Tranquillisers and sedatohypnotics Flashcards
Some small-molecule neurotransmitters:
Exitatory:
- acetylcholine
- norepinephrine
- dopamine
- Glutamate and Aspartate
- 5-Hydroxytryptamine, Serotonin
- Histamine
Inhibitory:
- acetylcholine
- norepinephrine
- dopamine
- Glycine
- GABA
Classification of CNS stimulants
based on their site of action:
Cortical: – xanthines (coffeine, teophylline, theobromine) – cocaine – ephedrine, amphetamines – Psychotomimetics (e.g. LSD)
• Medullar: – xanthines (coffeine, teophylline, theobromine) – pentetrazole – doxapram – picrotoxin
• Spinal:
– strychnine
Doxapram
Short-acting respiratory stimulan
Convulsants and respiratory stimulants
analeptics
- Doxapram
- Picrotoxin
- strychnine
Psychotomimetic drugs
hallucinogens
- LSD
- MDMA
- Mescaline
- Psilocybin
- Phencyclidine
Psychomotor stimulants
Amphetamine and related compounds:
e. g.dexamphetamine
- methylamphetamine
- methylphenidate
- fenfluramine
- Cocaine
- Methylxanthines, (e.g. caffeine,
theophylline)
CAFFEINE
four identifiable actions in vitro
- Adenosine receptor blockade. (primarily)
= nonselective antagonist - Phosphodiesterase inhibition
- Action at Ca++ channels to increase entry of Ca++ into
cells - Binding to GABA receptors at the benzodiazepine
site and decrease release
at high dosages may be associated with positiveinotropic and chronotropic effects on the heart + elevation of blood pressure.
Which drug can neutralize the effects of benzodiazepine tranquilizers?
Caffeine
Certain short-acting respiratory stimulant that can be used in acute respiratory failure
e.g. doxapram
a convulsant poison that acts mainly on the spinal cord by blocking receptors for the inhibitory transmitter
glycine.
Strychnine
acts as GABAA antagonists and appears to
block the ion channel:
Picrotoxin
A. TRANQUILLISERS /“Major”/:
A. TRANQUILLISERS /“Major”/
- PHENOTHIAZINE DERIVATIVES
- PROPIOPROMAZINE (Combelen)
- ACEPROMAZINE (Vetranquil, Atrovet)
- CHLORPROMAZINE (Hibernal)
- PROMETAZINE (Pipolphen) - BUTYROPHENONES
-AZAPERONE (Stresnil)
-(HALOPERIDOL, DROPERIDOL,
FLUANISONE) - (RAUWOLFIA ALKALOIDS - reserpine)
B. HYPNOSEDATIVES (SEDATIVE-HYPNOTICS)
4 groups and their drugs:
- ALPHA2-AGONIST
- XYLAZINE
- MEDETOMIDINE, DEXMEDETOMIDINE
- ROMIFIDINE
- DETOMIDINE
ANXIOLYTICS (Minor tranquillisers) - BENZODIAZEPINES
- DIAZEPAM
- CHLORDIAZEPOXIDE - PROPANDIOL-DERIVATIVES
- MEPROBAMATE - OTHER compounds
- BARBITURATES (long acting)
- Alcohols, Aldehydes, Br–and Mg2+-salts
TRANQUILLISERS
Uses of Phenothiazines:
- Calming, sedation
- Muscle relaxation
- Premedication
- All drugs in this group have similar efficacy,
they vary in potency and side effects - Slow onsets
Side effects-contraindication of Phenothiazines:
- Hypotention —> collapse
- Tissue irritation, allergy
- Penile prolapse (horses) and third eyelid
- Epilepsy, Extrapyramidal symptoms (high dose)
- not use before transportation
TRANQUILLISERS
Phenothiazine derivatives:
- CHLORPROMAZINE
- PROPIOPROMAZINE
- ACEPROMAZINE
- PROMETAZINE
- Perphenazine, Thiethylperazine, Fluphenazine, Trifluoperazine
CHLORPROMAZINE:
side effects -frequently
paradox reaction in horses (cyclic ataxic reaction with
excitation
- hypotension and tachycardia, rarely in other
animals), tissue irritation, allergy
PROPIOPROMAZINE
PROPIOPROMAZINE
more reliable, less side effects
ACEPROMAZINE
ACEPROMAZINE
more efficacious than chlorpromazine, less side effects
good oral bioavailability, Halothan hyperthermia and
arrhythmogenicity↓
PROMETAZINE
PROMETAZINE
less potent tranquillizer, increased antihistaminic
and anti-5-HT effect
Butirophenones
- potency:
- drugs:
- in combination with:
- side effects:
More potent than phenothiazines (some analgesic effect)
- In CNS dopamine-inhibition (D2),
NA-inhibition
anticholinergic effect
(with weaker antagonistic effect on α1-, H1-receptors)
Droperidol
Haloperidol
Fluanisone
AZAPERONE (only in Swine)
In combination with Metomidate.
Side effects-contraindication:
- transient salivation or panting,
- hypotension, respiratory stim., boar penile prolaps
- avoid use in very cold condition
(but can reduce hyperthermia caused by Halothane)
The Most characteristic effects of
SEDATIVE-HYPNOTICS
• Sedative effect • Anxyolytic effect • Hypnotic effect - Hypnotic effect – drugs induce sleep - Hypnogen drugs – to maintain sleep • Muscle relaxation • Anticonvulsive (exception alpha2-agonist)
These effects are dose dependent and the
efficacy of individual agents is different.
ALPHA2-AGONISTS
Effects:
ALPHA2-AGONISTS • Sedative: locus coeruleus • Analgesic: spinal cord • Reduced motor activity: spinal cord • Further effects: - relaxation of GI smooth muscle - mydriasis - bulbar tension ↓ - ACTH secretion ↑ - insulin, renin, ADH ↓ - hyperglycaemia - microsomal enzymes ↓
Side effects of alpha2- agonists:
- bradycardia
- vasoconstriction
- Hyoptension
- Hyperglycaemia
- AV block
- hypopnoe
- polyuria
- emesis
- tympanism
XYLAZINE
- effect
- side effect
Sedative-analgesic drug with depressed motor
activity can be used in all domestic animals.
Side effects:
– emesis and vomiting in cats and dogs
– bradycardia, malignant arrhythmias
– sweating in horses
– ecbolicaction: in late pregnancy its use is
contraindicated
– tympani in ruminants
DETOMIDINE
- characteristics
- side effects
- combinations?
More potent than xylazine, licensed for equine use
Does not cause loss of consciousness
Duration of action is dose dependent
Side effects:
- hypertension, then hypotension
- bradycardia, respiratory depression, diuresis
- hypothermia, sweating, snoring, tremor
Use: alone or in combination with ketamine,
thiopentone, opioid drugs
MEDETOMIDINE (M) DEXMEDETOMIDINE (DM)
- effect
- used in?
- Effects are similar to those of xylazine
but it seems to be more reliable and safer. - Developed for cats and dogs.
- Duration of action is dose dependent.
ALPHA2-ANTAGONISTS
- Drugs
- side effects
ATIPAMEZOLE:
Alpha2-adenoreceptor blocking agent.
Reverse the effect of medetomidine and other alfa2-agonists too
SIDE-EFFECTS: well tolerated by dogs and cats
tachycardia (high dose) transient hypotension, hypothermia, vomiting, defecation, panting, muscle tremor.
Contraindication: ketamin-medetomidine
YOHIMBINE and TELAZOLINE:
Much less specific alpha2-adenoreceptor antagonist than atipamezole, and so has significant alpha1-antagonistic action. Reverse the effect of xylazine.
Yohimbine is mainly used in conjunction with FAMPIRIDINE which facilitate the release of neurotransmitters form nerve
endings.
BENZODIAZEPINES
- receptor action
- location
- effects:
- Receptoral action: they facilitate or amplify the inhibitory
activity of GABA (Positive Allosteric Modulators) - BZD-receptors are located in all levels of CNS
(and in muscle). - Effects: sedation and anxiolytic effect anticonvulsive effect, muscle relaxation, hypnotic
Benzodiazepine antidote:
Flumazenil and Sarmazenil
DIAZEPAM
- administration
- clinical use
DIAZEPAM Oral absorption is good. IM delayed. Significant binding to plasma proteins. • Clinical uses - Premedication and combination (ketamine) - Muscle relaxation - Prevention and control of epilepsy - Sedation (taming during grouping of animals)
Midazolam
MIDAZOLAM
Shorter effect, produces less sedation than diazepam
Anxiolytic drugs:
3 most NB
- diazepam
- midazolam
- zolezepam
BARBITURATES
- effects
- classification
Effects:
- decrease in Ca2+ accumulation
- stabilisation of membranes
- CNS, circulation, respiration
Classification according to the duration of action:
long acting e.g. Barbital, Phenobarbital,
middle-long acting e.g. Amobarbital, Butobarbital
SIDE-EFFECTS OF ALFA2-ADRENOCEPTOR:
”AV” BLOCK BRADYCARDIA VASOCONSTRICTION HYPOTENSION HYPERGLYCEMIA HYPOPNOE POLYURIA EMESIS (dogs, cats) TYMPANISM (cattle)
