Topic 9 - Sedato-Hyponotics

Question 1

Name the groups of sedato-Hyponotics

Answer 1

1. Alpha 2 agonists
2. Alpha 2 antagonists
3. Barbiturates
4. Benzodiazepines

Question 2

Active substances of Alpha 2 agonists

Answer 2

Xylazine
Medetomidine
Dexemedetomidine
Romifidine
Detomidine

Question 3

Active substances of Alpha 2 antagonists

Answer 3

Atipamezole
Yohimbine
Telazoline

Question 4

Active substances of Barbiturates

Answer 4

Long Acting:
Barbital
Phenobarbital

Middle long acting
Amobarbital
Butobarbital

Question 5

Active substances of Benzodiazepines

Answer 5

Diazepam
Alprazolam
Lorazepam
Zolazepam
Midazolam

Question 6

Mechanism of action for alpha 2 agonists

Answer 6

1.Postsynaptic alpha 2 ⭢ Alpha 1 activation
2. Presynaptic alpha 2 activation

Question 7

Effects of Postsynaptic alpha 2 ⭢ Alpha 1 activation

Answer 7

vasoconstriction, transient hypertension, reflex bradycardia hypotension

Question 8

Effects of Presynaptic alpha 2 activation

Answer 8

sedation, analgesia (short term)
Decreased motor activity recumbency
+ GNG hyperglycemia
GIT relaxation : bloat, tympani

Question 9

Alpha 2 agonists pharmacokinetics: Xylazine

Answer 9

A: Fast
D: Good
M: liver (2-amino metabolite)
E: with urine

Transport: bounded to plasma proteins

Onset of sedative effect: IV few min. IM 10-15min

Duration of sedation: 0.5-1 hour

Question 10

Alpha 2 agonists pharmacokinetics: Detemodine

Answer 10

A: Fast
D: Good
M: Liver
E: with urine

Transport: bounded to plasma proteins

Onset of sedative effect: IV immediately, IM few min

Duration of sedation: 1-6 hours

Question 11

Alpha 2 agonists pharmacokinetics: Medetomidine

Answer 11

A: fast
D: good
M: liver (hydroxyl met)
E: with urine

Transport: bounded to plasma proteins (85%)

Onset of sedative effect: IV immediately, IM few min

Duration of sedation: 0.75 - 1.5 hour

Question 12

Side effects of Xylazine?

Answer 12

Emesis and vomiting in cats and dogs.
Bradycardia, malignant arrhythmias, sweating in
horses, ecbolic action: in late pregnancy its use is contradicated. Tympani in ruminants

Question 13

Side effects of Detomidine

Answer 13

Hyper tension, then hypotension, bradycardia, respirstory depression, diuresis (micturition),
hypothermia,sweating, snoring, tremor

Question 14

Indications of xylazine

Answer 14

Sedative-analgesic drug with depressed motor activity can be used in all domestic animals
(swine low potency). Analgesic effect is short (10-15 min.).

Question 15

Indications of Detomidine

Answer 15

More potent drug than xylazine, licensed for equine use. Does not cause total loss of consciousness (at therapeutic dose). Duration of
action is application route and dose dependent.

Use: alone or in combination with ketamine, thiopentone, opioids

Question 16

Indications of Medetomidine and Dexmedetomidine

Answer 16

Effects are similar to those o f xylazine but it seems to be more reliable and safer.

• Developed for cats and dogs. Duration of action is dose dependent. Sedation 1-3 hours (DM 2 hours). Analgesia 5-15 min., however DM 90 min.

Question 17

Indications of Romifidine

Answer 17

(Frequently in combination with Buthorphanol (20 μg/kg)).

Duration: Sedation a bit longer and causes less ataxia or recumbency than Xylazine
and Detomidine.

Question 18

Pharmacological effect of alpha 2 Agonists

Answer 18

1. Activation of Postsynaptic (peripheral)
2. Activation of Presynaptic (Central)
3. Sedative
4. Analgesic
5. Reduced motor activity

Question 19

Antidotes of alpha 2 agonists

Answer 19

Atipamezole, Tolazoline, Yohimbine

reverses the effect of alpha 2 agonists

Question 20

Dosage of xylazine

Answer 20

horse: 2-3 mg/kg IM, 0.5-1.0 mg/kg IV
cattle: 0.05-0.2 mg/kg IM
dog:1-2 mg/kg IM
cat: 3 mg/kg IM (emesis induction 0.5-1 IV).

Growth hormone stimulation
test (100 μg/kg b.w. IV)

Question 21

Dosages of detmodine

Answer 21

10-80 μg/kg IM or IV

40 μg/kg PO

Question 22

Dosage of Medetomidine

Answer 22

Dogs: 10-80 μg/kg (alone) IM
or IV 10-20 μg/kg (combination)

cats: 50-150 μg/kg IM

Question 23

Dosage of Dexmedetomidine

Answer 23

dogs & cats: 375 μg/m2 IV, 500 IM μg/m2* (cats only IM) premedication 125-375 μg/m2
Dog 125 μg/m2 PO

Question 24

Dosage of Romifidine

Answer 24

Horse, dog: 40-120 μg/kg IV, IM
Cat: 200-400 μg/kg IV, IM

(Frequently in combination with Buthorphanol (20 μg/kg))

Question 25

Mechanism of action of Alpha 2 Antagonist

Answer 25

**Atipamezole:** Alpha 2 adenoreceptor blocking agent. Reverses the effect of medetomidine (and other alpha 2 agonists) **Yohimbine and Telazoline:** much less specific alpha 2 adenoreceptor antagonists than atipamezole, and so have significant alpha 1 antagonistic action. Reverses the effect of Xylazine

Question 26

Side effects of Alpha 2 Antagonist

Answer 26

Well tolerated by dogs and cats. tachycardia (high dose), transient hypotension, hypothermia, vomiting, defecation, panting, muscle tremor

Question 27

Contraindications of Alpha 2 Antagonist

Answer 27

Ketamin-medetomidine (horse, dog)

Question 28

Dosage of Alpha 2 Antagonist

Answer 28

Atipamezole: **horse:** 150 μg/kg, **dogs:** 5 times he dose of medetomidin **cats:** 2.5 times the dose of medetomidin

Question 29

Mechanism of action of Barbiturates

Answer 29

Decrease in Ca2+ accumulation → inhibition in release of stimulatory transmitters, stabilisation of presynaptic membranes. General inhibition of CNS, but sensitivity of certain structures differs (paradox phenomenon, some are suitable for general anaesthesia)

Question 30

Pharmacological effect of barbiturates

Answer 30

CNS, circulation, respiration – inhibition (last two only in case of overdosing), sedative, hypnotic and mild anxiolytic effect, significant anticonvulsant effect*

Question 31

Side effects of barbiturates

Answer 31

Ataxias, over sedation, longer use CYP450 induction, liver toxicity, PU/PD, polyphagia, obesities

Question 32

Dosage of barbiturates

Answer 32

**Dogs, cats:** PO 1.5-5 mg/kg B.I.D. **Tetanic horses:** IV 12 mg/kg initial, 6 mg/kg B.I.D. to maintain

Question 33

Mechanism of action of benzodiazepines

Answer 33

Facilitate or amplify the inhibitory activity of GABA, possibly by eliciting a structural alteration in the GABA-receptor complex, which results in the opening of chloride ion channels. (Positive Allosteric Activators). BZD-receptors are located in all levels of CNS (and in muscles). Open GABA-gated Cl- ion channels CNS, muscle depression Bind at BZD site open GABA-gated Cl- channel: hyperpolarization

Question 34

Pharmacological effect of benzodiazepines

Answer 34

Sedation and anxiolytic effect Anticonvulsive effect Muscle relaxation Hypnotic **In animals:** they are primarily sedatives, but they also have a hypnotic effect with increasing dose. They can be combined with other agents; sedatives, hypnotics, and anaesthetics. Sedation of patients requiring intensive care and/or in high risk patients (e.g. patients at cardiovascular risk). Sedation and pre-anesthetization of animals, safely even in very young animals (e.g. young foals) and in the elderly - Epileptic seizure. Decreases possibility of seizures caused by other drugs. Before myelography.

Question 35

Pharmacokinetics of benzodiazepines

Answer 35

**Diazepam:** **A:** Oral absorption is good. IM delayed Significant binding to plasma proteins (interactions) **E:** after demethylation and conjugation via the kidney (first metabolite is active: entero-hepatic recirculation, liver disease may prolong activity, interactions)

Question 36

Indications of benzodiazepines

Answer 36

**Diazepam:** **1.** Premedication and combination (ketamine) **2.**Muscle relaxation **3.** Prevention and control of epilepsy **4.** Sedation (taming during grouping of animals)

Question 37

Contraindications of Benzodiazepines

Answer 37

**Diazepam** **-** Paradoxical reaction in Cat, Greyhound **-** Inhibition of respiration (aminoglycosides increase) **-** Before and during deliver y (high doses are contraindicated) **-** Liver diseases (rare hepatotoxicity mainly in cats and foals)

Question 38

Antidotes of Benzodiazepines

Answer 38

**In case of overdoses!** Flumazenil (F) Sarmazenil (S)

Question 39

Dosages of Benzodiazepines

Answer 39

100 (F) μg/ttkg or 40 (S) μg/ttkg (horses) IVq24h ***Diazepam:*** **sedation:** 1-1.5 mg/kg PO **pre-medication:** 0.2 mg/kg IV **status epilepticus:** 5-10 mg/dog IV or rectally (if needed then 2-5 mg/hour IV glucose inf.) Cats 2-3 mg IV induction of prot feed intake ***Midazolam:*** **Horses:** 0.05-0.2 mg/kg IV **Dogs, Cats:** 0.1-0.5 mg/kg IV, 0.3-1 IM