Inhalation anesthetic agents
Solubility constant
the ration of gas dissolved in solution to its tension
Partition coefficient
the solubility of an agent is best expressed in terms of ___________
Protein theory
theory of anesthesia where anesthetics interacts with protein targets to modify central synaptic transmission
Lipid Theory
theory of anesthesia where the anesthesia dissolve in the lipid bilayer thereby altering the physical properties of the cell membrane
Protein theory
theory of anesthesia where there is a reduction of pre-synaptic neutrotransmitter release, largely through inhibition of voltage gated channels when post synaptic effects include depression of excitatory neutrotransmission or potentation of inhibitory neurotransmission
Anesthetic agents,
these agents are able to induce this state through reversible and controlled CNS function.
GABA-B receptors
this GABA receptor is linked to potassium channels
GABA -A receptors
this GABA receptor opens the chloride channels
Sevoflurane
this anesthetic has many feature common to desflurane is more potent and does not cause airway irritation; more suitable for mask induction
Chloroform
this anesthetic is Heavy sweet-smelling liquid; neither flammable nor explosive; vapor is not irritating; decomposed by air and light; a powerful anesthetic, just 0.035% in blood causes anesthesia; 0.06 is fatal.
Nitrous Oxide
this anesthetics is mainly used as an adjunct to anesthesia induced and maintained by other agents; not sufficiently potent to be used alone; unusual in having analgesic property; an upper limit of 66% inspired nitrous oxide (or minimum 33% oxygen) should be observed to avoid hypoxemia.
Administration of inhalation anesthetics requires special breathing apparatus that incorporates a source of carrier, usually oxygen, a source of anesthetic and a breathing system to convey the gases to the patient.
How do you administer Inhalation anesthetics
inhaled gas ---> gas diluted with residual air in the lungs ---> gas distributed to alveoli ---> alveolar gas (and anesthetic) equilibrates with pulmonary blood ---> gas dissolved in blood distributes into interstitial fluid ---> anesthetic in interstitial ---> diffuses to brain.
Sequence of flow of anesthetic from source to the brain:
FALSE: the tension of an anesthetic agent in the brain is maintained when its concentration (tension) in the alveoli is kept constant. As the concentration of anesthetic in the alveoli decreases, the tension in the brain also decreases. Therefore, to maintain anesthesia, a minimum alveolar concentration (MAC) of the anesthetic must be maintained.
TRUE OR FALSE: The amount of anesthetics in the alveoli does not affect the amount of anesthetics that's going to the brain
TRUE : Blood from tissues returns to the lungs still carrying some of its original content of anesthetic. The returning blood to the lungs is again equilibrated with fresh alveolar gas now containing more of the anesthetic. The amount of anesthetic absorbed by the returning blood is less than it had absorbed the first time (because of the remaining anesthetic that had been absorbed during the previous circulation). This will eventually result in the gradual rise of the tension of anesthetic toward equilibrium with inspired tension.
TRUE OR FALSE: The amount of inhaled anesthetics decreases per blood flow cycle
tension
The _______ of an agent dissolved in a liquid (e.g. in plasma) refers to the pressure of the agent in gas (e.g. diethyl ether in air) with which the liquid is in equilibrium. --> the mass of gas dissolved in a solution varies directly with its tension.
▪ Pulmonary ventilation ▪ Uptake of anesthetic by blood ▪ Concentration of anesthetic in inspired air
The rate at which tension of anesthetic in the alveolar air approaches its tension in the inspired air depends upon:
Anesthesia
a state of unconsciousness in which there is a reduced sensitivity and response to noxious stimuli.
Enflurane
an anesthetics introduced in human anesthesia in the 1960s; initially used as an alternative to methoxyflurane and halothane; has never been widely used in veterinary medicine.
Desflurane
anesthetics that is not so much used in Veterinary medicine because its extremely expensive; used in day case surgery of humans
by increasing hydrostatic pressure --> a process known as "pressure reversal" --> hydrostatic compression of membrane lipids will oppose volume expansion.
how do you reverse the effect of the anesthesia
Pressure reversal
increasing the hydrostatic compression of the membrane lipids to oppose the volume expansion
Isoflurane
increasingly used in veterinary medicine; may well replace halothane as most prevalent inhalation anesthetic; inhalation agent of choice in critically ill patients; for use in most animals including dogs, cats, and horses; used popularly in some exotic animals.
Anesthesia
is indicated when painful surgical or diagnostic procedures are to be performed, to minimize patient suffering and operator risk to facilitate the procedure through immobilization of the patient.
Methoxyflurane
this anesthetics is used primarily in small animal anesthesia; has been largely superseded by newer safer agents; today, mainly of interest as an example of less than ideal volatile anesthetic.
Halogenation
this increase anesthetic potency while improving stability
Inhalation Anesthetic agents
this is a halogenated organic substance and undergone halogenation
Diethyl ether (Ether)
this is a transparent colorless liquid; lighter than chloroform but is 2x heavier than air; with ether, the possibility of explosion is good without good room ventilation; this is decomposed by light, air, heat and may cause death if liquid is aspirated into nasal pasages
GABA (gamma-aminobutyric acid)
this is the main inhibitory neurotransmitter in the brain
Nervous effect
this pharmacologic effect of diethyl ether is characterised with initial excitement; delirium during induction, then brain depression; medullar center not paralyzed by anesthetic dose; with wide margin of safety; failure of respiration always precedes to cardiac failure; resuscitation is simple
Respiratory effect
this pharmacologic effect of diethyl ether is characterised with irritation of the mouth, pharynx and respiratory tract, simulation of salivation; coughing and breath holding
Neuromuscular effects
this pharmacologic effect of diethyl ether is characterised with the relaxation of muscles; curare like effect; depresses impulse transmission in the spinal cord motor neurons
Halothane
this potentiates the action of non depolarizing neuromuscular drugs
Inhalation anesthetics
unusual drugs in that they are administered and subsequently removed from the body as patient breaths; easily controllable
Halothane
used primarily to maintain anesthesia following induction with injectable anesthetics
1, Unconsciousness 2. Analgesia (inability to feel pain) 3. Muscle relaxion
what are the 3 components of balanced general anesthesia
▪ Mild elevation in temperature produces increase the volume and fluidity of cell membrane comparable to those induced by clinical concentrations of anesthetics. ▪ Some anesthetic agents show stereoselectivity, implying that interaction between drug and specific receptors occurs.
what are the Problems with lipid theory
ew; patients susceptible to hyperthermia
what are the contradictions of Isoflurane
elevated intra-cranial pressure; pneumothorax; gastric dilatation and volvulus; intestinal obstruction; lung pathology; anemia.
what are the contradictions of Nitrous Oxide
o Patients with space-occupying intracranial lesions or elevated cerebrospinal fluid (CSF) pressure o Patient with cardiac dysfunction, especially cardiomyopathy or dysarrhythmias. o Patients with hepatic disease o Patient susceptible to malignant hyperthermia
what are the contraindications in halothane
o Either gas or volatile liquid o Most require breathing device for delivery into the alveoli o Ways of quantifying the amount of anesthetic vapor or gas in a mixture: ▪ Concentration (volume %) ▪ Partial pressure (mm Hg) ▪ Mass (mg or g)
what are the general physical properties of inhalation anesthetic agents
o Lipid theory o Protein theory
what are the two main theories of anesthesia
1. GABA-A receptors 2. GABA-B receptors
what are the two types of GABA receptors
o An extremely potent anesthetic o Depression of myocardial contractility; sensitizes heart to catecholamines o Potentially nephrotoxic because of fluoride metabolite.
what is the adverse effect o Methoxyflurane
o Dose-dependent CNS depression without significant analgesia o Reduced cardiac output and blood pressure; sensitizes the myocardium to arrhythmogenic effects of catecholamines. o Less respiratory depression than other inhalation anesthetics o Will reduce renal blood flow and glomerular filtration rate o Most potent trigger of malignant hyperthermia in susceptible subjects o Most potent trigger of malignant hyperthermia in the susceptible subjects
what is the adverse effect of Halothane
o Has analgesic property (more on people than animals); increased cerebral blood flow and intracranial pressure o Direct myocardial depression o Mild direct respiratory depression o Bone marrow suppression prolonged exposure to nitrous oxide leads to inactivation of a number of vitamin B12- dependent enzymes that are required for DNA synthesis --> bone marrow suppression results
what is the adverse effect of nitrous oxide
o Produces less cerebral vasodilation than halothane, while still reducing metabolic oxygen consumption. o Unlike halothane it does not impair the responsiveness of cerebral circulation to carbon dioxide. o Depresses myocardial contractility but to a lesser extent than halothane; associated with lower incidence of arrhythmias than halothane. o Depresses ventilation to an equal if not greater extent than halothane o Hepatic blood flow is better maintained during isoflurane anesthesia o Some reduction of renal blood flow and glomerular filtration rate o Can also trigger malignant hyperthermia in susceptible patients, but produces good muscle relaxation
what is the adverse effects of Isoflurane
o Seizure activities during anesthesia o Cardiovascular depression; potentiates myocardium to catecholamines but to lesser degree than halothane o Potent respiratory depression
what is the adverse effects of enflurane
1. Reduces cerebral metabolic rate; increases cerebral blood flow and intracranial pressure 2. Increases heart rate and arterial blood pressure; does not sensitize heart to catecholamines 3. Dose dependent respiratory depression 4. Minimal depression of hepatic renal blood flow
what is the adverse effects of the Desflurane
effects are complex because the heart, meducallry centers and peripheral blood vessels are all affected; cardiac failure may occur during induction.
what is the cardiovascular pharmacological effect of chloroform
non-flammable and stable anesthetic vapor; not degraded by UV light; has lower blood/gas partition coefficient than halothane, therefore associated with more rapid induction; extremely low rate of metabolism; virtually all isoflurane exhaled unchanged.
what is the pharmacokinetics o Isoflurane
has lowest blood/gas partition coefficient of the volatile anesthetic currently available; may react with carbon dioxide absorbent soda lime to generate carbon monoxidde
what is the pharmacokinetics o the Desflurane
Non-flammable and is degraded by UV light; has low blood/gas partition coffecient (but not as low as newer agents_; low solubility in blood results in moderately rapid induction rate of change of anesthetic depth. About 70-80% of inspired halothane is exhaled unchanged; metabolized by cytochrome P450 in the hepatocytes
what is the pharmacokinetics of Halothane
non-flammable but is unstable; with unusually low vapor pressure, which limits usefulness as inhalation anesthetic; blood/gas partition coefficient is high thus induction, recovery and rate of change in anesthetic depth are slowed; high solubility in rubber; under extensive hepatic metabolism.
what is the pharmacokinetics of Methoxyflurane
non-irritant, non-flammable, although it can support combustion; nitrous oxide cylinders must be weighed to determine gas remaining in tanks (pressure gauge will not accurately reflect the contents of the cylinder); very low blood/gas partition coefficient; inclusion of nitrous oxide in the inspired gas mixture may cause expansion of gas-filled spaces within the body ---> may cause bloat, pneumothorax, gastric dilatation and volvulus; not metabolized.
what is the pharmacokinetics of Nitrous Oxide
a structural isomer of isoflurane; non-flammable and stable; has slightly lower blood/gas partition coefficient than halothane; undergoes hepatic metabolism to trifluoroacetic acid and free fluoride ions
what is the pharmacokinetics of enflurane
has very low blood/gas partition coefficient with rapid onset of action; approximately 3% is metabolized
what is the pharmacokinetics of sevoflurane
1. Nervous effect 2, Respiratory Effect 3. Neuromuscular effects
what is the pharmacologic effect of diethyl ether
direct and indirect effects; depressed sensitivity to carbon dioxide; breath slow and shallow; respiratory failure may occur during anesthesia.
what is the respiratory pharmacological effect of chloroform