PCOL Finals- General Anesthetics

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

a. Sevoflurane b. Isoflurane c. Desflurane d. Halothane e. Nitrous Oxide

d. Halothane

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

● Tachypnea (_____)

● Tachycardia (____)

● inc. rate of respiration = faster onset of action

● inc. heart rate

Loss of sensation by alteration of function of sensory nerve fibers

Anesthesia

Type of general anesthetic agent?

○ Profound effects on the body

General

Type of general anesthetic agent?

○ Affects a specific site in the body

Local/Regional

Relief of pain (decrease awareness of pain)

Analgesia

Analgesia

• Add ___ analgesics to those anesthetic drugs with no analgesia

opioid

For centuries, human relied on natural medicines and physical method to control ___pain.

surgical pain

First public demonstration of anesthesia date?

1846

NEUROPHYSICAL STATE produces by general anesthetics is characterized by 5 primary effects:

○ Unconsciousness

○ Amnesia

○ Analgesia

○ Inhibition of autonomic fibers

○ Skeletal muscle relaxation

_____ produces by general anesthetics is characterized by 5 primary effects:

○ Unconsciousness

○ Amnesia

○ Analgesia

○ Inhibition of autonomic fibers

○ Skeletal muscle relaxation

NEUROPHYSICAL STATE

Ideal anesthetics should also induce rapid, smooth loss of consciousness, be rapidly reversible upon discontinuation & possess a wide margin of safety.

○ No single agent anesthetics could produce these effects. Usually, we use ____.

combined anesthetics

Balanced Anesthesia technique

● Combination of _____anesthetic drugs to take advantage of favorable properties of each agent while minimizing their side effects.

IV and Inh (Inhalational)

STAGES OF ANESTHESIA (GOUDEL’S)

● Decrease awareness to pain, sometimes with anesthesia

● Consciousness may be impaired but not lost

ANALGESIA (STAGE 1)

STAGES OF ANESTHESIA (GOUDEL’S)

● Patient appears to be delirious and excited

● Amnesia, hyperreflexia (overstimulation of reflexes)

● Irregular respiration, Incontinence may occur

DISINHIBITION/ EXCITEMENT (STAGE 2)

STAGES OF ANESTHESIA (GOUDEL’S)

● Unconscious, no pain reflexes

● Regular respiration, BP is well maintained

SURGICAL ANESTHESIA (STAGE 3)

STAGES OF ANESTHESIA (GOUDEL’S)

● Severe respiratory & Cardiovascular depression

MEDULLARY DEPRESSION (STAGE 4)

PHASES OF ANESTHESIA

● Time from administration of potent anesthetic to develop unconsciousness

● Usually gives drugs with fast onset of reaction

● Propofol + NMB (Neuromuscular blocker) - adults

● Sevoflurane - pediatric patients

INDUCTION

INDUCTION PHASE OF ANESTHESIA

drug given to adults

Propofol + NMB (Neuromuscular blocker)

INDUCTION PHASE OF ANESTHESIA

drug given to pediatric patients

Sevoflurane

PHASES OF ANESTHESIA

● Sustained period of anesthesia

● Volatile anesthetics + opioid analgesics

● Propofol - can be given as induction or maintenance agent

MAINTENANCE

MAINTENANCE PHASE OF ANESTHESIA

combination of anesthetic and analgesic?

Volatile anesthetics + opioid analgesics

MAINTENANCE PHASE OF ANESTHESIA

What drug can be given as induction or maintenance agent?

Propofol

PHASES OF ANESTHESIA

● Recovery from anesthetics until the return of consciousness and protective reflexes

RECOVERY

MOA of General Anesthetics:

The exact mechanism is unknown, but the effects are:

○ ↑ ____ Activity (decrease firing of neurons) = ↓___ Activity

GABA; Glutamate

Rare life-threatening condition in which inhaled anesthetics or succinylcholine induces a severe muscle contractions & hyperthermia.

Malignant Hyperthermia

Secondary to a mutation in voltage-gated ryanodine receptors (RY1 gene) → inc Ca2+ release from sarcoplasmic reticulum

Malignant Hyperthermia

Malignant Hyperthermia

Secondary to a mutation in voltage-gated ____ → inc Ca2+ release from ____

ryanodine receptors (RY1 gene); sarcoplasmic reticulum

Malignant Hyperthermia Treatment

Dantrolene (Ryanodine receptor antagonist)

a type of Calcium channel, when stimulated, release calcium from calcium store

Ryanodine receptor

Ryanodine receptor

○ Too much calcium in the neuromuscular junction, it can cause excessive muscle contractions, leading to ____

○ ______ is addressed using Dantrolene or Dantrolene + Cooling blankets.

hyperthermia

Inhaled Anesthetic Gaseous examples

Nitrous oxide & Xenon

Inhaled Anesthetic Volatile Liquids examples

(Halogenated Hydrocarbons) - Halothane & “--fluranes”

Volatile Liquids -All possess the ____, all require the use of vaporizer

fluorine atom

PHARMACOKINETIC PROPERTIES

Anesthesia is produced when the pressure of the gases is equal on both ___ and ___.

alveoli and CNS

Anesthesia’s Concentration is measured by ____

○ Concentration = ___

partial pressure

SOLUBILITY

○ The more _____, the more quickly drug passes into the brain to produce anesthetic effects

rapidly a drug equilibrates with the blood

Drugs with a _________equilibrates rapidly than with higher blood solubility

low blood:gas partition coefficient

↑ solubility of agents ↑____(directly proportional)

blood:gas partition coefficient

PHARMACOKINETIC PROPERTIES: SOLUBLITY

Effect on onset of action:

■ ↓ solubility ↓ blood:gas partition coefficient =_____

■ Onset of action & solubility + gas:blood partition coefficient –____

• faster onset of action

• indirectly proportional

PHARMACOKINETIC PROPERTIES: BLOOD FLOW

○ Greater the blood flow, ___ onset of action

○ ↑___ ↑___= slow equilibrium between alveolar and CNS compartments = Slow onset of action

• slow onset of action

• ↑ blood flow ↑ tissue distribution

PHARMACOKINETIC PROPERTIES: VENTILATION RATE

○ _____ventilation, faster onset of action

■ Sige ginhawa ang pasyente (tachypnea), mas mabilis ma absorb ang medication (mas mabilis ma equilibrate sa CNS and Alveolar compartments) = faster onset of action

Greater ventilation

PHARMACOKINETIC PROPERTIES: ELIMINATION

○ Inhaled anesthesia is terminated by redistribution of the drug from the brain to the blood, blood to the alveolar air, and elimination of the drug through the lungs

○ Redistribution: B__ → b____ → a_____ → e_____

Brain → blood → alveolar sacs/air → exhaled by patient

MINIMUM ALVEOLAR anesthetic CONCENTRATION (MAC)

● Potency of inhaled anesthetics

○ Potency in graded dose response curve– ____(dose needed to produce a 50% effect)

EC50

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

MINIMUM ALVEOLAR anesthetic CONCENTRATION (MAC)

Which is more potent? ○

↓ ____ = ↑ Potency -

↓ MAC (indirectly proportional)

From the table 25-1:

○ _____= ↑ MAC (least potent)

○ _____= ↓ (most potent)

• Nitrous oxide

• Methoxyflurane

What INHALED ANESTHETICS?

USES: ● Anesthesia for minor surgery and dental procedures

NITROUS OXIDE (N2O)

What INHALED ANESTHETICS?

AE/SE:

● Megaloblastic anemia on prolonged exposure

● Euphoria (laughing gas)

● Bronchodilation

NITROUS OXIDE (N2O)

What INHALED ANESTHETICS?

NOTES:

● Highest MAC (lowest potency)

● Least cardiotoxic among inhalation anesthetics

● Increased intracranial pressure

NITROUS OXIDE (N2O)

What INHALED ANESTHETICS?

USES: ● General anesthesia

DESFLURANE,SEVOFLURANE,ISOFLURANE,ENFLURANE,HALOTHANE,METHOXYFLURANE

What INHALED ANESTHETICS?

AE/SE:

● Bronchospasm (pulmonary irritant) → very pungent

○ Not used, specifically in pediatric patients bcos of its smell

● Peripheral vasodilation

DESFLURANE

What INHALED ANESTHETICS?

NOTES:

● Contraindicated in patients with asthma and hyperreactive airways

○ Bcos it is a pulmonary irritant - can cause bronchospasm

● LOWEST Blood:gas partition coefficient = faster induction and prompt awakening

○ Least soluble among inhaled anesthetic

DESFLURANE

What INHALED ANESTHETICS?

AE/SE:

● Peripheral vasodilation

● Renal insufficiency (compound A formation)

○ With soda lime, ____ will form compound A – nephrotoxic

● Bronchodilation

SEVOFLURANE

With ____, sevoflurane will form compound A – nephrotoxic

soda lime

What INHALED ANESTHETICS?

NOTES:

● Sweet smelling → preferred for pediatric patients

● Induction for patients with asthma

SEVOFLURANE

What INHALED ANESTHETICS?

AE/SE:

● Peripheral vasodilation

● Bronchodilation

● Catecholamine-induced arrhythmias

● Coronary steal syndrome

○ Blood circulates from ischemic areas to non-ischemic areas – can lead to necrosis (pagkamatay ng cells sa ischemic areas due to lack of oxygen)

○ Ischemic - low oxygen/ blood flow received in the heart

ISOFLURANE

low oxygen/ blood flow received in the heart

Ischemic

What INHALED ANESTHETICS?

NOTES:

● Pungent

● Least appropriate to patients with heart problems

ISOFLURANE

What INHALED ANESTHETICS?

AE/SE:

● Spike-and-wave activity in EEG → Epileptogenic

● Renal insufficiency ○ Can release fluorine

● Bronchodilation

ENFLURANE

What INHALED ANESTHETICS?

NOTES: ● Pungent

ENFLURANE

What INHALED ANESTHETICS?

AE/SE:

● Catecholamine-induced arrhythmias

● Hepatitis (highest propensity)

● Bronchodilation

HALOTHANE

What INHALED ANESTHETICS?

NOTES:

● Stores in amber colored bottles

○ Easily oxidized

HALOTHANE

What INHALED ANESTHETICS?

AE/SE: ● Renal insufficiency

METHOXYFLURANE

What INHALED ANESTHETICS?

NOTES:

● Lowest MAC = highest potency among inhalational anesthetic

● Highest blood;partition coefficient = slowest onset of action

METHOXYFLURANE

What inhaled anesthetics have AE/SE of being pungent

Desflurane, Isoflurane, Enflurane

What inhaled anesthetics have AE/SE of catecholamine induced arrythmia

isoflurane,halothane

What inhaled anesthetics have AE/SE of renal insufficiency

Sevoflurane,enflurane,methoxyflurane

What inhaled anesthetics cause bronchodilation

Nitrous oxide, sevoflurane, isoflurane,enflurane,halothane

INTRAVENOUS ANESTHETICS examples

● Propofol

● Barbiturates (Thiopental, Methohexital)

● Benzodiazepines (Midazolam, Triazolam, Diazepam)

● Ketamine

● Opioid analgesics (Fentanyl)

● Etomidate

● Dexmedetomidine

Barbiturates examples

Thiopental, Methohexital

Benzodiazepines examples

Midazolam, Triazolam, Diazepam

Opioid analgesics examples

Fentanyl

What IV Anesthetic?

Most frequently administered for anesthesia induction (replaces BZDs)

PROPOFOL

What IV Anesthetic?

Fully water soluble (formulated as an emulsion, containing soybean and egg phospholipid) – gives the characteristic milky color

PROPOFOL

What IV Anesthetic?

Aka milk of amnesia

PROPOFOL

What IV Anesthetic? MOA:

● Potentiates GABA A receptors

○ GABA A receptors coupled with chloride channels → open chloride channels → cells become negative → hyperpolarization → decrease in neuronal firing

PROPOFOL

What IV Anesthetic? USES:

● IV anesthetic of choice

● Sedation for ICU patients and outpatient procedures

PROPOFOL

What IV Anesthetic? USES:

● IV anesthetic of choice

● Sedation for ICU patients and outpatient procedures

PROPOFOL

What IV Anesthetic? AE/SE:

● Hypotension, Bradycardia

● Pain at injection site

● ____infusion syndrome – characterized by metabolic acidosis (acidic blood, esp. If is administered for longer than 24 hours)

PROPOFOL

What IV Anesthetic?

NOTES:

● Alternative GA maintenance for patients susceptible to malignant hyperthermia

● Anti-emetic

PROPOFOL

What IV Anesthetic?

MOA:

● Increases the frequency of GABA mediated chloride channel opening

BENZODIAZEPINES

What IV Anesthetic?

USES:

● Anesthesia induction (previously, but replaced with propofol now), Preoperative sedation

BENZODIAZEPINES

What IV Anesthetic?

AE/SE:

● Anterograde amnesia

● Decreased psychomotor skills, Unwanted daytime sedation

● Tolerance, Dependence

● Additive CNS depressant effect (w/ other medications, like TCA, alcohol, and antihistamines)

BENZODIAZEPINES

What IV Anesthetic?

TX: ● Flumazenil - antagonizes ____s at ___ receptors

BENZODIAZEPINES (BZD)

What IV Anesthetic?

MOA: ● Increases the duration of GABA Mediated chloride channel opening

BARBITURATES

What IV Anesthetic?

USES:

● Anesthesia induction (Old)

● Increased Intracranial pressure

○ Not given in patients w/ brain pathology (like tumor sa brain, it causes extra pressure in the brain)

BARBITURATES

What IV Anesthetic?

AE/SE:

● Extension of CNS depressant action

● Decreased psychomotor skills, Unwanted daytime sedation

● Tolerance, Dependence

● Additive CNS depressant effect

BARBITURATES

What IV Anesthetic?

MOA:

● Primarily acts on GABA A receptors

ETOMIDATE

What IV Anesthetic?

USES:

● General anesthesia (patients with limited cardiac or respiratory reserves)

ETOMIDATE

What IV Anesthetic?

AE/SE:

● Adrenocortical suppression – limits its use

○ Suppresses the formation of cortisol by Inhibiting 11B-hydroxylase

ETOMIDATE

What IV Anesthetic?

MOA:

● NMDA receptor antagonist

KETAMINE

What IV Anesthetic?

USES:

● Dissociative anesthesia

○ Patient remains conscious but has marked catatonia, analgesia, and amnesia ○ People feel separated from their body or physical environment

KETAMINE

What IV Anesthetic?

AE/SE:

● Increases Intracranial Pressure (ICP)

● Cardiovascular stimulation

● Respiratory depression

● Emergence reaction – limits use ○ Vivid colorful dreams, Hallucination, Out of body experiences

KETAMINE

What IV Anesthetic?

MOA:

● Highly selective alpha 2 agonist

○ Stimulation of A2 antagonist – prevents release of catecholamines (NE, EPI, Da)

DEXMEDETOMIDINE

What IV Anesthetic?

USES:

● Short-term sedation of intubated and ventilated patients (ICU)

DEXMEDETOMIDINE

What IV Anesthetic?

MOA:

● Interacts with mu, delta, & kappa receptors

OPIOID ANALGESICS

What IV Anesthetic?

USES:

● Analgesia, Neuroleptanesthesia (Fentanyl + Droperidol + N2O)

OPIOID ANALGESICS

What IV Anesthetic?

AE:

● Respiratory depression, Chest wall rigidity

OPIOID ANALGESICS

What IV Anesthetic?

TX: ● Naloxone/Naltrexone (opioid antagonist)

OPIOID ANALGESICS