Inhalant anesthetics Flashcards
use of nitrous oxide as anesthetic?
- Patients remain conscious (not a true general anesthetic) but alleviates anxiety and is an excellent analgesic
- Very safe; still used to alleviate anxiety & pain
drawbacks of early inhalant general anesthetics
- Explosive when administered with oxygen
- Produce toxic metabolites
ether plus oxygen creates what? how can we solve this problem?
-Ether is flammable, and can be explosive when mixed with O2
-Substituting halogens for hydrogens reduces the flammability of a hydrocarbon
To be both safe and effective, general anesthetics must:
inhibit cerebrocortical activity while maintaining brainstem function (cardiovascular & respiratory system regulation)
All areas of the brain are reversibly inhibited by general anesthetics in a dose-dependent manner
The cerebral cortex is most sensitive, and its function is virtually abolished at concentrations that inhibit brainstem function only partially
The safety of general anesthetics is therefore dependent upon the extent to which cardiovascular & respiratory functions are impaired at concentrations required to maintain general anesthesia
The other major safety issue relates to the toxicity of the inhalant’s metabolites
-In general, hepatic and renal toxicity are directly related to the extent to which an inhalant is metabolized
In general, hepatic and renal toxicity are directly related to: (regarding inhalant anesthetics)
the extent to which an inhalant is metabolized
difference in metabolism between halothane and isofluorane, and consequences?
Halothane: up to 40% metabolized > significant hepatotoxicity
Isofluorane: <0.2% metabolized > no organ toxicity
issues with halothane? how did this inform us about inhalant safety?
Halothane sensitizes the myocardium to epinephrine, promoting arrhythmias
Early testing of various halogenated hydrocarbons revealed that those with an ether linkage do not have this property
> the ether linkage C-O-C is therefore desirable for safety
The main inhalants used today in veterinary medicine are:
– Isoflurane
– Sevoflurane
Characteristics of an ideal inhalant anesthetic: (7)
- Produces unconsciousness while maintaining
brainstem function (respiration, circulation) - Negligible visceral toxicity
(i.e. no metabolism > 100% of drug exhaled intact) - Non-flammable
- Non-pungent odour
- Compatible with anesthetic machine materials (does not degrade rubber or metal parts or react with soda lime)
- Chemically stable without preservatives
- Potent
mechanism of action of inhalant anesthetics?
Uncertain:
“Volatile general anesthetics inhibit neurotransmitter release by a mechanism not fully understood.”
Facilitation of GABA is one known effect and
possibly the main mechanism
Pharmacokinetics of inhalant anesthetic
Anesthetic vapour delivered w/ oxygen
> absorbed from lungs into blood
> distributed to the tissues
Constant delivery of fresh gas with controlled % of anesthetic maintains anesthesia (like a constant rate IV infusion)
Eliminated mainly by exhalation; some metabolism
the depth of anesthesia is proportional to what property created by the anesthetic?
The depth of anesthesia is not, however, proportional to the concentration of the anesthetic in the brain, it is proportional to the partial pressure created by the anesthetic
ANESTHETICS THAT ARE HIGHLY SOLUBLE IN TISSUES PRODUCE a partial pressure that is higher or lower? why?
Anesthetics that are highly soluble in tissues interact in some manner with the tissue (e.g., form reversible bonds with molecular constituents of the tissue) and therefore move less rapidly, producing a lower partial pressure compared to anesthetics that are relatively insoluble in the tissue and do not interact as much with its molecules
rate of onset and recovery for an anesthetic depends on _____
The rate of onset and recovery also depends on partial pressure
If a conscious patient inhales an anesthetic, how will the tissue solubility affect how fast they are rendered unconscious?
If a conscious patient inhales an anesthetic, they will be rendered unconscious quickly if it is a drug with low tissue solubility because a small quantity of that drug will be enough to produce the necessary partial pressure.
-also will recover quickly when drug is removed
In comparison, if the patient were to inhale an anesthetic that is highly soluble in tissues, it would take longer to become unconscious because much more drug would have to be absorbed before it created a sufficient partial pressure.
If a conscious patient inhales an anesthetic, how will the tissue solubility affect how fast they are rendered unconscious?
If a conscious patient inhales an anesthetic, they will be rendered unconscious quickly if it is a drug with low tissue solubility because a small quantity of that drug will be enough to produce the necessary partial pressure.
-also will recover quickly when drug is removed
In comparison, if the patient were to inhale an anesthetic that is highly soluble in tissues, it would take longer to become unconscious because much more drug would have to be absorbed before it created a sufficient partial pressure.
factors that influence the delivery of inhalants from the lungs to the brain:
1) Solubility of drug in tissues (e.g., blood or brain) vs. alveolar gas
2) Concentration of anesthetic in the inspired gas mixture
3) Ventilation rate
4) Pulmonary blood flow
5) Arterial/venous concentration gradient
>cannot readily manipulate these two factors
How does solubility of drug in tissues (e.g., blood or brain) vs. alveolar gas affect delivery of inhalant from lung to brain?
Called the “blood:gas partition coefficient” (BGPC; lambda, λ)
* Varies slightly between species
* Indicates relative solubility of the drug in tissues vs. alveolar gas
> if you administer some % of anesthetic, you get some other % in the tissues
Onset of unconsciousness (if no induction drug used) & recovery are fast with poorly soluble drugs, and slow with highly soluble drugs.
How can we take advantage of this?
We can take advantage of this by using drugs with low tissue solubility
Onset of unconsciousness (if no induction drug used) & recovery are fast with poorly soluble drugs, and slow with highly soluble drugs.
How can we take advantage of this?
We can take advantage of this by using drugs with low tissue solubility
How does concentration of anesthetic in the inspired gas mixture affect delivery of inhalant to brain?
- We can control the inspired anesthetic concentration using a precision vaporizer
how does ventilation rate affect delivery of inhalant to brain?
- The faster the patient breathes, the faster the drug is delivered to & absorbed by the lungs
- We can control this if necessary, with artificial or manual ventilation
elimination of an inhalant anesthetic is influenced by:
elimination is mainly by exhalation
1) Solubility in tissues
* Poorly soluble drugs leave tissues faster > faster recovery
2) Resp Rate
3) Pulmonary blood flow
how do inhalant anesthetics affect thermoregulation?
- Depressed
- Usually some degree of hypothermia
metabolism of inhalant anesthetics is related to?
Extent of metabolism is related to toxicity:
* Halothane ~25-40%
* Isoflurane ~0.2%
* Sevoflurane ~3-5%
what is MAC? MAC50?
Used to compare potency of inhalant anesthetics
* MAC50 = [drug] in inspired air that will prevent 50% of patients from feeling a painful stimulus
* With very potent drugs, only a low concentration is needed to cause unconsciousness
what is MAC reduction?
Most patients are premedicated, and many sedatives and analgesics reduce the concentration of inhalant required (called a “MAC-sparing” or “MAC reduction” effect), therefore the initial vaporizer setting may be close to the MAC50 value
what is malignant hyperthermia?
- This is an inherited susceptibility in some human, pig, and dog family lines
- It is caused by mutations of the calcium release channel in skeletal muscle
- Mutated channels work normally except when exposed to any halogenated hydrocarbon anesthetic, which triggers uncontrolled muscle contraction > body temp rise > brain damage
Now the most commonly used inhalant anesthetic in vet med
Isoflurane
isofluorane toxicity
Virtually no hepatic or renal toxicity since <0.2%
metabolized (dogs)
solubility of isofluorane in tissues and consequence of this?
Low solubility in tissues > moves in and out of the body rapidly > very rapid changes in depth are possible by adjusting vaporizer
isofluorane plus desiccated CO2 absorbents makes what
forms CO when exposed to desiccated CO2 absorbents
isofluorane drawbacks?
- Dose-dependent drop in BP due mainly to vasodilation
>Usually not a problem when patient is being stimulated - All halogenated hydrocarbon anesthetics interact with desiccated CO2 absorbents to produce carbon monoxide > change CO2 absorbents regularly
- Has a pungent odour > can cause laryngospasm (gagging) in conscious patients (but still possible to mask down patients if necessary) The pungent odour is isoflurane’s only real drawback
isofluorane drawbacks?
- Dose-dependent drop in BP due mainly to vasodilation
>Usually not a problem when patient is being stimulated - All halogenated hydrocarbon anesthetics interact with desiccated CO2 absorbents to produce carbon monoxide > change CO2 absorbents regularly
- Has a pungent odour > can cause laryngospasm (gagging) in conscious patients (but still possible to mask down patients if necessary) The pungent odour is isoflurane’s only real drawback
sevofluorane properties in comparison to isofluorane?
- Even less soluble in tissues (BGPC ~0.68)
> even faster induction & recovery - Main advantage:
It is the least irritating to the airway of all the inhalants, so best for mask inductions of conscious patients (less struggling when masking down conscious animals vs. isoflurane)
>good for animals that can hold breath for a long time
nitrous oxide advantages and disadvantages
- Provides excellent analgesia and alleviates anxiety
- Little effect on CVS unless high conc. used
- Causes very rapid uptake of other anesthetics > risk of animal becoming too deep before it is realized
- Forms gas pockets in digestive tract
