7th lecture - general anesthetics Flashcards
General anaesthesia is a condition characterised by
a loss of sensation,
loss of consciousness,
loss of some reflexes and/or control of them,
absence of muscle tone,
all whilst vital functions are maintained.
is a reversible phenomenon.
'’Narcosis’ is also used in reference to medical general anaesthesia.
Generalized CNS depression, the degree of depression is described as depth of anesthesia.
During narcosis or gen. anesthesia, the cell membrane permeability to
Na+ ions is reduced, the same applies to K+ and Ca2+ ions.
Postsynaptic membrane stabilisation will occur. The capability of neurons to generate impulses in response to stimulus is reduced.
General anaesthesia (narcosis) is based on
the inhibition of synaptic transmission mechanisms.
The exact molecular and cellular mechanisms of action of inhalation anesthetics remains unknown.
gen.anesthetics are divided into 2 main groups:
Inhalation general anaesthetics
Parenteral (injectable) general anaesthetics
Inhalation general anaesthetics are divided into 2 further groups:
Volatile and gaseous
though gaseous aren’t really used in vet med today
Name min. 3 volatile Inhalation general anaesthetics
Halothane
Isoflurane, enflurane and sevoflurane
Methoxyflurane
The aim in administering an inhalation anesthetic is to achieve
an adequate partial pressure of anesthetic in the CNS to cause a desired level of anesthesia.
Main Components of general anesthesia: (4)
loss of consciousness,
amnesia,
analgesia,
immobility
(and suppression of autonomic reflexes)
General inhalation anesthetic effect on the resp. system
All inhalation anesthetics depress alveolar ventilation.
Airway irritaion is not generally recognized as a problem associated with anesthesia in animals.
Inhalation anesthetic effect on the cardiovascular system (4)
Drug specific and dose related effects.
All volatile anesthetics decrease cardiac output; depress myocardial contractility.
Decrease in arterial blood pressure.
Inhalation anesthetics, especially halothane, may sensitize the heart to arrhythmogenic effects of catecholamines.
inhalation anesthetic effect on the liver
Hepatocellular injury – a consequence of a reduction in hepatic blood flow or direct toxicity.
inhalation anesthetic effect on the kidneys
All volatile anesthetics reduce renal blood flow and glomerular filtration.
During anesthesia even healthy animals produce small volumes of concentrated urine.
In most cases the effects are rapidly reversed after anesthesia.
what does volatile mean when speaking of general anesthetics?
The volatile anesthetics (halothane, isoflurane, desflurane, and sevoflurane) are liquids at room temperature and require the use of vaporizers for inhalational administration.
(And e.g. the gaseous anesthetic Nitrous Oxide is already a gas under normal conditions of temperature and pressure)
describe Halothane (5)
Clear, volatile liquid.
Does not irritate the respiratory tract.
Depresses CNS in a dose-related manner.
Skeletal muscle relaxation.
Cerebral blood fow usually increases, this may result in an increase in cerebrospinal fluid pressure.
Some drowsiness remains evident for several hours after halothane anesthesia.
Halothane effect on the heart
strongly negative inotrope, chronotrope an dromotrope, blood pressure decreases, the sensitivity of the organism to blood loss increases.
Some anesthetics may increase (xylazine, thiopental) and others may decrease (acepromazine, lidocaine) the arrhythmogenic dose of epinephrine during halothane anesthesia.
Halothane effect on resp. system
Halothane depresses respiration
(dose-related)
Halothane effect on liver and kidneys
Hepatic blood flow is decreased.
Hepatic dysfunction that may occur following inhalation anesthesia is most often associated with halothane.
Nefrotoxic.
Isoflurane and enflurane are what to each other?
structural isomers.
Isoflurane effect on resp. tract
It slightly irritates the respiratory tract.
Depresses respiration.
Isoflurane cerebral and pressure effects
Causes less cerebral vasodilation than halothane.
Blood pressure drops, there is a risk that arrhythmia may develop.
Isoflurane affects cardiac output less than
halothane does.
Isoflurane effect on liver and kidneys
Risk of liver damage, but blood flow to the liver is altered less than by halothane.
Effects on kidney similar to halothane - nefrotoxic.
More potent to enhance the neuromuscular blocking effect.
describe Desflurane
Causes dose-related depression in the CNS.
Does not predispose the heart to ventricular arrhythmias, sensitizes to arrthymogenic effects of epinephrine.
Desflurane general effects are similar to
isoflurane.
Sevoflurane does what
“Switches off” consciousness (similar to isoflurane).
It may increase intracranial pressure.
Sevoflurane cardiovascular effects
It causes systemic vasodilation, a decrease in MAP depending upon the dose, decrease in the heart minute volume and contraction strength, suppresses breathing.
Does not increase the arrhythmogenicity of the heart.
Sevoflurane effect on liver and kidneys
In general does not produce hepatic or renal injury.
Enhances the action of neuromuscular blocking drugs.
Describe laughing gas as a general anesthetic
Nitrous oxide is Colorless, nonirritant, slightly sweet-smelling gas. Not a potent anesthetic.
Usually it is not used as a mono preparation, it is used in conjunction with an injectable and/or another inhalation anesthetic.
Causes an increase in cerebral blood flow, cerebral metabolic rate and intracranial pressure.
It is not recommended to be used on ruminants as it mixes with gases inside the rumen (can cause tympany).
Gen. anesthetics pharmacokinetics (5)
Administered through inhalation.
Absorption occurs through diffusion.
Are all of high lipid solubility, penetrating the brain tissue that are richest in lipids.
Excretion also occurs through diffusion depending upon the partial pressure of gas.
Are metabolised to a small extent in the liver.
Gen. anesthetics pharmacodynamics (3)
Stages of general anaesthesia
Classic excitement stage - the period following loss of consciousness and regaining consciousness is drug-dependent.
Death in case of overdose as a result of cessation of respiration, life-threatening heart function failures may also occur.
Injectable general anaesthetics main groupings: (4-5)
Propofol
Dissociative general anaesthetics
Etomidate
Alfaxalone
(Barbiturates)
Dissociative general anaesthetics examples (2)
Ketamine,
tiletamine
Barbiturates examples (3)
Pentobarbital (short-acting)
Thiopental sodium (ultrashort-acting)
Methohexital (ultrashort-acting)
no longer really used as anesthetics - now they’re use is euthanasia.
Propofol is Used for
sedation,
induction and maintainance of anesthesia,
treament of status epilepticus in some cases.
Propofol interacts with what receptors (2)
Interaction with GABA and
N-methyl-D-aspartate receptors.
Propofol metabolism
Rapid and extensive hepatic metabolism (except cats).
In cats extrahepatic metabolism in pulmonary tissue.
Recovery in Greyhounds and older dogs slower.
Propofol effect on the cardiovascular system
Decrease in arterial pressure.
Cardiovascular effects more profound in patients that are hypovolemic, geriatric, or with compromised left ventricular function.
Does not sensitize the myocardium to epinephrine.
Propofol effect on organ systems other than the cardiovascular system (5)
Dose-dependent depression of ventilation.
Does not adversely affect hepatic blood flow or glomerular filtration.
An effective antiemetic in humans.
Produces muscle relaxation.
Recovery time can be longer in Greyhounds.
Propofol effect on cats
Repeated daily administration of propofol can induce oxidative injuries to feline red blood cells (Heinz body formation, facial oedema, anorexia, dierrhea).
Ketamine produces dissociation of the
thalamocortical and limbic systems, causing a change in awareness.
Dissociative anesthesia – a cataleptic state in which the patient doest not appear to be asleep, but does not respond to external stimuli.
Abnormal behaviour may occur during recovery from anesthesia. Coadministration of CNS depressants (benzodiazepines) may decrease these reactions.
Ketamine pharmacokinetics
Absorbed and distributed quickly, biotransformation in the liver,
excreted with urine.
Used in a combination with other general anaesthetics and muscle relaxants.
Ketamine acts via which receptors
opioid and GABA receptors, blocks a number of mediatory systems.
ketamine effects on the Cardiovascular system
Low cardiotoxicity, wide therapeutic margin.
Increased arterial pressure, heart rate, cardiac output.
Direct stimulation of CNS leads to increased sympathetic outflow.
Caution in animals that have cardiovascular disease.
ketamine effects on the Respiratory system
Does not cause significant respiratory depression.
When administered together with CNS depressants, respiratory depression occurs.
Causes bronchodilation, but increases salivation and respiratory tract secretions.
ketamine Analgesic effects
Ketamine produces analgesic effect.
Subanesthetic doses produce profound analgesia especially in situations of somatic pain (e.g. bone setting in ppl).
ketamine effects on muscle functions
Little relaxation
May cause muscle rigidity, spontaneous movements of limbs and head, cramps.
Not recommended for use as mono preparation, causes cramps, especially in cats.
Many patients do not close their eyes.
tiletamine is a
dissociative drug like ketamine
common drug combination using a dissociative
dissociative + poss. benzodiazepine + alfa2 agonist + opioid to produce excellent immobilization with muscle relaxation and analgesia.
Etomidate is
an independent anesthetic compound not belonging to other GA groups.
Minimally depresses the respiratory center, has a wide therapeutic index, decreases intracranial pressure.
Etomidate acts on what receptors?
GABA receptor agonist, produces hypnosis and CNS depression.
Etomidate effects on the cardiovascular system
Maintains cardiovascular function.
Baroreceptor and sympathetic nervous system refelxes remain intact.
Not arrthymogenic, does not sensitize the heart to catecholamines.
Etomidate effect on organ systems other than cardiovascular
Minimal respiratory effect.
Does not provide significant muscle relaxation; dystonia and tremor can occur.
Does not provide any analgesia, analgesia must be provided separately.
Alfaxalone is what type of drug
Neurosteroid, GABA agonist.
Alfaxalone general effects (5)
Produces CNS depression.
Decreases cerebral blood flow, intracranial pressure.
Produces dose-dependent cardiovascular and respiratory depression.
Provides good muscle relaxation, but may cause tremors during recovery.
May cause allergic reactions, anaphylaxis.
Barbiturates are
Derivatives of barbituric acid, used today as euthanasia substances.
Classified by their duration of action: long, intermediate, short and ultrashort.
Produce CNS depression by activating GABA receptors.
Metabolised in the liver, resulting in the occurrence of enzyme induction.
Excreted through the kidneys.
Barbiturate effect on the brain
Cerebroprotectant properties – cerebral metabolism of oxygen, cerebral blood flow and intracranial pressure are decreased.
Barbiturates do not produce antinociception – analgesia is present only during unconsiousness.
Barbiturate effect on the Cardiovascular system
Decrease in stroke volume and myocardial contractility.
Vasodilation of cutaneous and skeletal blood vessels – hypothermia.
Ventricular arrthymias, sensitization of myocardium to epinephrine.
Barbiturate effect on the Respiratory system
Dose-dependent depression of ventilatory centers, decreased responsiveness to hypoxemia and hypercapnia.
Decrease in respiratory rate and minute ventilation.
Thiopental can cause bronchoconstriction in dogs.
Greyhounds and barbiturates
Greyhounds are relatively deficient in the hepatic microsomal enzymes that are needed to metabolize thiobarbiturates – prolonged recovery from anesthesia.
Horses and barbiturates
Thiopental should not be administered to horses without prior sedation with alfa2 agonists, as significant excitement and incoordination may result.
What is Embutramide?
A potent analgesic and sedative euthanasia agent typically used in combination with e.g. a barbiturate.
Opioid, with very narrow therapeutic window.
GABA stands for
gamma-aminobutyric acid
