Sedatives Flashcards
3 categories of sedatives
- phenothiazines
- alpha-2 agonists
- benzodiazepines
Caution regarding many IV CNS depressants - what must we avoid upon injection? what will this look like?
Accidental injection into carotid artery may be fatal
-immediate violent seizures followed by collapse
-convulsive seizures and death
Common properties of most sedatives
Reduction of induction dose & MAC reduction
-~half dose of unmedicated patient
Improved quality of recovery from general anesthesia
-smoother
what type of drug is acepromazine? acepromazine main effects? main use?
Phenothiazine
-major tranquillizer & sedative
-anti-emetic
-anti-arrhythmic
-main use is restraint
onset of phenothiazines is fastest in a _____ environment?
quiet
mechanism of action of phenothiazines?
- Blocks dopamine D2 receptors in brain
> Dopamine is needed for wakefulness & motor activity
most adverse effects of phenothiazines are due to
especially peripheral α1 blocking (in addition to dopamine receptor targets)
what do α1 receptors do? what does stimulation cause? what about blockade? what do phenothiazines cause?
α1 stim > blood vessel constriction in most tissues
α1 stimulation by NE also causes constriction of G.I. & urinary tract sphincters
α1 blockade by phenothiazines causes vasodilation and sphincter relaxation > side effects
potential adverse effects of phenothiazines? Some particular adverse effects for ruminants and horses?
- Peripheral α1 blockade > vasodilation > hypotension
- Ruminants: regurgitation due to relaxed cardiac sphincter
Male horse: penile prolapse
* Dose-dependent duration, can last 1-2 hours > edema > constriction of blood supply > ischemic necrosis > amputation required in worst cases
acepromazine effect on blood pressure?
large decrease
how are phenothiazines related to seizures? Literature vs common conceptions.
-literature shows phenothiazines do not promote seizures, and possibly inhibit them
-widespread (false) belief that acepromazine causes seizures
what type of drug is azaperone? what is it used for and why?
-butyrophenone, sedative
* Used in swine practice in place of acepromazine because it has a 1-day meat WDT in swine, vs 7 days for acepromazine
4 important alpha-2 agonists
Xylazine
Detomidine
Dexmedetomidine
Romifidine
xylazine effects and timeline
- Sedation lasts ~2 h (dose-dependent)
- Analgesia is excellent but lasts only ~30 min (dose-dependent)
Alpha-2 Agonists mechanism of action
α2 stim. opens K+ channels > inhibits APs in pathways in brain related to:
* Wakefulness (> sedation)
* Pain (> analgesia)
* BP control (> hypotension)
* Motor activity (> muscle relaxation)
* Respiration: may be dramatic drop in O2 exchange
Pre-synaptic alpha-2a stimulation opens K+ channels
> inhibits NT release in various brain pathways
CNS effects
Alpha-2 Agonists mechanism of action
α2 stim. opens K+ channels > inhibits APs in pathways in brain related to:
* Wakefulness (> sedation)
* Pain (> analgesia)
* BP control (> hypotension)
* Motor activity (> muscle relaxation)
* Respiration: may be dramatic drop in O2 exchange
Pre-synaptic alpha-2a stimulation opens K+ channels
> inhibits NT release in various brain pathways
CNS effects
potential adverse effects of alpha2 agonists
Large animals:
– vasoconstriction (stim. of α1 and α2b R on blood vessels) > initial rise in BP, then see bradycardia due to slower central α2 stim. which inhibits SNS outflow > potential for hypotension
– These effects are highly variable; depend on dose and other factors
- significant muscle relaxation
Decreased GI motility > bloat (large dogs)
- May kill small ruminants, calves, sick cows via pulmonary edema
alpha2 agonist special effect for cats
cats will vomit
what happens if an alpha2 agonist is injected into the carotid?
“As with many tranquilizers, immediate violent seizures followed by collapse may result from inadvertent administration into the carotid artery”
how can we reverse the effects of alpha2 agonists?
alpha2 antagonist
Main uses of xylazine:
Few uses in small animals (e.g., to induce vomiting in cats) Large animals:
* Alone > restraint
* With ketamine > general anesthesia
* With opioid > short surgical procedure
* Epidural analgesia (horses)
* Has been used with acepromazine for heavy sedation
what animals are particularly sensitive to alpha2 agonists and why? Consequence?
- Many domestic ruminants are highly sensitive Possess an alpha-2D receptor that other species lack > require only 1/10th the dose of other species
detomidine uses? What should we watch out for? why would we use this vs xylazine?
-approved for horses only
-analgesia is thought to last as long as sedation
-Animals may kick even when fully sedated
-Used when pain greater, or longer effect desired
(main difference vs xylazine is duration of action)
dexmedetomidine uses? what species? advantages over xylazine?
Approved for use in dogs & cats
The most popular alpha-2 agonist in small animal practice
* Safer than xylazine
what is romifidine used for? what species? comparison to xylazine?
- For horses, alpha2 agonist
- 50% longer sedation than xylazine (0.5 – 3 h, depending on dose) & less head droop and ataxia than equipotent doses of xylazine or detomidine > helpful for dentistry
Alpha-2 Agonist Reversal Agents
Atipamezole, yohimbine
* α2 antagonists
* Atipamezole is more specific for α2 vs. α1
* Reverse sedation & most CV effects
> Titrate to effect – don’t be overzealous or may cause increased SNS effects and pain
benzodiazepines: main one used, and effects
Mainly diazepam
* Sedative, muscle relaxant, & anticonvulsant
mechanism of action of benzodiazepines
Inhibits APs in post-synaptic cells by facilitating GABA (the main inhibitory NT in brain)
why are benzodiazepines considered safe? what is a possible adverse effect?
- Safe because little effect on CV system
- Overdose effects can be reversed by flumazenil,
a competitive inhibitor of the BZD binding site - Dose-dependent respiratory depression
*hepatic necrosis in cats - Excitement & paradoxical aggression problems in healthy small animals & horses > administered in combination with other drugs
how are benzodiazepines metabolized? what is an issue that can arise in cats?
- Hepatic metabolism
– Cats: fulminant hepatic necrosis (lethargy, jaundice +/- death); idiosyncratic; may follow >2 days admin.
unique use of benzodiapzepines in cats
Effective appetite stimulant in cats – eat within seconds of injection
possible adverse behavioural outcome from benzodiazepines and how we can alleviate this
- Excitement & paradoxical aggression problems in healthy small animals & horses > administered in combination with other drugs
A 1:1 mixture of diazepam:ketamine is a very common
induction mixture in small animal medicine
similar drug to benzodiazepine - when would we use this instead?
Midazolam is similar but water soluble, so better for IM use when rapid effect is desired (also shorter T1/2)
