anesthetic drugs (injectible) Flashcards
(43 cards)
1
Q
what are the elements of the anesthetic state
A
- unconsciousness (hypnosis)
- amnesia
- analgesia (not same as antinociception) (inhibition but may not be sippression or reflex responses to noxious stimulation)
- immobility (skeletal muscle relaxation)
2
Q
what are the 4 stages of anethesia
A
- analgesia
- excitement
- surgical anesthesia
- medullary paralysis
3
Q
CNS sites of action
A
- cerebral cortex
- reticular activating system
- others (thalamus, substantia nigra, vestibular system, cerebellum, spinal cord)
4
Q
cellular sites of action
A
interference with synaptic mechanisms
- NT synthesis
- NT release
- NT clearance
- NT receptor binding
- postsynaptic membrane potential
- inhibition of axonal nerve impulse conduction
5
Q
molecular sites of action: membrane protein channels
A
interaction of anesthetics with specific NT receptor proteins (GABAa receptor)
6
Q
injectable anesthetics in clinical use
A
- barbituates (thiopental)
- phenols (propofol)
- steroids (alfaxalone)
- imidazoles (etomidate)
- cyclohezanones (ketamine, tiletamine)
7
Q
what is the main molecular mechanism of action of “classical” injectable anethetics
A
- allosteric modulation of the GABAa receptor (increase affinity)
- synergism with benzodiazepines
8
Q
what are the main mechanims of action of dissociative anethetics
A
- blockade of the NMDA receptor at subanesthetic dose (use-dependent block and closed channel block)
- decrease in central glutamatergic activity -> analgesia and anesthesia
9
Q
what is the common pharmacokinetic feature of all highly lipophilic injectable anesthetics
A
redistribution of drug from CNS to peripheral tissues causes the animal to wake up (needs to go below threshold)
10
Q
what are phenols
A
- sedative-hypnotic drug unrelated to barbituates
- risk of microbial growth in the vehicle (intralipid)
11
Q
gradual depression of CNS activity with phenols
A
titration of effect possible by increasing the dose: sedation -> hypnosis -> anesthesia
12
Q
general anesthesia pharmacologic effects of phenol
A
- rapid onset after IV bolus injection
- rapid recovery without residual CNS depression
- maintenance with repeated IV boluses or CRI
13
Q
IV, long-term sedation pharmacologic effects of phenols
A
low risk for drug accumulation
14
Q
non-hypnotic CNS effects of phenols
A
- decrease in CBF, ICP, CMRO2
- antiemetic effects
- none or no clinically relevant analgesic effect per se
15
Q
what systems effects are most severe upon administration at > 1 mg/kg/min
phenol
A
- respiratory
- cardiovascular
16
Q
respiratory system adverse effects
phenol
A
- central respiratory depression (Vt decreases, RR decreases)
- bronchodilation
- inhibition of laryngeal reflexes
17
Q
cardiovascular system adverse effects
phenol
A
- hypotension
- centrally (sympathetic vasomotor tone decreases)
- peripherally (neg. inotropic effect & direct vasodilation)
18
Q
excitatory effects (transient)
phenol
A
- 10% of dogs and cats
- limb paddling, nystagmus, muscle twitching, myoclonus, and opisthotonus
19
Q
why is there reduced elimination in cats
A
reduced conjugation capacity -> oxidative injury to feline RBCs -> Heinz body formation
20
Q
using propofol with caution
A
- patients with cardiovascular dysfunction
- patients that cannot be ventilated b/c not intubated
- patients with sepsis/systemic infections
- cats with anemia
21
Q
combining propofol with other preanethetic drugs
A
increases induction dose and makes it safer
22
Q
what is neurosteroid: Alfaxalone
A
- water soluble compound suitable for IM injection
- CNS depressant and hypnotic effects as origionally described for progesterone and its congeners in rats
23
Q
biotransformation and elimination of phenols
A
- extensive hepatic matabolism
- hydroxylation via CYP450 system
- glucuronide conjugation
24
Q
main effects of alfaxalone - progressive suppression of brain activity
A
- increasing doses of alfaxalon causes: sedation -> hyposis -> general anesthesia
- none or no clinically relevant analgesic effect per se
25
main effects of alfaxalone as a general anethetic
* **rapid onset of effect after IV bolus injection**
* relatively short anesthetic effect
* **prolongation of anesthesia with repeated bolus administration or with CRI**
* **however, not rarely central excitation during recovery, particuarly in cats**
26
main effects of alfazalone - **IM sedation**
* effective to sedate non-cooperating animals or animal patients at higher risk of anesthetic complications such as trauma patients, cat with FUS, anxious animals
* effective muscle relaxation when combined with benzodiazepines
27
adverse effects of alfaxalone
respiration
* **centrally mediated depression (Vt decreased, RR decreased)**
* **less than with propofol, if injected slowly IV to effect**
* suppression of swallow reflexes (-> intubate animal)
* **excitatory signs in recovery period** if: (NOT combined with sedatives and/or analgesics/opioids)
cardiovascular system
* **unlike, propofol, somewhat lesser side effects**
28
pharmacokinetics of alfaxalone
* fast hepatic metbolism
* **no risk for accumulation in cats or sighthounds**
29
principle pharmacologic effect of imidazoles (etomidate)
* **ultra-rapid onset of CNS depression with hypnosis in < 20sec**
* no antionociception/no analgesic effect per se
* **non-hypnotic CNS effects (decrease in EEG activity, decrease in CBF - direct cerebral vasoconstriction, decrease in ICP and CMRO2)**
30
adverse effects of etomidate
* **none or minimal respiratory and cardiovascular effects**
* **occasionally CNS excitatory effects**
* **inhibition of adrenal steroid genesis (11B-hydrozylase)** - responsible for cortisol production
* hemolysis due to high osmolality of solution
* pain upon IV injection
31
pharmacokinetics of etomidate
* **76% plasma albumin binding**
* ~25% total plasma protein binding
* incomplete placental transfer
* **fast decline in fetal plasma levels**
32
biotransformation and elimination of etomidate
* **extensive hepatic metabolism**
* **extrahepatic metabolism (plasma ester hydrolysis)**
* renal elimination of metabolites
33
use of etomidate in clinical practice
**cautious use in patients with:**
* **adrenal insufficiency (addison's disease)**
* **severe stress syndrome**
34
cyclohezanones produce anethesia-like state called:
**"dissociative anesthesia"**
* **intense analgesia, light sleep, amnesia and catalepsy**
35
ketamine is a racemic mixture of two optical isomers:
* **S(+) isoform 3-4 times more potent than R(-)**
* **S(+) isoform twice as long active as R(-)**
* **dysphoria: S(+) < R(-)**
36
what are the principle pharmacologic effects of ketamine
dissociative anesthesia
* **selective suppression of thalamoneocortical projection system** -> disconnection of thalamoneocortical from limbic and other subcortical areas
analgesia
* **at subanesthetic doses**
37
what are the typical features of dissociative anethesia
* **loss of consciousness despite neuronal activity outside neocortex**
* **catalepsy**
* **maintenance of protective reflexes**
* **skeletal muscle movements**
38
what are the CNS adverse effects of ketamine
* **increased EEG** activity associated with myoclonus and seizure-like activity
* **increase in CBF (cerebral vasodilation)**
* **emergence delirium** (dysohoria)
39
respiratory adverse effects of ketamine
* mild, transient decrease in RR and Vt
* **apneustic, shallow, and irregular breathing pattern**
* **breath-holding at peak of inspiration**
* bronchodilation
40
cardiovascular adverse effects of ketamine
* **indirect stimulation** -> increase HR, CO, MAP
* **direct negative inotropic and vasodilatory action** -> relevant in cases of compromised CVS
* pro-arrhythmogenic effects
41
digestive system adverse effects of ketamine
**increased salivation**
42
neuromuscular system adverse effects of ketamine
* **increased muscle rigidity** (catatonia)
* decreased nerve conduction
43
biotransformation and elimination of ketamine
* **extensive hepatic (CYP450) metabolism**
* **N-demethylation to norketamine (20-30% rest activity)**
* **exception cat: no metabolism to inactivate compounds**
