Vet 415 : Exam 4

Why do we often combine premed drugs?

- Many drugs act synergistically (permits lower dosages of each drug used) - Combinations can be used to minimize/offset unwanted side effects

T or F: Benzodiazepines have excellent analgesia.

False - these drugs produce no analgesia

Do Benzodiazepines cause sedation in dogs and cats?

Can cause sedation or excitation in adult dogs and cats, and which effect prevails is unpredictable

T or F : Acepromazine is an analgesic.

False

T or F: Anticholinergics have sedative and analgesic properties.

False

T or F: Benzodiazepines cause minimal CV/respiratory depression.

True

T or F: Mild sedation and heavy sedation differ in the amount of drug/combination of drugs given, with increased doses given to produce heavier sedation.

True

What is the most important side effect of alpha-2 agonists?

- Cardiovascular depression - Initially : vasoconstriction decreases peripheral perfusion (peripheral cyanosis) and induces hypertension that is followed by a reflexive bradycardia - Over time : decreased SNS output causes bradycardia - "Double whammy" bradycardia reduces cardiac output by 50-70% in dogs/cats

List the reversal agent for each drug: - Dexmedetomidine - Detomidine - Romifidine - Xylazine

- Dexmedetomidine :Atipamezole (SA) - Detomidine : Tolazoline (horses) - Romifidine : Tolazoline (horses) - Xylazine : Yohimbine (SA) or Tolazoline (horses)

List the recommended fasting time for each: - Dogs and cats - Horses - Ruminants - Neonates

- Dogs and cats : 6-8 hours - Horses : 6-12 hours - Ruminants : 24-48 hours (+ 24 hours off water, but this is temperature dependent) - Neonates : do not fast neonates

Risk of death from general anesthesia is far greater in ASA groups ________ compared to ASA groups _______. This trend is even more obvious between these ASA groups when classified as ________.

Risk of death from general anesthesia is far greater in ASA groups 3-5 compared to ASA groups 1-2. This trend is even more obvious between these ASA groups when classified as emergencies (E).

If bradycardia from alpha-2 agonist is life-threatening 30 minutes after the drug is administered, what can be done to resolve it?

- Later on after administration, bradycardia is due to decreased SNS output - Over time, vasoconstriction usually relaxes and animal may be trending toward hypotension (bradycardia + vasodilation) - Because vasoconstriction is no longer present, can use anticholinergic drug to increase sympathetic tone to increase heart rate

Which factors do you need to consider to determine if a procedure can be done with sedation?

- Patient factors (compliance, fasted status, ability to monitor/support) - Procedure (invasiveness, pain, length, consequences if animal moves) - Ability to provide local anesthesia - Staff availability/experience - Cost - Safety

What does the increased risk of mortality among ASA groups that have emergency status tell us?

- Patient preparation is extremely important, and if possible, patient status should be improved as much as possible before induction - Lack of patient preparation for a procedure (due to emergency status) greatly increases risk of mortality from general anesthesia

Which classes of premedicant drugs are commonly used in veterinary medicine?

- Phenothiazine (Acepromazine) - Alpha-2 adrenergic agonists - Anticholinergics - Benzodiazepines - Gabapentinoids - Opioids

What is morbidity in relation to general anesthesia?

- Rate of incidence of a condition/complication that arises due to general anesthesia - These are non-lethal complications (both expected and unexpected) - More difficult to assess (don't know what you aren't looking for)

Why are patients fasted before general anesthesia?

- Reduces risk of vomiting/regurgitation and thus reduces risk of aspiration pneumonia (SA, ruminants) - Reduces size of GI tract in large animals (improved cardiopulmonary function in LA when fewer GI contents in bowel to compress lungs)

What are qualities of the ideal premedication?

- Reliable sedation and anxiolysis - Minimal side effects - Provides analgesia - Reversible - Potent (small volume needed) - Anesthetic sparing *No single drug meets all criteria...

What are effects of alpha-2 agonists that warrant their use?

- Sedation (rousable and reversible) - Analgesia - Anxiolysis - Muscle relaxation - Potent anesthesia drug sparing

Which animal is susceptible to respiratory effects from alpha-2 agonists? What respiratory effects are seen?

- Sheep - Alpha-2 agonists activate pulmonary intravascular macrophages (PMIs) that induce pulmonary capillary damage, resulting in pulmonary edema

What are side effects of anticholinergic administration?

- Sinus tachycardia - Bronchodilation - Decreased/thickened secretions > dry mouth - Decrease GI motility - Decreased LES tone (increased regurgitation risk) - Mydriasis (Atropine) - Prolonged effect on autonomic balance

What is done to stabilize a patient before induction with general anesthesia?

- Thorough patient assessment - Correct systemic abnormalities (commonly fluid deficit and electrolyte abnormalities) to reduce ASA status as anesthesia abolishes physiologic compensation - May need additional time for diagnostics to determine what abnormalities there are, and this must balanced with urgency of procedure

When is the preanesthetic period? What is done in this time?

- Time between decision to anesthetize and induction of the patient - During this time you should : evaluate patient, develop anesthetic plan, stabilize patient, prepare facility/equipment, pre-medicate patient

What are important side effects of acepromazine?

- Vasodilation (via peripheral alpha-1 antagonism in blood vessels) can cause hypotension and lead to a reflexive tachycardia - Vasodilation can also induce splenic sequestration of RBCs, causing decreased hematocrit - Vasodilation induced peripheral hypothermia - Priaprism (breeding stallions) - Anti-emetic (targets CRTZ)

T or F: Opioids cause sedation in all species.

False - cause sedation in dogs, rabbits, and ruminants but cause excitation in cats and horses

T or F: ASA status is objective.

False - some degree of subjectivity (especially when you ask anesthesia vs. other services)

T or F : There are several reasons to not premedicate an animal before general anesthesia, including : drug interactions, cost, and increased time needed to give additional injection.

False - these are not good reasons, nor are there many valid reasons to not premed

Which drug is a mu antagonist / kappa agonist?

Butorphanol

What are important things to consider about how your animal patient is affected by sedation/anesthesia?

- Animal's ability to move may be limited - Protective reflexes may be blunted/absent - Muscle relaxation may compromise airway patency - Most drugs have side effects

What is ASA status? What does it account for?

- A way to categorize patients to enable estimation of risk of anesthetic death/complications - Only considers patient condition (no other factors are accounted for)

What are effects of benzodiazepines that warrant their use as a premed?

- Anxiolytic - Amnestic - Anticonvulsant - Muscle relaxant - Mild anesthesia drug sparing - Reversible - Sedation (reliable in sheep, goats, rabbits, neonates while +/- in dogs and cats)

Which two premed drug classes are controlled substances?

- Benzodiazepines - Opioids

What are side effects of alpha-2 agonists?

- CV depression (vasoconstriction > bradycardia) - Decreased SNS output (bradycardia) - Minimal respiratory effects (except sheep) - Diureses (decreased insulin > hyperglycemia > glucosuria > osmotic diuresis) - Vomiting (cats > dogs) - Reduced GI motility - Sweating (horses)

List some reasons for why anesthetic premedications are used.

- Decreased animal anxiety - Sedation to facilitate animal handling - Provide analgesia - Reduce induction/maintenance dose of general anesthetic - Minimize/mitigate side effects of other drugs - Smooth induction and recovery periods

Why do mu opioid receptor agonists (MORs) sometimes cause vomiting in dogs, and sometimes do not?

- Depends on lipophilicity of drug - High lipophilicity drug (fentanyl) : rapidly crosses BBB and acts on central vomiting center to prevent emesis - Lower lipophilicity drug (morphine) : doesn't cross BBB as readily, binds to CRTZ outside of BBB first and induces emesis

Why might you choose to use acepromazine as a pre-med?

- Enhances sedative effects of other drugs - Mild anesthetic sparing - Induces mild sedation to improve patient compliance

What are side effects of MOR agonists?

- Euphoria (cats, horses) - Dysphoria (all animals) - Vomiting (dogs) - Bradycardia (dogs with high vagal tone) - Respiratory depression (mostly MORs) - Dysregulation of thermoregulation (hyperthermic cats, hypothermic dogs) - Altered GI motility - Urinary retention - Histamine release (can decrease SVR) - Miosis (dogs), mydriasis (cats)

Which opioids are full mu agonists? Which are partial mu agonists?

- Full mu : morphine, methadone, fentanyl, hydromorphone, oxymorphone, mepiridine, sunfentanil - Partial mu : buprenorphine

Under what conditions is use of acepromazine as a premed contraindicated (or at least should be strongly considered before using)?

- In animals that are hypotensive, hypovolemic, or anemic - Geriatric and neonatal animals - Animals with hepatic insufficiency - Boxers (risk of CV collapse/syncope) - Breeding stallions (priapism risk)

Why is Midazolam preferred over Diazepam in the small animal clinic?

- Midazolam is water soluble unlike Diazepam, so can be given IM, SC, or IV and have adequate absorption while Diazepam can only be given IV - Diazepam also stings when it is injected, Midazolam does not

What is sedation? Why might we choose to sedate a patient?

- Mild to moderate depression of the CNS - May sedate to prepare patient for catheterization or to facilitate handling for minimally invasive/non-painful procedures

Which drugs are used to reverse the effects of opioids? Which opioid can these drugs not reverse?

- Opioid receptor antagonists - Naloxone, naltrexone - Cannot reverse buprenorphine because buprenorphine has a very high affinity for MORs and will not dissociate

What is the overall mortality rate for dogs due to general anesthesia? How does risk differ between healthy and sick individuals?

- Overall : 0.17 % mortality - Healthy : 0.01 - 0.05 % - Sick : 1.33 %

What is the overall mortality rate for horses due to general anesthesia? How does risk differ between healthy and sick individuals?

- Overall : 2.1 % mortality - Healthy : 0.9 % - Sick : 11.7 %

When are anticholinergics contraindicated?

- Pre-existing tachycardia - Glaucoma - Reflexive bradycardia secondary to systemic hypertension from vasoconstriction - Pre-existing ileus

What are effects of gabapentin that warrant its use as a premedication?

- Sedation (cats especially) - Analgesia (chronic pain) - Anxiolytic (cats) - Anesthesia drug sparing

What are effects of opioids that warrant their use as premedications?

- Sedation (dog, rabbit, ruminant) - Analgesia (mu opiate agonists are best) - Anesthetic drug sparing (dogs > cats > horses) - Minimal CV side effects

What are the most common indications for alpha-2 agonist use in horses?

- Standing sedation (+/- opioid) - Mildly painful procedures - Prior to induction of general anesthesia - Reduce induction dose - Aid in anesthetic recovery - Horses with colic

Which processes of noxious information transmission are inhibited by local anesthetics?

- Transduction (Nociceptors) - Transmission (Nerves) - Modulation (Spinal cord) *Depends on location of drug administration

What are the most common indications for alpha-2 agonist use in small animals?

- Used for sedation for brief procedures with or without opioids - Premedication for SA anesthesia for animals that are difficult to handle

What are common indications for anticholinergic use?

- Used to increase HR or to prevent vagally-mediated bradycardia - Antisecretalogue in cats - Decrease gastric acid secretion (increase stomach pH) - inhibit muscarinic effects of other drugs - Decrease GI motility for rectal exam (horse)

What are the three components of general anesthesia?

1. Immobility 2. Unconsciousness 3. Amnesia

Which four factors substantially increase risk of mortality from general anesthesia?

1. Systemic illness of patient 2. Emergency status of procedure 3. After hours (fewer resources) 4. Lack of familiarity between veterinary team members (human error)

You have a dog that is recumbent, in shock, and has suspected GDV present to the ER at 2:00AM. This dog needs surgery ASAP. What is the ASA status of this dog?

4-5 E

Acepromazine is categorized as a ______________. It is commonly used as a _________in both ________ and ________.

Acepromazine is categorized as a pheothiazine. It is commonly used as a tranquilizer in both dogs and horses.

Administration of an ________ along with an alpha-2 agonist can make the sedation less rousable.

Administration of an opioid along with an alpha-2 agonist can make the sedation less rousable.

Which anticholinergic has the most rapid onset after administration?

Atropine

Which anticholinergic should be used for CPR if high vagal tone is suspected? Why?

Atropine - rapid rate of onset compared to Glycopyrrolate

_________ can be used as a pre-med to prevent vagally-mediated bradycardia secondary to opioid administration.

Atropine can be used as a pre-med to prevent vagally-mediated bradycardia secondary to opioid administration.

Atropine should not be used in rabbits because __________. As an alternative, ____________ can be used as it does not have this enzyme.

Atropine should not be used in rabbits because plasma atropinesterases break down atropine, decreasing efficacy. As an alternative, Glycopyrrolate can be used as it does not have this enzyme.

Which anticholinergic is used to relax GI muscles in horses for rectal exams?

Buscopan

Which animal is 10x more sensitive to xylazine than horses?

Cattle

What is the MOA of acepromazine?

Central dopamine receptor antagonist that depresses the reticular activating system, inducing mild sedation *Also has peripheral alpha-1 antagonism (induces vasodilation)

Which alpha-2 agonist used in horses is more potent with a longer duration of effect : Detomidine or Xylazine?

Detomidine

Dexmedetomidine is most commonly used in ________ while Detomidine, Romifidine, and Xylazine are most used in _________.

Dexmedetomidine is most commonly used in dogs and cats while Detomidine, Romifidine, and Xylazine are most used in horses.

Dexmedetomidine, Xylazine, Romifidine, and Detomidine are categorized as _____________. These drugs are commonly used in ________.

Dexmedetomidine, Xylazine, Romifidine, and Detomidine are categorized as alpha-2 adrenergic receptor agonists. These drugs are commonly used in all animals.

Diazepam, Midazolam, and Zolazepam are classified as _______________.

Diazepam, Midazolam, and Zolazepam are classified as Benzodiazepines.

Duration of effect of acepromazine is ________.

Duration of effect of acepromazine is 4-6 hours.

What is a commonly used benzodiazepine antagonist used to reverse effects of benzodiazepines?

Flumazenil

What is the MOA of Benzodiazepines?

GABA receptor agonist increases CNS inhibition

What is the MOA of gabapentinoids?

Gabapentin inhibits VG Ca channels on presynaptic neurons to decrease release of excitatory NTs

General anesthesia inhibits movement via action in the _________, inhibits arousal via action in the ________, and inhibits consciousness/memory formation via action in the __________.

General anesthesia inhibits movement via action in the spinal cord, inhibits arousal via action in the thalamus, and inhibits consciousness/memory formation via action in the cortex.

Why is it recommended that alpha-2 antagonists be given IM?

Giving IM prevents sudden changes in autonomic tone (if given IV, give SLOW)

What are anesthetic premedications?

Medications administered prior to induction of anesthesia

What is the MOA of anticholinergics?

Muscarinic acetylcholine receptor antagonists (aka parasympatholytics)

Will giving a larger dose of alpha-2-agonist increase magnitude of effect?

Not necessarily, more likely to prolong duration of drug effect

This class of drugs is commonly used peri-operatively for their analgesic properties.

Opioids

_______ are first line therapy for acute pain in the clinic.

Opioids are first line therapy for acute pain in the clinic.

What is the ROA for gabapentin?

Oral

Order of risk of anesthesia related mortality by species : ________ < _________ < ________

Order of risk of anesthesia related mortality by species : dog < cat < horse

Profound bradycardia from alpha-2 agonist use can lead to ________.

Profound bradycardia from alpha-2 agonist use can lead to AV block.

When an animal is sedation, its protective reflexes are depressed and it is your responsibility to _______, _______, and ______ the animal.

When an animal is sedation, its protective reflexes are depressed and it is your responsibility to protect, support, and monitor the animal.

Which alpha-2 agonist used in horses can sensitize myocardium to catecholamine-induced arrhythmias due to peripheral alpha-1 activation?

Xylazine

If you are doing a minor surgery (i.e. laceration repair), should any drugs be given in addition to heavy sedation?

Yes - should also use local anesthetic for pain control +/- opioid for additional analgesia

Which premed drugs are reversible?

- Benzodiazepines - Mu opioid agonists - Alpha-2 agonists

Explain ASA status 1-5 and the additional classification of "E".

- 1 : normal, healthy patient - 2 : mild systemic disease - 3 : severe systemic disease - 4 : severe systemic disease that is life-threatening - 5 : moribund, will not survive without procedure - E : added to any status for an emergency

Explain operative risk status 1-5 and the additional classification of "E".

- 1 : normal, healthy patient, routine procedure - 2 : mild systemic disease, abnormal physiologic state, or unfamiliar procedure/drugs - 3 : severe systemic disease, abnormal physiologic state, unfamiliar procedure/drugs, or difficult procedure - 4 : severe systemic disease that is life-threatening, markedly abnormal physiology, difficult/extensive procedure - 5 : moribund, will not survive without procedure - E : added to any status for an emergency

What is operative risk? What does this risk assessment account for?

- A way to categorize patients to enable estimation of risk of anesthetic death/complications - Accounts for overall risk (includes patient and non-patient factors including extent/difficulty of procedure, staff skill/experience)

If bradycardia from alpha-2 agonist is life-threatening immediately after giving the drug IV, what can be done to resolve it? What should not be done?

- Administer reversal (alpha 2 antagonist) IM - DO NOT GIVE ANTICHOLINERGIC (initial bradycardia is reflexive from vasoconstriction > hypertension > reflexive bradycardia, so anticholinergic would increase HR without altering vasoconstriction, causing massive hypertension that increases myocardial work and increases myocardial O2 demand > myocardial ischemia !!)

What are side effects of Benzodiazepines?

- Agitation/mania/disinhibition in some healthy dogs/cats, particularly if handled - Appetite stimulation

What is a common drug combination to use for a bone biopsy in a healthy dog?

- Alpha 2 agonist : produces heavy (rousable) sedation - Opioid (butorphanol) : analgesia and enhanced sedation - Local anesthesia : local block for analgesia

What are three clinically and ethically desirable qualities of general anesthesia that are not essential?

- Antinociception (Analgesia) : most anesthetics only help with pain by decreasing consciousness, so great if they address pain in other ways - Muscle relaxation : decreased muscle rigidity makes tissue manipulation easier during surgery - Reversible state : want to be able to reverse effects so animal isn't anesthetized for longer than it needs to be

What are common side effects of gabapentin?

- Ataxia - Mild sedation - Minimal effects on other organ systems!

Which anticholinergic crosses the BBB? Which anticholinergic does not cross the BBB? What are the implications of this?

- Atropine crosses the BBB (causes mydriasis that increases intraocular pressure) - Glycopyrrolate does not cross the BBB (does not cause mydriasis/cause increased intraocular pressure)

Anticholinergics decrease __________ tone.

Anticholinergics decrease parasympathetic (vagal) tone.

Atropine, Buscopan, Glycopyrrolate are categorized as _____________. These drugs are commonly used as premed drugs in ________ and as emergency drugs in ________.

Atropine, Buscopan, and Glycopyrrolate are categorized as anticholinergics. These drugs are commonly used as premed drugs in dogs and cats and as emergency drugs in all animals.

How is noxious information transmitted from nociceptors to the cortex?

Nociceptors (transduction) > Nerves (transmission) > Spinal Cord (modulation) > Thalamus (modulation) > Cortex (perception)

The largest difference in risk of death due to anesthesia exists between which two groups of the same species?

Systemically healthy (far less risk) and systemically ill (far greater risk)

T or F: The cardiovascular effects of alpha-2 agonists are dose-dependent, but present at very low doses.

True