Topic 9 - Sedato-Hyponotics Flashcards
Name the groups of sedato-Hyponotics
1. Alpha 2 agonists
2. Alpha 2 antagonists
3. Barbiturates
4. Benzodiazepines
Active substances of Alpha 2 agonists
Xylazine
Medetomidine
Dexemedetomidine
Romifidine
Detomidine
Active substances of Alpha 2 antagonists
Atipamezole
Yohimbine
Telazoline
Active substances of Barbiturates
Long Acting:
Barbital
Phenobarbital
Middle long acting
Amobarbital
Butobarbital
Active substances of Benzodiazepines
Diazepam
Alprazolam
Lorazepam
Zolazepam
Midazolam
Mechanism of action for alpha 2 agonists
1.Postsynaptic alpha 2 ⭢ Alpha 1 activation
2. Presynaptic alpha 2 activation
Effects of Postsynaptic alpha 2 ⭢ Alpha 1 activation
vasoconstriction, transient hypertension, reflex bradycardia hypotension
Effects of Presynaptic alpha 2 activation
sedation, analgesia (short term)
Decreased motor activity recumbency
+ GNG hyperglycemia
GIT relaxation : bloat, tympani
Alpha 2 agonists pharmacokinetics: Xylazine
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
Alpha 2 agonists pharmacokinetics: Detemodine
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
Alpha 2 agonists pharmacokinetics: Medetomidine
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
Side effects of Xylazine?
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
Side effects of Detomidine
Hyper tension, then hypotension, bradycardia, respirstory depression, diuresis (micturition),
hypothermia,sweating, snoring, tremor
Indications of xylazine
Sedative-analgesic drug with depressed motor activity can be used in all domestic animals
(swine low potency). Analgesic effect is short (10-15 min.).
Indications of Detomidine
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
Indications of Medetomidine and Dexmedetomidine
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.
Indications of Romifidine
(Frequently in combination with Buthorphanol (20 μg/kg)).
Duration: Sedation a bit longer and causes less ataxia or recumbency than Xylazine
and Detomidine.
Pharmacological effect of alpha 2 Agonists
1. Activation of Postsynaptic (peripheral)
2. Activation of Presynaptic (Central)
3. Sedative
4. Analgesic
5. Reduced motor activity
Antidotes of alpha 2 agonists
Atipamezole, Tolazoline, Yohimbine
reverses the effect of alpha 2 agonists
Dosage of xylazine
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)
Dosages of detmodine
10-80 μg/kg IM or IV
40 μg/kg PO
Dosage of Medetomidine
Dogs: 10-80 μg/kg (alone) IM
or IV 10-20 μg/kg (combination)
cats: 50-150 μg/kg IM
Dosage of Dexmedetomidine
dogs & cats: 375 μg/m2 IV, 500 IM μg/m2* (cats only IM) premedication 125-375 μg/m2
Dog 125 μg/m2 PO
Dosage of Romifidine
Horse, dog: 40-120 μg/kg IV, IM
Cat: 200-400 μg/kg IV, IM
(Frequently in combination with Buthorphanol (20 μg/kg))
Mechanism of action of Alpha 2 Antagonist
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
Side effects of Alpha 2 Antagonist
Well tolerated by dogs and cats.
tachycardia (high dose), transient hypotension, hypothermia,
vomiting, defecation, panting, muscle tremor
Contraindications of Alpha 2 Antagonist
Ketamin-medetomidine (horse, dog)
Dosage of Alpha 2 Antagonist
Atipamezole:
horse: 150 μg/kg,
dogs: 5 times he dose of medetomidin
cats: 2.5 times the dose of medetomidin
Mechanism of action of Barbiturates
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)
Pharmacological effect of barbiturates
CNS, circulation, respiration – inhibition (last two only in case of overdosing), sedative, hypnotic and mild anxiolytic effect,
significant anticonvulsant effect*
Side effects of barbiturates
Ataxias, over sedation, longer use CYP450 induction, liver toxicity, PU/PD, polyphagia, obesities
Dosage of barbiturates
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
Mechanism of action of benzodiazepines
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
Pharmacological effect of benzodiazepines
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.
Pharmacokinetics of benzodiazepines
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)
Indications of benzodiazepines
Diazepam:
1. Premedication and combination (ketamine)
2.Muscle relaxation
3. Prevention and control of epilepsy
4. Sedation (taming during grouping of animals)
Contraindications of Benzodiazepines
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)
Antidotes of Benzodiazepines
In case of overdoses!
Flumazenil (F)
Sarmazenil (S)
Dosages of Benzodiazepines
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
