Exam 3 - Lecture 29, General anesthetics, anxiolytics & sedative, hypnotic drugs

• Action potential comes in • Cav Channels open, increase Ca in Sarcolemma • Activates RyR channels and Ca leaves Sarcoplasmic Reticulum, further raising Ca in Sarcolemma • High Ca causes muscle contraction • Ca returns to SR via SERCA (Ca ATPase)

Anesthesia causes over activation of Ryanodine Receptors Caused by mutation in RyR1

Myosin/Actin freeze, causing…. Heat -> Rapid Hyperthermia -> EHS-like symptoms -> multiple Organ failure Rigidity -> Skeletal Muscle Breakdown ->Rhabhdomyolysis (causing Myoglobinuria) -> Multiple Organ failure

Halt GA -> Give 100% O2 -> Dantrolene IV at 1mg/kg until symptoms go away or 10mg/kg is reached

Malignant Hyperthermia Neuroleptic malignant syndrome Muscle spasms

Speech and visual disturbance Confusion and headache Drowsiness and fatigue Diziness Muscle Weakness Diarrhea

Pt with liver disease Pt with reduced lung or cardiac function Pt under 5 yr old Pt who need good muscular balance HOWEVER, in med emergency its used unless pt has known hypersensitivity

Most common mental illness US, 40 mill adults or 18.1% of pop Highly treatable but only 36.9% get treatment Develop from complex set of risk factors Those with anxiety more likely to go to doctor and be hospitalized

develops slowly, often in teens or young adults

Sudden and repeated attacks of overwhelming anxiety or fear

MoA: Agonist at GABAA receptor (Narrow therapeutic index) Used as sedative, hypnotic, anxiolytic…muscle relaxant rarely Side effect: Drowsiness, Headache, Fatigue, Physical Dependence OD: Loss of motor control, Coma, Lowers Respiratory drive, SOMA on the streets Dangerous so replaced by Benzos, not used EU,Canada, controlled substance US

MoA: Agonist at 5-HT1A receptors (most highly expressed) Full agonist at presynaptic, partial at post synaptic Side effects: Nausea, vomiting Dizziness Drowsiness Miosis (small, pinpoint pupils)

No specific drugs available to treat, hard to do model in rats too To be diagnosed must have following for at least 1 month... 1 re-experiencing symptom 1 avoidance symptom 2 arousal and reactivity symptoms 2 cognition and mood symptoms

G-protein coupled inward rectifying potassium channels channels are activated by Gby subunits from Gai/o receptors Activation of them causes resistance of excitability, K+ flows out, making membrane potential more negative GIRKs are made of Kir3 subunits

MoA; PAM of specific GABA-A receptor Doesn’t bind to Benzo or Barbiturate Site Side Effect: Sleepiness, Dizziness, Nausea, Headache, Memory problems, hallucination, Sleepwalking, Recreational Abuse People have said stupid shit and blamed on Zolpidem

MoA: Agonist at melatonin receptor 1 and 2 Side effects: Sleepiness, Dizziness, Nausea, Hypothermia, Can reduce Follicle Stimulating Hormone (FSH) required for maturation + puberty, ovulation

GIRK1/2 (specific), KIR1 and 2

GIRK1/4 (nonspecific), Kir2 and 4

Inhibits Adenyl cyclase

Binds to particular potassium channels and activates them (GIRK)

production of Adenyl cyclase

activates phospholipase C, metabolizes PIP2 which affects m current

Barbiturates Benzodiazepines Carbamates Anti-histamines Opioids Antidepressants Sympatholytic agents (Beta blockers) Anesthetics, sedatives, hypnotics