Exam 3 - Lecture 29, General anesthetics, anxiolytics & sedative, hypnotic drugs Flashcards
Ryanodine Receptor Sequence
- 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)
Malignant Hyperthermia
Anesthesia causes over activation of Ryanodine Receptors
Caused by mutation in RyR1
Malignant Hyperthermia process
Myosin/Actin freeze, causing….
Heat -> Rapid Hyperthermia -> EHS-like symptoms -> multiple Organ failure
Rigidity -> Skeletal Muscle Breakdown ->Rhabhdomyolysis (causing Myoglobinuria) -> Multiple Organ failure
Treatment of Malignant Hyperthermia
Halt GA -> Give 100% O2 -> Dantrolene IV at 1mg/kg until symptoms go away or 10mg/kg is reached
Dantrolene uses
Malignant Hyperthermia
Neuroleptic malignant syndrome
Muscle spasms
Dantrolene Side effects
Speech and visual disturbance Confusion and headache Drowsiness and fatigue Diziness Muscle Weakness Diarrhea
Dantrolene cannot be used by…
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
Anxiety
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
Generalized anxiety disorder
develops slowly, often in teens or young adults
Panic Disorder
Sudden and repeated attacks of overwhelming anxiety or fear
Meprobamate (Equanil)
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
Buspirone
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)
PTSD
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
GIRK Channel info
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
Zolpidem (Ambien)
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
