Pharmacology I: CNS IV - General anesthetics

General anesthetics are administered to create a reversible surgical state characterized by … (2), given systemically and exert their main effects on the CNS

loss of consciousness, pain sensation

Two general ways of administering GA: … (2)

inhalation, intravenous

Four stages of anesthetics: … (4)

analgesia, disinhibition, surgical anesthesia, medullary depression

…: decreased awareness of pain, sometimes with amnesia, consciousness may be impaired but not lost

analgesia

…: patient becomes delirious and excited, amnesia, enhances reflexes (coughing and vomiting) but eyelash reflex disappear, irregular respiration (retching and incontinence may occur

disinhibition

…: unconscious, no pain reflexes, regular respiration and maintained bp

surgical anesthesia

…: severe respiratory and cardiovascular depression that requires mechanical and pharmacological support

medullary depression

For … → IV agents and local anesthetics → patient experiences profound analgesia and can respond to verbal commands

minor procedures (conscious sedation techniques)

For Extensive surgical procedures → IV drug to induce the anesthetic state, … (2) to maintain the state, neuromuscular blocking agents to promote muscle relaxation

inhaled anesthetics, IV agents

For extensive surgical procedures vital sign monitoring → assessing depth of anesthesia during surgery → …

eyelash reflex

MOA on anesthetic drugs → effects on ion channels by interaction with … (2) → central neurotransmitter mechanisms

membrane lipids, membrane proteins

MOA of most inhaled anesthetics … at moderate to high concentrations

inhibit nicotinic receptors

MOA of inhaled anesthetics, barbiturates, benzodiazepines, etomidate, propofol: …

GABA-mediated inhibition at GABAa receptors

Some anesthetics work by … on the NMDA receptors (ketamine)

antagonizing with glutamic acid

…: indicated for minor surgery, used with volatile or intravenous anesthetics, odorless rapid induction with minimal cardiovascular effects

Nitrous oxide

Nitrous oxide is associated with postoperative: … (3)

nausea, vomiting, synergistic respiratory depression,

Inhaled anesthetics (halogenated hydrocarbons): … (5)

desflurane, enflurane, halothane, isoflurane, sevoflurane

The inhaled gas concentration in the brain sufficient to achieve anesthesia depends on: … (5)

concentration, blood solubility, arteriovenous concentration gradient, pulmonary blood flow, pulmonary vent. rate

…: define as the concentration of inhaled anesthetics as a % of inspired air, at which 50% of patients do not respond to a surgical stimulus (measure of potency)

Minimal alveolar concentration (MAC)

The more … the anesthetic, the lower the MAC and the greater the potency

lipid soluble

CNS drugs must be lipid soluble to cross the BBB or other wise be …

actively transported

The more soluble the anesthetic in the blood the …

slower the anesthesia

Anesthetics with … are associated with slow onset and recovery

high blood-gas ratio

Anesthetics with … have has onset and recovery

low blood-gas ratios

Drugs with low solubility in blood  → … induction and recovery times

rapid

Drugs with high solubility in lipids have …

higher potency

… has high lipid and blood solubility and this high potency and slow induction

halothane

…: represented by the relative size of the blood compartment (the more soluble, the larger the compartment)

solubility

… of the agents in the compartments are indicated by the degree of filling of each compartment

relative partial pressures

For a given concentration or partial pressure of the two anesthetic gases in the inspired air, it will take much longer for the … of the more soluble gas to rise to the same partial pressure as in the alveoli

blood partial pressure

CNS effects of inhaled anesthetics: … (3)

decreased brain metabolic rate, decreased vascular resistance, increased intracranial pressure

Cardiovascular effects of inhaled anesthetics: … (3)

decreased arterial BP moderately, decreased cardiac output, decreased blood flow to liver/kidney

Respiratory effects of inhaled anesthetics: … (2)

decreased ventilatory response to hypoxia, bronchodilators

Toxicity effects of inhaled anesthetics: … (3)

renal insufficiency, hepatitis, malignant hyperthermia (in susceptible pt)

… (2) as treatment for malignant hyperthermia

supportive measures, muscle relaxants (dantrolene)

Parenteral anesthetics: … (5)

propofol, thiopental, etomidate, ketamine, midazolam

…: fast onset, and very fast recovery, cardiovascular and respiratory depression, pain at site of injection

propofol 

Propofol has potential agonist actions on …, commonly used in maintenance of anesthetic state and prolonged sedation

GABAa receptors

Propofol is a CNS and cardiac depressant and may cause marked … during induction of anesthesia 

hypotension

…: fast bit can accumulate leading to slow recovery, cardiovascular and respiratory depression, largely replaced by propofol, risk of precipitating polyphyaria in susceptible patients

thiopental

Thiopental is the only … in common use as an anesthetic

barbiturate

Thiopental has a very high lipid solubility, redistribution occurs first to … then more slowly to muscles, it has a long-lasting hangover due to its storage in fat

highly profuse organs

Thiopental is used exclusively as an …, produces little analgesic effects and profound resp depression

inducing agent

…: fast onset, fairly fast recovery, excitatory effects during induction and recovery, adrenocortical suppression, less cardiovascular and respiratory depression than with thiopental

etomidate

Etomidate has … on GABAa receptors, advantage for patients with circulatory failures due to lack of effects on cardio/resp

agonist action

…: slow onset, after effects common during recovery, psychotomimetic effects following recovery, postoperative vomiting, raised ICP, produces good analgesia and amnesia without rep. depression

ketamine

On ketamine the patient may be conscious but experiences: …(4)

marked catatonia, analgesia, amnesia, hallucinations

…: slow onset, may cause amnesia, but little analgesia, little cardoresp depression

midazolam