Ch.19: Sedatives and Tranquilizers (Pablo) Flashcards
Name 3 phenothiazines
acepromazine
promazine
chlorpromazine
Phenothiazine mech. of action
- inhibit DA receptors in CNS–> sedation and tranquilization
- block NE at alpha-adrenergic receptors in periphery
What kind of receptors are DA receptors?
G-protein coupled
phenothiazine indications
- sedation/tranquil.
- prevention of nausea and vomiting
other phenothiazine PK effects
- may see rigidity with high doses
- may lower seizure threshold***
- peripheral vasodilation
- splenic engorgement
- decreased afterload
- low effect on motor activity
Why is Ace not safe for Boxers?
can result in bradycardia dn hypertension
Important contraindication for Ace***
can lower seizure threshold
-caution with horses and boxers
primary use of chlorpromazine
antiemetic in D/C
Ace available in what admin routes?
IV, IM, SC, oral
phenothiazines have low/high therapeutic index
very high when used in NONanesthetized animals (lowered during anesthesia)
contraindicatons of phenothiazines
- dehydration
- hypovolemia (dec. blood volume)
- bleeding
- coagulopathies
- shock
3 major effects of alpha-2 agonists***
sedation
analgesia
master relaxation
basic structure of alpha-2 agonists
benzene ring with imidazole ring (exception = xylazine, which has a benzene + thiazole ring)
Name 6 alpha-2 agonists
xylazine detomidine medetomidine dexmedetomidine romifidine clonidine
most arrhythmogenic a2 agonist?**
xylazine (due to presence of thiazole ring)
mech. of action of a2 agonists (3 main parts)
- mimic the action of NE, therefore inhibiting further release of NE –> sedation
- also stimulates a1 receptor, which can result in adverse effects
- imidazoline receptor stimulation –> mediates hyptoension, antiarrhythmogenesis. Not involved in sedation
notable feature of promazine
similar to acepromazine. popular use as oral med
Why do you want a2 agonist with high a2 selectivity and low a1 stimulation (high a2:a1 ratio)
will be more selective for sedation/analgesic effects and less adverse effects
Xylazine has high/low a2:a1 ratio***
low! It is the least potent and has more neg. side effects
most specific alpha-2 agonist that we use***
dexmedetomidine (even though medetomidine is even more specific)
Does xylazine have imidazoline receptor stimulation activity?
No, b/c it doesn’t have an imidazole ring
Indications for alpha-2 agonists
- sedation
- chem. restraint
- preanesthetic
- analgesia
- emesis
CNS effects of alpha-2 agonists
- profound sedation via locus coeruleus stim.
- paradoxical excitement possible in less specific a2 agonists
- anesthetic sparing effect
CV effects of alpha-2 agonists***
-biphasic response:
Phase 1:
-activation of central a2 receptors –> dec. sympathetic outflow, inc. parasym. tone.
-activation of peripheral a1 and a2 receptors –> vasoconstriction, hypertension, reflex bradycardia
Phase2:
-dec. HR and BP (due to dec. NE), dec. cardiac output
(May see 2nd degree AV block)
effect of combining a2 agonist with anticholinergic agent
- increased risk of dysrhythmia
- hypertension
- cardiac output not normalized
Respiratory effects of alpha-2 agonists
- mild resp. depression
- cyanosis
xylazine in sheep
- can result in pulmonary edema and hypoxemia
- pulmonary macrophage activation –> damage endothelium
Musculoskeletal effects of alpha-2 agonists
- muscle relax
- twitch possible if given IV
Gastrointestinal effects of a2 agonits
- xylazine: vomiting
- reduced GI motility, acid secretion
Renal effects of a2 agonists
- diuresis (inhibit ADH, inc. Na excretion)
- dec. renin
- dec. bladder capacity
endocrine effects of a2 agonists
- dec. catecholamine lvls
- dec. stress response
metabolic effects of a2 agonists
-hyperglycemia (due to decreased insulin release)
Repro effects of a2 agonists
xylazine: premature parturition in cows
myometrial contraction in non-gravid uterus
decreased myometrial contraction at low doses only
thermoregulation effects of a2 agonists
-dec. body temp
a2 agonists help/hurt equine recovery from inhalation anesthesia
help
a2 agonists and analgesia
-profound analgesia
first a2 agonist used in vet med
xylazine
which animals are sensitive to sedative effects of xylazine?
cattle, ruminants
Why do different species have different sensitivity to xylazine
differences in G-protein signaling pathways
important chars. of detomidine*
- approved in horses**
- longest duration of action**
- higher a2:a1 ratio than xylazine
important chars. of medetomidine*
- can be used to tx emergence delirium in SA following anesthesia**
- provides sedation, anxiolysis, analgesia
important chars. of dexmedetomidine
-similar to medetomidine, but w/ higher HR/CO
chars. of Romifidine*
- produces less ataxia in horses than xylazine**
- longer duration of sedation than xylazine
chars. of clonidine*
- older human agent**
- not used in vet med
adverse effects of a2 agonists
- sudden arousal from sedation
- vomiting
- hyperglycemia
- diuresis
contraindications of a2 agonists
poor CO
3 a2 antagonists
tolazole
yohimbine
atipamezole
a2 antag. mech. of action
-REVERSAL of sedation, anxiolysis, analgesia, CV changes induced by a2 agonists
yohimbine best reverses which drug?**
xylazine
atipamezole best reverses which drug?**
dexmedetomidine and medetomidine
tolazoline reverses what?*
xylazine in cattle and SR
list yohimbine, tolazoline, and atipamezole in order of increasing selectiving for a2 receptors
tolazoline < yohimbine < atipamezole
adverse effects of a2 antagonists
- CNS excitement
- vasodilation
- tachycardia
- CV collapse
- delirium, aggression
Benzodiazepine mech. of action
-enhance GABA receptor –> Cl channel opening –> hyperpolarization –> sedation
indications of benzos*
- preanesthetic
- anticonvulsant
- m. relaxant
- phobia
CNS effects of benzos*
- paradoxical excitement**
- dec. cerebral blood flow/O2 consumption
- anticonvulsant
CV effects of benzos*
- minimal CV depression at clinical doses**
- high doses –> dec. MAP, inc. CO
Resp. effects of benzos*
-mild resp. depression
MS effects of benzos
- m. relax
- ataxia
- can cause agitation in horses
T/F: benzodiazepines can cause pain on admin*
T (due to propylene glycol vehicle)
Do benzos cause analgesia?
NO
Diazepam vs. midazolam***
- diazepam is lipid soluble, short duration of action, w/ unpredictable absorption IM or SC, can be given rectally.
- midazolam has ~2x potency of diazepam*, is water soluble due to presence of imidazole ring, has reliable bioavailability IM, IV, SC, has faster onset, and can be given nasally.
potency and duration of lorazepam vs. diazepam
lorazepam 10x more potent, and longer duration of action than diazepam
chars. of zolazepam*
- similar to diazepam
- only used in combo with tiletamine
- cats recover slower and calmer than dogs
benzo adverse effects
- agitation, vocalization, aggression
- hepatic failure in cats following repeated oral admin.
- abstinence syndrome (tremors, etc.) w/ sudden stoppage of tx
signs of benzo overdose
- ataxia
- depression
- agitation
- GI upset
- weakness
- tremors
- vocal
- tachycardia/pnea
- hypothermia
benzo antagonist drug
flumazenil
flumazenil mech. of action
-competitively antagonizes benzos on GABA receptor –> prevents hyperpolarization of postsynaptic memb.
PD Effects of flumazenil
- reverses electroencephalographic changes of benzos
- inc. BP
- inc. minute vent. and tidal volume
flumazenil adverse effects
- seizure in chronically tx benzo patients
- reduced activity in patients w/o benzo
- inflamm./necrosis when administered perivascularly
- dysrrhythmia
name 2 butyrophenone derivs
azaperone and droperidol
butyrophenone derivates mech. of action
-neuroleptic effect due to antagonism of D-2 receptors
Only FDA drug for sedation in pigs***
azaperone
indications for droperidol use
- antiemetic
- preanesthetic med
PD effects of butyrophenone derivs
-dec. HR, CO
-dec. Hb due to splenic sequestration of RBCs
-dec. m. tone
NO ANALGESIA**
T/F: droperidol used to be in combo with fentanyl
T (due to aggressive behavior)
