Test 1: 10 + 11: injectable inductions Flashcards
CNS sites of action of anesthetics
cerebral cortex
reticular activating system
thalamus
substantia nigra
vestibular system
cerebellum
spinal cord
cellular site of action of anesthesia
interfer with:
neuotransmitter release
neurotransmitter receptor binding
postsynaptic membrane potential
molecular site of action of anesthetics
Classic: propofol, alfaxalone, Etomidate
sedation no analgesia
bind to membrane bound ion channels
allows GABA to attaches to GABA receptor longer and allows Cl into the cell
Dissociative: Ketamine,Tiletamine
intense analgesia, light sedation, catalepsy
block NMDA receptor= inhibitory to cell
what are some rapidly acting anesthetics
(Barbiturates (Thiopental))
Phenols (Propofol)
Steroids (Alfaxalone)
Imidazoles (Etomidate)
Cyclohexanones (Ketamine, Tiletamine)
what are some slower acting anesthetics
potent opioids
classical injectable anesthetics works by
bind to GABA receptor and increase GABA binding, leading to longer opening and Cl into the cell
allosteric modulation of the GABA A receptor
synergism with benzodiazepine
classic injectables: thioental, propofol, alfaxalone, amidate (etomidate)
what are some dissociative anesthetics
ketamine
tiletamine
how do dissociate anesthetics work
cyclohexanones like ketamine and tiletamine
block NMDA receptors and prevent binding of glutamate or glycine
this stops the AP
causes analgesia and anesthesia
ketamine needs to work with other drugs to cause anesthesia
glutamate is an excitatory neurotransmitter: binds to NMDA, Kainate or AMPA receptors and cause K out and Na in
most anesthetics are lipophilic how does this effect distribution in the body
will go to brain and viscera first and cause sedation
but then levels in brain drop as drugs are redistributed into the fat
patient wakes up, but drug still in system
— is a phenol anesthetic
propofol
causes depression of the CNS activity: sedation→hypnosis →anesthesia
propofol has a — onset and a — recovery with —
rapid
rapid
without residual CNS depression
non hypnotic CNS effects of propofol
- decreases cerebral blood flow, intracranial pressure and cerebral metabolic rate or consumption of oxygen
- antiemetic
adverse effects of propofol on the respiratory system
respiratory depression (↓ tidal volume and ↓RR)
bronchodilation
inhibition of laryngeal reflexes- need to intubate
adverse effects of propofol on CV system
hypotension
* centrally (↓SYMP vasomotor tone)
* peripherally (negative inotropic effect and direct vasodilation)
NO change in HR
in 10 % of dogs and cats that are given propafol what adverse reaction can happen
excitaory- Limb paddling, nystagmus, muscle twitching, myoclonus, and opisthotonus
pts with hypoalbuminemia will need to — the dose of propofol
decrease
97-99% of propofol binds to albumin - if there is less albumin to bind to then there is increased free propofol- ↑ effects
propofol is metabolized in the
kidneys
lungs
liver
(can use med in pt with liver failure)
what animals can have difficultly metabolizing propofol
sight hounds- have problem with liver metabolism (hydroxylation via CYP450)
cats- can’t metabolize drug by glucuronide conjugation, but can still metabolize in the kidney and lungs →heinz body formation
when not to use propofol
Patients with cardiovascular dysfunction
* Cardiac failure (low cardiac contractility)
* Hypovolemia
* Hypotension
Patients with sepsis/systemic infections
Cats with anemia→heinz bodies
how to give alfaxalone
IV or IM
rapid onset, bolus or CRI
effects of alfaxalone
NO analgesia
suppression of brain activity: Sedation → Hypnosis → General anesthesia
central excitation during recovery can occur in cats with the use of — sedation
alfaxalone
this does not happen if you combine with sedatives and/or analgesics (opioids)
— is an effective IM sedation for non-cooperating animals or animals at higher risk of anesthetic complications
alfaxalone
adverse effects of alfaxalone on respiratory system
less effects than propofol when injected slowly
causes central respiratory depression (↓ tidal volume, and ↓RR)
↓ swallow reflex- need to intubate
can cause excitatory signs during recovery if not combined with sedative and/or analgesics
Adverse effects of alfaxalone on the CV system
unlike propofol, minimal side effects
metabolism of alfaxalone
liver
can be used in sighthounds and cats, unlike propofol
propofol causes the formation of heinz bodies in cats
when not to use alfaxalone
animals with respiratory problems ( alfaxalone causes ↓RR)
animals you can not intubate- (alfaxalone ↓ swallowing reflex, needs to be intubated)
animals with heart disease (even though alfaxalone has minimal effect on CV system)
— is a ultra short acting anesthetic with high therapeutic index
etomidate (imidazole)
nonhypnotic CNS effects of Etomidate
↓EEG activity
↓ cerebral blood flow- direct cerebral vasoconstriction
↓ intracranial pressure and cerebral metobolic rate or consumption of O2
onset of etomidate
CNS depression in < 20 sec (ultra rapid onset)
NO Pain relief
adverse effects of etomidate on respiratory system
none or minimal
adverse effects of etomidate on CV system
none or minimal
adverse effects of etomidate
Inhibition of adrenal steroid genesis (11β- hydroxylase)
Hemolysis due to high osmolality of solution
NO respiratory or CV effects
occasional excitatory effects: myoclonus, vomiting, opisthotonus
etomidate distribution and elimination rates
rapid onset, rapid peak CNS 3 mins
elimination 3 hrs
do you need to decrease dose of etomidate if you have hypoalbuminemia?
No only binds 76%
unlike propofol which binds 97-99%
how is etomidate metabolized
liver
plasma ester hydrolysis
renal elimination of metabolities
when to use etomidate
pts with heart failure, shock or sepsis
pts with increased intracranial pressure or seizures
has no CV or respiratory effects unlike propofol or alfaxalone
when not to use etomidate
addisons (↓ adrenal function)
severe stress syndrome
etomidate causes the ↓ production of steroids
effect of cyclohexanones
dissociative anesthesia
intense analgesia
light sleep
amnesia
catalepsy- rigid muscles
cyclohexanones cause dissociative anesthesia: ketamine, tiletamine
how does ketamine work
block NMDA glutamate receptors → analgesia and anesthesia
block nicotonic ACh receptors: (excitatory receptors)
interact with central opioid receptors, monoaminergic (NA, DA, serotonin) receptors and muscarinic ACh receptors
also block NE re-uptake
block voltage gated Ca channels in the heart
block peripheral nerve conduction
why dissociate anesthesia for ketamine
Selective suppression of thalamoneocortical projection system → disconnection of thalamoneocortical from limbic and other subcortical areas
clinical signs of dissociative anesthesia
- Loss of consciousness despite neuronal activity outside neo-cortex
- Catalepsy (catatonia)
- Maintenance of protective reflexes
- Skeletal muscle movements
ketamine + tiletamine
adverse effects of ketamine on CNS
increased EEG activity
increased cerebral blood flow (cerebral vasodilation)
emergence delirium(dysphoria) → violent recovery (horses)
opposite effect of classic anesthetics
cyclohexanones cause dissociative anesthesia: ketamine, tiletamine
adverse effect of ketamine on respiratory system
mild decrease in RR and tidal volume
cause apneustic, shallow and irregular breathing patterns, breath holding at peak inhale
bronchodilation
cyclohexanones cause dissociative anesthesia: ketamine, tiletamine
adverse effects of ketamine on CV system
indirect stimulation: ↑ SYMP and ↓NE reuptake causes ↑HR, ↑CO and ↑MAP
Can cause direct negative inotropic and vasodilatory actions in old or CV compromised patients
pro-arrhythmic
adverse effect of ketamine on digestive system
↑ salivation: may make intubation harder
adverse effects of ketamine on neuromusclar system
causes increased muscle ridigity- bad in pts with bone breaks
decreased nerve conduction
cyclohexanones cause dissociative anesthesia: ketamine, tiletamine
metabolism of ketamine
Extensive hepatic (CYP 450) metabolism
* N-demethylation to norketamine (20-30 % rest activity)
* then forms inactive compounds that go through glucuronide conjugation
cats no metabolism to inactive compounds
when not to use ketamine
Animals with cardiovascular dysfunction
* Cardiac failure (low cardiac contractility)
* Decompensated shock (ketamine causes vasodilation)
* Tachyarrhythmias
Animals with pheochromocytoma
Animals with hyperthyroidism
Animals with CNS excitatory signs (ketamine causes dysphoria)
Tiletamine can cause severe— therefore it is combined with zolazepam
catalepsy and convulsions
cyclohexanones cause dissociative anesthesia: ketamine, tiletamine
