General Anesthetics

Question 1

The state of “general anesthesia” includes:

Answer 1

• Analgesia
• Amnesia
• Loss of consciousness
• Suppression of reflexes
• Skeletal muscle relaxation

Question 2

Overview of balanced anesthesia?

Answer 2

• No single drug is capable of achieving all of the
desired goals of anesthesia.
• In balanced anesthesia, several drugs are
used in combination to produce the anesthetic
state.
• The onset of inhalational agents is not rapid:
patients are usually anesthetized with an IV
agent.
• Halogenated hydrocarbons are not good analgesics: a supplemental analgesic is
required.
• Neuromuscular blockers are used to provide
paralysis adequate for surgical access.

Question 3

Types of General Anesthetics?

Answer 3

• INHALED ANESTHETICS

* IV ANESTHETICS

Question 4

List inhaled anesthetics gases and 6 volatile halogenated hydrocarbons?

Answer 4

• Gases
▪N2O
• Volatile halogenated hydrocarbons
▪Halothane
▪Enflurane
▪Isoflurane
▪Desflurane
▪Sevoflurane
▪Methoxyflurane

Question 5

goals of IV anesthetics?

Answer 5

Used alone or with other drugs to:
• Achieve anesthesia
• As components of balanced anesthesia
• Sedate patients in ICUs who must be
mechanically ventilated for long periods.

Question 6

IV anesthetics include(list 4)

Answer 6

IV anesthetics include:
• Barbiturates
• Propofol
• Ketamine
• Etomidate

Question 7

inhaled anesthetic use? List 6 common features?

Answer 7

• Used for the maintenance of anesthesia after administration of an IV agent.
COMMON FEATURES
• Increase perfusion of brain.
• Cause bronchodilation.
• Decrease minute ventilation.
• Potency correlates with liposolubility.
• Rate of onset inversely correlates to blood
solubility.
• Recovery is due to redistribution from the brain.

Question 8

MOA of inhaled anesthetics?

Answer 8

• The actions of inhaled anesthetics are the
consequence of direct interactions with ligand gated ion channels.
• Positive modulation of GABAA and glycine
receptors.
• Inhibition of nicotinic receptors.

Question 9

Define MAC and its role in potency of anesthetics?

Answer 9

• Standard of comparison for potency of general
anesthetics: Minimum alveolar concentration
(MAC).
• MAC is the concentration that results in
immobility in 50% of patients when exposed to a noxious stimulus such as surgical
incision.
• MAC is expressed as % of the alveolar gas mixture.
• MAC is low for potent anesthetics and large for less potent agents.

Question 10

Feature of MAC values when determining requirements?

Answer 10

• MAC values are additive.
• Nitrous oxide can be used as a “carrier” gas,
decreasing the anesthetic requirement of
other inhaled anesthetics.
• 0.7 MAC of isoflurane and 0.3 MAC of nitrous
oxide yield 1 MAC.

Question 11

Order highest MAC to lowest MAC(not necessarily numbers)

Answer 11

Anesthetic MAC (%)
Nitrous oxide 104
Desflurane 6
Sevoflurane 2.0
Enflurane 1.7
Isoflurane 1.4
Halothane 0.75
Methoxyflurane 0.16

Question 12

Define THE MEYER–OVERTON CORRELATION

Answer 12

• The potency of an anesthetic can be predicted from its liposolubility.
• The oil:gas partition coefficient is a good measure of the liposolubility.
• The potency of an anesthetic increases as its solubility in oil increases.
• As λ(oil:gas) increases, the MAC decreases.

Question 13

Partition coefficient definition?

Answer 13

• The partition coefficient is the ratio of the concentrations of a compound in one solvent to
the concentration in another solvent.
• For example, an oil:gas partition coefficient of 19
means that the concentration of anesthetic in oil
is 19-fold that present in the alveolar gas when
the partial pressure of the anesthetic is identical
at both sites.

Question 14

POTENCY & LIPOSOLUBILITY relationship?

Answer 14

The potency of an anesthetic increases as

its liposolubility increases.

Question 15

Describe anesthetic induction and 5 dependent factors?

Answer 15

• Anesthesia requires transfer of anesthetic from the alveolar air to the blood and then to the brain.
• The rate at which a given concentration of
anesthetic in the brain is reached depends on:
• Solubility of the anesthetic
• Its concentration in the inspired air
• Pulmonary ventilation rate
• Pulmonary blood flow
• Arteriovenous concentration gradient

Question 16

Solubility of blood and onset of anesthetic? Define blood gas coefficient

Answer 16

• The blood:gas partition coefficient (gamma) is a useful index of solubility.
• It defines the relative solubility of an anesthetic
in the blood compared to air.
• When an anesthetic with low solubility in blood
reaches the arterial blood the arterial tension of
the anesthetic rises quickly.
• Conversely, if an anesthetic has high solubility in
blood, more molecules of the anesthetic will
dissolve in blood before the partial pressure
increases significantly.
• Consequently, the arterial tension of the gas
increases less rapidly.
• Therefore there is an inverse relationship
between the blood solubility of an anesthetic and
the rate of rise of its tension in arterial blood.
• A low blood:gas partition coefficient determines a faster onset of anesthesia

Question 17

Anesthetic potency and onset?

Answer 17

• Anesthetics with large λ(oil:gas) have large λ(blood:gas).

* High potency correlates with slow onset.

Question 18

effects of ANESTHETIC CONCENTRATION

IN THE INSPIRED AIR? Ventilation?

Answer 18

• Increase in anesthetic concentration increases
the rate of induction.
• Increase in ventilation rate
increases rate of induction.

Question 19

Effect of Pulmonary blood flow on anesthetic induction?

Answer 19

• An increase in pulmonary blood flow (increased
cardiac output) slows the rate of induction.
• This is because increased pulmonary blood flow
exposes a larger volume of blood to the anesthetic.
• Blood “capacity” increases and tension rises
slowly.

Question 20

Arteriovenous concentration gradient effect on anesthetic induction?

Answer 20

• Difference between the concentration of anesthetic in arterial and venous blood.
• Reflects the solubility of the anesthetic in
the tissues.
• Uptake by tissues slows down onset and
recovery.

Question 21

Describe elimination of anesthetics?

Answer 21

• Elimination of inhalational anesthetics is largely
the reverse process of uptake.
• For agents with low blood and tissue solubility,
recovery from anesthesia mirrors anesthetic induction, regardless of the duration of
anesthetic administration
• For agents with high blood and tissue solubility,
recovery depends on the duration of anesthetic
administration.
• This is because the anesthetic accumulates in
fat.

Question 22

CV effects of inhalants?

Answer 22

• Most inhaled anesthetics depress normal
cardiac contractility.
• As a result, they tend to decrease mean arterial
pressure.
• Halothane and enflurane reduce MAP mainly
by myocardial depression, with little effect on
PVR.
• Isoflurane, desflurane and sevoflurane
produce vasodilation and have minimal effect on
cardiac output.
• Isoflurane, desflurane and sevoflurane may
be better choices for patients with impaired
myocardial function.
• N2O lowers blood pressure less than other
inhaled anesthetics.
• Halothane sensitizes the myocardium to
circulating catecholamines, which may lead to
ventricular arrhythmias.
• This effect is less marked for isoflurane,
sevoflurane and desflurane.

Question 23

Respiratory effects of anesthetics?

Answer 23

• Volatile anesthetics are bronchodilators.
• Volatile anesthetics are respiratory depressants.
• Isoflurane and enflurane are the most depressant.
• N2O is the least depressant.

Question 24

CNS effects of anesthetics?

Answer 24

• Inhaled anesthetics increase intracranial pressure.
• Undesirable in patients who already have increased intracranial pressure because of brain tumor or head injury.
• N2O increases blood flow the least.
• Enflurane at high concentrations may cause tonic clonic movements.

Question 25

Consideration of N2O other effects?

Answer 25

• N2O exchanges with nitrogen in air-containing cavities in the body. • N2O enters the cavity faster than nitrogen escapes. • Therefore, it increases the volume and/or pressure of the cavity.

Question 26

• N2O should be avoided in the following clinical | settings:(list 7)

Answer 26

``` • N2O should be avoided in the following clinical settings: • Pneumothorax • Obstructed middle ear • Air embolus • Obstructed loop of bowel • Intraocular air bubble • Pulmonary bulla • Intracranial air ```

Question 27

Which two organ toxicities associated with anesthetics? Which anesthetics specifically?

Answer 27

HEPATOTOXICITY (HALOTHANE) • Some individuals exposed to halothane may develop a potentially severe and life-threatening hepatitis. • There is no specific treatment • Liver transplantation may be required. NEPHROTOXICITY • Methoxyflurane has nephrotoxic potential. • Due to fluoride released during metabolism.

Question 28

Describe malignant hyperthermia in relation to anesthetics?

Answer 28

• Potentially fatal genetic disorder of skeletal muscle. • Triggered in susceptible individuals by volatile inhalation anesthetics, such as halothane, and depolarizing skeletal muscle relaxants, such as succinylcholine. • Transmitted as an autosomal dominant trait. • Incidence is about 1:12,000. • Malignant hyperthermia is one of the main causes of death due to anesthesia.

Question 29

• The malignant hyperthermia syndrome includes: (list 6)

Answer 29

* Tachycardia * Hypertension * Severe muscle rigidity * Hyperthermia * Hyperkalemia * Acidosis

Question 30

Basis of Malignant hyperthermia?

Answer 30

• Malignant hyperthermia results from altered control of Ca2+ release from the SR. • In most cases, the syndrome is caused by a defect in the ryanodine receptor gene (RYR1). • Abnormal RYR receptors trigger unregulated release of calcium from the SR, which may lead to an acute malignant hyperthermia crisis.

Question 31

Mechanism and consequence of malignant hyperthermia?

Answer 31

• The increased Ca2+ concentration causes increased muscle contraction which generates heat. • Increased levels of aerobic metabolism produce CO2 and deplete O2 and ATP. • A switch to anaerobic metabolism worsens acidosis with the production of lactate. • Energy stores get depleted. • Muscle fibers die leading to hyperkalemia and myoglobinuria.

Question 32

MALIGNANT HYPERTHERMIA: TREATMENT?

Answer 32

• Dantrolene: blocks Ca2+ release from the sarcoplasmic reticulum. • Measures to reduce body temperature and restore electrolyte and acid-base balance.

Question 33

THE CAFFEINE-HALOTHANE MUSCLE CONTRACTURE TEST?

Answer 33

• The most reliable test to establish susceptibility to malignant hyperthermia. • A muscle sample is removed from the thigh. • The response to halothane and caffeine is assessed.

Question 34

Consequence of prolonged N2O exposure?

Answer 34

Hematotoxicity • Prolonged exposure to N2O decreases methionine synthase activity and causes megaloblastic anemia. • Potential occupational hazard for staff working in poorly ventilated dental operating suites.

Question 35

List 4 IV anesthetics?

Answer 35

▪ Barbiturates ▪ Propofol ▪ Ketamine ▪ Etomidate

Question 36

Describe Ultra short acting barbiturates?

Answer 36

Thiopental and Methohexital • Used for induction of anesthesia and for short surgical procedures. • Their anesthetic effects are terminated by redistribution from the brain to other tissues, but hepatic metabolism is required for their elimination from the body. • VRG: brain, liver, kidneys • MG: muscle, skin • FG: fat • They decrease intracranial pressure. • They do not produce analgesia. • They may cause hyperalgesia. • May cause apnea, coughing, chest wall spasm, laryngospasm and bronchospasm: a concern for asthmatic patients.

Question 37

Overview of propofol?

Answer 37

* Postoperative vomiting is uncommon. Antiemetic. * Used for induction and maintenance of anesthesia. * Produces no analgesia. * Rapidly metabolized in the liver. * Potent respiratory depressant. * Reduces intracranial pressure. * Causes hypotension through decreased PVR. * Fospropofol: prodrug converted to propofol in vivo.

Question 38

Overview of Etomidate?

Answer 38

* Primarily used for anesthetic induction of patients at risk for hypotension. * Causes minimal CV and respiratory depression. * No analgesic effects. * Reduces intracranial pressure. * Associated with nausea and vomiting.

Question 39

Overview of Ketamine?

Answer 39

• Produces dissociative anesthesia, characterized by catatonia, amnesia and analgesia, with or without loss of consciousness. • Mechanism of action may involve blockade of NMDA receptors. • Only IV anesthetic that possesses both analgesic properties and the ability to produce CV stimulation. • Increases intracranial pressure. • Causes sensory and perceptual illusions, and vivid dreams (‘emergence phenomena’). • Diazepam, midazolam, or propofol reduce the incidence of these phenomena.

Question 40

Overview of Neuroleptic-Opioid Combinations

Answer 40

Neuroleptic-Opioid Combinations • When a potent opioid analgesic, such as fentanyl, is combined with a neuroleptic such as droperidol, neurolept analgesia is established. • Neurolept analgesia can be converted to neurolept anesthesia by the concurrent administration of 65% N2O in O2 .

Question 41

adjuncts to anesthetics?

Answer 41

• Adjuvant drugs provide additional effects that are desirable during surgery but are not necessarily provided by the general anesthetics. • Benzodiazepines. For their anxiolytic and anterograde amnesic properties. • Opioids. For analgesia. • Neuromuscular blockers. To achieve muscle relaxation. • Antiemetics, eg ondansetron. To prevent possible aspiration of stomach contents. • Antimuscarinics, eg scopolamine • For its amnesic effects • To prevent salivation and bronchial secretions • To protect the heart from bradycardia caused by inhalation agents and neuromuscular blockers.