Sedative Drugs Flashcards
Define Premedication
Agent or several agents that are given in preparation of operation or other procedure or treatment (Sedatives, Analgesics and Anticholinergics)
Define Sedation
The act of administering a sedative to achieve a state of calm or sleep. Typically meds used for sedation are given in larger doses than those used for premedication
Define Tranquilizers
Sedate or make calm with the purpose of relieving anxiety or distress
Define Hypnosis
Sleep-like state
note: a patient can be easily roused by hypnotic drugs (unlike narcosis drugs)
Define Narcosis
State of stupor, drowsiness or unconsciousness
note: it is NOT easy to rouse the patient under narcosis (unlike hypnosis)
Name the Phenothiazine drug used as a sedative in animals? (1)
Acepromazine
aka ACE
Name the alpha2 agonist drugs used as a sedative in animals? (5)
- Xylazine, detomidine, romifidine
- Medetomidine and Dexmedetomidine
Name the Butyrophenones drug used as a sedative in animals? (1)
- Azaperone
Name the Benzodiazepam drugs used as a sedative in animals? (2)
- Midazalam, diazepam (valium)
How can Acepromazine be administered to a patient and how long is the onset of action?
- oral tablets/ liquid: unreliable results
- injectable IV/IM: onset 5-20mins IV, and 30-45mins IM
How long can the duration of action of Acepromazine be?
Up to 8 hours
What is the distribution of Acepromazine?
Highly protein bound
- Does cross the BBB
Where in the body is Acepromazine metabolized?
liver via P450
Where in the body is Acepromazine excreted?
Both unconjugated and conjugated metabolites are eliminated in the urine
What is the pharmacodynamics of Acepromazine?
Antagonist of:
Dopaminergic receptor 2 (D2): provides sedative and anti-emetic effects
Histamine receptor1 (H1): provides anti-histaminic effects
Cholinergic muscarinic receptors: provides spasmolytic effect in the GI
Alpha1 receptors in the peripheral vasculature: providing vasodilation
What are 4 sedatives also in the Phenothiazine family of drugs?
- Chlorpromazine
- Promazine
- Methotrimeprazine
- Prochlorperazine
Is Acepromazine considered to be an analgesic?
No! It should never be used for the purposes of pain relief
What are the effects of Acepromazine on the CNS, Cardiovascular System, GIT and histamine response
- CNS: sedation, anti-emesis, extrapyramidal effects (at high doses)
- CVS: hypotension due to vasodilation, and anti-arrhythmic (suppress abnormal arrhythmias)
- GIT: Antispasmodic, reduced LOS tone and increased risk of regurgitation
- Histamine response: anti-histamine effect, which can interfere with an intradermal skin test
note: LOS = lower esophageal sphincter
note: minimal effects on the respiratory system
If Acepromazine were to be given in too high of a dose (overdose), what can be done?
- No reversal agent
- Must combat each of the effects individually: e.g. Alpha1 agonist to combat the vasodilation (e.g. Phenylephrine), or fluid therapy to maintain normal BP
caution: Never use adrenaline as it can worsen vasodilation and drop BP further
What animals is Acepromazine contrindicated in?
- Very sick/ moribund animals
- Animals with an AV-block
- Animals with vasodilation/ syncope
- Very excitable animals (results can be uncertain and may not sedate them)
Why should adrenaline NOT be used to treat acepromazine-induced hypotension?
At low doses, adrenaline has a vasodilating effect because of Beta2 receptor agonism
At which receptors is Acepromazine an antagonist?
Antagonist of: Dopaminergic receptor 2 (D2) Histamine receptor1 (H1) Cholinergic muscarinic receptors Alpha1 receptors in the peripheral vasculature
Name a commonly used sedative that does NOT produce analgesia
Acepromazine
Can Acepromazine be administered to food producing species? Why?
No
Acepromazine can be used in dogs, cats and horses with a passport ONLY
What is the administration routes of the alpha2 agonists used in sedating animals?
- IM, IV, SC, PO, acupuncture needles, intranasal, perineurally and epidurally
What is the distribution of the alpha2 agonists in the body?
- Highly lipophilic
- Cross the BBB
- Highly protein bound
Where in the body are the alpha2 agonists metabolized?
Liver: by P450 pathways
Where in the body are the alpha2 agonists excreted?
- Primarily the kidneys
- the rest in the feces
Where in the body can the different Alpha 2-receptos be found, thus where the alpha2 agonists may take effect?
Alpha2 receptors can be found in: pre, post and extra-synaptic locations
Alpha2a: cerebral cortex, brainstem, locus coeruleus, dorsal horn
Alpha2b: vascular endothelium, thalamus
Alpha2c: spinal cord
Alpha2d: similar to A in location and function
note: the alpha2 agonists bind to the alpha2 receptors mainly on the pre-synaptic locations and inhibit the opening of Calcium channels and inhibiting the excitatory nerve impulses/ release of catecholamines
What are the effects of the Alpha2 agonists on the CNS, Cardiovascular System, GIT, respiratory system, kidney and urethra, and pancreas?
- CNS: profound sedation, anxiolysis and anti-depressant activity, supra-spinal analgesia and centrally-mediated bradycardia
- CVS: peripheral vasoconstriction, increased systemic vascular resistance and hypertension, this then causes a reflexive bradycardia in response to the vascular resistance, thus causing a marked reduction in the cardiac output and corresponding reduction in tissue oxygenation. After the initial hypertension, the body works to reduce the blood pressure to normal levels
caution: the use of anticholinergics to combat the bradycardia can lead to fatal arrythmias
- Respiratory System: reduced RR. In small ruminants profound bronchoconstriction occurs, followed by pulmonary hypertension and pulmonary edema which is usually fatal.
Will also cause profound muscle relaxation, and in brachycephalic breeds muscle relaxation of the head and neck can lead to obstructive airways and an inability to ventilate and oxygenate - Kidney: Anti-ADH effects –> increased urine production
- Urethra: Decreased urethral sphincter tone, which can allow for urine to leak out
- Pancreas: Reduced Insulin secretion leading to hyperglycemia, which can also increase urine production
GIT: Reduced motility, secretions and blood flow to GIT, also reduced LOS tone which can predispose patient to regurgitation
Uterus: stimulate the myometrium and must be avoided in pregnant animals (esp in the 3rd trimester)
Are the alpha2 agonist considered to be an analgesic?
Yes, with primarily spinal origin, they have a synergistic effects with opioids BUT, they are NOT suitable as a sole-analgesic and therefore need to be used as part of a multi-modal approach
What animal species is the alpha2 agonist Xylazine used in?
Cattle: but are very sensitive and require lower doses
Sheep and Goats: Hypoxemia and death can occur
Horses: spasmolytic and analgesic effect good for visceral pain (colic)
What animal species is the alpha2 agonist Detomidine used in?
Horses:
IV = infusion intraoperatively to maintain sedation or for standing sedation
Oral = for minor handling procedures like clipping
Cattle: sedation
note: can be used on pregnant animals
caution: not to be used with potentiated sulphonamides in horses as it can cause cardiac arrhythmias
What animal species is the alpha2 agonist Romifidine used in?
Horses: longest duration of action and provides the least amount of ataxia in horses and is often used intraoperatively
What animal species is the alpha2 agonist Medetomidine and Dexmedetomidine used in?
Small animals: have profound CVS effects (vasoconstriction, hypertension, bradycardia) which can deter vets
Can also cause vomiting
BUT are considered analgesic and appropriate for multi-modal analgesic protocols
What animals should you avoid alpha2 agonist in?
- Any animal with cardiac disease e.g. bradycardia or arrhythmias
- Pregnant animals
- Moribund or very sick animals
What happens if an animal has an overdose of alpha2 agonist?
- Can be reversed! Atipamezole (Antisedan)
other reversal agents include Yohimbine and Tolazoline
Which alpha2 agonist agent is appropriate for the use in pregnant cattle?
Detomidine
Which alpha2 agonist agent is the longest acting and causes the least ataxia in horses?
Romifidine
What causes the profound bradycardia observed when alpha2 agonists are used?
Peripheral vasoconstriction, increased systemic vascular resistance and hypertension, this then causes a reflexive bradycardia in response to the vascular resistance, thus causing a marked reduction in the cardiac output and corresponding reduction in tissue oxygenation
Which alpha2 agonist is appropriate for use in horses with colic due to its visceral analgesic properties?
Xylazine
What are the administration options for Benzodiazepams?
IV, PO, Per rectal
caution: ideally not IM because of side effects and poor absorption from IM
What is the distribution of Benzodiazepams within the body?
- Highly protein bound
- Highly lipophilic
- Can cross the BBB
Where in the body are Benzodiazepams metabolized and excreted?
Metabolized in the liver
Excreted in the urine
Which receptors do the Benzodiazepams bind to and how do they work?
- Bind to GABAa receptors and work to enahcne the binding of GABA to its receptor
- This causes a hyperpolarization of the post synaptic membrane, leading to a decrease in neuronal transmission and excitability
What are the effects of the Benzodiazepams on the CNS, CVS and Respiratory system?
- CNS: anxiolytic, sedation (unreliable), centrally-acting muscle relaxation, anti-convulsant, appetite stimulation (in cats) and cause a retrograde amnesia
- CVS: minimal effects, with some vasodilation
- Respiratory: very little depression
Are Benzodiazepams considered to be analgesic?
No
If an animal is overdosed on Benzodiazepams, what can be done?
- Can be reversed: Flumazenil, which is an inverse agonist at the GABA receptor
note: Flumazenil administered on its own can lead to convulsions and anxiety
caution: resedation can occur due to the longer action of the Benzodiazepam compared to Flumazenil, and thus repeated doses may be necessary
Is Flumazenil (Benzodiazepam reversal agent) licensed for use in food-producing species?
No
Are alpha2 agonists licensed for use in food-producing species?
Yes
What licensed version of Diazepam is available in Ireland?
Diazedor
This particular type is solubilized in propylene glycol
What is the administration route for Diazedor?
Licensed for IV use only
What drug interactions are present with Diazepam?
Metabolism of Diazepam is inhibited by microsomal enzyme inhibitors such as: Cimetidine, erythromycin and omeprazole
What are the administration routes for Midazolam?
IV, IM, SC and intranasal
In what circumstance is Midazolam more suitable than Diazepam?
CRI
What animal species are the Butyrophenones used for to achieve sedation?
Pigs
Which Butyrophenone is licensed for use in pigs in Ireland?
Azaperone
How is Azaperone administered?
IM injection
important: once adminstered, the pig should NOT be disturbed for 30 mins
Where is Azaperone metabolized?
Liver
Where is Azaperone excreted?
Primarily urine
about 13% in the feces
What are the effects of Azaperone on the CVS and CNS?
CNS: anti-emetic and causes sedation
CVS: little effect, but may cause hypotension and have anti-arrhythmic effects
Is Azaperone considered to be an analgesic?
No
What are the side effects associated with Azaperone administration in pigs?
- Transient salivation
- Piling
- Panting
- Shivering
What agents are suitable for premedication of pigs prior to a surgical procedure?
- Azaperone + Butorphenol + Detomidine
- alpha2 agonists are usually preferred though, and do so through the cascade
Which agents may be used to antagonize the effects of midazolam in horses?
Flumazenil
Why is the IM route administration not recommended for injection of diazepam presented as an emulsion e.g. diazemuls?
ideally not IM because of side effects and poor absorption from IM
What medication can be administered to prevent bradycardia during GIT endoscopy?
Atropine
What medication can be administered to prevent coughing during bronchoscopy?
Butorphenol
What medication can be administered to prevent histamine release during a mast cell tumour removal?
H1 and H2 blockers
- H1 blocker: Acepromazine, Diphenhydramine
- H2 blocker: Cimetidine, Ranitidine, Famotidine
Which group of sedatives provides the widest therapeutic index?
Benzodiazepines: Midazalam, diazepam (valium)
Which group of sedatives provides minimal CVS side effects?
Benzodiazepines: Midazalam, diazepam (valium)
Which group of sedatives provides minimal Respiratory side effects?
Acepromazine and Butyrophenones (e.g. Azaperone)
Which group of sedatives is considered the most reliable?
Alpha 2 agonists:
- Xylazine, detomidin, romifidine
- Medetomidine and Dexmedetomidine
note: following stimulation though, the animal can sometimes wake up, bite and then fall back to sleep
Which group of sedatives provides analgesic?
Alpha 2 agonists:
- Xylazine, detomidine, romifidine
- Medetomidine and Dexmedetomidine
note: the way we get around by using the other sedatives is by combining with an opioid. Even with alpha2 agonists, we still use a multimodel approach to analgesia
Which group of sedatives has a reversal agent?
- Alpha 2 agonists (Atipamezole: Antisedan)
- Benzodiazepines (Flumazenil)
What are the main uses of Acepromazine, in dogs and cats?
- Sedation and premedication (+/- opioid)
- Long term sedation post-op
- Travel sickness (gel-like oral paste)
What are the main uses of Acepromazine, in horses?
caution: ONLY horses with a passport can have ACE
- Sedation and premedication (+/- opioid)
- Clipping, grooming and travel: does NOT cause sweating unlike the alpha2 agonists
- Improve blood supply via vasodilation to prevent post-op myopathy
Can Acepromazine be used in farm animals?
No, ACE is not licensed for use in farm animals, hence why only horses with passports can be given ACE
What are the cautions associated with using Acepromazine in dogs? (6)
- dogs with uncorrected hypovolemia/ dehydration
- Brachycephalic breeds: cause excess sedation and respiratory obstruction
- Boxers: high doses will cause syncope
- Giant Breeds: long duration of action
- Dogs with MDR 1 gene mutation: excessive sedation
- Dogs with epilepsy: might reduce the epileptic threshold
note: this doesn’t mean ACE cant be used in these dogs, it must be used in small or very small doses
What are the cautions associated with using Acepromazine in horses?
- In males, it can cause priapism and penile prolapse
What are the main uses of alpha2 agonists, in dogs and cats (and rabbits)?
- Sedation and premedication (+/- opioid)
- Intra-op CRI to reduce inhalation agent needed
- Post-op CRI for analgesia and sedation
What are the main uses of alpha2 agonists, in horses and farm animals?
- Sedation and premedication (+/- opioid)
- Intra-op CRI to reduce inhalation agent
What are the main uses of benzodiazepines, in dogs and cats?
- Premed or sedation of very young, very old and sick patients: causes a paradoxal excitement in healthy young/ adult dogs and cats
- Co-induction agent with propofol, ketamine or alfaxalone
- Treatment of seizures
What are the main uses of benzodiazepines, in horses?
caution: horse must have a passport
- Co-induction agent with Ketamine to improve muscle relaxation and conditions for endotracheal intubation
- Sedation of foals
Can benzodiazepines be used in farm animals in Ireland?
No, they are not licensed for use
What are the main uses of butyrophenones, in pigs?
Only Azaperone is available in Ireland
- Premedication and sedation of pigs
What is the reversal agent for dex(medetomidine), and how should it be used in dogs and cats?
Atipamezole
- Post-sedation: use full dose IM to wake up dog. use half dose IM to wake up cat
- Post general anesthesia: draw up full dose, dilute in 5-10mls of saline, then give 1/4 aliquots IV to allow for a slower/ smoother recovery
What are the 2 anticholinergic agents used in vet practice?
- Atropine
- Glycopyrrolate
What are the main uses of the anticholinergic agents?
- Prevent and treat bradycardia
- To reduce saliva production
- To induce bronchodilator and pupil dilation
- To treat some types of heart blocks
- To treat organophosphate poisoning
When should anticholinergic agents be avoided?
- Animals with pre-existing tachycardia
- Glaucoma
- Breeds of dogs that are naturally slobbery- saliva production doesn’t reduce, it just thickens
- Horses: atropine should be avoided as it causes pupil dilation and blurred vision, which can spook the horse (use Glycopyrrolate instead)
- Horses: both atropine and Glycopyrrolate can reduce gut motility and create signs of colic
- Farm animals: not licensed for use
- AVOID their use with alpha 2 agonists
A very lively and excitable 1 year old Husky comes in for anesthesia for her routine spay surgery, she has no IV cannula and therefore premeds need to be given IM. Which meds are most suitable for sedation?
- ACE + opioid
OR - (Dex)medetomidine + opioid
Potential opioids include:
Morphine: analgesic + sedation, may vomit
Methadone: analgesia, poor sedation
Pethidine: analgesia + sedation, short duration of action
A 1 year old golden retriever comes in for anesthesia for her routine spay surgery, she DOES have an IV cannula and therefore premeds can be given IV. Which med is most suitable for sedation?
- ACE (at half dose because goldens are not that excitable and we are giving IV, not IM)
- (Dex)medetomidine (at a reduced dose, as we are giving IV, not IM)
A 3 year old male tabby cat is suspected to have a dislocation of the femoral head. There are no obvious other injuries. Radiographs are needed and no IV cannula has been placed. Which med is most suitable for sedation?
- ACE or (Dex)medetomidine + opioid + ketamine
Potential opioids include:
Buprenorphine: works well in the cat
Morphine: analgesia + sedation, may vomit
Methadone: analgesia, poor sedation
Pethidine: analgesia + sedation, short duration of action
A 4 year old gelding that has been lame for several weeks but otherwise well. Does have an IV cannula in place and needs to be anesthetized for arthroscopy. Which med is most suitable for sedation?
- ACE + alpha2 agonist + opioid
1) ACE (always)
2) followed by an alpha2 agonist (Xylazine, detomidine or romifidine)
3) Opioid (Morphine or butorphanol)
Induction is then with Ketamine + Diazepam
