Pre-medication Drugs Flashcards
Opioid Examples
Methadone - Mu agonist
Fentanyl - Mu agonist
Pethidine - Mu agonist
Morphine - Mu agonist
○ Not licensed in veterinary
Buprenorphine - Partial Mu agonist (kappa antagonist)
Butorphanol - Mu antagonist, Kappa agonist
Opioid Licensing
Morphine - Not licensed
Methadone - Licensed in dogs/cats
Pethidine - Licensed in dogs. cats, horses
What schedule are Opioids?
Schedule 2
Except Buprenorphine (schedule 3)
What do opioids do?
Sedation
Analgesia
Used in sicker animals
Used for painful surgeries
Pharmacodynamics of Opioids
Act peripherally and in CNS on 4 main receptor types:
○ Mu - most profound analgesic effects
○ Kappa
○ Delta
○ Nociceptin
Mu Agonist Examples
Methadone
Fentanyl
Pethidine
Morphine
Buprenorphine - Partial Mu agonist (lesser effects)
What is important to remember about Butorphanol
Mu antagonist and Kappa agonist
Good sedation but poor short-lived analgesia
Might use for non-painful procedures
Birds have high proportion of kappa receptors so could be good analgesic in birds
Effects of opioids on Cardiovascular system
Generally considered to cause minimal cardiovascular depression
○ Some vagally mediated bradycardia can be seen at high doses
Effects of opioids on Respiratory system
Respiratory depression usually minimal at clinical doses
○ Might be seen with fentanyl or high doses of methadone given IV
○ Sometimes if given intraoperatively you might see apnoea
Effects of opioids on Gastrointestinal system
Opioids reduce gastrointestinal motility and decrease gastric emptying
○ Morphine may also induce emesis, but not very commonly used (other than in a CRI)
Methadone is licenced and doesn’t seem to cause nausea and sickness
Can you antagonise opioids?
Yes
Reversed by naloxone
Alpha-2 Agonist Examples
Medetomidine (faster acting and more effective)
Dexmedetomidine
Xylazine
Detomidine
Romifadine
Alpha-2 agonist Licensing
Medetomidine - small animals (most common)
Dexmedetomidine - small animals
Xylazine - Small animals, cows and horses
Detomidine - Horses and cows
Romifadine - Horses
What are alpha-2 agonists used for?
Sedation
Often used in combination with opioid
Short lived analgesia
Useful in lively/aggressive patients
How do Alpha-2 agonists affect balanced anaesthesia
Selective alpha-2 agonists reduce the amount of anaesthetic drug required to induce and maintain anaesthesia
Reduce MAC - less isoflurane needed
How do Alpha-2 agonists work?
Bind to presynaptic Alpha-2 receptors
Sympathetic nervous system activity decreases
This reduces the release of noradrenaline and ACh
Therefore HR and BP drop
Effects of Alpha-2 agonists on Cardiovascular system
Can cause significant cardiovascular depression
DO NOT USE IN PATIENTS WITH CARDIOVASCULAR DISEASE
Not used in sick patients
Effects are biphasic
Initially peripheral vasoconstriction results in an increase in blood pressure
In response there is a reflex bradycardia and reduction in cardiac output
After something like 15-20 minutes blood pressure and heart rate return to normal
Effects of Alpha-2 agonists on Respiratory system
Minimal respiratory depression
Can cause upper respiratory tract obstruction in brachycephalic
Effects of Alpha-2 agonists on Gastrointestinal system
Can cause emesis in cats if used alone
Reduce endogenous insulin production
DON’T USE IN UNSTABLE DIABETIC
Increases urine production as a result of reduced renin and vasopressor secretion
DON’T USE IN BLOCKED ANIMALS
Can you reverse Alpha-2 agonists?
Yes
Atipamezole
Antagonises sedative, drug sparring and analgesic properties
Properties of Alpha-2 agonists
Marked sedative, muscle relaxant and analgesic properties
Associated with marked bradycardia/hypotension
Rapid onset
Short duration
Examples of Phenothiazines
Acepromazine (ACP) - only one licensed for veterinary use
Common component in premedication
Often combined with Alpha-2 agonist
Acepromazine Licensing
Cats
Dogs
Horses
What are phenothiazines agonists used for?
Contributes to sedation or tranquillisation (mild-moderate)
Provides anxiolysis
No analgesia
Relatively slow to take effect (30-40 minutes)
Long acting (6-8hrs)
Not suitable for:
Sepsis
Hypovolaemia
Cardiovascular compromise
Dogs with MDR1 mutations can be more sensitive
What are the pharmacokinetics of ACP?
- Oral absorption can be erratic and unpredictable
Hence IM or IV preferable - Rapid distribution and will cross BBB and placenta
- Absorbed in fat and released slowly
- High plasma protein binding
Not active when bound - Slow elimination with half-life of 24-28 hours
Longer duration of action
How do phenothiazines work?
Centrally acting by antagonising:
○ D1 and D2 receptors
○ Alpha-1 receptors
○ Muscarinic receptors
○ H1 receptors
Effects of Phenothiazines on Cardiovascular System
Causes vasodilation - can result in hypotension and hypothermia
Giant breeds are more susceptible to these effects
Considered antiarrhythmic
Effects of Phenothiazines on Respiratory System
Minimal depression in healthy patients
What is Neuroleptanalgesia?
Combination of an opioid and a tranquilizer/sedative
Reduces amount of each required
Results in improved sedation
E.g. Opioid + ACP
Examples of Benzodiazepines
Diazepam (IV only)
Midazolam (IV and IM but stings)
Licensing of Benzodiazepines
Diazepam - dogs/cats
Midazolam - horses
What are Benzodiazepines used for?
Not analgesic
Anxiolysis
Sedation - often poor and can result in disinhibition
Hyponosis
NOT normally used in healthy patients
Used in ‘Quad’ for cats IM
Midazolam lowers dose of propofol needed
Sometimes used in sick patients as co-induction agent
Contributes to muscle relaxation
USE IN SEIZURING ANIMAL - anticonvulsant
How do Benzodiazepines work?
Centrally acting via GABA-A receptor
Binds to alpha subunit (GABA binds to beta)
Enhances effect of GABA binding
More CL- ions released post-synaptically preventing AP
Pharmacokinetics of Benzodiazepines
High lipid solubility - aids oral and IM absorption
Widely distributed in body
Metabolised by liver
Effects of Benzodiazepines on Cardiovascular System
Minimal cardiovascular depression - useful in sick patients with opioid or ketamine
Effects of Benzodiazepines on Respiratory System
Minimal cardiovascular depression - useful in sick patients with opioid or ketamine
Can Benzodiazepines be reversed?
Yes
Flumazenil - compete for receptor without producing effects
Short lived and doses may need repeating
Expensive
Examples of NMDA Receptor Agonists
Ketamine
Licensing of Ketamine
Dogs
Cats
Horses
Cows
What is ketamine used for?
Dissociative anaesthetic at high doses
*Depresses thalamocortical system and activates limbic system
* Profoundly reduces the amount of induction agent and inhalation anaesthetics you might otherwise need
Sedation at lower Doses
Only analgesic induction drug
Analgesia at even lower doses - Infusion
Short acting
When used alone it’s a poor muscle relaxant
○ Often used in combination with something that causes good muscle relaxation
E.g. midazolam or alpha-2.
Common combination would be ketamine and midazolam in a sick cat
How does Ketamine work?
Blocks NMDA receptor activity
Blocks signal transduction of Na and Ca ions going through channel
Blocks glutamate action (excitatory neurotransmitter)
Not totally selective
○ Weak Mu opioid agonist
○ Weak GABA-A agonist
○ Anti-cholinergic effects
How does Ketamine effect the Cardiovascular System?
Good cardiovascular stability
Transient increase in Cardiac output and BP
In some sick patients administration has caused a reduction in blood pressure probably due to myocardial depression in the presence of altered sympathetic tone
How does ketamine effect Respiratory System?
Dose dependent respiratory suppression
More concern at pre-med doses
Examples of Anticholinergic Drugs
Atropine
Glycopyrrolate
(AKA parasympatholytic/vagolytic drugs)
Licensing of Atropine
Dogs
Cats
Horses
How does Atropine effect the Cardiovascular System?
Reduces bradycardia
Often used intraoperatively to combat bradycardia
DON’T use in presence of Alpha-2s
How does Atropine effect the Gastrointestinal System?
Anti-emetic
When is atropine used?
To combat bradycardia during anaesthesia
Not routinely used in pre-med:
○ Mydriasis
○ Reduced gut motility
○ Bronchodilation
How does Atropine affect respiratory system?
Bronchodilation - improve ventilation
What is alfaxalone?
Neuroactive steroid
What is alfaxalone used for?
Induction agent via IV
General anaesthetic agent
Can be used to sedate sick patients
Occasionally given if robust pre-med didn’t provide enough sedation
Alfaxalone effects on Cardiovascular system
Few adverse effects
Mild vasodilation following IV
Cardiac output and tissue perfusion maintained
Alfaxalone effects on Respiratory system
Apnoea reported when IV
