Premedication Flashcards
Aims of premed?
- reduce anxiety (stress hormones affect reocvery and healing)
- facilitate handling
- contribute to peri-operative analgesia (pre-emptive analgesia, usually opioids)
- facilitate smooth induction, maintainence and recovery (before anaesthesia fully set in, excitement can be seen)
- reduce dose of anaesthesic drugs (and hence side effects)
- reduce risk of specific complications
What are anticholenergics used for? Common nowadays?
- counteract secretions (esp airways)
- usually only when vagus stimulated or vagomimetic drugs (opioids used)
- resuscitation
anjuncts to antagonism or muslce blockers - used to be used routinely, less common now
Main effects of anticholinergics?
- ^ HR
- bronchodilation
- v secretions (watery part, so become more viscous)
- mydriasis (^ pupil size)
- v GIT motility
Give 2 common anticholinergics.
Atropine - crosses BBB so can cause excitement - rabbit has atropine esterase so can break down Glycopyrrolate - lower magnitiude ^ HR - longer acting - NOT LICENSED for use in animals
Define anxiolytics
- calming effects
- less interest in environment
- still aroused by stimuli
- tranquilisers/neuroleptics
Define sedatives
- calming efffect
- less responsive to sstimuli (pain, loud noise etc.)
- sleepiness
- some have analgesic properties (eg. opioids)
Define narcosis
- drug indiced deep sleep
- not easily aroused
Define hypnosis
Artificially induced sleep
- broader term
- eg. rubbing chickens on the neck
5 main classes of sedatives ?
- Phenothiazines
- Butyrophenones
- Benzodiazepines
- a2 adrenergic agonists
- opioids (?)
Phenothiazines - drug properties and impacts clinically? How are they excreted?
- highly protein bound (so if hypoproteinaemic will have less protein bound drug circulating)
- lipophilic (cross palcenta and BBB)
- hydrophilic (IM absorption good)
- hepatic metabolism (may last longer if liver or kidney function impaired)
- excretion via urine and bile
How do phenothiazines cause calming effect?
- blockade of DA-Rs in CNS
What effects do phenothiazines potentiate?
CNS depressant effects of other drugs
- opioids
- anaesthetics
What side effects may phenothiazines have at high doses?
> Extra-pyramidal effects - fine motorr control impaired - ataxia - restlessness (annoying, not serious) > Peripheral vasodilation - blockade of a1 Rs > anti-emetic - inhibition in CTZ of DA, H1, Ach > Anti-histaminic effects - H1-R blockade > Anti-muscarinic effects - anti-spasmodic in GIT >Hypothermia - depression of thermoreg centre - vasodilation
What is the most common and only licensed phenothiazine in UK? Other potential drugs?
> Acepromazine most common
- Promethazine (Phenergan) mainly used for anti-nausea in humans
- Chlorpromaine (Largactil) mainly used as anti-psychotic in humans
Good aspects of ACP? (Acepromazine)
- Anxiolytic at low dose, Sedative at high dose
> Long duration of action - anti-arrythmic (reduce activity SNS, membrane stabilising properties -> local anaesthetic effect, blockage cardiac a adrenoceptors. Less important now but useful esp. in horses
- may be absorbed PO (varibale absorption)
Down-sides to ACP
- hypotension (suppressing SNS< blockade of a1Rs)
- syncope (esp. brachycephalyic breeds, due to hypotension and bradycardia)
- relaxation of cardiac sphicter -> regurgitation and reflux
- decreased PCV and TS (dogs, cows and horses demonstrated, due to vasodilation or splenic sequestration?)
Annoying aspects of ACP?
- late duration of action (wait 30mins even IV)
- larger animals more sensitive (dose body surface area rather than weight?)
- concomitant use with adrenaline can cause vasodilation (ACP blocks a1-Rs (-> vasodilation) low dose adrenaline may lead to unoppoosed b2 activity -> further vasdiltion
How MAY ACP affect seizures?
POtentially lowers seizure theshold but propbably not - severala papers show otherwise
How may ACP affect thrombosis?
- decreased platelet count
- poor coagulation transiently only
What test should ACP not be used prior to?
intra-dermal skin tests
- anti-histamine effects
What drugs may ACP potentiate the action of ? How?
Organophosphates
- reversible inhibition of acetylcholinesterases
- beware recent ectoparasiticides
How may ACP cause problems in breeding animals?
- relaxation of retractor penis m
- mainly stallions, also geldings
- priapism reported
- may result in trauma/paraphimosis
Which animals should ACP not be given to?
- extremes of age
- renal/hepatic disease
- hypovolameia (except cardiogenic shock as may be helpful here)
- brachycephalic breeds
- breeding stallions
Which receptors do butyrophenones act on? What are their actions?
- mostly same as phenothiazines
- dopamine antagonism -> sedation
- antiemetic
- vasodilation and hypotension
What is the one butyrophenone licensed in the UK? What is it licensed for?
Azaperone
- healthy animals only
- sedation and behaviour modification (aggression control when mixing new pigs_)
Pharmacodynamics of azaperones?
- peak sedation 15-30ins IM
- Duration of action 2-3hrs
Physiological effects of azaperone?
- v HR, CO, ABP
- impaired thermoregulation (mild effects if used alone)
Brand name of azaperone?
Stresnil
What is Azaperone likely combined with?
- ketamine for anaesthesia or immobilisation
- opioids for painful diagnosics/minor surgical procedures
How is azaperone metabolised and excreted?
- Hepatic metabolism to inactive metabolites
- Renal excretion
What are neuroleptoanalgesics? Which is the only one licensed in the UK? For which species?
- combination of anxiolytic and analgesic (Hypnorm, Innovar Vet [droperidol and fentanyl, USA license = hypnorm], Immobilon [ACP and etorphine, extremely potent, used for large wild animals])
> Hypnorm (fluanisone and fentanyl)
> licensed UK for.. - mice, rats, rabbits and guinae pigs
- diagnostics and minor surgery or major surgery with BDZs
Are benzodiazepines licensed in the UK? Are they used commonly?
- None licensed for vet use
- Used very commonly
Most commonly used benzodiazepines?
- Diazepam
- Midazolam
- (Zolazepam may be seen some places)
How do benzodiazepines work?
- potentiate effects of GABAa (inhibit CNS activity)
> allosteric modulation
> increase affinity and action of GABA (Inhibitory NT that ^ Cl conductance) - only works in presence of GABA
Main actions of bezodiazepines?
- anxiolytic
- anticonvulsant
- skeletal muscle relaxation
- anterograde amnesic
Side effects of Benzodiazipines?
- minimal CV and resp depression (mainly with other drugs exacerbated)
- induction of liver enzymes (may ^ metabolism of other drugs)
- possibility of paradoxical excitement (combine with something else to mitigate potential for this?)
What is the most common benzodiazepine ANTAGONIST used? Onset of action and elimination half life?
Flumazenil
- quick onset of action (5mins)
- short elimination t1/2 (1 hr in dogs) so unwanted signs of initial sedative may return
- may facilitate seizures in predisposed animals
Uses of benzodiazepines?
> convulsions/status epilepticus - not with hepatic encepalopathy > axiolytic/sedative > muscle relaxation - tetanus - urolithiasis (skeletal m. in uretrha) > with opioids for induction or enhanced sedation in anaesthesia > to counteract ketamine effects of muscle rigidity > behaviour modification
How can diazepam be administered?
- PO, IV, rectal/intracloacal
- IM maybe, poor absorption
What side effect can diazepam have in cats? Is this common?
Fulminant hepatic failure if given PO
- rare
What is another efect of diazepam in cats?
Appetite stimulant very effective
What are the 2 injectable forumlations of diazepam?
> Valium: Propylene glycol solvent (can cause pain on injection and haemolysis)
Diazemuls: Intralipid (milder formulation)
What are the metabolites of diazepam like?
Active so shouldn’t be given as a CRI
How does midazolam compare to diazepam in potency, time of action and administration routes?
- 2x as potent
- shorter acting
- PO, IM, IV, intranasal/transmucosal
- water soluble so doesnt have same problems with IM injection as diazepam
How do the metabolites of midazolam compare to diazepam?
not as active so can be given as a CRI
Egs. of a2-adrenoceptor agonists?
- xylazine
- detomidine
- romifidine
- medetomidine
- dexmedetomidine
Where are a2 adrenoceptors located? What are the actions of a2 agonists?
Everywhere! Pre, post and extra synaptically
- central and peripheral
> Pre-synaptic DECREASE the release of norepinephrine and v SNS activity
Pharmacodynamics of a2 ags? Efffects of this?
> high lipophylicity
- cross BBB (good)
- cross placenta (can be bad)
- cross mucous membrances (if squirted in eye can affect vet!)
Where are a2 ags metabolised and excreted?
Metabolised inthe liver excreted by the kidney
Effects of a2 ags
- Sedation
- dose dependant DURATION
- synergistic with opioids
What is a down side to a2 ags sedation?
- Able to rouse momentarily (if aggressive can come round and bite if stimulated)
- Very stressed patients may not work on until they calm down
Can a2 ags be given as a CRI?
Yes
How do a2 ags interact with anaesthetics?
> anaesthetic sparing
- IV agents should be given at lower doses as v HR caused by a2 ags mean it takes a lot longer for drug to distribute around the body
- 50-70% sparing
- can give as CRI
How may a2 ags affect the brain?
May be neuroprotective (not proven)
- reduce neuronal death by causing vasoconstriction and reducing ICP
- except for in DISEASED areas of brain - this can be useful, termed robin hood effect - allows vasodilation in diseased areas only thus ^ healing
Do as ags provide analgesia?
Yes
- mostly visceral, some superficial
- some have local anaesthetic properties (xyalzine if given as an epidural)
Side effects of a2 ags in CV system? How is this seen clinically?
- initial hypertension (vasoconstriction, stimulation of vascular a2 adrenoceptors)
- reflex bradycardia (vagally mediated) Sympatholysis
- hypotension potentially due to v NAdr release
> Pale/cyanotic mms
> Pro-arrythmic: bradyarrythmias and AV block
Side effects of a2 agonists in respiratory system?
- RR reduced, TV increased = minute volume maintained, no effects
- small ruminants (esp sheep)pulmonary resistance ^ -> pulmonary oedema formation and hypoxaemia
Side effects of a2 agonists in endocrine system?
> Diuresis due to v production and responsiveness of ADH
Insulin resistance -> hyperglycaemia
- Interference with RAAS
How do a2 ags affect the genito-urinary system?
- ^ uterine tone (can cause abortion) demonstrated in sheep
- vasoconstriction may affect o2 delivery to foetus
- can cross placenta
How do a2 agonists affect GIT?
- v motility and blood flow
- LOS tone reduced
- possible emesis esp. cats
How do a2 ags affect thermoregulation?
- central v heat production
- decreased heat loss? (look up)
How do a2 ags affect haematological parameters?
- v PCV and TS
- enhanced platelet aggregation?
How can a2 ags affect the eyes?
- v intraocular pressure
Which species if xylazine licensed for use in? How does species senstivity differ?
Dog, cat, horse, cattle
Sensitivity:
Ruminants > Horse/Dog/Cat > Pig
What effect does xylazine commonly have on cats?
EMesis
What is the t1/2 of xylazine like?
Short
WHich species is detomidine licensed for use in? ROA? (routes of administration)
Horse and cattle
- IV, IM and transmucosal in the horse
How does t1/2 of detomidine compare to xylazine?
longer action than xylazine
Which species is romifidine licensed for use in?
horses
How do the effects of romifidine compare to other a2 agonists?
Similar profile to detomidine
- produces less ataxia
What are medetomidine and dexmedetomidine?
Isomers of each other - one is active
Which species are medetomidine and dexmedetomidine licensed for use in?
Dogs and cats but used in many species
How is dexmed dosed in dogs?
to BSA not weight
What drugs can be used to antagonise a2 ags? What may overdose of these drugs cause?
- tolazoline
- yohimbine
- atipamezole
> overdose = excitement
Which is the most selective a2 antagonist (ie. a2 ag antagonist) available? ROA?
Atipamizole given IM
Which species are more senstitve to atipamizole?
cats
Which drugs is atipamizole most suitable for?
Newer a2 agonists
What are the main differences between different a2 agonists?
Selectivity for a2 receptor resulting in different levels of side effect
WHat is premedication?
Any medication prior to anaesthesia to facilitate peri-anaesthetic period
- long acting drugs may span whole period (up to 48hrs post-op)
- animals should always be maintained under observation
