Sedatives and Tranquilisers

Question 1

What do tranquilisers achieve and what are some examples?

Answer 1

Relieve anxiety without undue drowsiness
Phenothiazines and Butyrophenones (acepromazine)
Benzodiasepines (diazepam, midozalam and zolazepam)

Question 2

What do sedatives achieve and what are some examples?

Answer 2

Cause drowsiness of the patient

Alpha-adrenergic agonists (xylazine, detomidine, medetomidine and dexmedetomidine)

Question 3

What are other neuroleptic drug categories?

Answer 3

Anticholinergic agents (atropine, glycopyrrolate)
Opioid analgesics
Other centrally acting muscle

Question 4

What is a neuroleptanalgesia a combo of?

Answer 4

a tranquiliser or a sedative with an opioid analgesic to achieve pain relief

Question 5

What is the MOA of Acepromazine maleate(Penothiazine)?

Answer 5

Blocks excitatory dopamine (DA-2 receptors) altering motor control and inhibits stimulation of CRTZ (anti-emetic effect)
May have 5-HT2, histamine (H1) and a-adrenergic blocking effects controlling (mood, wakefulness, feeding, behaviour and vomiting) –> blocking vomiting for surgery is a +

Question 6

What can decrease the effectiveness of sedatives?

Answer 6

Excitement of the animal may override the sedation and increasing the dose may not increased sedation

Question 7

What is a very important consideration for Acepromazine(Penothiazines)?

Answer 7

Only potentiates analgesic and general anaesthetic agents they DO NOT have analgesic properties

Question 8

What are the CVS, GI and R effects from Acepromazine (Penothiazines)?

Answer 8

Alpha-adrengic blockage leads to peripheral vasodilation

Question 9

What is the A, D and E of Acepromazine?

Answer 9

A - Well absorbed by IM admin
D - most are lipophilic and well distributes has a duration of 4-6hrs
E - renal

Question 10

CNS effects of Acepromazine?

Answer 10

Dopamine controls motor activity and these drugs may cause restlessness, tremors and catalepsy
Can modify thermoregulatory centres (hypothalamus) inducing hypothermia
Can lower seizure threshold in dogs

Question 11

What are some possible adverse effects of Acepromazine?

Answer 11

Can cause hypotension use caution in hypovolemic and shock patients and epinephrine is contradicted in this cases due to epinephrine reversal which would further decrease BP
Bradycardia and sinoatrial arrest in dogs following high doses
Vaso-vagal synscopy may occur in bradycephalic dogs
General spasmolytic effect in GI motility (due to anticholinergic effects)
VERY IMPROTANT: can cause prolapse of the penis or penile paralysis in horses (caution if used in breeding stallions)

Question 12

What are some Benzodiazepines?

Answer 12

Diazepam, Midazolam, Zolazepam

Question 13

What are the effects of Benzodiazepines and what is an important consideration for them?

Answer 13

Hypnosis, sedation, anxiolytic, anticonvulsant and muscle relaxant
NB: not very reliable as a sedative in healthy animals

Question 14

MOA of benzodiazepines and what sedative effects do they have?

Answer 14

The GABAa receptor is a ligand-gates Cl- channel and when activated it causes hyperpolarisation leading to:
Sedation and hypnotics, anticonvulsants, anxiolytic effect BUT NO analgesic effects

Question 15

What are some other clinical uses of Benzodiazepines?

Answer 15

Induce minimal and unreliable sedation in healthy cats, dogs and horses
Mild sedation and muscle relaxation (improves sedation with opioids, improves muscle relaxation with Ketamine)
Used for acute anticonvulsant effects

Question 16

What is an important consideration about Flumazenil?

Answer 16

Antagonist can be used to reverse the effects of other drugs (antidote)

Question 17

What are some examples of alpha2-adrenocepter agonists?

Answer 17

Xylazine, Detomidine, Medetomidine, Dexmedetomidine

Question 18

MOA of alpha-2 adrenoceptor agonists?

Answer 18

Stimulation of presynaptic a2-recptors triggers G-protein coupled receptor signalling that leads to decreased sympathetic outflow (this is inhibitory)

Question 19

Where are a2a widely expressed?

Answer 19

CVS, RD, renal, endocrine, GIT and CNS

Question 20

What are the general effects of a2a?

Answer 20

Sedation (reversible), muscle relaxation, mild-moderate analgesia

Question 21

Effects of a2a on CNS?

Answer 21

CNS effects:
Startling arousal, aggression to touch in horses and dogs
A drop in body temp
Vomiting is common in cats and dogs
Convulsions are reported in fish

Question 22

Effects of a2a on GIT?

Answer 22

Depresses GI motility
Ruminal atony and bloat in ruminants (within 2hrs)
Gastric reflux in dogs and cats

Question 23

Effects of a2a on endocrine effects?

Answer 23

Reduced insulin release – hyperglycaemia and glycosuria
Reduced anti-diuretic hormone release – diuresis
Changes in growth hormone, testosterone and prolactin profiles
Induce uterine contractions avoid in 3rd trimester

Question 24

A, D, E of a2a?

Answer 24

A - well absorbed following IM and IV admin oral is not recommended because of the first pass effect
D - lipophilic
E - urinary

Question 25

Adverse effects of a2a?

Answer 25

CVS: Hypertension and bradycardia with decreased cardiac output can be prevented with atropine
Secondary rhythm-atrio block especially in dogs and horses

Respiratory:
In cats and dogs causes a drop in RR but not PaO2 = pale MM due to vasoconstriction
Decreased PaO2 and overt hypoxemia are seen in ruminants and can last a long time after sedation
Pulmonary oedema

Question 26

What are the major uses of neuroleptics?

Answer 26

Pre-anaesthetic medications (Premedication);
- Calming (sedating the patient)—reduce anxiety
- Decreasing the overall dose of the anaesthetic
- Promote recovery from anaesthetics
- Decrease salivary & bronchial secretions
- Block vagal reflexes and bradyarrhythmias
- Treat potential adverse effects of other drugs (e.g:
prevent CNS stimulation by ketamine & Opioids)