Pharmacology of Volatile & Gaseous Agents Flashcards
Inhalant anaesthetics are mainly used for…
maintenance of anaesthesia
Advantages of inhalant anaesthetics?
- Safe?
- Some situations IV anaesthesia is safer
- Can adjust the amount to the P quickly
- Rapid action, elimination and recovery
- Easy to prolong anaesthesia
- Minimal metabolism (newer agents)
- Reduced likelihood of arrhythmias
Disadvantages of inhalant anaesthetics?
- Expensive: Drug itself! The anaesthetic machine, O2 source, tubings/connections all also req’d
- Pollution → staff and environmental
- Cardiovascular and respiratory depression
- No analgesia – this must be provided
Molecular mechanisms of action
- classical lock & key
- efficacy of inhalant anaesthetic demonstrated humans, vertebrates, invertebrates, etc
Meyer-Overton Rule
- Site of Action: Lipid cell membane
- some correlation w/ potency & lipophilicty of drug
Inhalants depress the excitatory neurotransmission & enhance
inhbitory neurotransmission
Sites of Action of inhalant anaesthetics?
- spinal cord: muscle relaxation
- CNS: hypnosis
Volatile liquids
Halothane, isoflurane, sevoflurane, desflurane, enflurane, methoxyflurane
Compressed gases
Nitrous oxide
xenon
Saturated vapor pressure
- pressure the vapor molecules exert when liquid & vapor phases are in equilibrium
- measures volatility of the agent
- temperature dependent
- vaporisers are coordinated to specific agents, so one agent cannot go into the vaporiser for another agent
Solubility of inhalant anaesthetics
- solubility in liquieds & solids is different
- at some point, they are in equilibrium so they have the same partial pressures between all phases
- consists of partition coefficients, blood/gas coefficient, oil/gas partition coefficient
What is the blood/gas partition coefficient?
- lower solubility indicates speed of induction, recovery, & change of anaesthetic depth
- if low = gases will esert high partial pressure so changes will be fast –> blood quickly saturated & moves to brain
- if high = blood acts as sink so changes are slower
Oil/gas partition coefficient
- describes the ratio of a concentration of anaesthetic in oil & gas phases at equilibrium
- correlates w/ the potency of an anaesthetic drug
- High = low inhalant conc to maintain anaesthesia
MAC
“Minimum alveolar concentration of an anaesthetic at 1 atmosphere that produces immobility in 50% of subjects exposed to a supramaximal noxious stimulus”
Factors affecting uptake of volatile & gaseous agents
- you want to increase alveolar pressure –> equilibrium w/ CNS
- increased alveolar delivery: increase in Fi of anaesthetic, increase in alveolar ventilation, decreased removal from the alveoli
Factors affecting speed of induction
- to increase speed of onset you must increase PA of the agent, more to alveoli, more to brain
- Increased alveolar delivery (input) of agent –> increased inspired anaesthetic concentration, increased alveolar ventilation
- decreased removal from alveoli
How do you increase alveolar delivery of an agent
- increase vaporizer setting
- increase FGF
- decrease gas vol of breathing circuit on circle
- acts in first phase
How do you increase alveolar ventilation
- increase minute ventilation
- decrease fxnl residual conc
How do you decrease removal from alveoli?
- decreased blood:gas solubility
- decreased CO
- decreased tissue solubility
- acts btw alveoli & blood
What is the effect of CO on anaesthetic uptake?
- greater the CO, greater the amount of blood passing through the lungs carrying away anaesthetic
- takes longer for P to be deeper or achieve enough conc in the brain
Elimination of anaesthetic
Recovery: reduced partial pressure in the CNS to allow return to consciousness
Metabolism-dependent
How do you speed up recovery w/ circle breathing system?
- increase FGF
- increase Minute volume
- empty reservoir bag
How do you speed p recovery w/ non-rebreathing system?
- switch vaporizer off b/c anaesthetic is not returning to the system
Common characteristics of halogenates
- cardiovascular depression
- CO reduction
- direct myocardial depression
- peripheral vasodilation
- impairment of tissues’ auto-regulation mechanims
- CNS depression
- respiratory depression: reduction of MV via reducing TV/RR
- hepatic & renal blood flow
Isoflurane
- MAC: 1.2-1.7%
- physico-chemical properties: fast onset & recovery, pungent odour
- Metabolisation by liver, elimination by lungs
- dose-dependent vasodilation, respiratory depression
- CAUTION: CARBON MONOXIDE CAN FORM IF INTERACTS W/ DRY SODA LIME
What are isoflurane effects on hepatic blood flow?
- reduces flow on hepatic portal vein
- increases flow thru hepatic artery
- little cahnge in perfusion
- may result in improved oxygenation
- iso best for liver patients
Sevoflurane
- MAC: 2.3-2.6%
- Physico-chemical properties: pleasant smell, non-irritant for mm, fast onset/recovery
- Metabolization in the liver: 2-5%
- Compound A forms if degradation by soda lime –> nephrotoxic
- Preserves cerebral autoregulation compared to iso
Why does sevoflurane come in plastic bottles?
Impurities in the glass –> hydrofluoric acid (toxic volatile acid) –> glass –> silicon fluoride (volatile, pungent, highly toxic)
Nitrous oxide
- USE W/ EXTREME CAUTION
- gas at room temp
- MAC 200% (not possible), must use w/ other meds
- rapid onset
- no metabolism
- provides analgesia
- non-irritant
- need to give w/ O2 at the appropriate rate
- augments ventilation
- mild SNS stimulation
- reisk of hypoxia, arrhythmias, & death
What occurs when there is nitrous oxide that is diffused to air filled cavities?
- Pneumothx
- GDV
- colic (horses)
- ophthalmic procedures
- air embolism
- craniotome
- laparoscopic procedures
Environmental impact of gaseous agents
- low compared to CO2, but significant contribution
- volatile agents: potent greenhouse gases
- N2O lesser short-term impact, but longer in atmosphere
- contribution to global warming (des > sevo > iso) or switch to TIVA
Health hazards of volatile gases
- N2O: increase infertility/abortion risk
- mutagenic, carcinogenic, teratogenic, foetal death, spontaneous abortion, birth defects, cancer if exposed
