PreMedication Drugs for the Anesthetic Patient

Lecture 8

Why do we premedicate anesthetic patients?

ease of handling patient

manage expected complications

lower dose of induction and maintenance drugs —> more stable patient

pre-emptive analgesia

smoother recovery period

True or false: One of the benefits of premedication is that there is a synergistic effect from combining drugs which produces better results than a single drug alone.

True

True or false: Pre-emptive analgesia can be used to reduce the amount of analgesics required intra-operatively and postoperatively.

True

True or false: IM or IV administration of premedication is preferred over SQ injection.

True

What IM sites can be used for administration of premedication?

lumbar epaxial muscles on either side of the dorsal spinous processes

semimembranosus/semitendinosus

quadriceps femoris

cervical epaxial muscles

LA patients —> neck “triangle” area

What premedication drug class is preferred to be given only as required during anesthesia and is not routinely included unless high vagal tone is currently suspected or heart rate dependent patient?

anticholinergics (atropine, glycopyrrolate)

What may make anticholinergic drugs ineffective in patients?

hypothermia

What is the only anticholergic that causes pupil dilation, which impairs vision and may lead to poor recovery in some species such as cats?

atropine

Why should we use anticholinergics cautiously in horses and cattle?

high doses inhibit urinary and GI tract mobility, so it may cause colic and rumen stasis

What is the mechanism of action for anticholinergics (atropine, glycopyrrolate)?

antimuscarinic —> competitively inhibits acetylcholine

parasympatholytic

What is the duration of action for anticholinergics (atropine, glycopyrrolate)?

1 hour

What are side effects of anticholinergics (atropine, glycopyrrolate)?

increased heart rate

potential for increased blood pressure

changes to salivary and bronchial secretion consistency

What the mechanism of action for phenothiazines (acepromazine)?

dopamine (D1 and D2) receptor antagonist in the CNS

What is the time to peak effect for Acepromazine?

15 minutes given IV, 30 minutes given IM

How long do effects of Acepromazine last and what makes this concerning?

effects last 4-8 hours and there is no reversal agent

Acepromazine is an alpha 1 adrenergic blocker which causes vasodilation and may lead to what?

hypotension

In what situations should we avoid using Acepromazine?

fractious or aggressive patient or those with high anxeity

liver disease or portocaval shunts

valuable breeding stallions due to potential for paraphimosis (inability to retract penis)

von Willebrand’s disease or other clotting disorders

splenic entrapment of RBCs may complicate diagnostics/surgery

What may occur if you use acepromazine in boxers or boxer mixes?

spontenaous fainting or syncope due to sinoatrial block caused by excessive vagal tone

CV collapse

What class of sedative drugs includes xylazine, detomidine, romifidine, medetomidine, and dexmedetomidine?

alpha 2 adrenoreceptor agonists

What is the overall effect of alpha 2 adrenoreceptor agonists?

sedation, muscle relaxation, and analgesia

What is the mechanism of action for alpha 2 adrenoreceptor agonists?

produces CNS depression by stimulation of pre- and postsynaptic alpha 2 adrenoreceptors in the CNS and periphery

What are the alpha 2 adrenoreceptor antagonists?

yohimbine, tolazoline, and atipamezole

What are the cardiovascular effects of alpha 2 adrenoreceptor agonists?

bradycardia due to increased systemic vascular resistance in the periphery (baroreceptor response!)

1st or 2nd degree atrioventricular block

Which alpha 2 adrenoreceptor agonist can increase cardiac sensitivity to catecholamine induced arrythmias?

xylazine

Should you use an anticholinergic when giving an alpha 2 agonist?

not recommended to give together as a premed

If you are really concerned about the level of bradycardia created by an alpha 2 agonist, what steps should you consider?

1. determine patient’s BP

2. check in with surgeon (has stimulation started)

3. how long since drug’s were given?

If BP is low and it has been 30-45 minutes since alpha 2 agonist administration and surgical stimulation is either not helping or going to take a while to begin —> consider giving an anticholinergic IM or SQ - OR - reversal with atipamezole IM ± anticholinergic

What are behavioral effects of alpha 2 adrenoreceptor agonists?

aggression in horses

if patient is very nervous or excited, may show inadequate repsonse, startle when touched or in response to a loud noise

What are respiratory effects of alpha 2 adrenoreceptor agonists?

hypoventilation or apnea

decreased sensitivity to increased PCO2

horses and brachycephalic animals prone to stridor and dyspnea from upper airway obstruction

sneezing/itchy nose occasionally in donkeys

What are gastrointestinal and renal effects of alpha 2 adrenoreceptor agonists?

decreased gastric acid secretion and GI motility

may cause vomiting in dogs and cats

swallowing reflex obtunded

suppresses insulin release —> hyperglycemia and glucosuria

inhibits anti-diuretic hormone

increases release of atrial natriruetic peptide

What alpha 2 adrenoreceptor agonist has a fast onset within 1-5 minutes and effects lasting 20-40 minutes after IV injection but may induce premature delivery in cattle due to oxytocin like effects?

xylazine

What alpha 2 adrenoreceptor agonist can be given IM or IV, has a slightly longer onset of action compared to xylazine, and has effects lasting 90-120 minutes depending on dose and administration route?

detomidine

What alpha 2 adrenoreceptor agonist is thought to produce less ataxia than xylazine and has effects lasing 45-90 minutes after IV administration, but there is no FDA approved form of this drug in the USA?

romifidine

What alpha 2 adrenoreceptor agonist has a quick onset after IV (1-3 minutes) and IM administration (5-10 minutes), a slightly longer onset of action after transmucosal administration (30-60 minutes), has effects lasting 60-90 minutes, and can be reversed with atipamezole?

dexmedetomidine

What is the dextrorotatory isomer, the active optical enantiomer of medetomidine, that provides similar effect with a lower dose, so less drug must be metabolized by the liver?

dexmedetomidine

What drug has a trade name of Domitor with an onset of action in about 10 minutes after IM administration, and can be reversed with atipamezole?

medetomidine

What is the newer drug on the market that is a mixture of medetomidine and vatinoxan (peripheral alpha 2 antagonist) and labeled for IM use in dogs only?

Zenalpha

What are the four key points of using Zenalpha?

procedural sedation

short onset (5-15 minutes)

short duration (30-45 minutes)

cardiovascular stability/parameters maintained at more acceptable levels

What drug is typically used to reverse xylazine?

yohimbine

What alpha 2 antagonist should be avoided in camelids due to adverse effects?

tolazoline

What alpha 2 antagonist has a higher alpha2:alpha1 selectivity, so it is indicated for the reversal of medetomidine and dexmedetomidine?

atipamezole

What should you know regarding the concentration of atipamezole and dose of dexmedetomidine?

the concetration of atipamezole was formulated so that the volume of injectate is the same (mL for mL) as the dose of dexmedetomidine given

Atipamezole should always be given what route?

IM

What is the mechanism of action for Benzodiazepines?

enhances the activity of the CNS inhibitory neurotransmitter gamma aminobutyric acid (GABA) by binding to a specific site on the GABA(A) receptor, which opens chloride channels and hyper polarizes the membrane

Benzodiazepines have minimal cardiovascular and respiratory effects, but do not provide what?

analgesia

What benzodiazepine must be formulated in propylene glycol to make the drug soluble?

diazepam

Since diazepam must be formulated in propylene glycol, rapid IV adminisration can cause what?

bradycardia, hypotension, or apnea

What is the duration of action of diazepam?

1-4 hours

Why should diazepam never be given IM?

water insoluble (poor absorption and painful if given IM)

What are side effects of diazepam?

increased appetite

paradoxical excitement and aggression

What benzodiazepine is water soluble and more potent that diazepam?

midazolam

What makes midazolam a better choice in sick, debilitated, or older patients?

metabolized in liver, but metabolites are inactive (unlike diazepam), so shorter acting with less rick of accumulation

What can occur when using midazolam in healthy and excited patients?

paradoxical excitement and aggression

What drug is used to reverse benzodiazepines?

flumazenil

Should you give fluamzenil to reverse benzodiazepine effects if the patient is epileptic?

NO

What is the mechanism of action for opioids?

interaction with one or more receptors (mu, kappa) in the brain and spinal cord

coupled to G protein receptors in periphery —> hyperpolarization of membranes and decreased propagation of action potentials

Define affinity.

a measure of the tightness with which a drug binds to the receptor

Define potency.

refers to the concentration of a drug required to produce a given physiologic effect; drugs with higher receptor affinity will exhibit greater potency than those with lower affinity

Define efficacy.

often used to described the maximal level of response a drug can produce

Define intrinsic activity.

a measure of the ability of a drug that is bound to the receptor to generate an activating stimulus and produce a change in cellular actviity

Give an example of a full mu receptor agonist.

morphine, methadone

Give an example of a partial mu receptor agonist.

buprenorphine

Give an example of a mu receptor antagonist.

naloxone

What are CNS effects of opioids?

sedation, euphoria, dysphoria

What are respiratory effects of opioids?

depression of respiratory center response to hypercapnia and hypoxemia, cough suppression, and panting

What is the main cardiovascular effect of opioids?

bradycardia

What are the GI effects of opioids?

vomiting, defecation, salivation, decreased gastric emptying time, and ileus

When giving opioids, miosis occurs in ____ while mydriasis occurs in ____.

dogs; cats

What opioid has a high affinity for mu receptors, is hydrophilic, and causes histamine release and subsequent hypotension?

morphine

What is the duration of action for morphine?

4-6 hours

What is the semi-synthetic pure mu agonist with similar properties to morphine but more lipid soluble and may cause hyperthermia in cats?

hydromorphone

What is the duration of action for hydromorphone?

4-6 hours (3-4 hours if given for acute surgical pain)

What opioid is a synthetic pure mu agonist that is 100x more potent than morphine with a fast onset and short duration due to lipophilicty?

fentanyl

What is the dose of fentanyl?

5-10 mcg /kg IV bolus followed by CRI of 2-20 mcg/kg/hr

What opioid is a synthetic pure mu agonist with similar potency to morphine but causes less sedation and is the least likely of mu agonist opioids to cause vomiting?

methadone

Which opioid is an NMDA receptor antagonist and serotonin reuptake inhibitor?

methadone

What is the duration of action for methadone?

2-6 hours

Which opioid is a mixed agonist-antagonist (kappa agonist, mu antagonist) used for mild to moderate pain but not effective for severe or orthopedic/dental pain?

butorphanol

What is the duration of analgesia for butorphanol?

30 minutes-2 hours

What opioid can be used to reverse sedative or respiratory effects of pure mu agonists?

butorphanol

Are patients likely to vomit after receiving butorphanol?

most often, yes

What opioid is a partial mu agonist that is NOT adequate for severe pain and has a higher receptor affinity and can displace pure mu agonists which makes it difficult to antagonize?

buprenorphine

What is the duration of action for buprenorphine?

long duration of action 4-8 hours, maybe 12 hours depending on dose

What is the onset of action for buprenorphine?

slower onset, 30 minutes to an hour after IV administration

What is the buprenorphine SQ injectable for use in cats for 24 hour surgical pain control?

Simbadol

What is the transdermal buprenorphine for up to 4 days post op pain control in cats?

Zorbium

What drugs are opioid antagonists?

Naloxone

Nalmefene

Nalorphine and diprenorphine

Naltrexone

Which opioid antagonist can be used to reverse pure mu and mixed agonist/antagonists because it has a high affinity for mu and kappa receptors, with a rapid onset (1-2 minutes) and duration of action lasting 30-60 minutes?

Naloxone

Define neuroleptanalgesia.

a state of CNS depression and analgesia produced by the combination of a tranquilizer or sedative and analgesic drug

Give an example of a drug combination providing a moderate sedative level.

acepromazine + opioid

Give an example of a drug combination providing a mild to variable sedative level.

benzodiazepine + opioid

Give an example of a drug combination providing a variable sedative level.

alpha 2 agonist + opioid

What drug combination is called “Kitty Magic” in some practices and is used to produce heavy sedation to anesthesia in cats having castration performed?

20mcg/kg dexmedetomidine + 0.2 mg/kg butorphanol + 5 mg/kg ketamine given IM

What drug combination can be used for a dental or standing procedure in a horse?

detomidine 40mcg/kg IV + morphine 0.3 mg/kg IV

What resource can be used for a veterinarian to determine meat and milk withdrawal times for various anesthetic drugs in food animals?

Food Animal Resiude Avoidance Databank (FARAD)