasing epilepsy and increasing anesthesia effects

not voltage gated 2 subunits Subunit made of 4 Transmembrane proteins, 2 P loops

Cheap & easy to make, no longer recommended by WHO MoA: Positive Allosteric modulator at GABAa receptor Agonist at GABAa-receptor at higher dose Sympathomimetic effect, maintains BP Side effect: Post operative nausea and vomiting Seizures and tremors V flammable and explosive mixed with Oxygen

Laughing gas, non-flammable roomtemp MAC >100% Fast acting, can cause euphoria MoA: Weak PAM of GABAa and glycine receptor Weak activator K2P, blocker NMDA, AMPA, kainite and GABAc

MoA: #1 - Agonist at GABAa receptors Agonist at glycine receptors Antagonist at NMDA receptors and Nav channels Activates K2P channels Side effect: Arrhythmia Respiratory depression Hepatoxicity (metabolized into trichloroacetic acid = 30-70% mortality) Not used in US anymore

Widely used, non explosive MoA: #1 Agonist at GABAa receptors Agonist at glycine receptors Antagonist at NMDA receptors and Nav channels Activates K2P channels side effect: Cardiac arrhythmia Respiratory depression

widely used, expensive bc hard to make MoA: #1 Positive allosetic modulator at GABAa (and GlyR?) receptors NMDA receptor antagonist Activated K2P channels side effect: Amongst safest agents available All gas anesthetics associated with neurotoxicity Neurodev/behavior abnormalities in kids?

• BP (low, ~2%)/ + Heart Rate

More potent than gas ones Not appropriate for long surgery, often used to induce anesthesia