General Anesthetics

Front 1

Thiopental, Methohexital
Class?
Administration & Onset?
Toxicity?
Contraindications

Back 1

Thiopental, Methohexital
Class: Barbituates

Administration & Onset: IV, Rapid onset
1. Terminated by redistribution
2. Terminal half-lives longer with continued infusion (but methohexital has relatively rapid clearance)
3. Neonates require higher induction dose

Toxicity:
1. Decreased cerebral metabolism
2. Decreased cerebral blood flow
3. Decreased blood pressure
4. Decreased respiration

Barbiturates have antiseizure activity

Contraindications:
1. Patients with porphyria
2. Poor analgesia, little muscle relaxation

Front 2

Propofol
Administration & Onset?
Problems/Toxicity?

Back 2

Propofol

Administration & onset
1. High degree of clearance so rapid recovery after infusion.
2. Onset and duration similar to barbiturates (redistribution is still important)
3. Rapid clearance compared to barbiturates
4. Can be used for maintenance and induction (Less of a hangover than thiopental)

Problems:
1. Poor analgesia
2. Slight muscle relaxation

Toxicity Includes:
1. Decreased cerebral metabolism
2. Decreased cerebral blood flow
3. Decreased blood pressure
4. Depressed respiration
5. PAIN IN INJECTION (irritates nerve endings on veins)

Front 3

Etomidate
Administration and Onset?
Uses?
Problems?
Toxicity?
Drug Interaction?

Back 3

Etomidate

Administration: IV

Uses: Used for induction
1. Cardiostable - used in patients with a risk of hypotension

Problems:
1. Poor analgesia

Toxicity:
1. Decreased cerebral metabolism
2. Decreased Cerebral blood flow
3. Depressed respiration (less than thiopental)
4. PAIN on INJECTION
5. Significant nausea/vomiting
6. Suppression of adrenocortical stress response

Drug Interaction: Fentanyl prolongs elimination half-life

Front 4

Ketamine
Mechanism?
Uses?
Metabolism?
Toxicity?
Drug interactions?

Back 4

Ketamine

Meachanism: Blocks glutamate receptors

Uses: Can be used for IV anesthetic by itself, usually for short procedures, but can give multiple injections (therefore it can be used for maintenance). Also could be used for induction and followed by a different agent.
1. Used in patients with risk for hypotension or bronchospasm since it increases blood pressure and is a bronchodilator
2. Useful in children undergoing short painful procedures
3. Analgesic
4. Amnesia despite the patient being awake (dissociative amnesia)

Metabolism: Liver

Toxicity:
1. Increased cerebral blood flow
2. Cataleptic state
3. Emergence Delirium
4. Analog of PCP

Drug interactions: Potentiates nondepolarizing muscle relaxants. Ketamine + Theophylline can predispose to seizures.

Front 5

Clinical problems of IV Anesthetics?

Back 5

Clinical problems of IV Anesthetics?
1. Depression of respiratory drive because of lower to CO2 or to hypoxia
2. Depressed cardiovascular drive
3. Muscular rigidity (opioids, ketamine)
4. Ketamine - hallucinations and emergence delirium
5. Etomidate - steroidogenesis inhibition
6. Thiopental - May reduce pain threshold??

Front 6

Halothane

Back 6

Halothane

Induction:
1. Relatively high blood/gas partition coefficient leading to slow induction time
2. Very Potent - MAC = 0.75%

Uses:
1. Largely used for maintenance of anesthesia
2. Effective bronchodilator and some relaxation of skeletal muslce
3. Weak analgesic
4. Significant metabolism

Toxicity:
1. Concentration dependent reduction in arterial BP
2. Potent myocardial depressant
3. Increased incidence of arrhythmia and bradycardia
4. Increased cerebral blood flow with potential to increase intracranial pressure
5. LIVER TOXICITY - Drug induced hepatitis and hepatic necrosis
6. MALIGNANT HYPERTHERMIA

Front 7

Enflurane

Back 7

Enflurane - MAC = 1.6%

Induction:
1. Relatively high blood/gas partition coefficient, thus induction of anesthesia is slow

Uses:
1. Largely used for maintenance
2. Effective bronchodilator and significant relaxation of skeletal muscle
3. Significant Metabolism

Toxicity:
1. Concentration dependent reduction in arterial blood pressure
2. POTENT Myocardial depressant
3. Increased cerebral blood flow with potential to increase intracranial pressure
4. Inhibits ventilatory response to increased CO2 or to hypoxemia
5. INCREASED SEIZURE ACTIVITY
6. Malignant Hyperthermia

Front 8

Isoflurane

Back 8

Isoflurane

Induction: Can be achieved within 10 minutes

Uses:
1. Pungent odor and thus is used mostly for maintenance
2. Eliminated unchanged through expired air
3. Good muscle relaxant

Toxicity:
1. Tachycardia
2. Peripheral vasodilation and hypotension
3. Dilates coronary arteries (potential for "coronary steal", use avoided in patients with coronary heart disease)
4. Concentration dependent depression of ventilation
5. Dilates the cerebral arteries with possible increase in intracranial pressure
6. Malignant hyperthermia

Front 9

Desflurane

Back 9

Desflurane

Induction
1. Lowest blood gas coefficient, low fat solubility
2. Very rapid onset, allows for rapid changes, allows for rapid emergence (5-10 minutes)
3. Minimal drug metabolism (<1%)

Uses
1. Effective bronchodilator, direct skeletal muscle relaxation
2. Useful for outpatient surgeries

Toxicity
1. Concentration dependent decrease in blood pressure, but cardiac output is not affected
2. Transient tachycardia
3. Concentration dependent increase in respiratory rate and decrease in tidal volume (depressed ventilation)
4. Increase cerebral blood flow with potential to increase intracranial pressure
5. Coughing, salivation, bronchospasm in awake patients
6. Strong airway irritant and therefore not used for induction
7. May produce carbon monoxide with dry soda lime (CO2 absorbent)
8. Malignant Hyperthermia

Front 10

Malignant Hyperthermia

Back 10

Malignant Hyperthermia

May occur with any of the halogenated inhalation anesthetics.

MH is a potentially fatal disease that predisposes patients to muscle rigidity and sudden rises in body temperature after exposure to volatile anasthetics such as halothane or depolarizing muscle relaxants such as succinylcholine
- These agents trigger and increase in intracellular calcium in skeletal muscle of patients with MH, which can directly cause muscle rigidity

Treatment: Dantrolene

Front 11

Sevoflurane

Back 11

Sevoflurane - MAC= 2%

Induction:
1. Low blood/gas partition coefficient - can be used for induction
2. Rapid onset/rapid recovery

Uses
1. Widely used for outpatient anesthesia and pediatrics since not irritating to airway
2. Potent bronchodilator
3. Direct relaxation of skeletal muscles
4. No significant Tachycardia

Toxicity
1. Concentration-dependent decrease in arterial blood pressure and cardiac output
2. Reduced ventilation
3. Increased cerebral blood flow
4. "Compound A" - nephrotoxic substance elicited due to interaction with soda lime
5. Malignant hyperthermia

Front 12

Nitrous Oxides

Back 12

Nitrous Oxide

1. Insoluble in blood and tissues so rapid induction and emergence
2. WEAK ANESTHETIC AGENT but produce SIGNIFICANT ANALGESIA
3. Cannot be used at a concentration above 80% since this will result in hypoxia. Must use in conjunction with other anesthetics
4. 99% eliminated unchanged in lungs
5. Used primarily as an adjunct to other anesthetics

Side Effects:
1. Accumulates in gas-filled spaces and can cause bowel distention, pneumothorax, pain with obstructed inner ear
2. Need to give 100% OXYGEN AT END OF ANESTHESIA to avoid diluting O2 in lung, causing a diffusional hypoxia
3. Increased Cerebral blood flow and potential for increased intracranial pressure
4. Contraindicated in patients with pulmonary hypertension due to increased vascular resistance

Front 13

Methoxyflurane

Back 13

Methoxyflurane

An inhalation anesthetic used in the past, but withdrawn because of detrimental effects on KIDNEYs. Extensive metabolism in the kidney (only 35% excreted unchanged by exhalation) results in the production of substantial amount of fluoride ions

Slow onset and offset
Relatively good analgesic

Front 14

Therapeutic Considerations for Inhalation Anesthetics

Back 14

Therapeutic Considerations for Inhalation Anesthetics
1. Chemical Stability
2. Irritation upon inhaling
3. Speed of onset (time to loss of consciousness
4. Ability to produce analgesia, amnesia, and muscle relaxation
5. Side effects, especially cardiovascular and respiratory depression and toxicity to liver
6. Speed and safety of emergence
7. Extent of metabolism

Front 15

Clinical Problems on Inhalation Anesthetics

Back 15

Clinical Problems on Inhalation Anesthetics
1. Depression of respiratory drive because of lower response to CO2 or to hypoxia
2. Depressed cardiovascular drive
3. Gaseous space enlargement by nitrous oxide
4. Metabolite toxicity
5. Malignant hyperthermia with halogenated agents (All but Nitrous Oxide), halothane may be the worst