Test 1- Pre-meds Flashcards
Purposes of premedication
Sedation, analgesia
Anesthetic sparing effect
Reduction of stress and catecholamine release Reduction of O2 demand
Increased safety for animals and humans!
Decreasing parasympathetic tone
Others: antibiotics, antihistamines
Anticholinergics
Atropine and Glycopyrrolate
Atropine
Lipid soluble
Absorbs well IM, SC, PO
Crosses the BBB and placental barrier Dose: 0.01 – 0.04 mg/kg iv
Glycopyrrolate
Water soluble
Absorbs slowly IM, SC, PO
Onset of effect is slower than atropine even IV Doesn’t cross the BBB and placental barrier
Dose: half of that of atropine
Advantage over atropine is debated
What are indications of anticholinergics?
Increasing heart rate
o Treatment of opioid induced bradycardia
o Prevention/treatment of reflex bradycardia
o Young animals and brachycephalic breeds
o Routine use is not recommended!
Decreasing salivation and bronchial secretion o Smaller amount but thicker mucus is not better
What are the contraindications of anticholergenics?
Tachycardia
Hyperthyroidism
Most heart diseases
o Except when needed for treatment of bradycardia
Narrow angle glaucoma
CV S/E of Anticholingerics
IT’S ALL ABOUT THE AV NODE!
2o AV block, bradycardia, cardiac arrest Tachycardia, hypertension
SA node: atrial conduction (p wave)
AV node: ventricular conduction (QRS)
Anticholinergics easily affect on the SA node o Lot’s of P waves
Effect on AV node is weaker and comes later o AV blocks, bradycardia (vagal tone increased?)
When the AV node finally conducts o Excessive tachycardia
What can you not use with atropine?
alpha 2 agonist
though you can use medetomidine +atropine— but measure the bp before giving atropine
What are anticholergics used for?
Treatment of bradycardia
Be careful and think before you act!
Is there a problem? Yes or no?
o Consider species, age and disease of the patient.
o Is the patient hypotensive?
o Is the ET CO2 adequate (assuming constant ventilation)?
Treatment plan:
o Drugs: atropine, naloxone, othersH o Dose? Monitoring? Plan B?
Alpha 2 agonists
Strongest available sedatives (except pigs)
Have important cardiovascular side effects
Myriad of other effects
Have specific antagonists
Appropriate use is debated (crashing opinions)
MOA of alpha 2 agonist
Competitive agonist of α2 adrenergic receptors
Location
o CNS: presynaptic membrane (autoreceptor)
o Post-synaptic membrane (vascular smooth muscle) o Extra-synaptic sites (e.g. pancreas, lipocytes etc.)
sedation, vasoconstriction
what are the CNS effects of alpha agonist
Sedative effect is species specific
o Strong: dogs, cats, horses, ruminants o Weak: pigs
Some analgesic effect o Synergistic with opioids
Muscle relaxation
CV effects of alpha 2 agonist
Strong vasoconstriction
Leads to high SVR and BP
Reflex bradycardia develops
Result: low CO and tissue perfusion
BP may decrease later on (hypotension)
Common recommendation
o Don’t use atropine
o If necessary, give specific antidote (e.g. atipamezole)
Respiratory effects of alpha 2 agonists
Mild respiratory depression
RR decreases but tidal volume increases
Upper airway resistance increases
o Relaxation of larynx, pharynx and nares o Head dropping in horses: nasal edema
V/Q mismatch in horses
o Low V/Q resulting in decreased PaO2
Mostly with xylazine in sheep
α2 agonists: indications
Sedation of aggressive animals
Sedation in the ICU
Sedation to manage post operative airway
obstruction (e.g. after brachycephalic surgery) Prevention/treatment of seizures (epilepsy)
α2 agonists: contraindications
Too young or too old
Hemodynamic instability
Severely debilitated patient
Not suitable for most risk patients
Available α2 adrenergic agents
Agonists
Xylazine
Medetomidine
Dexmedetomidine
Detomidine
Romifidin
Antagonist
Atipamezole Yohimbine Tolazoline
α2 agonists
Specificity to α2/α1 receptor differ
Medetomidine >>> detomidine > xylazine
Most effects are mediated by α2 receptors
The main effects are very similar
Pharmacokinetics and purchase price may differ
Xylazine
Dog: 0.25 – 2 mg/kg
Horse: 0.5 – 1 mg/kg
Cattle: 10% of the horse’s dose
Small ruminants: between dogs and horses The dose of medetomidine does not differ Duration: 20-40 min
Detomidine
Used for large animals
Dose: 0.01-0.02 mg/kg
Route: IM, IV, sublinqual
Duration: 90-120 min
What is the main indication to use an anticholergic during anesthesia?
Increase HR and inhibit PSNS
What are the main indications to give an alpha 2 agonist?
SEDATION
What are the biggest SE of alpha 2 agonists?
- reflex bradycardia
- vasoconstriction—> decreased CO, decreased tissue perfussion
- increased bp, increased vascular resisitance
Which is more potent dexmedetomine or Medetomidine?
Dexmedetomidine is about twice as potent as medetomidine, but they act the same
Phenothiazines
Acepromazine, (chlorpromazine, etc.)
Acting as antagonist on multiple receptors o Dopamine
o Serotonine o α1
o Histamine
Acepromazine
Long acting drug (depending on dose) o 4–8hours
o 48 hours for liver patients
o Shorter if given in low doses (e.g. 10 μg/kg)
Phenothiazines: CNS effects
Actions on dopamine and serotonine receptors
Weaker sedative effects compared to α2 agonists
No analgesic effect
Antiemetic effect
Mild respiratory depression
Phenothiazines: CV effects
Actions on α1 receptors
Vasodilation and hypotension
Especially in hypovolemic animals
May cause death of hypovolemic patients
Measure blood pressure, give fluids!
Phenothiazines: indications
Mild sedation for premedication or post OP
Prevention / treatment of opioid dysphoria
Prevention of emesis caused by morphine
Sedation for dogs with laryngeal paralysis
Enhance the sedative effect of xylazine in
horses
Phenothiazines: contraindications
Hypovolemia, hemodynamic instability
Very young or very old patient
Von-Willebrand disease (Doberman)
Boxers may be sensitive (bradycardia)
Breeding stallions
Butyrophenones
Similar drug family to phenothiazines
Drugs: droperidol and azaperone (Stresnil)
Sedative effect is similar to acepromazine
More likely to cause behavioral side effects
Less hypotensive and stronger antiemetic then acepromazine
Less effect on platelets
Anti arrhythmogenic, not seizurogenic
Benzodiazepines
GABA receptor agonists
Sedative, anticonvulsant, muscle relaxant effects
Minimal CV and respiratory effects
No analgesia
Sedative is species specific
Benzodiazepines
Agonists
o Diazepam
o Midazolam o Zolazepam (Zoletil or Telazol)
Agonists
o Diazepam
o Midazolam o Zolazepam (Zoletil or Telazol)
Benzodiazepines: sedation
Species specific effect
Dogs, cats horses: disorientation, excitation may
occur when used alone
Better sedative effects in ruminants, camelids, pigs, birds, and ferrets
Rarely used alone
Benzodiazepines: indications
Premedication: combine with
o Opioids
o α2 agonist o Or both
Induction: combine with
o Dissociative anesthetics (ketamine)
o Barbiturates or propofol
Treatment of seizures (status epilepticus)
Diazepam
Lipid soluble
Formulated in propylene glycol or lipid emulsion
Chemical compatibility is limited
Give slowly IV
Poor absorption and pain on IM injection
Metabolized in liver and duration of action is 1 to 4 hours
Midazolam
Water soluble (no propylene glycol)
Good chemical compatibility
More potent than diazepam
Shorter acting than diazepam
Metabolized in liver, but metabolites are inactive (unlike diazepam).
Can be given IM, IV or via mucus membranes
Better choice than diazepam
Opioids
Exogenous substances that bind to opioid receptors and activate them
Strongest available systemic analgesics
Best choice for treatment of acute pain (e.g.
surgery!)
Decreases the doses of anesthetics
Minimal CV side effects
Suitable for most risk patients
Opioid receptors
μ: strong analgesia, resp. depression, dependency
κ: weaker analgesia
δ: weaker analgesia (human relevance)
Location o Brain
o Spinal cord (dorsal horn)
o Peripheral nerves
o Inflamed organs (e.g. arthritis)
Classification of opioids
Full agonists: activate receptors and trigger full tissue response
Partial agonists: activate receptors but do not trigger full tissue response even at high doses
Antagonists: bind to receptors but do not activate them
These drugs concentration dependently compete for receptor binding
Potency
Potency: tells you the dose
Efficacy:
Efficacy: tells you the strength of the effect
Pharmacokinetics:
Pharmacokinetics: onset, duration of effect, administration strategy etc.
Opioids: CNS effects
Analgesia
o Excellent for acute pain
o Less good for chronic pain
Decreasing the MAC of inhalants
o Species dependent
o Primates > dogs > cats > pigs > horses o May increase the MAC in horses
Sedation depends on
o Species: primates and dogs sedate better o Pain level: stronger if there was pain
Excitation, dysphoria
o Cats may become excited o Horses after high doses
Tolerance
Dependence
Opoids cause what clinic sign?
Opioids may trigger or may inhibit vomiting
They stimulate the chemoreceptor trigger zone
outside of the BBB and may trigger vomiting
After entering the brain they inhibit the vomiting center
Water soluble opioids (morphine) enter the brain slowly: cause more vomiting
Lipid soluble opioids (e.g. fentanyl) enter the brain fast, vomiting does not occur.
Opioids: CV effects
No direct negative inotropy or vasodilation
Indirectly may reduce sympathetic outflow
from the brain and reduce Bp that way
Increase parasympathetic tone and may cause bradycardia, this is treatable with atropine
Suitable for most risk patients
Improves CV function by allowing to reduce the doses of anesthetics
Opioids: respiratory effects
May depress respiration but not as strongly as in humans and primates
Healthy small animals tolerate high doses well
Be careful with combinations and sick patients
Opioids have antitussive effect: therapy
May inhibit airway protective reflexes (e.g. coughing)
Opioids: GI effects
Nausea, vomiting
Defecation
Obstipation
Spasm of the sphincter of Oddi (hepatopancreatic sphincter)
Opioids: other effects
Hypothermia
Post OP hyperthermia (in cats)
Myosis (dogs), mydriasis (cats)
Inhibition of urination
Noise sensitivity
Morphine
Cheap and strong analgesic, water soluble
Slow onset (30-45 min) long duration (4-6 hours)
High individual variability in elimination
Metabolized in the liver to an active metabolite
Elimination is slow in liver and renal patients
May cause histamine release, especially after high iv doses
Duration of epidural analgesia is 12-24 hours
Hydromorphone, oxymorphone
Strong analgesics (full μ agonists)
Duration is about 4 hours
Reliable metabolism
No histamine release
Better choices than morphine
Fentanyl
Strong analgesic (full μ agonist)
Fast onset short duration (15-20 min)
No histamine release
May accumulate after long infusions
Remifentanil
Similarly potent to fentanyl
Very short acting (5 min) and does not
cumulate, ideal for CRI
Metabolized by non-specific esterases in muscles and intestines
Caution: accidental disruption of administration may trigger strong pain
Boluses may cause sudden bradycardia
Butorphanol
Butorphanol is a mu ANTAGONIST and kappa agonist
Weak and short acting analgesic
It may worsen pain sensation in case of strong
pain
May be used for premedication in combination
with benzodiazepines or α2 agonists if there is no
strong pain (e.g. radiology) May partially antagonize full μ agonists
Buprenorphine
Partial μ agonist
Stronger analgesic than butorphanol
Relatively long acting: 6-8 hours
Onset is slow (20-40 min iv)
Often given to cats because may cause less excitation than full μ agonists
The owner of cats may continue giving is via the oral mucosa
Tramadol
Weak analgesic
Metabolizes in the liver and its metabolite is μ
opioid agonist Inhibits
Tramadol itself inhibits NE and serotonin
reuptake (analgesia)
Not scheduled drug
Can be given PO
Opioid antagonists
Naloxone: 30 min duration
o May be used in small animals to reverse respiratory
depression
o Routine use is not recommended (reverses analgesia)
Naltrexone: long acting (~10 hours). Used to antagonize wild animals after long acting opioids e.g. carfentanyl or etorphine
