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17 Cards in this Set

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Ketamine (Ketanest, Ketaset, and Ketalar )
Analgesia, Amnesia, Unconsciousness
Structural similarities to phencyclidine
pKa 7.5, formulated pH 3.5 – 5, IV and IM
Prepared as racemate
NMDA non-competitive Antagonist
Binds to PCP site
Possible opioid - mosly kappa though weakly binds others, muscarinic, voltage gated, etc.
Suppress neutrophil production of inflammatory mediators
Improve blood flow, Inhibit cytokines
Ketamine MOA?
Amnesia is dissociative. Dissociates thalamus (responsible for relaying impulse from RAS) to limbic cortex (responsible for awareness of sensation).
How it is does: NMDA is a glutamate (excitatory) receptor. Blocks the excitatory effects. Could interact with other receptors

Analgesic effect could come from neutrophil supression – if inhibit cytokines, do not get inflammation and pain.
ketamine facts
Structure: Structural similarities to PCP – hallucinogenic and nuerotoxic
Racemic mixture but S is more active which indicates must interact with receptors
Formulated as salt-conjugate acid, so should not be mixed with any basic solution otherwise will precipitate.
Ketamine ADME
A: rapid like thiopental, highly non-ionized, peak 1 min IV 5-10 min IM, not highly bound to plasma proteins.
D: quickly to highly perfused tissues (brain), redistribution leads to awaken, large VD.
M: high hepatic clearance with high extraction ratio, some active and inactive metabolites
E: elim t1/2 2-3 h, <4% recovered unchanged in urine< 5% in fecal material (so mostly renal), can cause induction
other Ketamine ADME facts
Actually more lipid soluble than thiopental (5 to 10 times) , highly non-ionized ~60%
Because highly liphophilic, quickly distributed, also since ketamine does increase CBF this facilitates even more entry to brain.
Volume of distribution 3L/Kg
Extraction ration 0.9
Can see tolerance develop
Ketamin side effects
Cardio: Increased HR, art. BP, CO
Can help with hypovolemic shock
Catecholamine stores exhausted will see depression
Resp: Minimal depression (the least of all options), **Bronchodilation, increased airway secretions
Cereb: vascular dilator, increased O2 consump., CBF, ICP
Emergence Delirium: terrible dreams, illusions, hallucination, nausea, vomiting
Hypertonus (muscle spasm)
Nystagmus (involuntary eye movement)
other Ketamine facts
Do not use in case of ICP, use other options

Secretions may cause more laryngospasm and coughing
Secreations may be descreased by using an antimuscarinic (glycopyrrolate)

Because of emergence delirium, can give a benzodiazepine
Other etomidate facts
Good for higher risk patients
with theophylline may cause seizures
With Diazepam increase cardio stimulatory effects and increase elimintation t1/2.
Sympathetic antagonists will unmask cardio stimulatory effects
Inhaled anesthetics will minimally increase myocardial depression (negative inotrope)
Lithium increased duration
With Ketamine, avoid the following...
Cardiac Patients (cardio effects)
Coronary heart disease
Hypertension
Heart failure
Arterial aneurysms
Glaucoma Patients (eye pressure)
Patients with increase ICP
Etomidate (Amidate)
Anesthesia, Amnesia (low), no analgesia
Structure has imidazole,gives H2O solubility
pKa 4.2, Formulated pH 7 fat emulsion, IV
Prepared as racemate
GABA Modulator
Binds to alpha, increases affinity for GABA
Depresses RAS
Disinhibition of control of extrapyramidal motor activity
30 – 60% myoclonus
etomidate ADME
A: rapid, highly non-ionized (99%), peak 1 min IV, 76% bound,.
D: quickly to highly perfused tissues (brain), redistribution leads to awaken, large VD.
M: fast with hepatic and plasma esterase giving biotransformation, high extraction ratio, inactive metabolites
E: elim t1/2 2-5 h, context sensitive less than thiopental
etomidate S/A's
Cardio: minimal effect – Best stability of all options
Mild decrease peripheral vascular resistance
At clinical conc. No negative inotropic effect.
Resp: Minimal,
Cereb: vasoconstriction, decrease O2 consump., CBF, ICP same as thiopental
Emergence: nausea, vomiting (mixed data)
Endocrine: Adrenocortical suppression
Inhibits cortisol and aldosterol synthesis (4-8 hrs)
Immune: Depresses immune system(lowers plasma cortisol)
Other etomidate facts
Fentanyl, Alfentanil increase plasma levels and decrease elimination t1/2
Opioids decrease myoclonus
Propofol
Anesthesia, Amnesia , Anti-convulsant, no analgesia
Induction drug of choice
Structure is alkylated phenol, insoluble in H2O
Formulation: 1% in (10% soybean, 2.2% glycerol, 1.2% lecithin)
GABA Modulator, decreases rate of release of GABA
Anti-pruritic effects
Anti-emetic, acts on chemoreceptor trigger zone and vomiting center
Waken faster than methylhexital/thiopental/etomidate – and waken more complete. The major advantage

Antiemetic also makes induction agent of choice
propofol ADME
A: rapid almost as fast as thiopental, non-ionized
D: quickly to highly perfused tissues (brain), may be taken into lungs, large VD.
M: fast with hepatic and extrahepatic giving biotransformation, hydroxylation, glucoronidation, sulfonation, 4-hydroxy weakly active,
E: clearance exceeds hepatic blood flow. elim t1/2 0.5-1.5 h, context sensitive less than 40 min., mostly urinary excretion
Though clearance is high and very dependent upon liver, cirrhosis does not slow elimination
Renal failure not affect clearance
propofol S/A's
Cardio: decrease vascular resistance (vasodilation) venodilation, decreased contractractility, decreased BP, CO, more hypotension than thiopental.
Usually no change in heart rate, impairs baroreflex
Usually not a concern
Resp: Profound Respiratory depressant
Apnea, Conscious sedation decreases ventilatory drive, Decreases upper airway reflexes, bronchodilatation
Cereb: Decrease O2 consump., CBF, ICP
Can still be used with patients with space occupying lesions
Histamine Release: minor
No change in heart rate indicates sympatholytic/parasympathomimetic action
Propofol other
Increase dose needed for elderly with lower VD.
Increased dose needed for women.
Causes some muscle twitching and hiccups
Reduces intraocular pressure
Fentanyl and alfentanil increase concentration
Versed is synergistic but not sure this is a valuable mixture