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Pharmacology - Anasthetics (*Anasthetic Agents (*Inhaled Anasthetic Agents…
Pharmacology - Anasthetics
*Anasthetic Agents
*Inhaled Anasthetic Agents
*Halothane
most widely used anesthetic worldwide
NOT used in the US and Canada as much due to hepatotoxicity you can get from it
--> this is rare and is a hypersensitivity reaction to halothane
--> rare, but mortality = 50%
--> extremely dangerous
Drug induced liver injury
Halothane drug induced liver toxicity
halothane = most widely used anesthetic worldwide
NOT used in the US and Canada as much due to hepatotoxicity you can get from it
--> this is rare and is a hypersensitivity reaction to halothane
--> rare, but mortality = 50%
--> extremely dangerous
Drug induced liver injury
note that acute vs chronic liver disease proteins in bloods
albumin has long half life = 20 days
--> thus only gets low in chronic diseases like CHF
factor 7 extrinsic pathway
--> shortest halflife of all the clotting factors
--> thus you see a high PT = prothrombin time in acute liver problems
Clinical Cases
Clinical Case
Clinical Case
Notes
:
note that
*IV Anasthetic Agents
*Propofol
"Proposals comes FIRST"
--> Propofol used for induction
--> "white inducer"
extremely fast acting
--> 30 secondas
very short duration = 30 minutes
recall that the more lipophillic a drug is the faster acting it is
--> it can diffuse readily across the Blood BB and anywhere there is high blood need
after it saturates the high blood volume organs, it diissapates into other organs and collect in the addipose, etc.
--> reason for its short duration also
Lipophillic drugs
*Drug distribution with lipophyllic drugs
propofol is a good example of this
distributes quick in high blood flow organs
--> brain, liver,, kidney lungs
then it gets stored later and accumulates in lower blood flow organs
--> as final resting place in skeletal muscle and fat
*Local Anasthetic Agents
*Organ System Effects from anesthetics
note that MOSTLY ALL organs are depressed from anesthesia
--> the ONLY exception is the brain, that has increased blood flow
Cardiac, Resp, Kidneys and liver all have decreased blood flow
Respiratory depression is what actually causes cerebral blood flow to increase
--> recall for raised ICP patients you can use therapeutic hyperventilation to expel CO2 and make them hyocpnic
--> less CO2 in the brain blood vessels
--> vasoconstriction in the brain
In Anesthesia, respiratory depression
--> hypercapnea and raised CO2
--> higher CO2 in brain
--> vasodilation and increased Cerebral BF
*Malignant Hyperthermia
defect in voltage gated Ryanidine receptors of skeletal muscle
--> succinylcholine = suxamethonium NMJ muscle relaxant
--> anesthetics
keep releasing Ca++ into the cell
--> waster ATP and sustained contractions
--> fever and muscle rigidity
Tx =
Dantrolene
-->
"DANTRO Mark RAE Malignant Hyperthermia"
*Muscle relaxants and MG = Myasthenia Gravis
MG have autoantibodies against post synaptic ACh receptors
--> have reduced reaction to ACh normally
Non-depolarizing NMJ = competitive ANTAGONISTS
tubocurarine derivatives
MG patients have little receptors so if they get blocked they are paralyzed
-->
MG can't handle Non-depolarizing
NMJ muscle relaxants
DEPOLarizing NMJ competitive AGONISTS
MG patients have little receptors so if they can't actually be activated by suxamethonium
-->
MG doesn't respond to hand depolarizing
NMJ muscle relaxants
--> require high doses
*Pathophys of anesthetics
must move through 3 major compartments
--> lungs
--> other tissues on the way
--> brain = target organ
factors in each compartment determine the concentration of anesthetic
*arterovenous Concentration gradient of Anesthetics
high gradient = high peripheral tissue take up of drug
--> SLOWER onset of action
--> since need more drug for it to reach brain when all other tissues are easily taking it up
*Pharmacodynmics and kinetics of anesthetics
potency = 1/MAC
MAC = minimal alveolar concentration
lipophillic
drugs --> determines
potency
solubility
in the blood of anesthetic --> determines how
FAST onset
is
--> high solubility in blood = means SLOW onset
--> takes longer to be released from the blood since it gets dissolved in it
*Solubility = blood/gas partitian coefficient anesthetics
solubility
in the blood of anesthetic --> determines how
FAST onset
is
--> high solubility in blood = means SLOW onset
--> takes longer to be released from the blood since it gets dissolved in it
blood is saturated with the drug
--> this happens at the point when the partial pressure of the gas in the blood is the same as in the inhaled gas
--> recall the gas is either dissolved or released as partial pressure in the blood
blood/gas partitian coefficient = measure of solubility
--> High B/G ratio coefficient 1 = high solubility in blood
--> SLOW onset and slow recovery from drug
--> slow recovery makes sense since highly soluble drugs require more drug to reach the equilibrium partial pressure
low BG ratio = 0 -- FAST onset and fast recovery
*N2O = Nitrous Oxide vs Halothane for solubility = blood/gas ratio coefficient
N2O = high solubility = blood/gas ratio coefficient
--> FASTonset
Halothane = high solubility = blood/gas ratio coefficient
--> SLOW onset
*lipophillic property of anesthetics
potency = 1/MAC
MAC = minimal alveolar concentration
lipophillic
drugs --> determines
potency
