Sedatives and Opioids Flashcards
describe the reasons for premedication (7)
- facilitate restraint
- anxiolysis
- muscle relaxation
- pre-emptive analgesia
- decrease required induction and maintenance anesthetics
- smooth induction
- modulate autonomic reflex activity
categorize the drugs used for premedication based on class and drug enforcement agency (DEA) scheduling
5 classes
1. phenothiazines
2. alpha-2 agonists
3. opioids
4. benzodiazepines
5. anticholinergics: now only if indicated by patient blood pressure and heart rate
describe the 5 DEA scheduling levels
Schedule 1:
-no currently accepted medical use; high potential for abuse (ILLEGAL); heroin, LSD< marijuana, ecstasy, peyote
Schedule II:
-high potential for abuse, but do have a medical reason for use
-pure mu agonists
Schedule III:
-moderate to low potential for dependence or abuse
-ketamin/buprenorphine
Schedule IV:
-low potential for abuse
-tramadol, benzodiazepines, butorphenol, alfaxolone
Schedule V:
-very low potential for abuse
-cough medicine with less then 200mg codeine
propofol and etomidate not controlled!
describe phenothiazines (acepromazine)
- sedative effect via antagonism of dopamine receptors
- label dose is 0.45mg/kg but this is hella high!
-clinical dose is 0.01-0.05mg/kg - does NOT provide analgesia
- onset of action takes up to 20 min and duration of action is 6-8 hours (long! but variable based on metabolic rate)
- there is no reversal and no way to increase clearance so if overdose = fucked until patient clears it itself
- can give IV, IM, SQ; can be mixed with other drugs
- NOT controlled by DEA
describe the effects of acepromazine on the body (pharmacodynamics)
CNS: dose dependent sedation
cardiovascular: vasodilation, unresponsive hypotension, anti-arrhythmic
respiratory: minimal
GI: anti-emetic
other:
-splenic sequestration of RBCs (can decrease PCV 20-30%)
-anti-histaminic
-paraphimosis in horses: makes it easy to clean sheath and more likely to die from anesthesia than to have its penis amputated!
-decreases platelet aggression: not super clinically relevant
give indications and contraindications (6) of acepromazine
indications: suitable for exercise tolerant adult patients
contraindications/avoid in patients that are/have:
1. neonates
2. geriatric
3. heart disease
4. anemic
5. coagulopathic
6. hypotensive or cardiovascularly unstable
what 4 alpha agonists are available?
- dexmedetomidine: 1620:1
-most frequently used in small animal, available in a gel for thunderstorm anxiety
-much safer than xylazine for small animals - romifidine: 340:1
-associated with less ataxia in horses - detomidine: 260:1
-used frequently in horses, available in a gel - zylazine: selectivity is 160 alpha 2 receptors for every alpha 1 receptors
-oldest, still frequently used in horses, produces largest increase in blood glucose
-ruminants are very sensitive! so only use 1/10 of the equine dose
difference in selectivity for alpha 2 over alpha 1 receptor = slightly different effects despite same MOA
describe alpha 2 agonists
- produce sedation and hypnosis
-activate alpha-2 receptors in locus ceruleus of brain
-decreases norepi centrally and peripherally resulting in sedation and analgesia - rapid onset, short duration
- IV, IM, SQ; can be mixed with other drugs
- reversible
- not controlled by DEA
describe the cardiovascular effects of alpha 2 agonists
phase 1: vasoconstriction causes increased blood pressure causes reflex bradycardia and decreased CO but this is appropriate bc compensation
phase 2: resolution of vasoconstriction, persistent low HR (vagal effect) causes decreased blood pressure and decreased CO- up to 50% (doesn’t really effect them bc they’re sleeping)
arrhythmias:
1. sinus bradycardia
2. AV block (1st, 2nd, 3rd)
3. ventricular arrhythmias
describe respiratory, GI, genitourinary, and metabolic effects of alpha 2 agonists
respiratory: mild respiratory depression and mild pulmonary edema in small ruminants
-all small ruminants will have some measure of pulm edema but will occasionally be life threatening so be ready always! reverse and give furosemide or lasix
GI: decreased motility and occasional vomiting (xylazine to make cats vomit)
genitourinary:
-inhibit ADH = causes patients to urinate
-causes increased uterine wall tone
metabolic: inhibition of insulin release can lead to hyperglycemia
describe indications and contraindications (7) for alpha 2 agonists
indications: suitable for exercise tolerant adult patients
contraindications:
1. neonates
2. geriatrics
3. heart disease
4. anemic
5. cardiovascularly unstable
6. diabetic
7. pregnant
describe reversal agents for alpha 2 agonists
- atipamizole: used to reverse dexmedetomidine (equal volume given even though actual reversal dose given is 10 times admin dose based on concentration)
- yohimbine: used in horses to reverse xylazine, romifidine, detomidine
- tolazoline: commonly used in food animals
what opioids are available?
- morphine
- hydromorphone
- oxymorphone
- methadone
- meperidine
- fentanyl
- buprenorphine
- butorphenol
commonly used for acute pain; animals can become biologically addicted so be careful
how are opioids classified?
based on receptor selectivity
pure mu: morphine, hydromorphone, oxymorphone, methadone, meperidine, fentanyl
-give most profound analgesia, moderate sedation
partial mu: buprenorphine; moderate analgesia (species dependent), moderate sedation
mixed agonist/antagonist: butorphernol, nalbuphine
-mild analgesia (think enough for a nail trim), moderate sedation
describe opioid receptors
- mu, kappa, delta
- present throughout body: brain, spinal cord, peripheral nociceptors, joint spaces, circulating immune cells
- endogenous ligand is endorphins
describe opioids
- mainstay of veterinary analgesia
- CONTROLLED by DEA
-pure mu = Schedule II
-partial mu = schedule III
-mixed agonist/antagonist (butorphenol): schedule IV - diversion is a big problem
- give IV, IM, SQ, transdermal, epidural; can mix with other drugs
- reversible
describe the CNS, cardiovascular, respiratory, and GI effects of opioids
CNS: analgesia with species dependent sedation, euphoria, dysphoria, excitement
cardiovascular: may cause bradycardia (dose and drug dependent)
respiratory: dose dependent respiratory depression
GI: decreased motility, nausea, vomiting
all can cause histamine release! but worse with morphine, meperidine; may see hives, hypotension, hyperthermia, tachycardia
describe specific adverse effects, duration of action, and water solubility of morphine
specific adverse effects: vomiting, histamine release
duration of action: 2-4 hours
water soluble so onset of action is 10-20 minutes, but in epidural space duration of action is up to 24 hours
describe specific adverse effects and duration of action hydromorphone
vomiting, panting, hyperthermia in cats (only opioid that can increase temp!)
duration of action: 4-6 hours
describe adverse effects and duration of actions of meperidine, of methadone, and of fentanyl and of buprenorphine and of butorphenol
meperidine: DOA 1 hour, may cause increase in heart rate
methadone: DOA 1-2 hours, can cause tremendous bradycardia requiring reversal, NMDA antagonist
fentanyl: DOA 30 min; administered as a CRI
buprenorphine: DOA 6-8 hours, mild adverse effects but DEA schedule III!
butorphenol: DOA 1-2 hours, mild adverse effects, causes more sedation than pure mu opioids via agonism of kappa receptors and can be used to reverse pure mu opioids
what is neurolept analgesia?
opiod + major sedative; work synergistically to give more effective sedation and more profound analgesia
can use a lower dose of each drug for the same effect
describe opioid antagonists
- naloxone:
-most commonly used in vet practice
-duration of action is 20-30 min so patients may re-narc when naloxone wears off - naltrexone, nelmefene: longer DOA than naloxone, used commonly in wildlife/zoo immobilization
what are 3 benzodiazepines?
- diazepam
- midazolam
- zolazepam
how do benzodiazepines work?
- causes sedation and anxiolysis via action at GABA receptors
- zolazepam only available as telazol with tiletimine
- midazolam is water soluble:
-can be given IV, IM, SQ and can be mixed with other drugs - diazepam is not water soluble, containing propylene glycol and ethanol
-on admin it burns and has erratic absorption when given IM or SQ and should only be given IV
-should NOT be mixed with any drug other than ketamine - benzodiazepines are CONTROLLED by the DEA; schedule IV
- benzodiazepines do NOT provide analgesia
describe CNS, cardiovascular, respiratory, GI, and musculoskeletal effects of benzodiazepines
CNS:
-depress limbic system, thalamus, and hypothalamus creating a calming effect
-anticonvulsant
-sedation is mild and usually not effective as a sedative in healthy adult patients
cardiovascular: minimal
respiratory: minimal
GI: diazepam is an appetite stimulant in cats
musculoskeletal: causes MSK relaxation
describe clinical utility of benzodiazepines
- good choice for pre-med if
- neonates
- geriatric patients
- debilitated patients
- can cause excitement/dysphoria when used in healthy adult patients
- often used as a co-induction agent with NMDA agonists
describe reversal of benzodiazepines
flumezenil: GAGA receptor antagonist, rarely necessary; usually only if bad trip
how do you choose what drug to use to premed?
- species
- degree of analgesia necessary
- degree of sedation required
- personality of patient (bouncing lab versus calm greyhound)
- concurrent disease processes (avoid morphine in a patient with a mast cell tumor- histamine)
- presence or absence of IV catheter
