Sedatives and Anesthetics Part 1 Flashcards
Name the alpha 2 drugs?
- Dexmedetomidine
- Medetomidine
- Xylazine
- Yohimbine
Alpha 2 effects on nociception?
Perception, Modulation, and Transmission
Describe some general info on alpha 2 agonist receptors?
- Brain & spinal cord
- Vascular endothelium
- Endocrine organs
↓ Insulin
↓ Renin
↓ NE release
↓ Pancreatic secretion
Which alpha 2 agonist do we use for Dogs, cats, exotics?
Dexmedetomadine
Which alpha 2 agonist do we use for horses, deer, and elk?
Xylazine
Name the alpha 2 antagonists and which alpha 2 drug they antagonize?
Atipamezole (antagonizes dexmedetomidine)
Yohimbine (antagonizes xylazine)
Name the alpha 2 agonists?
Dexmedetomidine
Xylazine
Name the mechanism of action for sedative and analgesic effects?
Competitive agonism of the alpha 2 receptors (located in the brain/spinal cord)
Name the mechanism of action for ANS effects?
Competitive agonism of α1-receptors (vasculature–> vasoconstriction)
Varying degrees of α1-adrenergic receptor agonism can cause these two reactions?
Paradoxical CNS excitement
Peripheral vasoconstriction
Out of the alpha 2 drugs who is most selective and who is least selective?
- Dexmedetomidine
2. Xylazine
Most common routes of adm.?
IV or IM are the most common routes of administration
- Also can be given as a CRI and epidurally
- Oral transmucosal administration
Do they cross the BBB?
yes! Widely distributed to all tissues
Describe the onset and duration of action of Xylazine? What about Medetomidine and detomidine?
Xylazine onset of action is rapid within min IV
-15 minutes IM)
Duration of sedation ~1–2 hr
Analgesia ~15 to 30 min recovery up to 4 hr
Medetomidine & detomidine slightly longer
Describe the metabolism and elimination?
Rapid hepatic metabolism (short T1/2) followed by urinary excretion
Alpha 2 agonism main effects in the CNS?
- Sedation (alpha 2 receptors in the brain, CNS excitation in large doses)
- Pain Modulation and Analgesia (α2 receptors in brain and spinal cord)
- Muscle relaxation (spinal cord interneurons)
- Emesis (Stimulation of α2 receptors in the emetic center & CRTZ)
What is the drug of choice for emetic effects in cats?
Xylazine
What is unique about their cardiovascular effect? Name the phases
It’s a BIPHASIC Effect
Phase I – Peripheral Phase
Phase II – Central Phase
Describe the Phase 1 - Peripheral Phase
- Mediated by α1 receptors
- Peripheral vasoconstriction (↑ systemic vascular resistance (SVR) causes transient ↑ in mean arterial blood pressure (MAP) causes reflex bradycardia
- HR drops to maintain constant cerebral perfusion pressure (CPP)
if anticholinergics are given at this time they will force the heart to beat faster against the high SVR
Contraindicated - will cause ↑ myocardial workload and oxygen demand, can exacerbate pre-existing heart disease, can cause or worsen arrhythmias
Describe Phase II – Central Phase?
Mediated by α2 receptors
Decreased sympathetic tone (↓ NE) heart rate stays low
↓ Dronotropy (rate of conduction) & ↓ SA node firing
Peripheral vasodilation due to central effects on vasomotor center + low catecholamine levels
Often results in hypotension and bradycardia
Cardiac output can decrease 30-50% with α2 - agonists
Summary of the Cardiovascular effects?
↓ Cardiac output due to ↑ BP and reflex bradycardia
Bi-phasic effect due to initial vasoconstriction and hypertension followed by vasodilation and hypotension due to CNS depression
Bradyarrhythmias (incomplete AV block (2◦ most common)
Myocardial depression
Sensitizes myocardium to catecholamines tachyarrhythmias also possible
All effects are reversible
Alpha 2 agonist other effects respiratory effects?
Centrally mediated decrease in respiratory rate
Mild respiratory depression compared to other drugs
Cats may be more sensitive
Sheep and goats and horses
Increased respiratory rate, airway pressures (resistance) and; pulmonary elastance
Activation of pulmonary macrophages
Leading to ↑ CO2, hypoxemia, pulmonary edema
Also seen in unborn, near term lambs (these drugs cross the placenta!)
What do they do to the GI?
↓ GI motility (esp. large intestine)
↓ acid secretion
What are their effects on the renal system?
Diuresis by reducing ADH release and function
WHat are their effects on the Uterus?
Simulate myometrial contractions
May cause abortion (ruminants)
Hyperglycemic effects?
↓ Release of insulin leading to transient hyperglycemia
Typically not clinically significant
Should not ↑ [glucose] over renal threshold (~180mg/dL in dogs and horses)
More pronounced in ruminants and horses
Hypothermia effects?
Reduction in vasoconstrictive and shivering thresholds
Clinical uses?
- Sedation (Procedural sedation) (laceration/wound repair, bandage changes, etc) Recovery from anesthesia (anxiolytic) Mechanical ventilation
- Pre-anesthetic: MAC-sparing effect, Muscle relaxation (useful with ketamine)
- Analgesia: Combined with other drugs – e.g. neuroleptanalgesia CRI (fentanyl, diazepam, etc), epidural anesthesia (bupivacaine + morphine) Colic in horses, Goats are most sensitive to sedative and analgesic effects, swine are least sensitive
Emetic: cats > dogs
Behavioral: Chemical restraint for out-patient procedures/examination. Treatment of noise/storm phobias (Sileo®) Chemical ejaculation in stallions
Precautions?
Cardiovascular disease/instability
Emesis
Liver disease
Kidney disease
Seizure disorder
Do not use alpha 2 agonists with these drugs?
epinephrine and atropine
Contraindicated in?
critically ill and patients with shock syndrome
Name the 2 drugs that are competitive alpha 2 antagonists?
Atipamezole
Yohimbine
Details about Atipamezole?
Approved in dogs
Reverses sedation and analgesic effects of
dexmedetomidine and medetomidine
Most selective for alpha 2 receptors
Details about Yohimbine?
Approved in dogs, deer, and elk
Reverses sedation and analgesic effects of xylazine
Describe the best route of administration for atipamezole and yohimbine?
Recommend IM administration due to greater possibility of side effects if given IV, including CV collapse
Can be given IV in emergency
Describe the selectivity of atipamezole and yohimbine?
Atipamezole (8526:1)
Yohimbine (40:1)
Main effects of alpha 2 antagonists in the CNS?
Antagonizes α2 receptor agonist to reverse sedative effects
Analgesia will also be reversed!!
Administration of α2 antagonist alone will cause CNS excitement
Adverse effect: CNS excitement/stimulation
Main effects of alpha 2 antagonists in the Cardiovascular system?
Can reverse cardiovascular effects of α2 agonist
Administration without α2 agonist will cause tachycardia and hypotension
Adverse effect: tachycardia and hypotension due to vasodilation
Main effects of alpha 2 antagonists in the Respiratory ?
Antagonizes respiratory depression of α2 agonist
GI side effects: salivation, diarrhea
Alpha 2 antagonists therapeutic used to reverse?
Used to reverse alpha 2 agonist toxicity
Specific antidote
Mitoban toxicity
Amitraz tick collars
Describe the effectiveness of sedation for alpha 2 agonists?
Very good sedation
Describe the effectiveness of muscle relaxation for alpha 2 agonists?
Good muscle relaxation
Describe the effectiveness of analgesia for alpha 2 agonists?
Good/moderate but short lived analgesia
Describe the effectiveness of Cardiovascular/Respiratory effects for alpha 2 agonist?
Biphasic cardiovascular effects
Mild respiratory depression (more sig. issues in sheep)
WHich drug has the most selectivity for the alpha 2 receptor?
Dexmedetomidine
Alpha 2 agonist often cause _______ and the most common is called?
bradycardia (most common is atrioventricular block 2* degree)
What is significant about yohimbine?
specific reversal agent for xylazine
