16 – Inhalation Anesthesia Pharmacology Flashcards
What is inhalation anesthesia?
- Commonly volatile LIQUIDS or compressed gases
- Device on machine vaporizes drug into a form which can be INHALED
- Vaporized gas=oxygen
- Entry into body is via lungs and pulmonary circulation (uptake)
How do inhalants work?
- *mechanism of action=UNKNOWN
- Most enhance inhibitory activity at
o GABA receptors in brain
o Glycine receptors in SC - May inhibiting excitatory effects
o Cholinergic
o Glutamate
o NMDA - May depress Ca channels
- May inhibit some Na or K channels
Inhalation (IH) compared to injectable anesthesia
- Controlled
o Anesthetic depth can be RAPIDLY changed - Provides O2 and ability to ventilate lungs
- Do NOT accumulate and recovery is rapid
- High safety margin
- Can produce MORE CV depression (dose dependant)
IH do NOT accumulate and recovery is rapid
- Very little liver metabolism
o Eliminated via lungs - Can maintain anesthesia as long as required
Minimum alveolar concentration (MAC)
- Concentration of vapour in alveoli of lungs that is NEEDED to PREVENT movement (motor response) in 50% of subjects in response to surgical (pain) stimulation
- Partial pressure (PP)
MAC as a measure of potency (strength) of IH drug
- High MAC=LESS potent
Dalton’s law of partial pressure
- TOTAL pressure is sum of its partial pressures
MAC and partial pressure: what is MAC in the equation?
- Partial pressure of VOLATILE ANESTHETIC IN ALVEOLI
Partial pressures in lungs (3 ‘types’)
- ‘partial pressure of gas in solution’
- Vapor pressure
- Atmospheric pressure
- *if all other variable remain constant=reach equilibrium
- *ALVEOLAR CONCENTRATION=BRAIN CONCENTRATION
‘partial pressure of gas in solution’
- Reflects a ‘force’ of gas to escape out of solution
- Fighting against the atmospheric pressure being exerted on it
Vapor pressure
- Pressure exerted by the gas on wall of the container
Atmospheric pressure
- Pushing down trying to force gas into liquid form OR prevent more liquid from converting to gas
Vaporizer dials in in concentration percent: sea level vs. altitude
*actual % output varies with atmospheric pressure
**PP remains the same
Anesthetic gas movement
- Moves down partial pressure gradients
- Until equilibrium occurs=MAINTENANCE
- Recovery reverses the gradient, so drug leaves the body
Uptake of IH drugs is equivalent to
- Absorption
Elimination of IH drugs is equivalent to
- Excretion
Uptake of IH via the
- Lungs
- *drug is DISTRIBUTED to the BRAIN
What are the factors affecting uptake?
- Physical properties of drug
- Inspired anesthetic agent concentration (achieved by altering vaporizer setting)
- Loss of agent (via diffuse through anesthetic breathing system)
- Alveolar ventilation rate
- Cardiac output
What are the 4 physical properties of drug affecting uptake?
- BLOOD:GAS solubility
- OIL:GAS solubility
- MAC as function of POTENCY
- Loss of agent
BLOOD:GAS solubility co-efficient refers to
- How soluble an IH drug is in blood compared to its vapour state
High B:G solubility coefficient
High B:G solubility coefficient
- More soluble in blood
o more needed to dissolve in blood to reach equilibrium
o slower onset of action
- *gas rapidly moves into blood, but concentration that reaches brain increases MORE SLOWLY (‘can fill the blood box more’)
Low B:G solubility coefficient
- less soluble in blood
o less needed to dissolve in blood to reach equilibrium
o faster onset of action
When is anesthetic effect achieved?
- ONLY when concentration of IH in blood/brain is the SAME as that in the gas in the ALVEOLI
Ratio of concentration of anesthetic in alveolar gas (Fa) to inspired gas (Fi)
- Least soluble drugs approach equilibrium (Fa/Fi) the FASTEST
- Ex. NO or desflurane
OIL:GAS solubility coefficient is a measure of
- How much IH will be taken up by adipose tissue
Lower OIL:GAS solubility coefficient
- Less lipid soluble the drug
- Less IH that gets deposited in fat
- Faster it’s elimination and recovery time
Higher OIL:GAS solubility and recovery time
- Longer recovery
3 compartment model:
- Blood
- Vessel rich (brain)
- Vessel poor (fat)
Distribution from blood to body tissues
- Rapid absorption in alveolar and vessel-rich, lower in muscle + fat
- *when turn off anesthetic: levels drop in vessel-rich and alveolar and remains in muscle and fat for longer
How is lipid solubility and potency related?
- More lipid soluble=more potent=MAC value is LOWER
- *but slower uptake and elimination
What are some patient characteristics that affect uptake?
- Lung ventilation
- Lung perfusion
Lung ventilation affect on uptake
- Higher minute ventilation (RRxTV) will INCREASE uptake
- Artificially ventilating lungs will INCREASE uptake
Lung perfusion affect on uptake
- Low CO increases ability of alveoli to reach a higher partial pressure (‘more time to move across the gradient’)
- *uptake will be FASTER with low CO states
- Excited animals are hard to ‘mask induce’ anesthesia using IH drugs
Elimination and metabolism
- 80-90% of IH must be eliminated for full RECOVERY through lungs
- Turn of vaporizer and let oxygen displace any IH drug in breathing system
- Lipid soluble drugs can produce ‘hang-over’ effect
- Rapidly eliminated IH drugs can cause ‘emergence delirium’
- Modern drugs have MINIMAL METABOLISM
Emergence delirium
- *inhalant causing behavioural abnormalities
- Have sedative ready to give IV
- Talk to patient
- Risk of bites and scratches!
Properties of an ideal IH agent
- Easily vaporized near ROOM T
- Non-flammable
- Stable on storage
- Does not react with materials of breathing system
- Compatible with soda lime (what gets rid of CO2)
- Non-toxic to tissues
- Minimally metabolised
- Environmentally friendly
- Non-irritant to MM
- Non-pungent
- Induction and recovery should be excitement free
- Allows rapid control of depth
- Some analgesia
- Some muscle relaxation
- Few cardiorespiratory effects (hypotension + hypoventilation)
- No renal or hepatic toxicity
- Inexpensive
- Not requiring an expensive vaporizer
Halogenated ethers: end with ‘flurane’
- Based on ETHER
- Reduced flammability and analgesia
- Minimal metabolism
- *LESS lipid soluble=
o Less potent=higher MAC
o Rapid elimination=little ‘hang-over’
o Easy to rapidly change depth of anesthesia - *improved delivery and reliability of IH
Examples of halogenated ethers
- Isoflurane
- Sevoflurane
- Desflurane
Isoflurane
- Rapid uptake and elimination
- Pungent smell (coughing and breath-holding)
- Very little hepatic metabolism
- Stable compound
- Very common in VET MED
Isoflurane MAC in dog and cat
- Dog: 1.28%
- Cat: 1.71%
Sevoflurane
- Rapid uptake and elimination
- Not pungent smelling
- 3x as expensive as Isoflurane
- 5% metabolized in liver
Sevoflurane MAC in cat and dog
- Dog: 2.4%
- Cat: 3.0%
Sevoflurane: 5% metabolized in liver
- Can produce Fl- ions=can be nephrotoxic
o Rapid elimination through lungs helps to reduce Fl- ions=NOT a PROBLEM - Can be broken down to CO and other nephrotoxic compound by older/cheaper types of CO2 absorber used in breathing systems
Desflurane
- Very rapid uptake and elimination
- Boiling point close to room temperature
o Requires expensive vaporizer with heating unit - Unlikely to enter vet med
Nitrous oxide (N2O)
- Not potent
- Used to supplement inhalant at 60% inhaled
- Delivered as gas (contributes to global warming)
- Action on NMDA and possibly opioid receptors=analgesic
- Used for analgesic properties only: childbirth and dentistry
- Bone marrow depression if inhaled for >24hrs or long term
Nitrous oxide MAC in dogs and cats
- Dog: 188%
- Cat: 255%
Bone marrow depression with nitrous oxide inhaled for more than 24hrs
- Inactivates vitamin B12 dependent methionine synthase
- Use OR scavenging
Waste gas scavenging
- AVOID inhalation of trace amounts of IH drug
o Headaches, tiredness, nausea
o *LEAK TEST - Divert gases to outside or a charcoal absorber
- Don’t place exhaust close to intake vent
- Don’t put scavenging hose into recirculating ventilation system
- *avoid spills, fill vaporizers with keys and when staff are around
Pregnancy and ORs (operating rooms)
- No known proof that IH drugs can cause problems in trace amounts
- Reported problems are from older drugs and ORs in dental practices NOT using proper scavenging
- Follow basic rules to limit exposure
- Use masks that absorb volatile compounds but uncomfortable for long periods
