Sedatives Flashcards
what classes are in sedative hypnotics?
phenothiazine derivatives
butyrophenone derivatives
benzodiazepine derivatives
alpha-2-adrenergic receptor agonists
what is the most common phenothiazine derivative?
acepromazine
what do phenothiazine derivatives do?
neuroleptics
major tranquilizer
antiemetic
what is the mechanism of action for phenothiazine derivatives?
D2 antagonist
sedate by inhibiting postsynaptic central dopaminergic receptors
D2 receptors are GPCRs
D2 receptors in chemoreceptor trigger zone produce antiemetic effects
peripherally block norepinephrine from binding alpha1 adrenergic receptors: peripheral vasodilation
what are the indications of phenothiazine derivatives?
routine sedation
preanesthetic period
often combined with opioids to produce synergic effects of each class (better sedation and analgesia)
what are some butyrophenone derivatives?
haloperidol
doperidol
what are butyrophenone derivatives?
antipsychotics
what is the mechanism of action for butyrophenone derivatives?
D2 antagonist
D1, 5HT, alpha1, and histamine antagonist
what are the indications for butyrophenone derivatives?
azaperone for swine for calming effects (mixing weanlings and feeder pigs)
transportation
obstetrical conditions
anesthetic adjunct for wildlife
what are the benzodiazepine derivatives?
diazepam (valium)
midazolam
lorazepam
zolazepam
what is the mechanism of action for benzodiazepine derivatives?
increase frequency of the opening of the chloride ion channel
majority GABAa receptors in cerebral cortex, very few outside of CNS
synergistic effect with barbituates
what are the indications for benzodiazepines?
anticovulsants
adjuncts to anesthetic induction agents
skeletal muscle relaxants
behavioral modification (anxiolysis and sedation)
what are the CNS effects of benzodiazepines?
often sedation
when administered alone: different effects can occur (excitement, agitation, vocalization, dysphoria)
reduction in cerebral blood flow and oxygen consumption
what are some side effects of benzodiazepines?
minimal cardiovascular effects
may decrease respiratory rate bur rarely affect ventilation and oxygenation at clinical doses (dose dependent respiratory depression)
relaxation, ataxia, recumbency in musculoskeletal
no analgesia
do benzodiazepines have analgesia effect?
no
when can benzodiazepines cause respiratory depression?
higher doses
exacerbated by other CNS depressants or in debilitated patients
where do many of the side effects of diazepam hydrochloride (valium) arise from?
vehicle: propylene glycol
what side effects can propylene glycol have?
hemolysis (especially in cats)
pain on infusion
what can repeated PO administration of diazepam hydrochloride lead to in cats?
hepatic necrosis
in what species does diazepam hydrochloride have a shorter half life?
dogs and cats compared to horses and primates
is midazolam maleate water or lipid soluble?
water soluble for administration
lipid soluble in body
why is midazolam becoming more popular in veterinary medicine than diazepam?
does not require propylene glycol
cheaper
why is lorazepam (ativan) used in veterinary medicine?
anxiolytic
is zolazepam water or lipid soluble?
water soluble
in what is zolazepam found?
telazol: combination NMDA antagonist/benzodiazepine
how are benzodiazepines metabolized?
primarily liver, pathway differs between drugs
many have active metabolites
what is the main metabolite of benzodiazepines in most species?
desmethyldiazepam: long half life
what are the adverse effects of benzodiazepines?
paradoxical excitation
behavioral disinhibition
hepatic necrosis in cats
addiction/physical dependence: dose tapering
what are some benzodiazepine antagonists?
flumazenil
how does flumazenil reverse benzodiazepines?
specific competive antagonist wtih high affinity for the benzodiazepine receptor site of the GABAa receptor
why are alpha-2-adrenergic receptor agonists popular in veterinary medicine?
profound, reliable sedation, analgesia as well as adjunct to anesthesia
easily reversed
what receptors do alpha-2-adrenergic receptor agonists have impacts on?
alpha-2
also some affinity alpha-1
what is the alpha-2 mechanism of action?
G-protein coupled receptors located both pre and postsynaptically in the CNS and periphery
extrasynaptically expressed on vascular endothelium of vessels and platelets
4 subtypes: contribute to species differences
sedative effects mediated by presynaptic binding supraspinally in the locus ceruleus of the pons: decreases release of norepinephrine and arousal
what is the analgesic effect of alpha-2s mediated by?
action in dorsal horn of spinal cord via decreased release of norepinephrine and substance P
what do the agonist effects of alpha-2s produce?
vasoconstriction in periphery
what are the side effects of alpha-2s?
bradycardia with biphasic vascular response (vasodilation then vasoconstriction)
centrally mediated reduction in respiration (exaggerated by additive effect of other CNS depressants)
what species has serious adverse effects to alpha-2s and what is that effect?
sheep
respiratory: activation of pulmonary macrophages that extensively damage the capillary endothelium and alveolar type I cells
intraalveolar hemorrhage/edema, hypoxia, death
not completely reversed by antagonist
what are the side effects of alpha-2s other than heart and respiration?
musculoskeletal relaxation
emesis (cats mostly)
decrease GI motility
renal diuresis
hyperglycemia
inability to thermoregulate
is xylazine specific for alpha-2?
no
what is medetomidine?
racemic mixture of enantiomers (dexmedetomidine and levomedetomidine)
what does medetomidine produce?
profound reliable sedation and analgesia
who is detomidine hydrochloride (dormosedan) used in?
horses
bovine
lesser degree small ruminants
is detomidine specific?
more specific for alpha-2 than xylazine
what are alpha-2-adrenergic antagonists used for?
to reverse alpha-2 agonists
what is the alpha-2-adrenergic antagonist to reverse xylazine?
yohimbine
what is the alpha-2-adrenergic antagonist to reverse detomidine?
tolazoline
what is the alpha-2-adrenergic antagonist to reverse demedetomidine and medtomidine?
atipamezole (antisedan)
what are the side effects of alpha-2-adrenergic antagonists?
CNS excitement
yohimbine may cause seizures at high doses
reverses analgesia as well
reversal cardiovascular effect of agonists but hard to predict
reversal respiratory suppression
reversal muscle relaxation and ataxia
