Inhalant Anesthetics: Pharmacokinetics/Dynamics Flashcards
To creat anesthesia, inhalants must go from the vaporizer to _____
The brain
________, not concentration, of anesthetic in the _____ produces anesthesia
Partial pressure; brain
Brain partial pressure equilibrates quickly or slowly with alveolar partial pressure?
Quickly -cardiac output to brain is high -brain partial pressure ALWAYS moves towards alveolar partial pressure
Alveolar partial pressure is a balance between what two things?
- input to the alveoli - Delivery
- Loss from the alveoli - Uptake
Factors that affect delivery
- inspired anesthetic concentration
- Vaporizer setting
- Fresh gas flow
- Volume of breathing circuit
- alveolar ventilation
Inhalants are removed from alveoli by _____
Pulmonary blood (this is uptake)
Factors that influence uptake
- solubility of anesthetic
- patient’s cardiac output
- alveolar-venous anesthetic partial pressure difference
How can we make an animal anesthetize quickly?
- Fast rise in alveolar concentration
- Increase delivery
- turn up vaporizer output
- turn up carrier gas flow rate
- minimize volume of breathing circuit
- increase ventilation
- Slow down uptake
- inhalant w/ low solubility
- slow down cardiac output
- minimize partial pressure gradient
What are the effects of solubility on the uptake and distribution of inhalants?
Less soluble = readily leaves blood to reach equilibrium with gas and tissues More soluble = greater tendency to stay in the blood
A low blood:gas partition coefficient will have what 3 effects on uptake and distribution?
- Rapid induction 2. Precise control of anesthetic depth 3. Rapid elimination and recovery
Why does decreased solubility result in rapid rise of anesthesia?
Decr solubility > faster alveolar rate of rise > faster brain rate of rise > rapid anesthesia
How does the amount of cardiac output affect uptake and distribution?
Amount of blood flow to lungs and tissues influences uptake
- high CO = greater amount of blood carrying inhalant away from alveoli to tissue
- low CO = less blood flow through lungs with less anesthetic removed
With lower cardiac output states, such as colic or sepsis, it is easier/harder to overdose on inhalants?
Easier
What is the effect of arterial to venous partial pressure gradient on uptake and distribution?
- venous blood returning to the lungs for re-oxygenation will retain some inhalant
- Pa - Pv gradient must exist fro uptake to occur
- as anesthetic duration progresses, alveolar rate of rise slows due to narrowing of the Pa-Pv gradient
What is uptake into muscle and fat slower than the brain?
Due to lower tissue perfusion and higher tissue:blood partition coefficients
Recovery from anesthesia is due to _____
Removal of inhalants from the CNS - Gradient: CNS > blood > alveoli > outside - decr partial pressure in alveoli & anesthesia circuit
4 factors that affect elimination of inhalants
- Alveolar ventilation 2. Inhalant solubility 3. Cardiac output 4. Duration of anesthesia
If a drug has a lower solubility, it will have a faster/slower recovery?
Faster
Other factors affecting inhalant recovery include:
- decr inhalant delivery > faster elimination - incr alveolar ventilation > faster elimination - incr CO > faster elimination -body temperature Decr temp > incr solubility > longer recovery -metabolism of inhalants (minimal)
Describe the role of inhalant metabolism on removal from the body?
-minimal role in removal - toxic metabolites can be produces E.g. Sevo > Compound A Iso, desflurane, enflurane > carbon monoxide
Which of these is incorrect? A. MAC is a measure of potency B. MAC is a measure of speed of induction C. MAC is additive among multiple inhalants
B
Name some desirable effects of inhalants
- reversible, dose-dependent general anesthesia -non-addictive -decrease cerebral metabolic rate -elimination not dependent on hepatic and renal function
What effects do inhalants have on the cardiovascular system?
-Major effect -all REDUCE cardiac output - decreased myocardial contractility Decr stroke volume and CO -decrease peripheral vascular resistance Hypotension -dose-dependent effects
What effects do inhalants have on the pulmonary system?
As inhalant dose is increased:
- decr spontaneous ventilation
- depressed tidal volume & resp frequency
- incr arterial CO2
- medically stimulation of respiration due to hypercapnia is reduced
- respiratory arrest occurs at 1.5-3 MAC
How the dose-related decrease in ventilation and blunting the response to increased CO2 act as a safety mechanism?
Incr partial pressure in brain > decr ventilation > decr uptake > decrease partial pressure of brain
What are the effects of inhalants on the CNS?
- Immobility and unconsciousness
- increase cerebral blood flow
- Cerebral vasodilation
- Hypoventilation > incr CO2 > vasodilation
- Leads to an incr in ICP (dose related)
- high doses of inhalants (>1 MAC) > loss of cerebral blood flow autoregulation
* these are often avoided with increased intracranial pressure b/c brain is within a fixed space and contains CSF, blood/vasculature, brain tissue
What are the effects of inhalants on the liver?
- Minimal hepatic metabolism of inhalants
- Possible prolongation of drug metabolism
- decr CO > decr hepatic blood flow
- decr hepatic metabolism co-administered drugs
- Isoflurane most likely to maintain hepatic blood flow
What are the effects of inhalants on the kidneys?
- Mild, reversible, dose-related decrease in renal blood flow & GFR - Related to overall decr CO 2. Nephrotoxicity - Rarely documented in domestic spp. - Breakdown of sevoflurane > free fluoride ions & Compound A
What is malignant hyperthermia?
- Reported in horses, dogs, pigs
- Myopathy secondary to inhalant exposure
- Genetic mutation of ryanodine receptor (in mm cells, important in mm contraction)
- massive incr in cytosolic Ca2+
- incr sk mm oxidative metabolism
- decr O2 supply and incr CO2
- eventually causes cric collapse & death
- Treatment:
- discontinue inhalant administration
- Dantrolene sodium - muscle relaxant
Isoflurane
High potency -MAC = 1.2-1.6% Intermediate solubility -Blood:gas partition coefficient = 1.4 Minimal liver metabolism -Best at maintaining liver perfusion Most common modern inhalant used (cheap)
Sevoflurane
Intermediate potency - MAC = 2.2-3% Low solubility - Blood:gas partition coefficient Small amount of liver metabolism (-5%) Compound A production - no real clinical significance
Desflurane
- Low potency (MAC 8%)
- Low boiling point (22 degrees C)
- High vapor pressure (700mmHg)
- Rapid induction/recovery
- VERY low solubility
- NO liver metabolism
- Needs a specialized heated & pressurized vaporizer
