Sedatives Flashcards
What are sedatives and what are they used for?
- A sedative is a substance that induces sedation by reducing irritability or excitement; some provide analgesia
- used to relax/calm an animal (e.g.,trimming nails, taking X-rays, or drawing blood)
- commonly used in combinations as preanesthetics before general anesthesia to relax and sedate the animal
Name the types of sedatives
• Tranquilizers – Phenothiazines – Butyrophenones – Benzodiazepines -Alpha-2 agonists
What are hypnotics?
• Hypnotics – drugs inducing sleep.
What are tranquilizers? Define major and minor tranquilizers
• Tranquilizer – a drug that induces tranquility (a state of calmness) in an individual; used to reduce stress or tension without reducing mental clarity.
- Major tranquilizers: antipsychotics-neuroleptics; psychoactive drugs commonly, but not exclusively used to treat psychosis (schizophrenia) (phenothiazines, butyrophenones)
- Minor tranquilizers: anxiolytic or anti anxiety agents for treatment of symptoms of anxiety (benzodiazepines); ataractics
What are phenothiazine derivatives and what are they used for?
• used in vet. med. as tranquilizers
-Phenothiazine is the parent compound for all the derivatives in this group.
Effects of phenothiazine derivatives and structures that they depress
• the effects of phenothiazines on the CNS were described firstly as “neuroleptic” but “major tranquilizer” is used now
• animals are usually calm and easy to handle, but they may be aroused by and respond to stimuli in a normal fashion (e.g., biting, scratching, kicking)
- ALL exert a sedative action by depressing the brain stem and connections to the
cerebral cortex
Name the phenothiazine derivatives
- acepromazine (ACP);
- promazine, and
- chlorpromazine
What are phenothiazine derivatives classified as?
Sedatives/Hypnotics/Anxiolytics, alpha-adrenergic antagonists
Phenothiazine derivatives mechanism of action
• The principal central activity is blockade of the effects of dopamine which is in charge of fine control of movement
• Phenothiazines inhibit central dopaminergic receptors (D2) - sedation and
tranquilization
- peripherally blocks norepinephrine at alpha1-adrenergic receptors to cause vasodilation and hypotension
• decrease spontaneous motor activity in animals
Effect of high doses of phenothiazine derivatives
– cataleptic effects - animals will remain immobile in a fixed position for long
periods;
– extrapyramidal symptoms (rigidity, tremor, akinesia)
Effects of phenothiazine derivatives on the musculoskeletal and analgesia???
MUSCULOSKELETAL
• provide good muscle relaxation
ANALGESIA
• little or no analgesic activity
Indications for using phenothiazine derivatives
- for general sedation, pre-anesthetically
- commonly administered with opioids (e.g., morphine) to produce neuroleptic analgesia (neuroleptanalgesia); the combination produces synergic effects of each class
- to prevent nausea and vomiting and some have antihistamine properties
Contraindications of using phenothiazine derivatives
• should be used cautiously in boxer dogs, brachiocephalic dogs, breeding stallions, and debilitated animals
Species differences to phenothiazine derivatives
Horse
• Chlorpromazine - not recommended - extreme ataxia and altered mentation.
Dog
• familial line of boxer dogs have an exaggerated reaction to acepromazine -
sedation and hypotension are greater than expected
Pig
• Acepromazine prevents
occurrence of halothane-induced malignant hyperthermia.
Describe acepromazine maleate
• Acepromazine is the most commonly used phenothiazine in vet. medicine.
• The primary use - as a preanesthetic agent in the dog, cat, and horse.
– It markedly potentiates barbiturates and facilitates handling and restraint of
animals.
Describe promazine hydrochloride use
- Major use: preanesthetic agent to facilitate handling through its sedative action - permits smoother induction of anesthesia and reduces the amount of anesthetic required by 30-50%.
- Indicated in animals manifesting nervous behavior and excitability.
- It has value in alleviation of self-inflicted mutilation associated with otitis, pruritus, and eczemic conditions.
- The drug assists in handling of animals for radiographic diagnosis or therapy and in other procedures where restraint is required
Describe chlorpromazine hydrochloride use
- primarily used as an antiemetic in dogs and cats, occasionally used as a preanesthetic sedative
- It is generally contraindicated for use with horses, due to a high incidence of ataxia and altered mentation.
- slight antihistaminic activity
- has been used in capture of African lions; for induction of neuroleptanalgesia in bears in combination with analgesic preparations.
Effects of alpha-2 adrenergic agonists and name the active substances.
• produce profound sedation (the best sedatives one can use), provide chemical restraint, and produce analgesia (the only sedatives which are able to provide analgesia)
• Furthermore, make drug tolerance of opioids better and act synergistically with opioids.
• Commonly used alpha-2 agonists in vet. medicine:
– xylazine,
– detomidine,
– medetomidine and dexmedetomidine.
- detomidine is like a xylazine for larger
animals. Produces less side effects - the last two are for small animals
Classification of alpha-2 adrenergic agonists
Sedatives/major tranquilizers that also possess significant analgesic properties and suppress the neuroendocrine stress response
Describe in detail the mechanism of action of alpha-2 adrenergic agonists
• Alpha-2-adrenergic agonists exert their mechanism of action on the α2-
adrenergic and/or imidazoline receptors.
• The α2-adrenergic rec. - subtypes A, B and C.
• The major sedative and analgesic effects are mediated via the activation of the
α2A- adrenergic receptor subtype
• Activation of the α2- adrenergic receptor will inhibit the positive feedback mechanism for the release of norepinephrine from the presynaptic nerve endings
- the attenuation of norepinephrine decreases arousal (causes sedation) and inhibits the afferent pain pathway.
• also have some agonistic activity on the α1-adrenergic receptor
• Imidazoline receptors – mediate central hypotension, antiarrhythmogenesis. Xylazine is not considered an imidazoline receptor agonist.
Effects of alpha-2 adrenergic agonists on the CNS
CNS
– Different species react differently to alpha-2 agonists (due to different receptor
subtypes - Ruminants have α2D-adrenergic receptors which makes them the most sensitive species to alpha-2 agonists!!!!!!!!!}
• Activation of α1-adrenergic receptors in the CNS will cause arousal, agitation,
increased locomotor activity, and vigilance - paradoxical excitement or movement.
• α2 -adrenergic agonists show profound anesthetic sparing effects with both
induction agents and inhalant agents (MAC=minimum alveolar concentration needed to induce general anesthesia-sparing of up to 90%).
Effects of alpha-2 adrenergic agonists on the GIT and endocrine system
GIT
• xylazine may cause vomiting in up to 90% in cats and 30% in dogs - acts on
the area postrema (chemotactic trigger zone) in the cat to cause emesis.
ENDOCRINE STRESS RESPONSE
• The suppression of the stress response - a reduction in catecholamine levels via
their actions on both α2-adrenergic and imidazoline receptors.
Indications of alpha-2 adrenergic agonists
• The α2-adrenergic agonists are major tranquilizers that are used in veterinary
patients for sedation, chemical restraint, and analgesia.
• Xylazine is also used as an emetic in feline patients.
Alpha-2 adrenergic agonists drug interactions
• α2-adrenergic agonists potentiate the effects of other sedative agents,
barbiturates, propofol, ketamine, etomidate, and inhalational agents. – The dosage of induction agents is greatly reduced and there is a profound MAC-sparing effect.
