PHARMACOLOGY - Sedative Drugs Flashcards
What are the four main classifications of sedative drugs?
Phenothiazines
Butyrophenones
α2 adrenoreceptor agonists
Benzodiazepines
What is the mechanism of action for phenothiazines?
Phenothiazines are non-selective dopamine antagonists
What is the most commonly used phenothiazine used in veterinary medicine?
Acepromazine
What are the two desired effects that acepromazine has on the central nervous system (CNS)?
Sedation
Antiemetic
How does acepromazine act as an antiemetic?
Acepromazine is a dopamine antagonist and thus will antagonise dopamine receptors in the chemoreceptor trigger zone
What are the eight side effects of acepromazine?
Hypotension
Anti-arrhythmic
Reduced gut motility
Antisialagogue
Hypothermia
Penile prolapse/Priapism
Mild antihistamine effect
Increase seizure activity
How does acepromazine cause hypotension?
Acepromazine is a non-selective antagonist meaning it will bind to and have an antagonising effect on receptors other than dopamine, such as α1 receptors on vascular smooth muscle, resulting in vasodilation and hypotension
How does acepromazine act as an anti-arrhythmic?
Acepromazine is a dopamine antagonist and thus reduces sympathetic nervous system activity which can protect against catecholamine driven arrhythmias
How does acepromazine reduce gut motility?
Acepromazine is a non-selective antagonist meaning it will bind to and have an antagonising effect on receptors other than dopamine, such as muscarinic receptors. Through binding to these muscarinic receptors, acepromazine can inhibit the binding and action of acetylcholine which is important for stimulating gut motility
How does acepromazine have a mild antihistamine effect?
Acepromazine is a non-selective antagonist meaning it will bind to and have an antagonising effect on receptors other than dopamine, such as histamine 1 (H1) receptors
For which species’ is acepromazine liscenced?
Dogs
Cats
Horses
How is acepromazine administered?
Usually intramuscular injection but can be administered via subcutaneous and intravenous injection
Why is oral administration of acepromazine unreliable?
Oral administration of acepromazine is unrealibale due to it’s variable bioavailability
(T/F) Acepromazine has a rapid onset and short duration of action
FALSE. Acepromazine has a slow onset and long duration of action
How does acepromazine interact with other drugs?
Acepromazine potentiates the effects of other sedative drugs as well as reduces the quantity of general anaesthetic required
What are the three main clinical indications for the use of acepromazine?
Sedative
Premedication
Antiemetic
What are the three main contraindications for the use of acepromazine?
Hypovolaemic patients
Breeding stallions
History of seizures
Why is acepromazine contraindicated in hypovolaemic patients?
Hypovolaemic patients have a reduced intravascular volume and thus already have hypotension which can be worsened by acepromazine administration as it will exacerbate the hypotension
Why is acepromazine contraindicated in breeding stallions?
Acepromazine is contraindicated in breeding stallions due to the risk of priapism (persistent erection)
In which dog breeds should lower doses of acepromazine be given?
Giant breeds
Brachycephalic
Herding breeds
Boxers
Why should lower doses of acepromazine be given to herding breeds?
Herding dog breeds often have a genetic mutation in the ABCB1 gene that allows certain drugs to cross the blood brain barrier (BBB) and accumulate in the brain
What side effect of acepromazine can be seen in boxers?
Vasovagal syncope
What is vasovagal syncope?
Acepromazine causes vasodilation which causes hypotension which can trigger an inappropriate vagally mediated bradycardia in boxers, exacerbating the hypotension resulting in syncope
How do you treat a vasovagal syncope episode?
Administer an antimuscarinic drug to block the vagal bradycardia
Give an example of an antimuscarinic drug
Atropine
How can you prevent a vasovagal syncope episode in boxers?
Administer a lower dose of acepromazine
Combine acepromazine with an antimuscarinic drug
What is the mechanism of action for butyrophenones?
Butyrophenones are non-selective dopamine antagonists
What are the two desired effects that butyrophenones have on the central nervous system (CNS)?
Sedation
Antiemetic
Give two examples of butyrophenones
Azaperone (stresnil)
Fluanisone
For which species is azaperone (stresnil) liscenced?
Pigs
How is azaperone (stresnil) administered?
Intramuscular injection
What are the three clinical indicators for the use of azaperone (stresnil) in pigs?
Sedation
Premedication
Behaviour modification
What are three of the side effects of azaperone?
Hypotension
Hypothermia
Priapism
What is Hyponorm?
Hyponorm is a mixture of fluanisone and
fentanyl
For which species’ is Hyponorm licensced?
Small mammals
How is Hyponorm administered?
Intramuscular injection
Intraperitoneal injection
What are the two clinical indicators for the use of Hyponorm in small mammals?
Sedation
Premedication
(T/F) Hyponorm has a rapid recovery
FALSE. Hyponorm has a prolonged recovery
What is the mechanism of action for α2 adrenoreceptor agonists?
α2 adrenoreceptor agonists bind to adrenergic receptors within the sympathetic nervous system
What are the effects of α2 adrenoreceptor agonists when they bind to presynaptic α2 adrenoreceptors?
α2 adrenoreceptor agonists have a sympatholytic effect when they bind to presynaptic α2 adrenoreceptors as this causes the inhibiton of adenylate cyclase which decreases cAMP and results in the inhibition of calcium influx into the cell, resulting in the inhibition of neurotransmitter release from the presynaptic terminal
What are the effects of α2 adrenoreceptor agonists when they bind to postsynaptic α2 adrenoreceptors?
α2 adrenoreceptor agonists have a sympathomimetic effect when they bind to post-synaptic α2 adrenoreceptors as they mimic neurotransmitters, resulting in inceased sympathetic activity
What are the effects of α2 adrenoreceptor agonists when they bind to postsynaptic α1 adrenoreceptors?
α2 adrenoreceptor agonists have a sympathomimetic effect when they bind to post-synaptic α1 adrenoreceptors as they mimic neurotransmitters, resulting in inceased sympathetic activity
What are the three desired effects that α2 adrenoreceptor agonists have on the central nervous system (CNS)?
Sedation
Analgesia
Muscle relaxation
(T/F) α2 agonists have the most reliable sedative effect
TRUE.
What are the thirteen side effects of α2 agonists?
Transient vasoconstiction and hypertension followed by hypo- or normotension
Bradycardia
Arrhythmogenic in horses
Mild to moderate respiratory depression
Artrial hypoxaemia in ruminants
Pulmonary oedema in small ruminants
Tachypnoea in pyrexic horses
Worsens airway obstruction in horses
Vomiting in some species
Reduced gut motility
Diuresis
Hyperglycaemia
Uterine contraction
How do α2 adrenoreceptor agonists cause hypertension?
When α2 adrenoreceptor agonists bind to post-synaptic α adrenoreceptors on vascular smooth muscle, they have a sympathomimetic effect which will trigger vasoconstriction and thus hypertension
How do α2 adrenoreceptor agonists cause bradycardia?
α2 adrenoreceptor agonists trigger hypertension which will stimulate baroreceptors to trigger a reflex bradycardia as a compensatory mechanism
How do α2 adrenoreceptor agonists cause diuresis?
α2 adrenoreceptor agonists inhibit the release of antidiuretic hormone
how α2 adrenoreceptor agonists cause hyperglycaemia?
α2 adrenoreceptor agonists inhibit insulin release
How can α2 adrenoreceptor agonists be administered?
Intramuscular injection
Intravenous injection
Subcutaneous injection
Epidural injection
What is oral administration of α2 adrenoreceptor agonists unreliable?
Oral administration of α2 adrenoreceptor agonists is unreliable due to first pass metabolism
How do α2 adrenoreceptor agonists interact with other drugs?
α2 adrenoreceptor agonists potentiate the effects of other sedative drugs as well as reduce the quantity of general anaesthetic required
What can be used to reverse the effects of α2 adrenoreceptor agonists?
α2 adrenoreceptor antagonists
Give an example of an α2 adrenoreceptor antagonist
Atipamezole
(T/F) Atipamezole is licensed in food producing animals
FALSE. Atipamezole is not licensed in food producing animals
What are the four clinical indicators for the use of α2 adrenoreceptor agonists?
Sedation
Premedication
Analgesia
Offset ketamine hypertonicity
What are the contraindications for the use of α2 adrenoreceptor agonists?
Take care administering α2 adrenoreceptor agonists to any patient with cardiovascular disease or in poor general health due to the extensive side effects
Give three examples of α2 adrenoreceptor agonists licensed in dogs and cats
Xylazine
Medetomidine
Dexmedetomidine
Give two examples of α2 adrenoreceptor agonists licensed in cattle
Xylazine
Detomidine
Give three examples of α2 adrenoreceptor agonists licensed in horses
Xylazine
Detomidine
Romifidine
Why should you use lower doses of xylazine in cattle compared to horses?
Xylazine is more potent in cattle compared to horses so a lower dose is required
Which species is relatively resistant to α2 adrenoreceptor agonists?
Pigs
What are the main differences between medetomidine and dexmedetomidine?
Dexmedetomidine is more potent but has a slightly shorter duration of action than medetomidine
Which α2 adrenoreceptor agonists are most specific to α2 adrenoreceptors and thus have fewer side effects?
Medetomidine
Dexmedetomidine
Which α2 adrenoreceptor agonists are least specific to α2 adrenoreceptors and thus have the most side effects?
Xylazine
Which α2 adrenoreceptor agonists has the longest duration of action?
Romifidine
Which α2 adrenoreceptor agonist has the shortest duration of action?
Xylazine
Which α2 adrenoreceptor agonist is best for sedating standing horses?
Romifidine as is has the least muscle relaxing properties which reduces ataxia in standing horses
What is the mechanism of action for benzodiazepines?
Benzodiazepines potentiate the activity of inhibitory GABAa receptors
Give two examples of benzodiazepines
Diazepam
Midazolam
Which species’ is diazepam liscensed in?
Dogs
Cats
Which species is midazolam liscensed in?
Horses
What are the four desired effects that benzodiazepines have on the central nervous system (CNS)?
Sedation
Anxiolytic effect
Antiepileptic
Muscle relaxant
How are benzodiazepines administered?
Intravenous injection
Intramuscular injection
Orally
Why is midazolam better for intravenous administration compared to diazepam?
Diazepam is insoluble in water so tends to be dissolved in solvents that can irritate the veins or in lipid emulsions resulting in poor bioavailability, however midazolam is soluble in water and thus can be given IV without irritating the veins
How do benzodiazepines interact with other drugs?
Benzodiazepines are eliminated through the action of microsomal hepatic enzymes and thus this elimination can be affected by drugs that act as microsomal enzyme inhibitors
Give an example of a drug that acts as a microsomal enzyme inhibitor
Erythromycin
What are the four main clinical indicators for the use of benzodiazepines?
Premedication in sick animals
Muscle relaxation
Antiepileptic
Why are benzodiazepines not very effective premedications in healthy animals?
Benzodiazepines by themselves produce little sedation in healthy animals and can even cause paradoxical excitement in healthy animals. However, they can be useful for premedication in sick animals as they have less side effects compared to other sedatives
What are the two main contraindications for the use of benzodiazepines?
Patients hepatic encephalopathy
Animals in early pregnancy
Why are benzodiazepines contraindicated in patients with hepatic encephalopathy?
Benzodiazepines are contraindicated in patients with hepatic encephalopathy as they are metabolised by the liver and thus can cause strong sedation in patients with liver dysfunction
Why are benzodiazepines contraindicated in patients in early pregnancy?
Benzodiazepines can cross the placenta
Which factors should you consider when determining which sedative you should choose for premedication?
- How much sedation is needed (consider patient temperament and the procedure taking place)
- Patient health (any contraindications, or alternatively any side effects that may benefit the patient)
- Pharmacokinetics
- Controlled drug legislation and veterinary medicine register
- Affordability for the client
What are the aims of premedication?
To provide a calming or sedative effect
To provide analgesia
To reduce dose of other drugs required
To counteract other unwanted drug affects
To provide a more smooth induction and recovery
