Anesthesiology > Premedication > Flashcards

Premedication Flashcards

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1
Q

What are the purposes of premedication (7)?

A
  1. Sedation, analgesia
  2. Anesthetic sparing effect
  3. Reduction of stress and catecholamine release
  4. Reduction of O2 demand
  5. Increased safety for animals and humans
  6. Decreasing parasympathetic tone
  7. Others–antibiotics, antihistamines
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2
Q

What are the drugs of premedication?

A
  • Anticholinergics
  • Alpha2 agonists
  • Phenothiazines and butyerophenones
  • Benzodiazepines
  • Opioids
  • Antihistamines and antibiotics
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3
Q

What do anticholinergics inhibit? Which receptors do they act on (and what do they do)? What are the specific drugs?

A
  • Inhibit the parasympathetic nervous system
  • Antagonists on muscarinic acetylcholine receptors
  • Atroine; Glycopyrrolate
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4
Q

Atropine: 3 aspects

A
  • Lipid soluble (= crosses cell membranes)
  • Absorbs well IM, SC, PO
  • Crosses BBB and placental barrier
    • Important when anesthetizing animal for C section
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5
Q

Glycopyrrolate–6 aspects

A
  • Water soluble
  • Absorbs slowly IM, SC, PO
  • Onset of effect is slower than atropine even IV
  • Doesn’t cross the BBB or placental barrier
  • Dose: half that of atropine (more potent)
  • Advantage over atropine is debated
    • Atropine faster in emergency situation
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6
Q

What are the indications for anticholinergics?

A
  • Increasing heart rate
    • Treatment of opioid induced bradycardia (common problem)
    • Prevention/treatment of reflex bradycardia
      • Eye surgery (inc. vagal tone)
    • Young animals and brachycephalic breeds
      • Heart and SNS not fully developed
    • Routine use is not recommended
  • Decreasing salivation and bronchial secretion
    • Smaller amount but thicker mucus is not better
    • Usually only indicated for lab animals
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7
Q

Contraindications of anticholinergics?

A
  • Tachycardia
  • Hyperthyroidism
    • Heart is vulnerable–>tachycardic
  • Most heart diseases
    • Except when needed for treatment of bradycardia
  • Narrow angle glaucoma
    • Inhibits drainage of aqueous humor–> acute glaucoma
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8
Q

Anticholinergics: cardiovascular side effects

A
  • 2o AV block, bradycardia, cardiac arrest
  • Tachycardia, hypertension
  • [SA node: atrial conduction (P wave)]
  • [AV node: ventricular conduction (QRS)]
  • Anticholinergics easily effect the SA node
    • Lots of P waves
  • Effect on AV node is weaker and comes later
    • AV blocks, bradycardia (vagal tone inc.?)
    • When the AV node finally conducts–>excessive tachycardia
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9
Q

Are medetomidine and atropine recommended to give together? Why/why not?

A
  • Not recommended to give together
  • Results in vasoconstriction, tachycardia, hypertension
  • Measure BP before giving atropine
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10
Q

What needs to be considered before treating bradycardia?

A
  • Consider species, age, and diseases of patient
  • Is the patient hypotensive?
  • Is the ET CO2 adequate (assuming constant ventilation)?
    • Can be a sign of cardiac arrest if ET CO2 drops suddenly
  • Treatment plan:
    • Drugs: atropine, naloxone, others
    • Dose? Monitoring? Plan B?
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11
Q

What are some other effects of anticholinergics?

A
  • Relaxes lower esophageal sphincter (regurg)
  • Mydriasis (may trigger acute glaucoma)
  • Bronchodilation (increases airway dead space)
  • Dries airway secretions
  • Intestinal paralysis (may cause colic in horses)
  • CNS toxicity
    • Atropine crosses BBB: may cause sedation, coma
    • Treatment with physostigmine (not neostigmine)
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12
Q

What about rabbits with anticholinergics?

A
  • 1/3-1/2 of all rabbits have high levels of atropinase enzyme, so atropine is quickly broken down and not effective
  • Glycopyrrolate is the preferred anticholinergic
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13
Q

What are the general characteristics of alpha2 agonists?

A
  • Strongest available sedatvies
  • Have important cardiovascular side effects
  • Myriad of other effects
  • Have specific antagonists
  • Appropriate use is debated (crashing opinions)
    • High caution for low CO (contraindicated in USA)
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14
Q

Alpha2 agonists: mechanism of action

A
  • Competitive agonist of alpha2 adrenergic receptors
  • Location
    • CNS–presynaptic membrane (autoreceptor)
    • Post-synaptic membrane (vascular smooth muscle)
    • Extra-synaptic sites (e.g. pancreas, lipocytes, etc.)
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15
Q

How do alpha2 receptors work on the presynaptic membrane? What are the effects?

A
  • Suppression of NE release by negative feedback
  • Effects
    • Sedation (brain: locus ceruleus)
    • Analgesia (spinal cord: dorsal horn)
    • Reduction sympathetic outflow from the brain
    • Reduction of stress response
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16
Q

How/where do alpha2 receptors work on the postsynaptic membrane?

A
  • Smooth muscle wall of arteries and veins
  • Along with alpha1 receptors
  • Both mediate vasoconstriction
  • Natural ligands
    • NE: from sympathetic nerve endings
    • Epi: from adrenal medulla
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17
Q

How/where do alpha2 receptors work on extra synaptic sites?

A
  • Lipocytes: inhibition of lipolysis
  • Pancreatic beta cells: inhibition of insuulin release, hyperglycemia
  • Natural ligand: Epi
  • Interaction with stress response
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18
Q

What are the CNS effects of alpha2 agonists?

A
  • Sedative effect is species-specific
    • Strong: dogs, cats, horses, ruminants
    • Weak: pigs
  • Some analgesic effect
    • Synergistic with opioids
  • Muscle relaxation
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19
Q

What are the cardiovascular effects of alpha2 agonists?

A
  • 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:
    • Don’t use atropine (debated)
    • If necessary, give specific antidote (e.g. atipamezole)
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20
Q

Alpha2 agonists: respiratory effects

A
  • Mild respiratory depression
  • RR decreases, but tidal volume increases
  • Upper airway resistance increases
    • Relaxation of larynx, pharynx, and nares
    • Head dropping in horses: nasal edema
  • V/Q mismatch in horses
    • Low V/Q resulting in decreased PaO2
  • Bronchoconstriction, V/Q mismatch, lung edema and hypoxemia in ruminants
    • May occur with any alpha2 agonist in any ruminant species
    • Mostly reported with xylazine in sheep (therefore, commonly disrecommended)
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21
Q

Alpha2 agonists: GI effects

A
  • Salivation decreases
  • Lower esophageal sphincter tone decreases (not specific for alpha2 agonists)
  • GI motility decreases
  • Vomiting may occur
    • Not good in animals with respiratory problems
    • Most likely in cats using xylazine
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22
Q

What is the specific concern with xylazine in cattle?

A

May cause uterine contractions and abortion

(Not documented in other species or reported in other alpha2 agonists)

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23
Q

Indications of alpha2 agonists?

A
  • Sedation of aggressive animals
  • Sedation in the ICU
  • Sedation to manage post-operative airway obstruction (e.g. after brachycephalic sx)
  • Prevention/treatment of seizures (epilepsy)
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24
Q

Contraindications of alpha2 agonists?

A
  • Too young or too old
  • Hemodynamic instability
  • Severely debilitated patient
  • Not suitable for most risk patients
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25
What are the available alpha2 adrenergic agents?
* Agonists * Xylazine * Highest effect on alpha1 but affects other receptors as well * Medetomidine * 'Cleanest'--most specific to alpha2 * Dexmedetomidine * Detomidine * Romifidine * Antagonists * Atipemezole * Extremely specific for alpha2 * Yohimbine * Acts on serotonin receptors--painful, slow (dogs) * Tolazoline * Many side effects
26
What are some of the characteristics among various alpha2 agonists?
* Specificity to alpha1/alpha2 receptor differ * Medetomidine \>\>\> detomidine \> xylazine * Most effects are mediated by alpha2 receptors * **The main effects are very similar** * Pharmacokinetics and purchase price may differ
27
What are some of the characteristics among alpha2 antagonists?
* Alpha2 receptor specificity * Atipamezole \>\>\> yohimbine \>\> tolazoline * Tolazoline and yohimbine are 'dirty drugs' acting on other receptors and may have many side effects * Suggestion: **always use atipamezole to antagonize any alpha2 agonist** * **Always give IM except for emergency (IV)**
28
What is the unique xylazine dose for cattle? Do xylazine doses differ from medetomidine? What's xylazine's duration?
* Cattle dose = 10% of horse's dose * Dose of medetomidine does not differ * 20-40 min
29
What is detomidine used for? What are routes? Duration?
* Used for large animals * IM, IV, sublingual * 90-120 min
30
Romifidine: used for? Route? Duration? What is it preferred for and why?
* Used for horses * IM, IV * 45-90 min * Preferred for standing dental surgery--thought to produce less ataxia than xylazine
31
What is the dosing for medetomidine based on?
* USA--body surface area * EU--body weight * Package insert doses are generally very high * Use in combination and reduce the dose
32
What can you give medetomidine in combination with in dogs?
Combination with opioids and benzodiazepines for premed
33
Dexmedetomidine--what is it?
* Medetomidine is a 50:50 racemic mixture * Dexmedetomidine is the active optical isomer * Levomedetomidine is the inactive isomer * Dexmedetomidine is twice as potent as medetomidine * Otherwise should have the same effects
34
Phenothiazines--agonists or antagonists? What receptors do they act on?
* Act as antagonist on multiple receptors * Dopamine * Serotonine * Alpha1 * Histamine
35
Is acepromazine a long or short-acting drug?
* Long acting--depends on dose * 4-8 hours * 48 hrs for liver patients * Shorter if given in low dose
36
Phenothiazines--CNS effects
* Actions on dopamine and serotonine receptors * Weaker sedative effects compared to alpha2 agonists * **No analgesic effect** * Antiemetic effect * Mild respiratory depression
37
Phenothiazines--CV effects
* Actions on alpha1 receptors * **Vasodilation and hypotension** * Especially in hypovolemic animals * **May cause death in hypovolemic patients** * Measure blood pressure, give fluids
38
Phenothiazines--other effects
* Antihistaminic * Anti-arrhythmogenic * Inhibit platelet function * Penile prolapses in horses * Certain older phenothiazines cause seizures (not proven about ace)
39
Indications for phenothiazines?
* Mild sedation for premedication or post OP * Prevention/treatment of opioid dysphoria * Prevention of emesis caused by morphine * Sedation for dogs w/ laryngeal paralysis * Enhance sedative effect of xylazine in horses
40
Contraindications for phenothiazines?
* **Hypovolemia, hemodynamic instability** * Very young or very old patient * Von-Willebrand disease (Doberman) * Boxers may be sensitive (bradycardia)--avoid * Breeding stallions--not recommended
41
Butyrophenones--general
* 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 than ace * Less effects on platelets * Anti-arrhythmogenic, not seizurogenic
42
Benzodiazepines--general
* GABA receptor agonists * Sedative, anticonvulsant, muscle relaxant effects * **Minimal CV and respiratory effects** * No analgesia * Can cause major behavior changes
43
Benzodiazepines--specific agonists and antagonists
* Agonists * Diazepam * Midazolam * Zolazepam * Antagonists * Flumazenil * Sarmazenil
44
Benzodiazepines--sedation?
* Species specific effect * Dogs, cats, horses: Disorientation * Excitation may occur when used alone * Better sedation effects in ruminants, camelids, pigs, birds, ferrets * Rarely used alone
45
Benzodiazepines--indications
* Premedication--combine with: * Opioids * Alpha2 agonists * Both * Induction--combine with * Dissociative anesthetics (ketamine) * Barbiturates or propofol * Treatment of **seizures** (status epilepticus)
46
Diazepam--general
* Lipid soluble * Formulated in propylene glycol or lipid emulsion * Chemical compatibility is limited * Give slowly IV * Poor absorption and pain IM * Metabolized in liver and duration of action is 1-4 hrs
47
Midazolam--general
* 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) * **Diazepam should be avoided in liver patients** * Can be given IM, IV, or via mucus membranes * **Better choice than diazepam**
48
Opioids--general
* Exogenous substances that bind to opioid receptors and activate them * Strongest available system analgesics * Best choice for treatment of acute pain (e.g. **surgery**) * Decreases the dose of anesthetics * Minimal CV side effects * Suitable for most risk patients * Not as effective for chronic pain
49
Opioid receptors (strength, location)
* μ: Strong analgesia, resp. depression, dependency * κ: Weaker analgesia * δ: Weaker analgesia (human relevance) * Location * Brain * Spinal cord (dorsal horn) * Peripheral nerves * Inflamed organs (e.g. arthritis)
50
What are the classifications of opioids?
* Full agonists--activate receptors and trigger full tissue response * Partial agonists--activate receptors but do not trigger full tissue response even at highest doses * Antagonists--bind to receptors but do not activate them
51
What do the following tell you? Potency Efficacy Pharmacokinetics
* Potency--tells you the dose * Efficacy--tells you the strength of the effect * Pharmacokinetics--onset, duration of effect, strategy, etc.
52
Opioids--CNS effects
* Analgesia * Excellent for acute pain * Less effective for chronic pain * Decreasing the MAC of inhalants * Species dependent * Primates \> dogs \> cats \> pigs \> horses * May increase the MAC in horses * Sedation depends on * Species--primates and dogs sedate better * Pain level--stronger if there was pain * Excitation, dysphoria * Cats may become excited * Horses after high dose * Tolerance * Dependence
53
Opioids--vomiting
* May trigger or may inhibit vomiting * Stimulate chemoreceptor trigger zone outside 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
54
Opioids--CV effects
* No direct negative inotropy or vasodilation * Indirectly may reduce sympathetic outflow from the brain (--\>reduce BP) * Increase parasympathetic tone and may cause bradycardia * Treatable with atropine * **Suitable for most risk patients** * Improves CV function by allowing to reduce the dose of anesthetics
55
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)
56
Opioids--GI effects
* Nausea, vomiting * Defecation * Obstipation * Spasm of sphincter of Oddi (hepatopancreatic sphincter)
57
Other effects of opioids?
* Hypothermia * Post-OP hyperthermia (cats) * Myosis (dogs), mydriasis (cats) * Inhibition of urination * Noise sensitivity
58
Indications for opioids?
* Premedication--alone or in combination with * Benzodiazepines * Benzodiazepines and ketamine (cats, small dogs) * Acepromazine * Alpha2 agonists (xylazine, medetomidine) * Perioperative analgesia * Treatment of acute and chronic pain
59
Opioids--administration (lots)
* IM, SC * IV boluses or CRI * PO (e.g. tramadol) * PCA--patient controlled anesthesia (human) * Epidural or spinal * Transdermal (fentanyl patch) * Transdermal fentanyl solution (Recuvyra) * Oral mucosa (buprenorphine for cats)
60
Morphine--all the things
* Cheap and strong analgesic; water soluble * Slow onset (30-45 min), long duration (4-6 hrs) * 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 * Not good * Duration of epidural analgesia is 12-24 hrs (need to control bladder)
61
Hydromorphone, oxymorphone
* Strong analgesics (full μ agonists) * Duration ~4 hrs * Reliable metabolism * No histamine release * **Better choices than morphine**
62
Methadone
* Similar properties to hydromorphone * But also acts as NMDA antagonist (another mechanism of analgesia)
63
Fentanyl
* Strong analgesic (full μ agonist) * Fast onset short duration (15-20 min) * No histamine release * May accumulate after long infusions * Bolus dose for small animals: 2-5 μg/kg IV * CRI dose * May be mixed with ketamine
64
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 interruption of administration may trigger strong pain** * Boluses may cause sudden bradycardia
65
Butorphanol
* Antagonist on μ and agonist on κ receptors * Weak and short acting analgesic * **May worsen pain sensation** in case of strong pain * May be used for premedication in combination with benzodiazepines or alpha2 agonists if there is no strong pain (e.g. radiology) * May partially antagonize full μ agonists
66
Buprenorphine
* Partial μ agonist * Stronger analgesic than butorphanol * Relatively long-acting: 6-8 hrs * Onset is slow (20-40 min IV) * Often given to cats because may cause less excitement than full μ agonists * Cat owners may continue giving via oral mucosa
67
Tramadol
* Weak analgesic * Metabolites in the liver * Metabolite is μ opioid agonist (?) * Tramadol itself inhibits NE and serotonin reuptake (analgesia) * Not scheduled drug * Can be given PO
68
Opioid antagonists (2)
* Naloxone--30 min duration * May be used in small animals to reverse respiratory depression * Routine use is not recommended (reverses analgesia) * Naltrexone--long acting (~10 hrs) * Antagonize wild animals after long-acting opioids (e.g. carfentanyl or etorphine)
69
Antibiotics
* Cefazolin * Amoxicillin clavulic acid * Give IV 20 min before surgery * Repeat every 90-120 min * **For prevention: give at least 4 hrs before**
70
Antihistamines
* H1 antagonist--Diphenhydramine * Antagonizes the CV effects of histamine in case of an anaphylactic reaction or histamine release * H2 antagonist--ranitidine, famotidine, cimetidine * Increase the pH of the stomach (GI protection) * Both can be given for premedication before mast cell tumor removal
Anesthesiology
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