Sedatives

Question 1

what classes are in sedative hypnotics?

Answer 1

phenothiazine derivatives
butyrophenone derivatives
benzodiazepine derivatives
alpha-2-adrenergic receptor agonists

Question 2

what is the most common phenothiazine derivative?

Answer 2

acepromazine

Question 3

what do phenothiazine derivatives do?

Answer 3

neuroleptics
major tranquilizer
antiemetic

Question 4

what is the mechanism of action for phenothiazine derivatives?

Answer 4

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

Question 5

what are the indications of phenothiazine derivatives?

Answer 5

routine sedation
preanesthetic period
often combined with opioids to produce synergic effects of each class (better sedation and analgesia)

Question 6

what are some butyrophenone derivatives?

Answer 6

haloperidol
doperidol

Question 7

what are butyrophenone derivatives?

Answer 7

antipsychotics

Question 8

what is the mechanism of action for butyrophenone derivatives?

Answer 8

D2 antagonist
D1, 5HT, alpha1, and histamine antagonist

Question 9

what are the indications for butyrophenone derivatives?

Answer 9

azaperone for swine for calming effects (mixing weanlings and feeder pigs)
transportation
obstetrical conditions
anesthetic adjunct for wildlife

Question 10

what are the benzodiazepine derivatives?

Answer 10

diazepam (valium)
midazolam
lorazepam
zolazepam

Question 11

what is the mechanism of action for benzodiazepine derivatives?

Answer 11

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

Question 12

what are the indications for benzodiazepines?

Answer 12

anticovulsants
adjuncts to anesthetic induction agents
skeletal muscle relaxants
behavioral modification (anxiolysis and sedation)

Question 13

what are the CNS effects of benzodiazepines?

Answer 13

often sedation
when administered alone: different effects can occur (excitement, agitation, vocalization, dysphoria)
reduction in cerebral blood flow and oxygen consumption

Question 14

what are some side effects of benzodiazepines?

Answer 14

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

Question 15

do benzodiazepines have analgesia effect?

Answer 15

no

Question 16

when can benzodiazepines cause respiratory depression?

Answer 16

higher doses
exacerbated by other CNS depressants or in debilitated patients

Question 17

where do many of the side effects of diazepam hydrochloride (valium) arise from?

Answer 17

vehicle: propylene glycol

Question 18

what side effects can propylene glycol have?

Answer 18

hemolysis (especially in cats)
pain on infusion

Question 19

what can repeated PO administration of diazepam hydrochloride lead to in cats?

Answer 19

hepatic necrosis

Question 20

in what species does diazepam hydrochloride have a shorter half life?

Answer 20

dogs and cats compared to horses and primates

Question 21

is midazolam maleate water or lipid soluble?

Answer 21

water soluble for administration
lipid soluble in body

Question 22

why is midazolam becoming more popular in veterinary medicine than diazepam?

Answer 22

does not require propylene glycol
cheaper

Question 23

why is lorazepam (ativan) used in veterinary medicine?

Answer 23

anxiolytic

Question 24

is zolazepam water or lipid soluble?

Answer 24

water soluble

Question 25

in what is zolazepam found?

Answer 25

telazol: combination NMDA antagonist/benzodiazepine

Question 26

how are benzodiazepines metabolized?

Answer 26

primarily liver, pathway differs between drugs many have active metabolites

Question 27

what is the main metabolite of benzodiazepines in most species?

Answer 27

desmethyldiazepam: long half life

Question 28

what are the adverse effects of benzodiazepines?

Answer 28

paradoxical excitation behavioral disinhibition hepatic necrosis in cats addiction/physical dependence: dose tapering

Question 29

what are some benzodiazepine antagonists?

Answer 29

flumazenil

Question 30

how does flumazenil reverse benzodiazepines?

Answer 30

specific competive antagonist wtih high affinity for the benzodiazepine receptor site of the GABAa receptor

Question 31

why are alpha-2-adrenergic receptor agonists popular in veterinary medicine?

Answer 31

profound, reliable sedation, analgesia as well as adjunct to anesthesia easily reversed

Question 32

what receptors do alpha-2-adrenergic receptor agonists have impacts on?

Answer 32

alpha-2 also some affinity alpha-1

Question 33

what is the alpha-2 mechanism of action?

Answer 33

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

Question 34

what is the analgesic effect of alpha-2s mediated by?

Answer 34

action in dorsal horn of spinal cord via decreased release of norepinephrine and substance P

Question 35

what do the agonist effects of alpha-2s produce?

Answer 35

vasoconstriction in periphery

Question 36

what are the side effects of alpha-2s?

Answer 36

bradycardia with biphasic vascular response (vasodilation then vasoconstriction) centrally mediated reduction in respiration (exaggerated by additive effect of other CNS depressants)

Question 37

what species has serious adverse effects to alpha-2s and what is that effect?

Answer 37

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

Question 38

what are the side effects of alpha-2s other than heart and respiration?

Answer 38

musculoskeletal relaxation emesis (cats mostly) decrease GI motility renal diuresis hyperglycemia inability to thermoregulate

Question 39

is xylazine specific for alpha-2?

Answer 39

no

Question 40

what is medetomidine?

Answer 40

racemic mixture of enantiomers (dexmedetomidine and levomedetomidine)

Question 41

what does medetomidine produce?

Answer 41

profound reliable sedation and analgesia

Question 42

who is detomidine hydrochloride (dormosedan) used in?

Answer 42

horses bovine lesser degree small ruminants

Question 43

is detomidine specific?

Answer 43

more specific for alpha-2 than xylazine

Question 44

what are alpha-2-adrenergic antagonists used for?

Answer 44

to reverse alpha-2 agonists

Question 45

what is the alpha-2-adrenergic antagonist to reverse xylazine?

Answer 45

yohimbine

Question 46

what is the alpha-2-adrenergic antagonist to reverse detomidine?

Answer 46

tolazoline

Question 47

what is the alpha-2-adrenergic antagonist to reverse demedetomidine and medtomidine?

Answer 47

atipamezole (antisedan)

Question 48

what are the side effects of alpha-2-adrenergic antagonists?

Answer 48

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