Induction agents Flashcards
What type of drug is ketamine
phencyclidine derivative
How is ketamine presented
colourless solution
Racemic mix or as pure S enantiomer
How does ketamine work?
NOn competitive antagonist at NMDA receptor
Weak agonist at MOP, KOP, DOP
Inhibits reuptake of serotonin. dopamine, NA
Effects of ketamine on systems
CVS:
- increase HR
-INcrease CO
-INcrease BP
-Increase O2 consumption
Resp
Bronchodilation
INcrease RR
No depression of laryngeal reflexes
CNS
Dissociative anaesthesia
Traditionally thought to increase ICP but probs just as much as opiods
amnesia
Muscle tone
Emergeence
Chemical properties of ketamine
chiral compound- S ketamine available on own
(twice as potent, 3-4x affinity for NMDA)
Water soluble, forms an acidic solution
Ketamine A/D
Well absorbed, poor oral bioavail (20%)
Protein binding of 20-50%
Vd of 3L
t1/2 of 2.5 hours
Ketamine M/D
Metabolised in liver to norketamine (30% potency)
Conjugated to inactive metabolites
Excreted in urine
What type of drug is etomidate
Imidazole
How is etomidate presented
clear, colourless solution
MOA etomidate
Increases duration of GABA cl channels in CNS
Only the D isomer causes hypnosis
Effects of etomidate on different systems
Most stable induction agent, very slight drop in SVR but Myocardial O2 consumption/BP are not effected
Resp- depression
No inhibition of hypoxic pulmonary vasoconstriction
CNS
HYpnosis, tremor and drop in tone
Decreased ICP,CPP.IOP
Epileptiform activity in a quarted
How does etomidate affect steroid synthesis ?
Inhibiting by inhibition of 11b and 17a hydroxylase- 24hours for just one dose. associated with deaths when used on ICU for sedation
pKa etomidate
4.1
Etomidate A/D
75% protein bound
Rapid distribution
Vd 3L/kg
Etomidate M/E
Rapidly metabolised by hepatic and plasma esterases
May inhibit plasma choninestrase
Excreted 90% in the urine, 10% in the bile
What is the name of propofol
2,6, diisopropylphenol
What else is in propofol
soy bean oil. egg phosphatide
MOA propofol
may be GABA potentiation, may be cannabinoid
Propofol effects on systems
CVS
Less BP/SV
Less CO
Vasodilation
Bradycardia
Resp
Depression,
Increased RR, dec. TV
bronchodilation
CNS
HYpnotic, smooth and rapid
decreases CPP + ICP
Gut- antiemetic, antagonist at D2
Propofol side effects
Pain on injection
Fat overload in kids
Green urine
INcreased energy for shocks
Chemical properties of propofol
Not water soluble, weak acid.
pKa is 11
Propofol A/D
98% protein bound
Vd 4L/kg
Rapid distribution
COntext sensitive but half time is about 1 to 5 hours
Propofol M/E
Hepatic metabolism to make glucuronide
Renally excreted
Dysfunction has little effect
Clearance >hepatic blood flow suggesting extrahepatic metabolism
No active metabolites
What type of drug is thiopentone
Barbituate
How is thiopentone presented
Yellow powder with sodium carbonate added (prevents accumulation of undissociated acid when dissolved)
= stored under N2 (prevents acidification of powder by CO2 in air
MOA of thiopentone
Increases duration of opening of gaba cl channels
Hyperpolarisation + neuronal inhibition
Thiopentone effects by system
CVS-
Reduced CO, SV, SVR
Can increase HR
REsp-
Depression, laryngo/bronchospasm
CNS-
Anaesthesia, decr. blood flow, decr. CSF pressure
REnal- reduces UO
Thiopentone S/E
Severe anaphylaxis
Precipitates porphyria
Intraarterial injection -> spasm and necrosis .
pKA of thiopentone
7.6
Thiopentoine A/D
80% protein bound. of remaining, 12% is unionised and available
Vd 2L/kg
Rapid emergence due to redistribution
Critically ill patients are acidotic, so less thiopentone is needed
NSAIDS reduce protein binding and increase free portion of the drug
Thiopentone M/E
Hepatix oxidation by p450 to inactive metabolites (bar pentobarbitone which is active)
Induces p450 after a single dose
zero order kinetics
