GENERAL ANESTHETICS

Which of the following inhalational anesthetics is associated with potentially severe & life-threatening hepatitis?

Halothane

A patient was given an inhaled anesthetic. What will happen to the onset of action in relation to the following parameters?

• Tachycardia (inc. in heart rate) 

• Loss of sensation by alteration of the function of sensory nerve fibers 

ANESTHESIA

• Relief of pain (decrease awareness of pain)

ANALGESIA

TYPES OF ANESTHETIC AGENTS

• General

• Local

• For centuries, humans have relied on natural medicines and physical methods to control this

SURGICAL PAIN

Produced by general anesthetics

NEUROPHYSICAL STATE

NEUROPHYSICAL STATE is characterized by 5 primary effects:

• Unconsciousness

• Amnesia

• Analgesia

• Inhibition of autonomic reflexes

• Skeletal muscle relaxation

• Should also induce rapid, smooth loss of consciousness, be rapidly reversible upon discontinuation, & possess a wide margin of safety

IDEAL ANESTHETICS

A combination of IV and inhalant (Inh) anesthetic drugs to take advantage of the favorable properties of each agent while minimizing their side effects

BALANCES ANESTHESIA

STAGES OF ANESTHESIA (GOUDEL’S)

1. Analgesia (Stage 1)

2. Disinhibition/Excitement (Stage 2) 

3. Surgical Anesthesia (Stage 3)

4. Medullary Depression (Stage 4) 

• Decreased awareness of pain, sometimes with anesthesia

• Consciousness may be impaired but not lost

1. Analgesia (Stage 1)

• Patient appears to be delirious and excited

• Amnesia, Hyperreflexia

• Irregular respiration, Incontinence may occur

1. Disinhibition/Excitement (Stage 2) 

• Unconscious, no pain reflexes

• Regular respiration, BP is well maintained

Surgical Anesthesia (Stage 3)

Severe respiratory & Cardiovascular depression

1. Medullary Depression (Stage 4) 

3 PHASES OF ANESTHESIA

Induction

Maintenance

Recovery

Time from the administration of a potent anesthetic to develop unconsciousness

Induction

Induction combo and drug

• Propofol + NMB

• Sevoflurane

• Sustained period of anesthesia

Maintenance

Maintenance combo and drug

• Volatile anesthetics + Opioid analgesics

• Propofol

Recovery from anesthetics until the return of consciousness and protective reflexes

Recovery

Mechanism of anesthesia

• ↑ GABA activity 

• ↓ Glutamate activity

A rare life-threatening condition in which inhaled anesthetics or ___ induce severe muscle contractions & hyperthermia.

MALIGNANT HYPERTHERMIA

succinylcholine

MALIGNANT HYPERTHERMIA has a mutation in ___ receptors (RY1 gene) → inc Ca2+ release from ___

voltage-gated ryanodine

sarcoplasmic reticulum

TX of MALIGNANT HYPERTHERMIA

• Dantrolene (Ryanodine receptor antagonist) 

Gaseous inhaled anesthetic that POSSESS THE FLOURINE ATOM & REQUIRE THE USE OF VAPORIZER

Nitrous oxide & Xenon

Volatile Liquids (Halogenated Hydrocarbons) inhaled anesthetic that POSSESS THE FLOURINE ATOM & REQUIRE THE USE OF VAPORIZER

Halothane & "- fluranes"

Anesthesia is produced when the pressure of the gases is equal in both ___and the ___

alveoli

CNS

• The more rapidly a drug equilibrates with the blood, the more quickly the drug passes into the brain to produce anesthetic effects

Solubility

• gas partition coefficient equilibrates rapidly than those with higher blood solubility 

Drugs with a low blood

The greater the ___, the slower the onset of action

blood flow

Greater ___, faster onset of action

ventilation rate

Elimination: Inhaled anesthesia is terminated by redistribution of the drug from the ___to the ___, ___ to the ___, and elimination of the drug through the ___

brain to the blood, blood to the alveolar air, and elimination of the drug through the lungs

what are the 7 anesthetic drugs

nitrous oxide

desflurane

sevoflurane

isoflurane

enflurane

halothane

methoxyflurane

blood-gas partition coefficient nitrous oxide

0.47

blood-gas partition coefficient desflurane

0.42

blood-gas partition coefficient sevoflurane

0.69

blood-gas partition coefficient isoflurane

1.40

blood-gas partition coefficient enflurane

1.80

blood-gas partition coefficient halothane

2.30

blood-gas partition coefficient methoxyflurane

12

• Potency of inhaled anesthetics

• Defined as the alveolar concentration required to eliminate response to a standardized painful stimulus (effect) in 50% of patients

MINIMUM ALVEOLAR ANESTHETIC CONCENTRATION (MAC)

Anesthesia for minor surgery and dental procedures

NITROUS OXIDE (N2O)

NITROUS OXIDE (N2O) causes ___ on prolonged exposure

Megaloblastic anemia

Euphoria (Laughing gas)

NITROUS OXIDE (N2O)

General anesthesia; Bronchospasm (Pulmonary irritant) → very pungent

DESFLURANE

bad for patients with asthma and hyperreactive airways 

DESFLURANE

in Desflurane, ____ : gas partition coefficient = faster induction and prompt awakening

low blood

General anesthesia, Sweet-smelling → preferred for pediatric patients, Induction for patients with asthma

SEVOFLURANE

SEVOFLURANE forms renal insufficiency (___ formation),

compound A

General anesthesia, Catecholamine-induced arrhythmias, Pungent

ISOFLURANE

in ISOFLURANE, Blood circulates from ischemic areas to non-ischemic areas

Coronary steal syndrome

General anesthesia, Spike-and-wave activity in EEG → Epileptogenic, Renal insufficiency, Pungent

ENFLURANE

General anesthesia, Renal insufficiency

METHOXYFLURANE

for methoxyflurane, Lowest MAC = ___ among inhalational anesthetic

highest potency among inhalational anesthetic

for methoxyflurane, Highest blood: partition coefficient = ___ of action

slowest onset

7 Intravenous anesthetics

• Propofol

• Barbiturates (Thiopental, Methohexital)

• Benzodiazepines (Midazolam, Triazolam, Diazepam)

• Ketamine

• Opioid analgesics (Fentanyl)

• Etomidate

• Dexmedetomidine

Most frequently administered for anesthesia induction, Pain at injection site

PROPOFOL

PROPOFOL potentiates

GABA A receptors

syndrome of propofol

Propofol infusion syndrome

• Alternative GA maintenance for patients susceptible to malignant hyperthermia 

• Anti-emetic

PROPOFOL

BENZODIAZEPINES drugs

Midazolam, Triazolam, Diazepam

Anesthesia induction, Preoperative sedation

BENZODIAZEPINES

• Anterograde amnesia

• Decreased psychomotor skills, Unwanted daytime sedation

• Tolerance, Dependence

• Additive CNS depressant effect

BENZODIAZEPINES

BARBITURATES

Thiopental, Methohexital

• Anesthesia induction (Old)

• Increased Intracranial Pressure

• Extension of CNS depressant action

• Decreased psychomotor skills, Unwanted daytime sedation

• Tolerance, Dependence

• Additive CNS depressant effect

BARBITURATES

General anesthesia (patients with limited cardiac or respiratory reserves)

ETOMIDATE

in etomidate, Adrenocortical suppression - limits its use

Inhibits 11B-hydroxylase

NMDA receptor antagonist, Dissociative anesthesia, Patient remains conscious but has marked catatonia, analgesia, and amnesia. People feel separated from their body or physical environment, Potent analgesia

KETAMINE

KETAMINE is a Chemical congener of

psychomimetic agent, Phencyclidine (PCP)

Highly selective alpha 2 agonist, Short-term sedation of intubated and ventilated patients

Dexmemdetomidine

Respiratory depression, Chest wall rigidity

Opioid Analgesics

TX of opioid analgesics

Naloxone/Naltrexone

Analgesia, Neuroleptanesthesia (Fentanyl + Droperidol + N2O)

Opioid Analgesics

• What is the common mechanism of action of the local anesthetics when in their usual dose?

Inhibition of voltage-gated Na+ channel

• Loss of sensation in a specific region of the body

• Administered near or directly to the target site

LOCAL ANESTHESIA

• Shorter duration of action due to the hydrolytic action of plasma esterases

• Have one "I" in their name

Esters (Tetracaine)

• Longer duration of action (metabolized by hepatic amidases)

• Have two "I" in their name

Amides (Lidocaine)

TYPES OF LOCAL ANESTHETICS

Esters

Amides

• 1st drug discovered to produce numbness

D/A: Abuse potential and CNS/CV toxicity

COCAINE

• Lipophilic ester of benzoic acid

• D/A: Methemoglobinemia (systemic route)

BENZOCAINE

• 1st injectable anesthetic

• D/A: Short acting

• Allergic reaction

PROCAINE

Longer duration of action, but limited spinal anesthesia

TETRACAINE

1st amide anesthetic with less toxicity and longer duration of action

LIDOCAINE

LIDOCAINE is most neurotoxic when given as?

spinal anesthetic

• Light-headedness or sedation

• Restlessness

• Nystagmus

• Tonic-clonic seizures → Coma→ Respiratory and cardiovascular depression

CNS

In CVS, ___ Severe hypertension with cerebral hemorrhage (drug of abuse)

Vasoconstrictor (Cocaine)

In CVS, Severe cardiotoxicity

 (Bupivacaine)

Methemoglobinemia

Prilocaine → o-toluidine

Allergic reaction

Procaine

Has a thiophene ring instead of a benzene ring → more lipid soluble

ATRICANE

Less associated with neurotoxicity

CHLOROPROCANE

Topical use on ENT; Controlled substance

COCAINE

• Reference standard; may cause neurotoxicity

LIDOCAINE

Metabolized to ortho-toluidine

PRILOCAINE