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Flashcards in Sedatives Deck (44)
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1
Q

What are sedatives and what are they used for?

A
  • 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
2
Q

Name the types of sedatives

A
• Tranquilizers
– Phenothiazines
– Butyrophenones
– Benzodiazepines
-Alpha-2 agonists
3
Q

What are hypnotics?

A

• Hypnotics – drugs inducing sleep.

4
Q

What are tranquilizers? Define major and minor tranquilizers

A

• 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
5
Q

What are phenothiazine derivatives and what are they used for?

A

• used in vet. med. as tranquilizers

-Phenothiazine is the parent compound for all the derivatives in this group.

6
Q

Effects of phenothiazine derivatives and structures that they depress

A

• 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

7
Q

Name the phenothiazine derivatives

A
  • acepromazine (ACP);
  • promazine, and
  • chlorpromazine
8
Q

What are phenothiazine derivatives classified as?

A

Sedatives/Hypnotics/Anxiolytics, alpha-adrenergic antagonists

9
Q

Phenothiazine derivatives mechanism of action

A

• 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

10
Q

Effect of high doses of phenothiazine derivatives

A

– cataleptic effects - animals will remain immobile in a fixed position for long
periods;
– extrapyramidal symptoms (rigidity, tremor, akinesia)

11
Q

Effects of phenothiazine derivatives on the musculoskeletal and analgesia???

A

MUSCULOSKELETAL
• provide good muscle relaxation
ANALGESIA
• little or no analgesic activity

12
Q

Indications for using phenothiazine derivatives

A
  • 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
13
Q

Contraindications of using phenothiazine derivatives

A

• should be used cautiously in boxer dogs, brachiocephalic dogs, breeding stallions, and debilitated animals

14
Q

Species differences to phenothiazine derivatives

A

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.

15
Q

Describe acepromazine maleate

A

• 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.

16
Q

Describe promazine hydrochloride use

A
  • 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
17
Q

Describe chlorpromazine hydrochloride use

A
  • 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.
18
Q

Effects of alpha-2 adrenergic agonists and name the active substances.

A

• 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
19
Q

Classification of alpha-2 adrenergic agonists

A

Sedatives/major tranquilizers that also possess significant analgesic properties and suppress the neuroendocrine stress response

20
Q

Describe in detail the mechanism of action of alpha-2 adrenergic agonists

A

• 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.

21
Q

Effects of alpha-2 adrenergic agonists on the CNS

A

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%).

22
Q

Effects of alpha-2 adrenergic agonists on the GIT and endocrine system

A

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.

23
Q

Indications of alpha-2 adrenergic agonists

A

• 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.

24
Q

Alpha-2 adrenergic agonists drug interactions

A

• 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.

25
Q

Species differences regarding alpha-2 adrenergic agonists

A

Ruminants are the most sensitive and small laboratory animals the least sensitive to alpha-2 adrenergic agonists. Cattle need 1/10 of the dose of xylazine compared with dogs

26
Q

Describe xylazine hydrochloride

A

• Xylazine is the α2-agonist most likely to cause vomiting in the dog, whereas almost all α2- agonists cause vomiting in cats.
-CATTLE: particularly sensitive - require ~ 1/10 the dose compared with other species.

27
Q

Describe Detomidine hydrochloride

A
  • a sedative-anagesic used in the horse, bovines
  • detomidine is the analgesic of choice for relieving equine colic pain
  • Detomidine is an effective preanesthetic for horses and cattle.
28
Q

Describe medetomidine hydrochloride

A

• approved for use in dogs and cats

29
Q

Describe dexmedetomidine hydrochloride

A
  • approved for use in the dog and cat.

* sedation and analgesia similar to medetomidine;

30
Q

Describe romifidine

A

• a more selective α2 -agonist than xylazine

31
Q

What are alpha2- adrenergic receptor antagonists

A

• Alpha-2-adrenergic receptor antagonists are used primarily to reverse the
effects of the α2-adrenergic agonists (CNS depression).
• The ability to reverse the α2- adrenergic agonists increases their appeal for use,
especially for the chemical restraint of exotic wildlife.
-alpha2- agonists and antagonists are extraordinarily similar compounds

32
Q

Name the alpha2-adrenergic receptor antagonists

A
  • yohimbine,
  • atipamezol (only one licensed for use in vet med.)
  • tolazoline
33
Q

Describe atipamezole

A

-a highly specific α2 -receptor antagonist that was designed to reverse the effects
of medetomidine in dogs, cats, and exotic species.
-Contains 5x the amount of sedative so need to apply the same quantity as used when giving the sedative because will competitively compete for binding sites

34
Q

Mechanism of action of alpha2-receptor antagonists

A
  • Drugs in this class are all alpha2-receptor ligands that are competitive antagonists at the receptor site.
  • blocks the negative feedback loop on the regulation of the norepinephrine release from the presynaptic nerve endings of the sympathetic nervous system.
35
Q

What are benzodiazepine derivatives?

A

Benzodiazepines are sedative-hypnotics due to their propensity to cause:
– anxiolysis,
– sedation, and
– sleep.
• minor tranquilizers, or ataractics
• belong to controlled drugs
• Many benzodiazepines are used in people and animals for behavioral modification; as sedatives and adjuncts to anesthesia:

36
Q

Name the benzodiazepine derivatives

A
  • diazepam,
  • midazolam,
  • lorazepam, and
  • zolazepam.
37
Q

Mechanism of action of benzodiazepines.

A

-Benzodiazepines bind to and activate the benzodiazepine receptor binding site
(BZ receptor), which is located on the γ subunit of GABA .
• Agonism of the BZ binding site on GABA rec. increases the frequency of the
opening of the Cl ion channels -> hyperpolarization of the postsynaptic neuron -> decreased neuronalt ransmission-> hypnotic,sedative,anxiolytic, anticonvulsant, and skeletal muscle-relaxant effects.
-highest concentration of GABA receptors is in the cerebral cortex with very few outside the CNS hence the minimal cardiovascular effects of benzodiazepines.

38
Q

Effect of benzodiazepines on the CNS and cardiovascular system

A

CNS

  • very important ANTICONVULSANT effect!!!
  • Clinical doses - minimal cardiovascular depression
39
Q

Effect of benzodiazepines on the muscles. Analgesia?

A
  • reliable muscle relaxation

- do not produce analgesia

40
Q

Indications of benzodiazepine derivatives

A
  • anticonvulsants, premedicants, adjuncts to anesthetic induction agents, skeletal muscle relaxants and for behavioral modification.
41
Q

Describe diazepam hydrochloride and it’s use

A

-The anticonvulsant properties are useful in treatment of:
– status epilepticus,
– tetanus,
– convulsions caused by metaldehyde toxicity, by overdoses of local anesthetics…
– Generally, diazepam and related benzodiazepines have been recommended as 1st agents in treatment of convulsions of different origin.
• Diazepam can be used in:
– dogs, cats, horses (in combination with ketamine and xylazine – smooth induction
of and recovery from anesthesia - also in other species),
– swine, mink (to prevent aggressivenes),
– goats, cattle, lab. animals and exotic species (for immobilization).
• diazepam and related drugs should not be used in breeding animals (possible teratogenic effect)
-Appetite stimulant in cats and goats

42
Q

Describe midazolam maleate

A

midazolam is classified as short lasting, whereas diazepam as long lasting.

43
Q

Describe lorazepam

A

-used for long-term treatment of epilepsy

44
Q

What is flumazenil used for and how does it work?

A

• is a specific and exclusive benzodiazepine (BZ) competitive antagonist with a high affinity for the benzodiazepine receptor sites on GABA receptor, thus preventing hyperpolarization of the postsynaptic membrane