Laughing Gas Inhaled Anesthetics, Dantrolene

2.2 – “Laughin “Laughingg gas”: inhaled anesthetics, dantr dantrolene olene Properties • Inhaled anesthetics are taken up by gas exchange through the alveoli of the lungs, with consequences for pharmacokinetics, uptake, and distribution and partitioning. • Solubility of gas in the blood is also referred to as the blood:gas partition coefficient (partition in the ball pit); the higher the coefficient, the higher the solubility. Solubility determines speed at which blood becomes saturated, and ergo uptake and duration in the CNS. o Less soluble → more rapid saturation → more rapid onset & offset of CNS effects (e.g. N2O) (Kid sleeping in vascular ball pit; immediately getting pulled to safety). Takes less anesthetic to saturate the blood (only one kid in the ball pit rather than 2). o More soluble inhaled anesthetics have a slower onset and longer duration (e.g. halothane) (kid moving freely in the ball pit; KO’d by the end; long tapering flag)) • Arterial tension curves correlate to solubility (side of ball pit) o steeper arterial tension curve = lower blood:gas partition coefficient o Less steep arterial tension curve = higher blood:gas partition coefficient • MAC (minimum alveolar concentration) (mac & cheese) is the percentage of anesthetic needed in inspired gas mixture that renders 50% patients unresponsive (1 kid awake, 1 kid asleep). Corresponds to ED50 on dose-effect curve. o The lower the MAC, the more potent the drug (i.e. potency of the inhaled gas is inversely proportional to MAC) (inverted bowl of mac’n’cheese). The potency for inhaled anesthetics is the minimal concentration that reaches the brain that results in sufficient anesthesia. Inversely proportional to MAC. • Solubility of anesthetic in peripheral tissues is a major factor in onset/offset as well as it affects how much of the anesthetic will make it to the brain. Can be measured by the arteriovenous concentration gradient; if tissue solubility is high, a large amount of anesthetic is taken up from arterial blood, resulting in low venous concentration and larger AV concentration gradient. • Gaseous anesthetics may be used to deepen anesthesia after induction with IV agents. Precise MOA not known; may involve glycine, GABA, or antagonism of NMDA receptors. • All can cause myocardial depression → ↓CO & ↑arterial & ventricular pressures (clown with heart balloon). May cause hypotension (kid passing out) • Can cause respiratory depression, leading to decreased minute ventilation & hypercapnia (deflating lung balloons). Also decrease mucociliary clearance which may contribute to pos-op atelectasis. Agents • Gaseous: Nitrous oxide = laughing gas (N2O) o Lowing boiling point, gaseous at room temperature (gas canister). o Physically impossible to overdose. o Fairly benign. • Volatile anesthetics o Include enflurane, isoflurane, halothane. All are fluorinated. End in -thane or -flurane (kid in pool holding flower) o High boiling point, liquid at room temperature (Air tank getting wet in pool) o Can decrease cerebral vascular resistance → increased cerebral blood flow →↑ICP (crown with red brain wig) o Halothane rarely used d/t hepatotoxicity with massive hepatic necrosis (liver with cracked piñata). Presents within 2d – 4w. Will have widespread centrilobular necrosis and up to 80% mortality. o Enflurane: nephrotoxicity (guy getting hit in the kidney with bat). Convulsions (shaking) o Malignant hyperthermia (Magnificent birthday) ▪ Life threatening. Presents with fever and muscle rigidity soon after surgery with inhaled anesthesia (flame hat) ▪ Muscular hypersensitivity to volatile anesthetics or succinylcholine (SUCKS poster). Results in excess Ca2+ release from defect in ryanodine receptors (RyR) in the sarcoplasmic reticulum (Ryan sign falling). Causes excessive ATP-dependent reuptake by the sarcoplasmic reticulum, resulting in heat production (flame theme) and consequent muscular damage (bitten drumstick) ▪ May see potassium, CK, myoglobin released into circulation on labs (chicken legs) ▪ Treatment: Dantrolene (mm relaxant) (trampoline). Blocks RyR and prevents further release of calcium into muscle fibers (adult blocking Ryan from getting on trampoline).