Pre-anesthetic and Induction drugs Flashcards
1
Q
name the Phenothiazine Tranquilizers used in vet med
A
- Acepromazine - widely used
- Chlorpromazine
- Promazine
2
Q
What animals are Phenothiazine Tranquilizers FDA approved for?
A
- Dogs
- Cats
- Horses
- Extra-label use is common
3
Q
What is the MOA of Phenothiazines?
A
-
Block D2 dopaminergic receptors in the brain
- Primary site of action is subcortical receptors in base ganglia, limbic forebrain and reticular activating system
- Suppress state of arousal and cause lack of motivation for response to external stimuli
- Block peripheral alpha-1 adrenergic receptors in vasculature
- structural similarity to other catecholamines
- Some antihistaminic and anticholinergic activity as well
4
Q
What are the effects of Acepomazine?
A
- Antiemetic
- Vasodilation
- antiarrhythmic
- Epinephrine reversal
5
Q
How does Acepromazine work as an antiemetic
A
- Act as a direct antagonist to dopamine (D2 receptor) in the CRTZ
- When given 15 minutes prior to opioids, it diminishes incidence of vomiting from 45% to 18%
6
Q
How does Acepromazine affect the cardiovascular system?
A
- Vasodilation (alpha adrenergic-blockade
- Doses of 0.125, 0.25 mg/kg IV cause 9.4% and 16.8% reduction of mean arterial pressure in anesthetized dogs
- Heart rate may increase slightly (baroreceptor - mediated response to hypotension)
- Antiarrhythmic effect
- decreases sensitivity to catecholamine-induced arrhythmias
7
Q
What are the effects of Phenothiazine Tranquilizers on the CNS?
A
- Sedation subsequent to depression of reticular activation system
- RAS is responsible for wakefulness, serves as a gatekeeper for incoming sensory information, modulates the fight-flight response (SNS) among other functions
- Decreased spontaneous motor activity is noted with phenothiazines
- NOT ANALGESIC
8
Q
How does Acepromazine work as epinephrine reversal?
A
- There is a paradoxical drop in blood pressure in response to epinephrine (“adrenaline”)
- Alpha1 - adrenergic blockade so the beta2 - receptor effect predominates revealing vasodilating action of beta-2 adrenergic receptor
- Occurs with endogenous epinephrine (adrenal release) or administered epinephrine
9
Q
What are the other effects of Phenothiazine Tranquilizers? why?
A
- Decreased hematocrit
- Splenic enlargement due to relaxation of smooth muscle in splenic capsule with sequestration of RBCs in the spleen
- Antihistamine effect
- Contraindicated for intradermal skin testing, interferes with wheal and flare response to antigens
- Hypothermia
- Effect on central thermoregulatory center
- Causes loss of body temp control at both low and high ambient temperatures
- Cutaneous vasodilation also contributes
- Ptosis and prolapse of third eyelid (dose - related)
- Persistent penile prolapse (paraphimosis) reported in horses
- incidence of 2.4% in male horses
- duration up to 4 hours
- irreversible trauma can occur
10
Q
How is acepromazine used in dogs? properties?
A
- Often combined with opioid analgesics for premedication
- Hepatic metabolism is slow
- elimination half-life is 7.1 hours
- long duration of action
- Reduce dose in puppies < 3 months of age and in geriatric dogs due to sensitivity to effects
11
Q
how do cats respond to acepromazine?
A
much less sensitive to the sedative effects
12
Q
How is acepromazine used in horses? effects? contraindications?
A
- Slow onset (15 - 30min) before adequate sedation even after IV administration
- Elimination half-life 3.1hrs
- Caution in excited animals
- high levels of endogenous circulating epinephrine may cause hypotensive crisis
- Contraindications:
- Shock, dehydration, hypovolemia
- contributes to ⇣ BP
- Significant CNS depression
- long-acting sedation is not reversible
- Altered liver metabolism
- Elimination half-life is already lengthy
- Shock, dehydration, hypovolemia
13
Q
What happens when there is an Overdose/Adverse Response to Acepromazine? Treatment?
A
- Extreme sedation and hypotension, acute collapse
- Treat with adequate fluid therapy to expand circulating blood volume
- In addition to fluid therapy or if fluids are not effective, use a vasopressor to counteract vasodilation
- Ephedrine
- stimulates release of NE from SNS nerve terminals
- Phenylephrine
- Direct alpha-1 agonist
- Ephedrine
14
Q
Name the benzodiazepines used in veterinary medicine?
A
- Diazepam (valium)
- Midazolam (versed)
- Zolazepam
15
Q
What is the MOA of Benzodiazepines?
A
- Benzodiazepine and GABAA receptors are coupled to chloride channel in nerve cell membrane
- GABA is the neurotransmitter and is inhibitory to neuronal activity
- GABAA receptor is activated by GABA causing ion channel to allow Cl- influx
- Hyperpolarizes the nerve and decreases neuronal transmission
- Benzodiazepines bind to the benzodiazepine receptor (separate from GABA binding)
- Potentiate GABA-induced chloride influx into nerve cells
- Benzodiazepines also interfere with GABA reuptake, prolonging its effect at the neuroeffector junction
- Benzodiazepines have no intrinsic effect on their own in the absence of GABA
16
Q
What effects do benzodiazepines have on the CNS?
A
- Anticonvulsant
- Anti-anxiety
- Sedation - variable and species dependent but most species only mild sedation
- Centrally-mediated muscle relaxation
- Amnesia
17
Q
What effects do benzodiazepines have on the cardiopulmonary system?
A
- Minimal cardiovascular effect
- vascular irritation may occur when diazepam is administered IV
- propylene glycol vehicle
- Minimal respiratory depression
18
Q
What are the properties of diazepam? uses?
A
- Propylene glycol carrier due to poor water solubility
- IV, IM, oral or rectal use
- Poor bioavailability if given subcutaneously
- Species-dependent sedation
- Anticonvulsant in all species
- Often combined with opioids for premed
- Often used with ketamine to improve muscle relaxation for anesthesia
- A good choice in sick or debilitated individuals
- Elimination half-life 3.2 hrs in dogs
19
Q
What are the properties of Midazolam? uses?
A
- More rapid and reliable absorption from IM injection due to higher water solubility properties
- 90% bioavailability after IM with peak plasma concentration in 15 min
- Also effective via subcutaneous route and reported to be effective with intranasal administration
- Commonly given by the IV route as well, often as IV co-induction agent with ketamine, propofol, or other anesthetic induction techniques
- Shorter acting than diazepam
- elimination half-life 77 minutes in dogs
20
Q
What is the antagonist for benzodiazepines?
A
- Flumazenil
- rarely used due to wide margin of safety of benzos
21
Q
Why are opioids used in pre-medication?
A
- Wide margin of safety
- Considered “gold standard”
- Fully reversible with opioid antagonists (naloxone)
- Often used as part of anesthetic protocol for very sick or debilitated animals
- Excellent analgesics
- Good sedatives in many species
- May produce paradoxical hyperactivity
- in other species (feline, equine) so used in combination with a sedative like acepromazine of alpha-2 agonist
22
Q
Why do we use anesthetic premedication?
A
- Calm the patient and aid in restraint
- Facilitate the process of IV catheterization
- Provide analgesia
- Smooth induction to and recovery from anesthesia
- Decreases the amount of other anesthetics drugs needed
- No drug class or combination of drugs should be routinely given to all patients
23
Q
What are the major classifications of Preanesthetic drugs?
A
- Alpha-2 Adrenergic Agonists
- Phenothiazine Tranquilizers
- Benzodiazepines
- Opioids
24
Q
What considerations need to be taken when deciding on preanesthetic drugs for a patient?
A
- Type of surgery
- duration of procedure
- anticipated complications
- Postoperative needs
- age
- temperament
- volume status
- medical condition
25
Name the alpha-2 adrenergic agonists
* Xylazine
* Detomidine
* Romifidine
* Dexmedetomidine
26
Name the alpha-2 adrenergic agonists
* Xylazine
* Detomidine
* Romifidine
* Dexmedetomidine
27
What do alpha-2 adrenergic agonists do? (general)
* Provide sedation
* analgesia
* muscle relaxation
28
What is the MOA of Alpha-2 Adrenergic Agonists
* Bind to and stimulate alpha-2 adrenergic receptors
* Part of the sympathetic nervous system, alpha-2 receptors are widely distributed throughout the body
* Receptors are located both pre-synaptically and post-synaptically and have both direct effects and modulatory effects on many systems other than SNS
* These drugs are not pure alpha-2 agonists but have some alpha-1 and alpha-2 adrenoceptor activity defined for each drug as its alpha-2 : alpha-1 selectivity ratio
* Alpha-2 adrenergic effects predominate
* Alpha-2 agonists activate central and peripheral alpha-2 adrenergic receptors
* Alpha-2agonsits activate both presynaptic and postsynaptic alpha-2 adrenergic receptors
29
What is the role of alpha-2 adrenoceptor in the sympathetic nervous system?
* SNS regulates many systems within the body
* part of this regulation involves the modulation of the release of neurotransmitters (nerve terminals) and neurohumoral (adrenal medulla) control
* Alpha-2 adrenoceptors are inhibitory presynaptic receptors
* within SNS called “autoreceptors”
* Norepinephrine (NE) released by nerve binds to alpha-2 receptor and diminishes further release of NE from SNS postganglionic fibers
* Negative Feedback System
30
What effect do alpha-2 adrenoceptors have on non-adrenergic nerves?
* can inhibit the release of neurotransmitters such as acetylcholine, serotonin, substance P and other neuropeptides
* Alpha-2 receptors that inhibit release of a neurotransmitter with which they are not activated are called heteroreceptors
31
How do alpha-2 receptors contribute to analgesia
* Pain pathway is highly modified within the dorsal horn of the spinal cord. This is a site where many of our analgesics are targeted
* Presynaptic alpha-2 receptors located on primary afferent C fibers cause decreased release of neurotransmitter from primary pain fibers (heteroreceptors)
* Postsynaptic alpha-2 receptors are located on spino-thalamic projection neurons in dorsal horn and inhibit ascending nociceptive transmission
32
What affects do alpha-2 adrenoceptors have on the CNS?
* Sedation
* alpha-2 receptors in locus coeruleus in the midbrain
* Analgesia
* dorsal horn of spinal cord
* Muscle relaxation
* Emetic action
* effect on adrenergic neurons in CRTZ
33
What are the cardiovascular effects of alpha-2 adrenoceptors
* "Biphasic"
* Initial increase in blood pressure (peripheral phase)
* agonist at postsynaptic alpha-1 and alpha-2 receptors in smooth muscle of vasculature
* These receptors mediate vasoconstriction
* Bradycardia
* Reflex response to initial hypertension
* Increases parasympathetic tone (baroreceptor reflex)
* May see second degree AV block occasionally
* Be cautious in use of atropine to treat this
* increased heart rate may increase hypertension and work of the heart
* Arrhythmogenic effects are common (bradyarrythmias)
* Decreased cardiac output (50% reduction is common) due mostly to reduced HR
* CO = HR x SV
* After initial BP increase, arterial pressure may decrease over time due a central depression of overall SNS tone (central phase)
* Cardiac contractility decreases
* manifestation of decreased SNS influence on the heart
34
What other side effects are common to alpha-2 adrenoceptors?
* **Potentiates central respiratory depression** caused by other drugs but very little respiratory depression if used alone
* **Depresses GI and ruminal motility**
* Activation of presynaptic alpha-2 adrenergic receptors in the enteric nervous system inhibit ACh release from cholinergic neurons (heteroreceptor activity)
* **Hypoinsulinemia** with possible subsequent hyperglycemia
* stimulation of alpha-2 receptors inhibits insulin release from pancreatic islet cells
* **Vomition**
* Common in cats (90% of cats with xylazine, 58% of cats with dexmedetomidine)
* less frequent in dogs (30% xylazine, 10% medetomidine
* **Diuresis**
* Alpha-2 adrenergic receptor stimulation blocks effect of vasopressin (ADH) on kidney
* **Hypothermia**
* Attenuate thermoregulatory control, reduce muscle activity, reduce shivering response, lower CNS shivering threshold
* **Increased intrauterine pressure in cattle**
* **Decreased uterine blood flow in all species**
35
What is the clinical use of xylazine?
* Most widely used alpha-2 agonist in large animal practice
* especially horses
* Alpha-2:alpha1 = 160:1
* Elimination half-life in minutes
* dog 30.1
* horse 49.5
* cattle 36.5
* Rapid onset after IV with 30 minute duration of sedation
* IM administration, peak plasma levels in 15 minutes
* Epidural analgesia in large animals
* analgesic for visceral pain
* Short term relief of colic pain in horses prior to transport
* motility and blood flow reduced
36
What is xylazine's affects on cattle?
* Very sensitive to the sedative effects of xylazine
* 1/10 equine dose
* Decreases rumen motility
* Hypersalivation can occur
* Predisposes to bloat, regurgitation
* May cause acute pulmonary edema in sheep due to induction of severe inflammatory response in lung or acute changes in pulmonary hydrostatic pressures
* To avoid overdose in ruminants a 20 mg/ml form of xylazine is available in contrast to the 100 mg/ml formulation used in equids
37
What are the properties of Detomidine?
* Dormosedan used in horses
* Injectable and oral gel form available
* Selectivity ratio is 260:1
* Longer duration sedation (1hr) compared to xylazine
* Elimination half-life
* horse 26-53 min (dose dependent)
* Cattle 79 minutes)
* Used for standing sedation, analgesia for colics, and less frequently as premed prior to gen anesthesia
38
What are the properties of Romifidine?
* Developed for use in equine sedation and premedication
* Use in other species
* Longer duration of action than xylazine and at higher end of dose range has longer duration than detomidine (up to 2hr)
* Elimination half-life in horse 138.2 min
* Less ataxia than xylazine or detomidine
* sometimes preferred for standing procedures
* All other effects similar to other alpha-2 agonists
39
What are the properties of Dexmedetomidine?
* Active isomer in the racemic mixture of the drug medetomidine
* levomedetomidine provided very little of agonist effect of parent drug
* Selectivity ratio 1620 : 1
* Used primarily in small animals for sedation or as preanesthetic. Also used extensively in exotics
* Can be used as a Sedative, analgesic, for restraint, for short term pain control
* long term pain control as CRI
* Adverse effects:
* substantial bradycardia, development of hypertension or signs of poor tissue perfusion
* Avoid in patients with poor cardiac output, or where increased afterload could be detrimental
40
What are the antagonists for Alpha-2 adrenoceptor?
* May be associated with rapid and occasionally rough recovery due to immediate loss of sedation and analgesia
* **Atipamezole** - use with dexmed
* **Yohimbine -** use with xylazine
* **Tolazoline** - use in Large animals when yohimbine is unavailable
41
What kind of opioid is Buprenorphine? Properties?
* Partial µ - agonist (CIII)
* Duration of action longer than other opioids (4-8hr)
* High affinity for µ receptors
* displace µ agonists
* More resistant to naloxone reversal
* Less vomiting, sedation than morphine, hydromorphone
* ~1 hr to produce maximum effect (IV), clinical efficacy in 10-30 min
* Oral bioavailability \<20% - **not effective PO**
42
What are the different classes of induction agents capable of producing general anesthesia?
* Phenol derivatives (Propofol)
* Dissociatives (Ketamine, Tiletamine)
* Imidazole derivatives (etomidate)
* Steroid anesthetics (Alfaxalone)
43
How fast are induction agents?
* Rapidly acting
* high lipid solubility results in rapid arrival in CNS often in one “circulation time” 15-30 sec
44
How do induction agents produce anesthesia?
* Achieving sufficient plasma level which is dependent on:
* Speed of injection
* rapid injection = higher concentration in a small quantity of blood passing the brain (rapid IV bolus)
* Concentration of Drug
* higher the concentration of drug in solution that is administered the higher the concentration reaching the brain rapidly
* Not a critical factor in that most drugs are marketed at a precise concentration
45
What does delivery of intravenous anesthesia to the brain depend on?
* Brain Blood Flow
* vessel rich tissues
* Only 10% body mass gets very high CO (75% at rest)
* Depends on total CO
* Low CO states can result in more rapid onset of anesthesia
* less distribution of blood flow to all body tissues
* blood flow to brain is preserved
* Higher peak plasma concentration is delivered due to less “dilution” with lower CO
* Lipid Solubility of drug
* more lipid soluble agents move into and out of the brain more quickly
* blood-brain barrier
* Protein binding
* only ‘free’ drug can move into brain
* Propofol is about 98% protein-bound
* if changes to 96% drug activity has doubled
* Can improve activity with
* hypoproteinemia
* other protein bound drug competition (NSAIDS, antibiotics)
* Renal Disease (azotemia)
46
How do patients recover from IV anesthetic?
* Depends on decreased CNS drug concentration
* decreasing CNS conc depends on redistribution of drug away from brain
* 1 minute Brain level peaks
* 2 minutes Plasma level is 20% of original concentration
* Muscle level peaks at 20 min
* Fat level peaks at 45 - 60
* Hepatic metabolism
* after CRI of highly lipid soluble drugs there is a context-sensitive half-life
* Renal Excretion
* ketamine in cats only
47
What is anesthetic recovery vs total elimination?
* Recovery occurs faster than whole body elimination
* blood levels must be reduced below what is required for anesthetic effect for recovery to occur
* Hangover from lingering drugs can persist with drugs that have a slow metabolic elimination (compared to those with rapid metabolism/clearance)
* especially true after CRI
48
What is Propofol? use? types? properties?
* IV anesthetic agent
* Ideal for outpatient procedures - rapid recovery
* clear awakening, little “hangover”
* **INsoluble** in water
* 2 formulations
* formulated in emulsion
* soy & egg lecithin - support bacterial growth
* No preservatives - limited shelf-life (\<24hr)
* _Microemulsion formulation_
* benzyl alcohol preservative - 28 day shelf-life
* Ultrashort acting induction agent
* rapid recovery due to redistribution away from vessel-rich tissues
* **NOT** cumulative
* liver metabolism very rapid
* 60% of clearance
* extrahepatic sites have yet to be clearly ID (renal? lung?)
49
What is the MOA of Propofol?
* Activate GABA receptors in the CNS (similar to benzos)
* Specific binding sit on the GABAA receptor, separate from benzo site
* Depress polysynaptic responses, major inhibitory control in the CNS
* At low conc - can augment the affinity of the GABAA receptor for GABA and increase the mean chloride channel opening time
* Increases chloride conductance and hyperpolarizes neurons
* at high conc - anesthetic - directly increases channel openings, even in the _absence_ of GABA
* Summary:
* Increases inhibitory effect of GABA at the GABAA receptor
* CNS depression
* sedation/anesthesia
* muscle relaxation
* myoclonus can occur
* little analgesia
* only through CNS depression
50
What are the cardiovascular effects of propofol?
* transient effects
* Minimal effect on myocardial contractility
* short term vasodilation ( ⇣ cardiac preload)
* mild to moderate hypotension
* no reflex tachycardia to offset ⇣ BP
* Reduced CO - dose dependent
* Slower infusion at induction is safer than rapid bolus
51
What are the respiratory effects of Propofol?
* Depressant
* decrease in tidal volume and RR
* May produce apnea
* more common w/ rapid infusion rate/high doses
* Be prepared to intubate and ventilate until breathing resumes
52
What are the advantages of Propofol?
* Rapid onset
* short duration of action
* rapid smooth recoveries
* Non-cumulative - unless prolonged CRI
* Context-sensitive half time increase with CRI
* Useful for anesthetic induction and/or maintenance by CRI
53
What are the disadvantages of Propofol?
* Moderate Hypotension
* Respiratory depression (apnea)
* Poor analgesia (need alternative source)
* Drug vehicle may support bacterial growth
* Formulation can cause pain on IV injection
* Heinz body hemolysis reported with repetitive use in cats
* more than 3 consecutive days
54
Name the dissociative anesthetics used in vet med
* Ketamine
* Tiletamine (with zolazepam in Telazol)
55
What is the MOA of Dissociative anesthetics?
* Effects NMDA receptor-ion channel complex
* neurotransmitter -glutamate
* 1° excitatory neurotransmitter of CNS
* Non-competitive NDMA receptor antagonist
* Binds to the pore of the NMDA receptor channel
* Prevents influx of calcium into the cell
56
What are the pharmacokinetics of ketamine?
* Termination of effect due to redistribution
* Undergoes hepatic metabolism to _norketamine_, an active metabolite with less potency
* Cats eliminate unchanged ketamine via the kidney
57
What are the CNS affects of Ketamine?
* Anesthesia with amnesia
* Analgesia and Catalepsy
* trance-like state characterized by loss of sensation, loss of consciousness with body rigidity
* Dissociates the cortex from lower centers
* out of body experience
* Both excitatory & depressant effects
* May produce seizure discharges seen on EEG
* Increase cerebral blood flow, intracranial pressure
* Prior administration of benzodiazepine reduces effect
* Hallucinogenic, vivid dreaming, dysphoria
* **As sole induction agent produces both unsatisfactory muscle relaxation and poor calming effects**
* **Almost always combined with benzos or alpha-2 adrenergic agonist**
58
What are the cardiovascular effects of ketamine?
* Secondary to increase SNS tone
* increase HR
* increase BP
* increase cardiac contractility
* increase CO
* Increased myocardial work
* Endogenous catecholamine release
* plasma catecholamine levels rise
* Ketamine inhibits norepinephrine reuptake into nerves
59
What are the respiratory effects of ketamine?
* Does **not** cause significant respiratory depression
* Ventilatory response to elevation in PaCO2 remains intact
* Bronchodilator
* Airway reflexes are maintained
* apneustic ventilation pattern
* prolonged inspiratory time with inspiratory breath holding before rapid exhalation
* Despite abnormal pattern
* PCO2 and minute ventilation is normal
* Glutamate plays a role in rhythmicity of brainstem respiratory pattern generator
60
What other effects are common with ketamine use?
* increased salivation
* muscle rigidity
* Increased intraocular pressure
* Increased intracranial pressure
* fetal depression
* negative effect shown on fetal outcome if used for C-sections in SA patients
61
What are the clinical uses of ketamine?
* Chemical restraint (IM)
* Minor sx as part of multi-drug combo approach with various sedative/analgesic agents
* Anesthetic induction (IV) all species
* In IV combination s to produce anesthetic induction or short term anesthesia
* Midazolam/ketamine (many species)
* Xylazine/Ketamine (LA species)
* Low dose CRI is an effective analgesia supplement
* subanesthetic dose can produce profound analgesia
* prevent or minimize central sensitization and wind-up in the nociceptive pathway
62
what is the recovery quality of Ketamine?
* Dysphoric rapid emergence common in dogs
* slow disoriented recovery in cats
* animals may benefit from additional tranquilization in recovery
63
how long does ketamine last?
* Variable, depending on dose/route
* PO 6-10
* IV 0.5 - 2
* nasal 6-10
* IM 3-10
* Rapidly absorbed via many routes
* Most species, recovery due to redistribution & metabolism
* In cats, urinary excretion of unchanged drug
64
What is Etomidate?
* Non-barbiturate, imadazole-derivative anesthetic agent
* Commercial formulations contains purified R(+) sterioisomer only
* Not water soluble - in a 35% propylene glycol diluent
* may cause pain on injection
* can cause intravascular hemolysis
* may not be clinically significant, but can result in hemoglobinemia and hemoglobinuria
65
What is the MOA of Etomidate
* GABA-agonist
* Sedation - hypnosis - anesthesia
* Binding sit identified on B subunit
66
What are the cardiovascular Effects of Etomidate
* Minimal CV effects
* Very little effect evident even in the presence of severe CV disease
* No change in HR, SV, CO, BP
* No change in SNS tone
* Highest therapeutic index (LD50/ED50) of the IV induction agents
* therapeutic index = 26
67
What are the CNS effects of Etomidate?
* Decreased cerebral blood flow
* Decreased cerebral O2 consumption
* Decreased intracranial pressure
68
What is Myoclonus? why does Etomidate cause it?
* Involuntary muscle contractions
* Disinhibitory effect on extrapyramidal (involuntary) motor activity
* Incidence decreased with prior administration of benzos or adequate premedication
* Incidence may be decreased by low dose incremental “pretreatment” with etomidate
* “split-dose induction”
69
How does Etomidate cause Adrenocortical Suppression?
* Inhibits 11 - B - hydroxylase
* Enzyme necessary for synthesis of cortisol and aldosterone
* Adrenal suppression lasts for 5-8 hrs after single IV bolus
* Contraindication for repeated use or CRI sedation
* Contraindicated in animals with Hypoadrenocorticism (Addison's)
70
name the steroid anesthetics
* alphaxalone
* alphadolone
71
What is Saffan?
* mix of alphaxalone and alphadolone
* alphaxalone was most active portion
* alphadolone improved solubility
* Cremophor EL vehicle caused allergic reaction involving histamine release
* contraindicated in dogs due to severe release
* cats experienced edema +/- hyperemia of paws and ears with occasional laryngeal or pulmonary edema
72
What is Alfaxan?
* Modern formulation - **Alphaxlone only**
* formulated inside a cyclodextrin ring which opens to release drug as a result of pH change post-injection
73
What is the MOA of alfaxalone?
* GABA agonist
* Binding site on B-subunit
74
what are the uses of alfaxalone?
* sedation, hypnosis, anesthesia
* IV as anesthesia induction
* IM for sedation
75
What are the effects of Alfaxalone?
* minimal hypotension (dose dependent)
* increase in HR
* Slight increase in cardiac index (secondary to ⇡HR)
* Mild respiratory depression (dose dependent)
* No tissue irritation when used IM
* Excellent muscle relaxation
76
How is Alfaxalone cleared from the body?
* Rapid metabolic clearance
* Hepatic metabolism
* BOth Phase I (cytochrome P450) and Phase II (glucuronidation and sulfation) pathways
* Elimination half-life
* dogs 34 minutes
* cats 43 minutes
77
What are the available formulations of alfaxalone?
* Preservative-free formulation
* opened bottles discarded within 24 hours of initial use
* Multi-dose formulation
* 28 day shelf-life
* Ethanol, chlorocresol, and benzethonium chloride as preservative
78
What are the inhibitory receptors for pain?
* Opiate - spinal and supraspinal (some peripheral)
* GABA (gamma-aminobutyric acid) - peripheral, spinal, and supraspinal
* Serotonin (many different subtypes and locations - some inhibit pain, some enhance pain transmission
* Alpha-2 (NE): binds presynaptically to decrease neurotransmitter release - spinal and supraspinal
79
how are opioids metabolised?
Primary hepatic metabolism (Phase I and/or Phase 2)
80
What effects other than analgesia do Mu opioids have?
* Dose-dependent respiratory depression
* clinical significance minimal in healthy animals
* Caution in animals w/ preexisting respiratory comprimise
* head trauma (cerebral edema)
* respiratory disease
* other respiratory depressants (inhalant anesthetics, propofol)
* Bradycardia - parasympathetic mediated
* Cardiac Output - minimal effects
* proportional increase in Stroke volume relative to bradycardia
* high doses can lead to mild/moderate decrease in CO
* Vascular Effects:
* Primary hypotensive effects when combined with propofol, inhalants, acepromazine
* hypothermia
81
What effects do mu agonists have on the urinary system?
* Urinary retention - increases tone of sphincters and inhibit micturition
* Decreased urine production - mech unknown
* Not commonly recognized clinically in animals
82
what are the adverse effects of morphine
* bradycardia
* hypothermia
* dysphoria
83
Why should buprenorphine not be given with Mu agonists?
* Partial agonist with high affinity for receptors.
* will displace mu agonists
* more resistant to naloxone reversal
