Pharmacology Chapter 25: General Anesthetics

Stem of all Inhaled anesthetics, and the MOA?

All end with "-ane" except (Nitrous oxide - Desflurane Enflurane Halothane Isoflurane Sevoflurane) MOA: Facilitate GABA-mediated inhibition • block brain NMDA and ACh-N receptors

Which inhaled anesthetics have bronchodilating actions - (drugs of choice in patients with asthma, bronchitis, COPD)

Halothane and sevoflurane

Give examples of inhaled anesthetics:

Halothane; nitrous oxide; isoflurane; enflurane; sevoflurane; desflurane; methoxyflurane

As lipid solubility of an inhaled anesthetic increases, what happens to the concentration of inhaled anesthetic needed to produce anesthesia, that is, does it increase or decrease?

It decreases.

What is the blood/gas partition coefficient? The ratio of the total amount of gas in the blood relative to the gas equilibrium phase ?

It refers to an inhaled anesthetic's solubility in the blood.

If an inhaled anesthetic has a high blood/gas partition coefficient, will times of induction and recovery be increased or decreased?

It will be increased because the time to increase arterial tension is longer.

only iv anesthetic with both analgesic and anesthetic properties

Ketamine

With regard to inhaled anesthetics, what does MAC stand for?

Minimum alveolar concentration. Note: this is not to be confused with monitored anesthesia care also commonly referred to as MAC, which is a combination of regional anesthesia, sedation, and analgesia.

Primary MOA of Inhaled Anesthetics?

Primary target is the GABAA chloride channel - may also act through hyperpolairzation of neurons through activation of potassium channels - may also block the excitatory actions of Ach at nicotinic receptors and their cation channel receptors

Give examples of intravenous (IV) anesthetics:

Propofol; fentanyl; ketamine; midazolam; thiopental; etomidate

For potent inhaled anesthetics, is the MAC small or large?

Small (inverse of the MAC is used as an index of potency for inhaled anesthetics)

State which stage of anesthesia each of the following descriptions refers to? Stage I: ? Stage II: ? Stage III: ? Stage IV: ?

Stage I (analgesia): Loss of pain sensation; patient is conscious; no amnesia in early part of this stage. Stage II (excitement): Delirium; violent behavior; increased blood pressure; increased respiratory rate; irregular breathing rate and volume; amnesia; retching and vomiting with stimulation; disconjugate gaze. Stage III (surgical anesthesia): Eye movements cease; fixed pupils; regular respiration; relaxation of skeletal muscles. Stage IV (medullary depression): Depression of vasomotor center; depression of respiratory center; death may occur.

Which statement concerning nitrous oxide is accurate? (A) A useful component of anesthesia protocols because it lacks cardiovascular depression (B) Anemia is a common adverse effect in patients exposed to nitrous oxide for periods longer than 2 h (C) It is the most potent of the inhaled anesthetics (D) There is a direct association between the use of nitrous oxide and malignant hyperthermia (E) Up to 50% of nitrous oxide is eliminated via hepatic metabolism

The answer is A. Anemia has not been reported in patients exposed to nitrous oxide anesthesia for periods as long as 6 h. Nitrous oxide is the least potent of the inhaled anesthetics, and the compound has not been implicated in malignant hyperthermia. More than 98% of the gas is eliminated via exhalation.

If ketamine is used as the sole anesthetic in the attempted reduction of a dislocated shoulder joint, its actions will include: (A) Analgesia (B) Bradycardia (C) Hypotension (D) Muscle rigidity (E) Respiratory depression

The answer is A. Ketamine is a cardiovascular stimulant, increasing heart rate and blood pressure. This results in part from central sym- pathetic stimulation and from inhibition of norepinephrine reuptake at sympathetic nerve endings. Analgesia and amnesia occur, with preservation of muscle tone and minimal depres- sion of respiration.

A 23-year-old man has a pheochromocytoma, blood pressure of 190/120 mm Hg, and hematocrit of 50%. Pulmonary function and renal function are normal. His catecholamines are elevated, and he has a well-defined abdominal tumor on MRI. He has been scheduled for surgery. Which one of the following agents should be avoided in the anesthesia protocol? (A) Desflurane (B) Fentanyl (C) Isoflurane (D) Midazolam (E) Sevoflurane

The answer is C. Isoflurane sensitizes the myocardium to catecholamines, as does halothane (not listed). Arrhythmias may occur in patients with cardiac disease who have high circulating levels of epinephrine and norepinephrine (eg, patients with pheo- chromocytoma). Newer inhaled anesthetics are considerably less arrhythmogenic.

For which of these drugs is the following true? Postoperative vomiting is uncommon with this intravenous agent, and patients are often able to ambulate sooner than those who receive other anesthetics. (A) Enflurane (B) Etomidate (C) Propofol (D) Remifentanil (E) Thiopental

The answer is C. Propofol is used extensively in anesthesia protocols, including those for day surgery. The favorable properties of the drug include an antiemetic effect and recovery more rapid than that after use of other intravenous drugs. Propofol does not cause cumulative effects, possibly because of its short half-life (2-8 min) in the body. The drug is also used for prolonged sedation in critical care settings.

A 20-year-old male patient scheduled for hernia surgery was anesthetized with halothane and nitrous oxide; tubocurarine was provided for skeletal muscle relaxation. The patient rapidly developed tachycardia and became hypertensive. Generalized skeletal muscle rigidity was accompanied by marked hyperthermia. Laboratory values revealed hyperkalemia and acidosis. The patient should be treated immediately with (A) Atropine (B) Baclofen (C) Dantrolene (D) Edrophonium (E) Flumazenil

The answer is C. The drug of choice in malignant hyperthermia is dantrolene, which prevents release of calcium from the sarcoplasmic reticulum of skeletal muscle cells. Appropriate measures must be taken to lower body temperature, control hypertension, and restore acid-base and electrolyte balance.

Which statement concerning the effects of anesthetic agents is false? (A) Bronchiolar smooth muscle occurs during halothane anesthesia (B) Chest muscle rigidity often follows the administration of fentanyl (C) Mild, generalized muscle twitching occurs at high doses of enflurane (D) Severe hepatitis has been reported after the use of desflu- rane (E) The use of midazolam with inhalation anesthetics may prolong the postanesthesia recovery period

The answer is D. Hepatitis after general anesthesia has been linked to use of halothane although the incidence is very low (1 in 20,00- 35,000). Hepatotoxicity has not been reported after adminis- tration of desflurane, or other inhaled anesthetics.

Total intravenous anesthesia with fentanyl has been selected for a frail elderly woman about to undergo cardiac surgery. Which statement about this anesthesia protocol is accurate? (A) Intravenous fentanyl will provide useful cardiostimulatory effects (B) Marked relaxation of skeletal muscles is anticipated (C) Opioids such as fentanyl control the hypertensive response to surgical stimulation (D) Patient awareness may occur during surgery, with recall after recovery (E) The patient is likely to experience pain during surgery

The answer is D. Intravenous opioids (eg, fentanyl) are widely used in anes- thesia for cardiac surgery because they provide full analgesia and cause less cardiac depression than inhalation of anesthetic agents. They are not cardiac stimulants, and fentanyl is more likely to cause skeletal muscle rigidity than relaxation. Disadvantages of this technique are patient recall (which can be decreased by concomitant use of a benzodiazepine) and the occurrence of hypertensive responses to surgical stimulation. The addition of vasodilators (eg, nitroprusside) or a β blocker (eg, esmolol) may be needed to prevent intraoperative hyper- tension.

Which statement concerning anesthetic MAC (minimum anesthetic concentration) value is accurate? (A) Anesthetics with low MAC value have low potency (B) MAC values increase in elderly patients (C) MAC values give information about the slope of the dose-response curve (D) Methoxyflurane has an extremely low MAC value (E) Simultaneous use of opioid analgesics increases the MAC for inhaled anesthetics

The answer is D. MAC value is inversely related to potency; a low MAC means high potency. MAC gives no information about the slope of the dose-response curve. Use of opioid analgesics or other CNS depressants with inhaled anesthetics lowers the MAC value. As with most CNS depressants, the elderly patient is more sensitive, so MAC values are lower. Methoxyflurane has the lowest MAC value of the inhaled anesthetics.

A new halogenated gas anesthetic has a blood:gas partition coefficient of 0.5 and a MAC value of 1%. Which prediction about this agent is most accurate? (A) Equilibrium between arterial and venous gas tension will be achieved very slowly (B) It will be metabolized by the liver to release fluoride ions (C) It will be more soluble in the blood than isoflurane (D) Speed of onset will be similar to that of nitrous oxide (E) The new agent will be more potent than halothane

The answer is D. The partition coefficient of an inhaled anesthetic is a determi- nant of its kinetic characteristics. Agents with low blood:gas solubility have a fast onset of action and a short duration of recovery. The new agent described here resembles nitrous oxide but is more potent, as indicated by its low MAC value. Not all halogenated anesthetics undergo significant hepatic metabolism or release fluoride ions.

A 20-year-old male patient scheduled for hernia surgery was anesthetized with halothane and nitrous oxide; tubocurarine was provided for skeletal muscle relaxation. The patient rapidly developed tachycardia and became hypertensive. Generalized skeletal muscle rigidity was accompanied by marked hyperthermia. Laboratory values revealed hyperkalemia and acidosis. This unusual complication of anesthesia is most likely caused by (A) Acetylcholine release from somatic nerve endings at skeletal muscle (B) Activation of brain dopamine receptors by halothane (C) Block of autonomic ganglia by tubocurarine (D) Pheochromocytoma (E) Release of calcium from the sarcoplasmic reticulum

The answer is E. Malignant hyperthermia is a rare but life-threatening reaction that may occur during general anesthesia with halogenated anesthetics and skeletal muscle relaxants, particularly succi- nylcholine and tubocurarine. Release of calcium from skeletal muscle leads to muscle spasms, hyperthermia, and autonomic instability. Predisposing genetic factors include clinical myop- athy associated with mutations in the gene loci for the skeletal muscle ryanodine receptor or L-type calcium receptors.

Sevoflurane is degraded in the respiratory machine into what toxin?

The carbon dioxide absorbent in anesthesia machines producing a vinyl ether which can cause kidney damage.

What is MAC in regard to inhaled anesthetics?

The concentration of inhaled anesthetic required to stop movement in 50% of patients given a standardized skin incision; a measure of potency for inhaled anesthetics.

a) What is dissociative anesthesia?

The patient is unconscious and feels no pain, yet appears awake. Eyes may open and the swallowing reflex is present, but the patient is sedated, immobile, and usually amnestic. Hallucinations and delirium are common.

a) What adverse drug reaction may be caused by fentanyl when given intravenously? b) Does propofol have good analgesic properties?

a) Chest wall rigidity b) No

a) Malignant Hyperthermia is caused by? b) Treated with?

a) Condition induced by general anesthetics and succinylcholine (skeletal muscle relaxant) b) Treat with dantrolene which blocks the release of Ca from SR

a) Do inhaled anesthetics increase or decrease the response to Pco2 levels? b) Do inhaled anesthetics increase or decrease cerebral vascular flow? c) Do inhaled anesthetics increase or decrease intracranial pressure?

a) Decrease b) Increase c) Increase

a) About which allergies should a patient be questioned before administration of propofol? b) Does propofol increase or decrease blood pressure?

a) Egg and soybeans. Propofol is prepared as a lipid emulsion using egg and soybean lecithin. This gives propofol its white color and can cause allergic reactions in patients with sensitivities to these substances. b) It decreases blood pressure.

a) Which inhaled anesthetic is associated with malignant hyperthermia? b) What characterizes malignant hyperthermia?

a) Halothane b) Hyperthermia; muscle rigidity; acidosis; hypertension; hyperkalemia

a) Which inhaled anesthetic, halothane or nitrous oxide, will take longer to change the depth of anesthesia when the concentration of the inhaled anesthetic has been changed? b) Are MAC values additive?

a) Halothane b) Yes

a) Is thiopental used for induction, maintenance, or both? b) Pharmacodynamically, how does recovery occur with the rapid-acting barbiturates?

a) Induction b) Rapid redistribution from the central nervous system (CNS) to peripheral tissues

a) Which inhaled anesthetic is associated with increased bronchiolar spasms? b) Which inhaled anesthetic relaxes bronchial smooth muscle? c) Which inhaled anesthetic is associated with cardiac arrhythmias?

a) Isoflurane b) Halothane c) Halothane

a) Which inhaled anesthetic is associated with increased bronchiolar secretions? b) Which inhaled anesthetic is associated with hepatitis? c) Halothane is not hepatotoxic in what patient population? d) Which inhaled anesthetic is the least hepatotoxic?

a) Isoflurane b) Halothane c) Pediatric patients d) Nitrous oxide

a) Which inhaled anesthetics increase heart rate (via reflex secondary to vasodilation)? b) Which inhaled anesthetics decrease heart rate? c) Which inhaled anesthetic decreases renal and hepatic blood flow?

a) Isoflurane; desflurane b) Halothane; enflurane; sevoflurane c) Halothane

a) Is propofol used for induction, maintenance, or both? b) Which IV anesthetic causes dissociative anesthesia?

a) It is used for both. b) Ketamine

a) Give an example of an inhaled anesthetic with a low blood/gas partition coefficient (low blood solubility): b) Give an example of an inhaled anesthetic with a high blood/gas partition coefficient (high blood solubility):

a) Nitrous oxide (0.5); desflurane (0.4) b) Halothane (2.3); enflurane (1.8)

a) Which inhaled anesthetic has the largest MAC? b) Which inhaled anesthetic has the smallest MAC?

a) Nitrous oxide (>100%) b) Halothane (0.75%)

State whether thiopental increases, decreases, or does not change each of the following physiologic effects: a) Cerebral blood flow: ? b) Respiratory function: ? c) Blood pressure: ?

a) No change b) Decreases c) Decreases

a) Which anesthetic has antiemetic properties? b) Which IV anesthetic is a cardiovascular stimulant (increases blood pressure and cardiac output)? c) Which IV anesthetic causes vivid dreams and hallucinations? d) Does ketamine increase or decrease cerebral blood flow? e) What is the most cardiac-stable IV anesthetic agent?

a) Propofol b) Ketamine c) Ketamine d) Increase e) Etomidate

a) Do inhaled anesthetics relax or strengthen uterine smooth muscle contractions? b) Which of the inhaled anesthetics is not a halogenated hydrocarbon? c) Are the inhaled halogenated hydrocarbon anesthetics volatile or nonvolatile gases?

a) Relax (except methoxyflurane when briefly inhaled, therefore, can be used during childbirth) b) Nitrous oxide c) Volatile gases

a) Are MAC values higher or lower in elderly patients? b) Are MAC values higher or lower when opioid analgesics and/or sedative hypnotics are used concomitantly?

a) They are lower, thus elderly patients generally require lower concentrations of inhaled anesthetics. b) They are lower.

a) Which of the previously mentioned IV anesthetics is a barbiturate? b) Which of the previously mentioned IV anesthetics is a benzodiazepine? c) Which of the previously mentioned IV anesthetics is an opioid?

a) Thiopental b) Midazolam c) Fentanyl

a) Should a patient with a family history positive for malignant hyperthermia be concerned? b) What drug is given to treat malignant hyperthermia?

a) Yes, because a genetic defect in ryanodine receptors may be inherited. b) Dantrolene

Inhaled anesthetics: a) Decrease cardiac output? b) decrease peripheral vascular resistance? (c) Causes bradycardia through direct vagal stimulation? d) increase heart rate?

a) halothane and enflurane b) iso-flurane, desflurane, sevoflurane. c) halothane d) Enflurane, sevoflurane no effect, desflurane and isoflurane

Ketamine causes emergence phenomena following use as an anesthetic (perceptual illusions, vivid dreams) - what drug reduce this?

diazepam or midazolam reduces incidence of emergence phenomena

Effects of Ketamine?

drug produces dissociative anesthetic state, which includes catatonia, amnesia, analgesia with or without loss of consciousness (hypnosis).

Liver biotransformation of enflurane and sevoflurane can produce

fluoride ions which produce kidney damage, more pronounced with methoxyflurane (rarely used for this reason)

All (except which inhaled anesthetics) produce a decrease in tidal volume and an increase in respiratory rate ?

nitrous oxide

Which inhaled anesthetics less likely to increase cerebral blood flow?

nitrous oxide

How to screen for Malignant Hyperthermia?

skeletal muscle biopsy and caffeine-halothane contracture test required to screen for malignant hyperthermia

clearance of inhaled anesthetics via

the lungs is the major route of elimination from the body

liver biotranformation of fluoride containing inhaled anesthetics can lead to ?

the production of chlorotrfluoroethyl free radicals which can produce an halothane hepatitis