Use of Sedative/Premedication Drugs Flashcards
(30 cards)
TRANQUILLIZERS
Classically, ‘sedative’ drugs are defined as TRANQUILLIZERS (reduce apprehension and fear)
Sedatives
- make the animal sleepy, but it is easily aroused
- Sedatives are NOT ANAESTHETICS – there is a limit to their action
Hypnotics
induce sleep and at high doses some may produce general anaesthesia
Alpha-2 agonists Structure
Structure: many (but not xylazine) are based on imidazole
Alpha 2 receptors are associated with sympatholytic properties.
Alpha-2 Agonists in Veterinary Use
(5)
- Xylazine (Rompun, various generics), Routes of administration (ROA): IV, IM, epidural. Used in all species (except pigs). Very low doses needed in ruminants.
- Detomidine (Domosedan or Dormosedan in USA). Generics include Equimidine, Domidine, Medesan. ROA IV, IM, trans- mucous membranes (TMM), epidural.
- Romifidine (Sedivet - horses). ROA IV, IM. Main use in horses – less ataxia than others (also less sedation and less analgesia). Longest duration of effect.
- Medetomidine (Domitor; Sedator), ROA IV, IM, TMM. Epidural. Licensed in dogs and cats. Wide use in rodents etc. Also has been used in all domestic species. Very powerful sedative/hypnotic/analgesic.
- Dexmedetomidine (Dexdomitor) – launched in 2008. Watch this space.
Alpha-2 Antagonists in Use
- Atipamezole (Antisedan. Generics include Atipam) Veterinary Licence in UK and most countries world-wide.
- Yohimbine (veterinary authorisation in many countries but not UK), idazoxan and analogues (no licence - some ‘wild-life’ use).
- Antagonists are used to reverse sedative and other actions of alpha2-agonists.
NB. Antagonists have actions of their own: anti-depressant, anti-obesity, aphrodisiac!
List the main cardiovascular side effects of alpha 2 adrenoceptor agonist drugs
- Bradycardia and fall in cardiac output (CO).
- Initially vasoconstriction (peripheral action of drug on the blood vessels) and increase in peripheral resistance.
- Initial hypertension, then slight fall as CO drops.
- Much later (? after sedation has waned) long lasting centrally mediated vasodilation and some hypotension.
Alpha-2 Agonists and Colic
- Alpha 2 agonists are excellent analgesics in colic, possibly partly because they inhibit gut motility.
- They cause marked bradycardia.
- Vasoconstriction (and hence colour of mucous membranes) may be seen in early colic (due to pain) but can also be caused by alpha-2 adrenergic agonists.
- Splenic contraction means that they cause a small rise in PCV.
- All these changes must be taken into account if a horse with colic has been given an alpha 2 agonist.
Alpha 2 adrenoceptor agonists inhibit ADH (arginine vasopressin) release. What practical effect does this have?
Name one clinical condition where, as a result of this effect, there is an absolute contraindication to the use of alpha 2 agonists.
- Reduced ADH (arginine vasopressin) release will increase urine production.
- Main CI is blocked urinary outflow (most commonly a blocked urethra).
Benzodiazepines
(Mech of Action)
- Agonists act at several sites in CNS, especially cerebral cortex, limbic system and midbrain.
- Benzodiazepines are agonists for the BZ1/BZ2 sites on the GABAa receptor, producing enhanced chloride conductance; they alter receptor structure to increase the number of chloride channels opened by the binding of GABA.
- No effect on peripheral GABAa receptors (because of the absence of a benzodiazepine binding site), central GABA receptors (calcium and potassium channels) and glycine receptor sites.
List five major actions of benzodiazepines.
- Anti-anxiety
- Hypnosis (sleep)
- Muscle relaxation
- Anti-convulsant,amnesia
- Also used IV to stimulate appetite in cats.
Which benzodiazepine is water soluble and non-irritant to the vein?
Midazolam
Name an antagonist to diazepam
- Flumazenil (trade name Anexate) available in UK.
- Sarmazenil available in some other European countries.
Phenothiazines and Butyrophenones
Mech of Action
- Antagonists for dopamine-2 (DA2) receptors in the CNS.
- Principal sites of action believed to be the reticular activating system (RAS) and hypothalamus.
- Side effect is alpha-1 receptor blockade – causes hypotension and is probably contributes to sedative effects.
At what receptors does acepromazine exert its effect? Is it an agonist or an antagonist?
- Major effects as an antagonist at dopamine and alpha-1 adrenoceptors.
- Minor effects at a number of other receptors.
Which other group of sedative drugs exerts its effect at the same receptors as acepromazine?
- Butyrophenones
- Butyrophenones include azaperone (licensed for use in pigs) and fluanisone (a component of Hypnorm, licensed for use in rabbits).
By what routes can acepromazine be administered? For each route, indicate the time from administration until maximal effect is achieved.
- IV 20+ mins
- IM/SC 40+ mins
- Oral 40+ mins (horses are very sensitive to oral doses!)
List FOUR contraindications or partial contraindications to the use of acepromazine.
Only ABSOLUTE CI would be severe liver failure.
Routinely not used if there is:
- Hypovolaemia (blood loss, toxaemia, shock etc) as vasodilation will make animal faint – however, once fluid deficits have been replaced may use with care to counteract vasconstriction of shock, although better agents exist to do this.
- Use with care (low doses and be ready to counteract side effects) in Boxer dogs (vasovagal bradycardia and fainting), giant breed dogs (deep long lasting sedation), stallions (priapism a very rare complication, treatable if noticed as it happens).
- Product information CI epilepsy, but neurologists argue this one
What is the antagonist to acepromazine?
- None are available
- If serious hypotension does occur after giving acepromazine, treat with IV fluids.
- Do not give adrenaline!
- Acepromazine causes alpha-1 adrenergic blockade, so that adrenaline may stimulate an unopposed beta-2 adrenergic receptor action. This effect will increase vasodilation and so hypotension may become even worse
Which agent has marketing authorisation as a sedative agent in the pig?
- Azaperone
antagonist for Medetomidine
- antagonise with Atipamezole
- Atipamezole is a specific alpha 2 adrenoceptor ANTAGONIST
What are good Sedative Drugs indicated for Horses?
- detomidine and butorphanol
- Xylazine
- Romifidine
In a Detomidine and Butorphanol combo, what is the purpose of the opioid?
- Butoprhenol is the the opioid
- to reduce the reaction to touch
List THREE methods that you could use to reduce the dose of induction agent required in a patient with cardiovascular disease, with the aim of minimising the adverse cardiovascular effects on the patient
- Use premedication: drugs such as opioids provide analgesia, but they also produce good sedation with minimal cardiovascular side effects.
*However, you should be cautious about using medetomidine: although it provides profound sedation and reduces the dose of induction agent required, it also has profound adverse cardiovascular effects.
*ACP is fine to use in some types of cardiovascular disease but should be avoided in others.
- Use a co-induction technique, combining your induction agent with a benzodiazepine (diazepam or midazolam).
*Benzodiazepines can cause excitement if administered alone as a pre-med in healthy patients but this problem is minimised if they are used at the time of induction. Benzodiazepines reduce the dose of induction agent required and have minimal cardiovascular side effects.
- Administering the induction agent slowly to effect (rather than giving a rapid bolus) will also often reduce the dose which is required for induction.
