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RUSVM Pharmacology I > Sedatives / Tranquilizers > Flashcards

Sedatives / Tranquilizers Flashcards

1
Q

Drugs acting on the CNS

A

Sedative & Tranquilizers - Alpha 2 agonists & antagonists - Opioids - Injectable anesthetics - Inhalant anesthetics

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2
Q

Tranquilizer aka..

A

Neuroleptic, anxiolytic

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3
Q

Tranquilizer effects

A

Induces state of behavioral change, anxiety relieved, patient is relaxed & aware of surroundings

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4
Q

Sedative

A

CNS depression & drowsiness, decreased awareness of surroundings

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5
Q

Hypnotic

A

Induces sleep

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6
Q

Narcotic

A

Induces stupor bordering general anesthesia

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7
Q

Local/Regional anesthesia

A

Loss of sensation to a circumscribed body area

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8
Q

General anesthesia

A

Drug-induced unconsciousness with controlled, reversible CNS depression & analgesia. Patient cannot be aroused. Sensory, motor and autonomic reflexes reduced

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9
Q

Dissociative anesthesia

A

Dissociate thalamacortic & limbic systems. Catatonic state with open eyes & swallowing reflexes remain functional. Skeletal muscles maintain tone

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10
Q

4 parts of pain pathway

A

Transduction - Transmission - Modulation - Perception

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11
Q

Transduction

A

Nociceptive Input (turn physical stimulus into electrical signal for nerves) - PGs, Substance P, K+, Bradykinin, increase peripheral sensitization (when light touch feels painful)

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12
Q

Transmission

A

Afferent nerve: A-delta fibers (sharp pain) & C fibers (dull pain)

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13
Q

Modulation

A

To spinal cord via Dorsal Horn - Enhanced/Diminished depending on neurotransmitters & drugs - “Spinal cord windup” at this level (sensitization of nerves)

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14
Q

Perception

A

In cerebral cortex - Experience/Be aware of the pain - Somatic=bones/muscles/joints

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15
Q

Excitatory neurotransmitters

A

Glutamate (NMDA receptor) & ACH (acetylcholine)

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16
Q

Inhibitory neurotransmitters

A

GABA - Glycine (spinal cord)

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17
Q

Neurotransmitters metabolized by MAO

A

MAO=Monoamine Oxidase - Dopamine, NE, 5-HT (serotonin), Histamine

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18
Q

Goals of sedative use

A

What is signalment of patient? What is temperament of patient? What is the goal of drug use? Medical conditions/other drugs to consider?

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19
Q

Phenothiazines -Drug list

A

Acepromazine - *Proclorperazine - *Chlorpromazine - *Trimeprazine w/prenisolone - Promethazine - Ethylisobutrazine - Triflupromazine

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20
Q

Phenothiazine uses

A

Sedative - Premed - Antiemetic - Antihistamine - Antipsychotic (human)

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21
Q

Phenothiazine mechanism

A

Block dopamine receptors in CNS!! (also- block H1/ A1/ ACH-muscarinic receptors)

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22
Q

Phenothiazine effects overview

A

Sedation - Some muscle relaxation - No analgesia - Hypotension & minimal effects on respiration

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23
Q

Phenothiazine Effects on CNS

A

Emotional quieting - Sedation - Decreased spontaneous motor activity

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24
Q

Which Phenothiazines have less of a sedative effect?

A

Prochlorperazine / Chlorpromazine

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25
Q

What can large doses of Phenothiazine cause

A

Extrapyramidal signs (rigidity, tremors, akinesia)

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26
Q

Other CNS mediated effects of Phenothiazine

A

Hypothermia (hypothalamus) - Antiemetic (CRTZ) - Hyperprolactinemia (hypothalamus)

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27
Q

Phenothiazine effects on ANS

A

Blocks Alpha-1 receptors - Weak anti-cholinergic (block M receptors)

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28
Q

Phenothiazine blocking Alpha 1

A

Vasodilation –> hypotension - “Epinephrine reversal” (Block A1, epinephrine still promoting vasodilation. It’s vasoconstrictive effects are blocked)

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29
Q

Phenothiazine anticholinergic efect

A

Not usually clinically significant - Decreased tear production in cats & rabbits

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30
Q

Phenothiazine CV effects

A

Hypotension - Bradycardia - Anti-arrhythmic

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31
Q

Which dog breed is more susceptible to Phenothiazine

A

Boxers sensitive to CV effects

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32
Q

Phenothiazine Respiratory effects

A

Minimal @ therapeutic doses (may decrease rate, not oxygenation) - Depression possible @high doses or used with opioids (&other respiratory depressants)

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33
Q

Phenothiazine effects at skeletal muscle

A

Moderate muscle relaxation

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34
Q

Phenothiazine other effects

A

Reduced hematocrit (splenic sequestration) - H1 antagonist/ Antihistamine - Reduced platelet function - ADH inhibition causing mild diuresis? - Hyperglycemia? - Hyperprolactinemia?

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35
Q

Phenothiazine reduced platelet function

A

In vitro hanges in platelet aggregation - Not demonstrated with acepromazine in healthy dogs in vivo

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36
Q

Phenothiazine Administration

A

IV, IM, SQ, PO

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37
Q

Phenothiazine PO

A

Oral bioavailability low (~20%)

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38
Q

Phenothiazine bound in plasma?

A

Highly protein bound, unclear clinical significance when % varies

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39
Q

Phenothiazine distribution

A

High Vd - well distributed, crosses BBB into CNS

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40
Q

Phenothiazine Metabolism

A

In liver

41
Q

Phenothiazine excretion

A

Metabolites excreted in urine

42
Q

Phenothiazine duration of action variables

A

Depends on route of admin, species, breed, etc

43
Q

Phenothiazine clinical uses

A

Preanesthetic (usually with opioids) - Tranquilizer - Chemical restraint - Antiemesis (motion sickness) - Antihistamine

44
Q

Which Phenothiazines are used for antiemesis?

A

Chlorpromazine & Prochlorperazine

45
Q

Phenothiazine Cautions

A

Boxer dogs sensitive - Stallions get penile prolapse & paraphimosis - MDR1 mutants have more, prolonged sedation - Aggressive dogs startle more easily & CNS stimulation sometimes (reduced sedative effect in excited patients)

46
Q

Phenothiazine vasodilation contraindications

A

DON’T use if vasodilation is contraindicated (Cardiac dz, hypovolemia, dehydration etc)

47
Q

Phenothiazine Toxin contraindication

A

Tetanus, strychnine, etc because of extrapyramidal effects

48
Q

Phenothiazine contraindication in cattle

A

Not approved in food animals, ruminal regurgitation sometimes seen

49
Q

Phenothiazine Other contraindications

A

Liver disease - concurrent Epinephrine dosing - epidurals

50
Q

Drug interactions with acepromazine

A

Epinephrine/ephedrine - Other CNS depressants - Metoclopramide (& others that cause extrapyrimidal signs) - Cholinesterase inhibitors - Emetics - Opiates - Misc. other drugs

51
Q

Miscellaneous other drugs that interact with acepromazine

A

Dopamine, phenytoin, procaine, propanolol, quinidine, antacids, acetaminophen, antidiarrheals

52
Q

Butyrophenones main action

A

Dopamine antagonist!!

53
Q

Butyrophenone dopamine antagonist effects

A

Antipsychotics in human med - Declining use in vet med - Very similar to phenothiazines (vasodilation, minimal analgesia, paraphimosis in boars) - No approved products in US

54
Q

Azaperone / Stresnil

A

Labeled for IM in UK swine (reduce aggression during group mixing, control sow aggression) A in BAM (darting wild ungulates)

55
Q

BAM

A

Butorphanol- Azaperone - Medetomidine - used for darting wild ungulates

56
Q

Haloperidol

A

To birds for feather picking

57
Q

Benzodiazepines - 3 categories

A

Agonists - Antagonist - Inverse agonist

58
Q

Benzodiazepine - Agonists

A

*Diazepam (valium) - *Midazolam - *Alprazolam (xanax) - Lorazepam (ativan) - Oxazepam - Clonazepam - *Zolazepam/Tiletamine (telazol)

59
Q

Benzodiazepine - antagonist

A

Flumazenil (romazicon)

60
Q

Benzodiazepine - Inverse agonist

A

B-carboline

61
Q

Review! Agonist/Inverse Agonist / Antagonist

A

Agonist (binds & causes effect of usual ligand) - Inverse Agonist (binds & causes opposite effect of agonist) - Antagonist (binds and does nothing but block, “neutral agonist”)

62
Q

Benzodiazepine mechanism of action

A

Bind site on GABAa receptors (Cl- channels) –> hyperpolarization of neurons

63
Q

Benzodiazepine Overview of pharmacological effects

A

Some Sedation - Good Muscle relaxation - No Analgesia - Minimal Cardiorespiratory effects - Anticonvulsant - Appetite stimulant (unk mechanism)

64
Q

Benzodiazepine CNS effects

A

Sedative-hypnotic (mild) - Anxiolytic - Centrally mediated muscle relaxation (supraspinal GABA) - Anticonvulsant -

65
Q

Benzodiazepine CV & respiration effects

A

Minimal at therapeutic doses - Depression seen at larger doses

66
Q

Benzodiazepine clinical uses

A

Anxiolytics/behavior modifier - Anticonvulsants (emergency seizure treatment) - Preanesthetic (in combo) - Sedation in ruminants - Muscle relaxation (anesthesia, urinary) - appetite stimulation

67
Q

Benzodiazepine Administration types

A

Different products for different routes: Diazepam IV - Midazolam IM - Oral - Transmucosal/intranasal/rectal

68
Q

Diazepam IV administration

A

Most common route - give slowly to avoid hypotension

69
Q

Midazolam IM

A

Better IM choice than diazepam

70
Q

Oral benzodiazepines

A

Generally good oral absorption - Diazepam=short duration - Alprazolam/lorazepam better

71
Q

Problematic Diazepam administrations

A

Has slow & poor absorption IM & is painful from propylene glycol - Oral=short duration & hepatic necrosis in cats

72
Q

What can oral diazepam cause in cats?

A

Hepatic necrosis

73
Q

Transmucosal administration of diazepam

A

Decent bioavailability

74
Q

Benzodiazepine Distribution

A

Lipid solube - wide distribution - cross BBB - protein bound

75
Q

Benzodiazepine Metabolism

A

In liver into active metabolites

76
Q

Benzodiazepine excretion

A

Primarily in urine

77
Q

Benzodiazepine caution in cats

A

Hepatotoxicity with oral diazepam

78
Q

Benzodiazepine caution in horses

A

Muscle fasciculations seen, ataxia @higher doses

79
Q

Benzodiazepine benefits

A

Generally very safe bc lack of CV / respiratory depression (good in very young, old, sick)

80
Q

Benzodiazepine paradoxical excitement

A

Sometimes seen - usually in combo with other animals or in fear-aggressive animals (disinhibition)

81
Q

Benzodiazepine caution with diazepam injection

A

Propylene glycol causes pain IM - Hypotension with rapid IV injection - Hemolysis with large IV doses

82
Q

Benzodiazepine caution in pregnancy

A

Maybe teratogenic (causes birth defects)

83
Q

Benzodiazepine caution in liver/kidney disease

A

Altered metabolism / excretion

84
Q

Benzodiazepine - Reversal

A

Flumazenil - Often unneccessary. B-carboline not used clinically

85
Q

Most important phenothiazine for sedation

A

Acepromazine

86
Q

Acepromazine + opioids = ?

A

Neuroleptanalgesia for chemical restraint - Or as pre-anesthetic

87
Q

Acepromazine effects

A

Effective sedation - Some muscle relaxation - No analgesia

88
Q

Acepromazine adverse effects

A

Hypotension - Always use with caution when hypotension is already a risk (epidurals)

89
Q

What dog breed is sensitive to Acepromazine?

A

Boxers - Suffer worse cardiovascular effects

90
Q

What happens to dogs with MDR1 mutations that are given Acepromazine

A

Have more profound clinical effects - Longer duration

91
Q

What horrifying thing can happen to stallions on acepromazine?

A

May exhibit paraphimosis (can’t put foreskin back over the head) can lead to penile injury #gladIdon’thaveone

92
Q

Trimeprazine Use & formulation

A

Antihistamine effects - Often combined with prednisolone “Temeril-P” - May see some sedative side effects, but not main use

93
Q

Acepromazine & seizures

A

Once thought to lower seizure threshold, now thought to pre-dispose patients to them.

94
Q

Butyrophenones Uses

A

Similar to phenothiazines - Human med: antipsychotic - Use in Vet Med declining

95
Q

Butyrophenones - Name them

A

Azaperone - Droperidol - Haloperidol

96
Q

Azaperone use

A

Swine, in UK - Reduce aggression

97
Q

What is BAM?

A

Butorphanol-Azaperone-Medetomidine for darting wild ungulates

98
Q

Haloperidol uses

A

Sometimes to control feather-picking in birds (psitticines)

RUSVM Pharmacology I (19 decks)

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