Anesthetics: Organ effects, Toxicity, IV drugs, Adjuncts

Question 1

Moving on to the effects of inhaled anesthetics on organs. What are the CVS effects?

Answer 1

Inhaled anesthetics depress normal cardiac contractility
Halothane and enflurane reduce arterial pressure mainly by myocardial depression, with little effect on vascular resistance
Isoflurance, desflurane and sevoflurane produce greater vasodilation and have min effect on cardiac output
Isoflurance, desflurance, and sevoflurane may be better choices for patients with impaired myocardial function
Halothane sensitizes the myocardium to circulating catecholamines, which may lead to ventricular arrhythmias

Question 2

What are the respiratory effects of inhaled anesthetics?

Answer 2

Isoflurane and Desflurane are pungent –less suitable for induction anesthesia in patients with bronchospasm
Halothane, sevoflurane, and NO are nonpungent
All volatile anesthetics are resp depressants with iso and des being the most and NO being the least

Question 3

What are the CNS effects of inhaled anesthetics?

Answer 3

Increase cerebral blood flow and they reduce cerebral vascular resistance which leads to increase in intracranial pressure
NO increases blood flow the least
Enflurane may lead to development of a spike and wave pattern and mild muscle twitching
NO has low anesthetic potency, but exerts marked analgesic and amnesic actions

Question 4

What are the effects on the kidney, liver and uterine smooth muscle of inhaled anesthetics?

Answer 4

Kidney:
--decrease GFR and renal blood flow
Liver:
--decrease hepatic blood flow 
Uterine Smooth Muscle
--halogenated hydrocarbon anesthetics are potent uterine relaxants 
Other effects: 
N2O should be avoided in pneumothorax, obstructed middle ear, air embolus, obstructed loop of bowel, intraocular air bubble, pulmonary bulla, and intracranial air.

Question 5

Moving on to toxicity of inhaled anesthetics. Discuss hepatotoxicity with halothane and nephrotoxicity

Answer 5

Hepatotoxicity (halothane)
–can cause life threatening hepatitis
Nephrotoxicity:
–nephrotoxic potential of methoxyflurane has limited its clinical use in anesthesia.

Question 6

Next toxicity is malignant hyperthermia (AD), what is this?

Answer 6

Fatal genetic disorder of skeletal muscle that is triggered by halogenated hydrocarbon inhalation anesthetics and depolarizing skeletal muscle relaxants, succinylcholine
–most incidents arise from the combo of succinylcholine and an halogenated anesthetic

Question 7

Malignant hyperthermia is one of the main causes of death due to anesthesia. What does it result from?

Answer 7

Altered control of Ca2+ release from the sarcoplasmic reticulum
–in most cases, the syndrome is caused by a defect in the ryanodine receptor gene (RYR1)

Question 8

Muscle cells possess Ca2+ channels called ryanodine receptors (RYRs), because of their sensitivity to the plant alkaloid ryanodine. Explain the action of these receptors

Answer 8

In skeletal muscle cells, these receptors are located in the membrane of the sarcoplasmic reticulum and associated with the cytoplasmic domain of the dihydropyridine receptor (DHPR)
–in response to depolarization, the DHPRs undergo a confirmation change, this produces a conformational change in the associated RYRs, opening them, so that Ca2+ is released from the sarcoplasmic reticulum in the cytosol.

Question 9

Abnormal RYR1 receptors therefore trigger what?

Answer 9

Unregulated release of calcium from the sarcoplasmic reticulum
–this leads to an acute malignant hyperthermia crisis

Question 10

What is the treatment for acute malignant hyperthermia?

Answer 10

Dantrolene (Which prevents Ca2+ release from the sarcoplasmic reticulum)

Question 11

What is the most reliable test to establish susceptibility for malignant hyperthermia?

Answer 11

In vitro caffeine- halothane muscle contracture test
–a response to halothane or response to low concentrations of caffeine are diagnostic for malignant hyperthermia susceptible muscle.

Question 12

What is one chronic toxicity that is of concern esp dental operating suites?

Answer 12

Prolonged exposure to NO decreases methionine synthase activity and causes megaloblastic anemia

Question 13

IV agents are commonly used for the rapid induction of anesthesia, which is then maintained with an appropriate inhalation agent. What are the ultra short acting barbiturates?

Answer 13

Thiopental and Methohexital

• -thiopental is more often used
• -high liposolubility (results in rapid entry into the brain)
• -anesthetic effects are terminated by redistribution from the brain to other tissues
• -they decrease intracranial pressure
• -do not produce analgesia

Question 14

Propofol has become the most popular IV anesthetic. Used for outpatient surgical procedures, in intensive care settings, and in balanced anesthesia. What are some features of propofol?

Answer 14

Postoperative vomiting is uncommon; has antiemetic actions
Used for induction and maintenance
Rapidly metabolized in the liver
Reduces intracranial pressure
Causes hypotension through decreased peripheral vascular resistance
Fospropofol is a prodrug

Question 15

Etomidate is the next IV anesthetic used for the induction of patients at risk for hypotension. What are some features?

Answer 15

Reduces Intracranial pressure
Associated with nausea and vomiting
May cause adrenocortical suppression via inhibitory effects of steroidogenesis

Question 16

Ketamine is the next IV anesthetic. What are some features?

Answer 16

Produces Dissociative Anesthesia (Cataonia, amnesia, and analgesia)
Only IV anesthetic that possesses both analgesic properties and the ability to produce CV stimulation (Therefore HR and arterial blood pressure should increase) – cardiostimulatory
Increases intracranial pressure
Postoperative disorientation, sensory and perceptual illusions and vivid dreams (emergence phenomena)

Question 17

Neuroleptic opioid combinations can be used as an IV anesthetic, Droperidol. What are some features?

Answer 17

Produces a state of quiescence with reduced motor activity, reduced anxiety, and indifference to the surroundings.

Question 18

Neurolept analgesia can be converted to neurolept anesthesia by the concurrent administration of 65% nitrous oxide in oxygen. The combination of fentanyl and droperidol is available as a fixed ratio prep called?

Answer 18

Innovar

Question 19

Adjuvant drugs provide additional effects that are desirable during surgery but are not necessarily provided by the general anesthetics. What are these drugs?

Answer 19

Benzos (diazepam, lorazepam, midazolam) given for their anxiolytic and anterograde amnesic properties
Opioids (morphine and fentanyl): used for their ability to produce analgesia
Neuromuscular Blockers: achieve muscle relaxation (reversed by neostigmine)
Antiemetics (ondansetron): prevent aspiration of stomach contents
Antimuscarinics (scopolamine): administered for its amnesic effect, to prevent salivation and bronchial secretions, and to protect the heart from arrhythmias, particularly bradycardia.