Pharmacology of inhaled anesthetics (Gatson) Flashcards
Pharmacokinetics
Uptake/Distribution
Elimination & Recovery
Pharmacodynamics
Effect of inhalants on the body
Physiochemical property affecting stability and potency
Chemical structure
Physiochemical property affecting amount of inhalant delivered to the patient
vapor pressure
physiochemical property affecting the kinetics within the body
Solubility
MAC
Minimum Alveolar Concentration
- Determines dosing of an inhalant
- Equivalent to ED50
- Inversely related to potency
- Can be altered by many factors
Uptake and Distribution
Delivery to sites of action => anesthesia
- Movement along a partial pressure gradient
Gases move
Across a partial pressure gradient
Partial pressure…
1.
2.
3.
- Partial pressure in brain and not the concentration of anesthetic produces anesthesia
- Brain partial pressure equilibrates quickly with alveolar partial pressure
- Brain partial pressure always moves towards alveolar partial pressure
Partial pressure in alveoli
Balance between
- Input to alveoli : delivery
- Loss from alveoli: uptake
Three factors influencing uptake
1. solubility of anesthetic
2. Patient’s cardiac output
3. Alveolar-venous anesthetic partial pressure difference
Inhalents removed from alveoli
by pulmonary blood: UPTAKE
Delivery depends on
Inspired anesthetic concentration
- Vaporizer setting
- Fresh gas flow
- Volume of breathing circuit:
- larger for a horse, slows delivery
Alveolar ventilation
Uptake and Distribution:
CO
INC CO = greater amount of blood carrying inhalant away from alveoli to tissue
DEC CO = less blood flow through lungs, less anesthetic removed
- This patient will be induced much quicker
PA - PV
Venous blood returning to the lungs for re-oxygenation will retain some inhalant
PA - PV gradient must exist for uptake to occur
Elimination and Recovery
Decreasing the alveolar partial pressure
- dec partial pressure in breathing circuit
- Reverses gradient from blood to alveoli
Rate of elimination affected by
- Inhalant solubility: low solubility recovers faster
- Cardiac output
- Duration of anesthesia
Elimination/recovery
Less soluble agents
Recover more quickly
Less soluble agents
Sevoflurane
Desflurane
If inhalant A is highly soluble in blood (high blood:gas partition coefficient) and inhalent B is not, this means that:
Inhalant B will cause a faster induction
Which are Correct:
a. MAC is a measure of potency
b. MAC is a measure of speed of induction
c. MAC is additive among multiple inhalents
a. MAC is a measure of potency
b. MAC is additive among multiple inhalents
MAC is additive
More inhalants you use, more MAC adds up
MAC is JUST
Potency
Fluorine is toxic to
Kidneys
Toxic metabolites
Sevoflurane => Compound A
- Kidney toxicity
Drugs causing production of carbon monoxide: change out Sodasorb every MONDAY
- Isoflurane
- Desflurane
- Enflurane
Pharmacodynamics
Desirable effects:
Reversible, dose dependent general anesthesia
Non-addictive
Decrease cerebral metabolic rate
Not dependent on hepatic and renal function
Pharmacodynamics
CNS
Inhalants increase cerebral blood flow
- Decreased ventilation => Inc CO2 => vasodilation
- Decreased systemic vascular resistance => vasodilation of intracranial vessels
- Related to inhalant dose
- Detrimintal if ICP is elevated
Cardiovascular and respiratory centers in ….
Medulla
Inhalants increase intracranial pressure
Parallels increase in CBF
Space within calvarium is fixed
Pre-existing intracranial disease
- cerebral damage
- herniation of brain
Pharmacodynamics:
Cardiovascular
All inhalants reduce cardiac output
- negative inotropic effect
- dec in stroke volume
- decrease in peripheral vascular resistance
- negative effect on B:
- dose dependant
Pharmacodynamics
Enhanced cardiovascular compromise
Mechanical ventilation
PaCO2 changes
Surgical stimulation
Lenth of inhalant administration
Concomitantly administered drugs
Pharmacodynamics
Pulmonary System
Dose related decrease in ventilation
- blunt the response to increased CO2
- can act as a safety mechanism
Inc Pbrain => Dec ventilation => dec uptake => dec PBRAIN
*Monitor pulmonary function carefully of patient under anesthesia
- Pulse Ox
- Capnography
Pulmonary system
Inc inhalant dose:
Depressed spontaneous ventilation
Depresses tidal volume followed by respiratory frequency
Inc arterial CO2
Medullary stimulation of respiration due to hypercapnia is reduced
Respiratory arrest occurs at 1.5-3 MAC
Inc MAC = higher blood…
CO2
Inhalant causing airway irritation
Desflurane
Pharmacodynamics
Hepatic
Minimal hepatic metabolism
Prolongation of drug metabolism
- Due to decreased CO leads to decreased hepatic blood flow
- impact of hepatic metabolism of co-administered drugs
- Isoflurane most likely to maintain hepatic blood flow
Malignant Hyperthermia
White breed pigs
Greyhounds
Myopathy seondary to inhalant exposure
- Muscle contracture => RYR1, Ca2+ channels
- skeletal muscle oxidative metabolism
- decreased oxygen supply and increased CO2
- Circulatory collapse and death
Treatment
-
Discontinue inhalant administration
- Also change rubber parts of circuit
- Dantrolene sodium: muscle relaxant
- acts on calcium channels to reverse this