Sedation 1 Flashcards
why do we use chemical restraint (6)
-To control dangerous/uncooperative patients
-For minor diagnostic/surgical procedures
-Prior to anesthesia
-To control intra-op & post-op pain
-To smooth recovery
-To facilitate post-op treatments
three categories of chemical restraint
tranquilizers/sedatives, aesthetics, opiods
types of sedatives (3)
phenothiazines, alpha-2 agonists, benzodiazepines
what is a big caution to be aware of when using IV CNS depressants
Accidental injection into carotid artery may be fatal!!!
common properties of most sedatives (2)
1) Reduction of induction dose & MAC reduction
-Sedated patients require lower dosages of induction agent (depends on dose, but often on the order of HALF the dose that would be required to induce an un-premedicated patient), and may require lower dosages of inhalant anesthetic, compared to un-premedicated patients
2) Improved quality of recovery from general anesthesia
-Sedatives allow patients to experience a smoother recovery from general anesthetics
what is the main phenothiazine
acepromazine
what does acepromazine do
A major tranquillizer & sedative!!
-Reduces fear & anxiety calms patient
-Reduces response to stimuli
-Induces lethargy
-Relaxes muscles
main use of acepromazine
restraint
time to clinical effect of acepromazine
15 min (IV)
30 min (IM)
60 min (oral)
what is required for fast onset of most sedatives
a quiet environment
mechanism of action for phenothiazines
Blocks dopamine D2 receptors in brain
-Dopamine is needed for wakefulness & motor activity
-Excessive D2 stimulation = schizophrenia
-D2 blockade = sedation, reduced anxiety
what is the reason for side effects when using phenothiazines
Unfortunately, phenothiazines also block other receptors, especially peripheral α1 = side effects
what happens when phenothiazines block alpha 1 receptors
causes vasodilation and sphincter
relaxation = side effects
what are alpha1 receptors normally doing in terms of vessels and GIT/bladder
stimulated by NE causes vasoconstriction
α1 stimulation by NE also causes constriction of G.I. & urinary tract sphincters
what is the overall main adverse effect of phenothiazines and another specific to ruminants
-Peripheral α1 blockade = vasodilation = hypotension (MAIN)
-Ruminants: regurgitation due to relaxed cardiac sphincter
what is an adverse effect of acepromazine in male horses
-Retractor penis muscles are adrenergic
-Penile prolapse occurs, even with low doses
-Intensity of effect varies widely from horse to horse
-Dose-dependent duration, can last 1-2 hours = edema = constriction of blood supply = ischemic necrosis
= amputation required in worst cases
cautions to take with acepromazine in male horses
-Use with caution (or avoid), esp. in breeding stallions
-Do not use in male horses (intact or not) with prior episode of prolonged protrusion following acepromazine admin.
contraindications of phenothiazines (6)
-Hypovolemic/shocky patients
-Valuable breeding stallions? Or use with caution and monitor?
-Unattended animals (esp. large animals: injury during onset)
-Organophosphate poisoning
-OPs cause cholinergic PSNS overstimulation
-Phenothiazines inhibit ACh esterase
-Even OP-containing flea collars are a label contraindication
-Herding breeds with p-gp/MDR1 mutations are more sensitive (e.g., Collies, Australian Shepherds, Whippets, others)
-Some Boxer families appear to be esp. sensitive to cardiac effects (syncope & collapse) so to be safe acepromazine should be avoided in this breed
what is an example of a butyrophenone
azaperone
what species is azaperone used for and why
pigs - Used because it has a 1-day
meat withdrawal time in swine, vs 7 days for acepromazine
what are four alpha-2 agonists
-Xylazine
-Detomidine
-Dexmedetomidine
-Romifidine
anagelsia vs sedation of xylazine
-sedation lasts 2h
-analgesia is excellent but it only last 30 minutes
mechanism of action of alpha-2 agonists and specific changes that occur
α2 stim. opens K+ channels = inhibits APs in brain pathways related to:
* Wakefulness (= sedation)
* Pain (= analgesia)
* BP control (= hypotension)
* Motor activity (= muscle relaxation)
* Respiration: may be dramatic drop in O2 exchange
-overall In the brain, pre-synaptic alpha-2a stimulation opens K+ channels = inhibits NT release in various brain pathways
mechanism of adverse effects of alpha-2 agonists
-Side effect: Transient vasoconstriction
-Alpha-2 agonists also stimulate peripheral alpha 1 & alpha 2b receptors on blood vessels to some extent = initially see vasoconstriction & increased BP
-A slower activation of pre-synaptic alpha 2a receptors in ganglia then inhibits NT release, which inhibits SNS outflow = subsequent drop in BP
potential adverse effects of alpha-2 agonists in 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 (a potentially serious effect)
-Significant muscle relaxation (most animals lie down, which may be a benefit)
what happens in cast 2-5minutes after administration of an alpha-2 agonist
they will vomit
how do you reverse alpha 2 agonists
Can reverse with α2 antagonists
two possible issues that can occur when giving alpha-2 agonists to dogs or small ruminants/calves/sick cattle
-Decreased GI motility = bloat (large dogs)
-Degranulation of pulmonary intravascular macrophages in ruminants = May kill small ruminants, calves, sick cows via pulmonary edema
are xylazines normally used in small or large animals
usually large, only a few uses in small animals
what do you need to remember about sensitivity in large animals
Many domestic ruminants are highly sensitive; Possess an alpha-2D receptor that other species lack
= require only 1/10th the dose of other species
main uses of xylazine in 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 species is demotidine approved in
horses
features of demotidine in horses
- Analgesia is thought to last as long as sedation (1-2 h)
- Animals may kick even when fully sedated
- If light, can top up with guaifenesin or add opioid, rather than using more detomidine (animal may be resistant or agitated)
- Peak sedation in 5-20 min
- Used when pain greater, or longer effect desired
what is the main difference between xylazine and demotidine
duration of action
what species is dexmedetomidine approved in
dogs and cats
what is the most popular alpha 2 agonist is small animal practice
dexmedetomidine
what species is romifidine used in and why
horses
-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
what are two alpha 2 antagonists
Atipamezole, yohimbine
specificity of atipamezole
Atipamezole is more specific for α2 vs. α1
what could happen if you dont titrate a2 antagonists
Titrate to effect – don’t be overzealous or may cause increased
SNS effects and pain
what is the main benzodiazepine
diazepam
what is diazepam used for
Sedative, muscle relaxant, & anticonvulsant
mechanism of action of benzodiazepines
-Inhibits APs in post-synaptic cells by facilitating the action of GABA at the GABAa receptor (the main inhibitory NT in brain)
-GABAa receptors are a type of ligand-gated chloride channel = open in response to binding of GABA = hyperpolarizes cell= inhibits excitation
why are benzos safe when used alone
because little effect on CV system
how can you reverse benzo overdose effects
Overdose effects can be reversed by flumazenil, a competitive inhibitor of the BZD binding site
what is an effective appetite stimulant in cats
benzos
what can happen with hepatic function in cats when giving benzos
Cats: fulminant hepatic necrosis (lethargy, jaundice +/- death); idiosyncratic; may follow >2 days admin.
what is a dose dependent side effect of benzos
Dose-dependent respiratory depression
why is midazolam used instead of diazepam
Midazolam is similar but water soluble, so better for IM use when rapid effect is desired (also shorter T1/2)
what is a common induction mixture in small animal medicine
A 1:1 mixture of diazepam:ketamine is a very common induction mixture in small animal medicine
what is a problem that might be seen in small animals and horses with benzo use
Excitement & paradoxical aggression problems in healthy small animals & horses = administered in combination with other drugs
what is guaifenesin used for and in what species? how does it act?
-A muscle relaxant (sedation occurs only at high doses)
-Used in horses at induction to relax muscles to help a sedated horse go down smoothly
-Acts centrally: inhibits excitatory interneurons in motor pathways
