Test 1: Ketamine Flashcards
What is Ketamine a derivative of?
Phencyclidine (PCP)
-1/10th as potent as PCP
What is the MOA of Ketamine?
-NMDA Receptor antagonist in the spinal cord and brain, which results in a selective depressant effect on the medial thalamic nuclei that is responsible for blocking afferent signals of pain perception to the thalamus and cortex (Thalamic nuclei = functional dissociation of the cerebral cortex and the thalamus).
-Non-competitive binding with the ion channel pore
-Inhibits nicotinic Ach receptors (analgesia)
-Also inhibits TNF-alpha and IL-6 (anti-inflammatory effects)
New evidence of binding: (causes local anesthetic properties)
-Na+ Channels
-ĸ and μ – opioid receptors
What is Dissociative Anesthesia?
A unique, catatonic state in which the patient feels separated from the environment and has profound analgesia and amnesia yet retains most protective reflexes.
-Hypnosis + analgesia
-Psychological SEs like hallucination and emergence delirium limit its use
-Evidence showing subanesthetic doses can be used for tx of acute/chronic pain
What are the Pharmacokinetics associated with Ketamine?
-Onset = 1-2 minutes
-Low protein binding = 12%
-Highly lipid soluble
-Metabolism: Hepatic CYP = demethylation to form an active metabolite = Norketamine (1/3 - 1/5 as potent as Ketamine)
-DOA = 5-15 minutes
1/2 life = 2.5 -3 hours (dependent on liver blood flow)
What is the Induction dose of Ketamine?
1-2 mg/kg IV or 4-6 mg/kg IM
What are the maintenance doses for Ketamine?
-30 - 90 mcg/kg/min
OR
-15-45 mcg/kg/min + 50-70% N2O
What are the CNS effects of Ketamine?
-Profound analgesia
-Cataleptic state = eyes open, pupils reactive to light, corneal reflexes intact, lacrimation, blinking, involuntary muscle mvmt (nystagmus)
-Salivary glands increased
-CBF increased 60-80%
-Increased CMRO2, CBF, and ICP and IOP
-Being studied in Germany for neuro surgery due to improved cerebral perfusion, but impedes patient’s ability to follow commands postop.
What are the Respiratory effects of Ketamine?
-Bronchodilation
-Maintenance of Respiratory muscle tone and respiratory drive
-Increased salivation (counter with glycopyrrolate but beware of tachycardia)
-Airway reflexes intact (potential for laryngospasm)
-Potential for silent aspiration
-Respiratory depression can occur at high doses or when used with opioids
What are the CV effects of Ketamine?
-A useful induction agent for patients with hypovolemia
-Increased SNS tone = Increased CO (if normal catechol stores)
-Direct myocardial depressant effect (bad for patients in shock with depleted catecholamine stores)
-Increases BP, CO, HR, CVP, myocardial contractility, and myocardial O2 consumption
What are the Misc. effects of Ketamine?
-Aqueous solution = NO pain on injection
-Tracheal, bronchial, and salivary muscle gland secretions are increased with ketamine, which may require the use of an antisialagogue (risk for laryngospasm).
-Ketamine usually increases IOP, but the effect appears dose dependent.
-Ketamine causes nystagmus, increased muscle tone, and muscle spasms, which may not be appropriate for some ophthalmic procedures.
-Moderate analgesia
-Crosses into placenta (highly lipid soluble)
-Onset of effect is relatively slow compared to other induction drugs (2–5 min).
How does Ketamine have such a rapid onset?
-Depressed consciousness + increased sympathetic tone
-Increased SNS tone leads to an increased in CO (if normal catechol stores)
-More lipid soluble and less protein bound than other IV induction agents
-Inc CO + inc CBF = rapid cerebral uptake and then redistribution to peripheral compartments
What is Norketamine?
The active metabolite of Ketamine.
-1/3 to 1/5 as potent as Ketamine
-Has the potential to contribute to clinical effects with long infusions or chronic use
What are the anesthetic uses for Ketamine?
Enhances opioid-induced analgesia and prevents hyperalgesia
-Used as an adjunct at low doses to augment RA for C/S when block is inadequate for delivery
-Induction agent for patients with asthma or hypovolemia
-Adjunct bronchodilator in status asthmaticus (relaxes bronchial smooth muscle)
-Analgesic for burn therapy dressing changes
-Generally avoided in neuroanesthesia
-Aids in fiberoptic intubation, both awake and asleep
What conditions is Ketamine C/I in?
-CHF
-CAD
-Uncontrolled HTN
-Neuro & cerebral aneurysms
Requires caution in patients with hypertension, angina, congestive heart failure, increased intracranial pressure, increased intraocular pressure, psychiatric disease, and airway problems
Explain the mechanism of the NMDA Receptor.
The NMDA receptor is a ligand-gated ion channel where anions Ca 2+ and Na + are voltage dependent. L-glutamate, an amino acid, is probably the most important excitatory neurotransmitter in the CNS. At the NMDA receptor, it causes the opening of the ion channel. A rapid influx of Na + , Ca 2+ , and K + results in the depolarization of the normally negative postsynaptic membrane that initiates the action potential. Ketamine is a noncompetitive antagonist at this receptor.
