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75 Cards in this Set
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Drug class that induces sedation without drowsiness. - Calming effect |
TRANQUILIZERS e.g. phenothiazines, butyrophenones |
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Drug class that induces sleep. |
HYPNOTIC e.g. Benzodiazephines (thiopentone, propofol, etc) |
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Drug class that induces sedation with drowsiness. |
SEDATIVES - e.g. Alpha-2 Adrenoreceptor Agonists |
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List the four main drug classes used for sedation in vet med, in order of increasing UNRESPONSIVENESS. |
1. Tranquilizers - sedation without drowsiness 2. Neuroleptic - type of tranquilizer used in treatment on psychoses 3. Sedative - sedation WITH drowsiness 4. Hypnotic - induces sleep |
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What are the most common tranquilizers used in vet med? |
PHENOTHIAZINES - Acepromazine/acetylpromazine (ACP) = most commonly used in small animals! - Others: Chlorpromazine, promazine, etc...
BUTYROPHENONES - Azaperone = only used in pigs - Hypnorm = licensed for use in small furies = Fluanisone + fentanyl (full opioid agonist = 100x more potent than morphine) |
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What are the five neurotransmitters involved with CNS physiology? |
1. Amino acid NT - Glutamate = excitatory - y-aminobutyric acid (GABA) = most imp; inhibitory - Glycine = inhibitory 2. Noradrenaline (NA) - Controls mood/alertness 3. 5-HT - NT controls emesis, mood; # of diff receptors 4. Dopamine - Precursor for NA; D2 most imp receptor wrt to this lecture... 5. Acetylcholine - Nicotinic & muscarinic rec = diff effects |
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Describe the mechanism of action of phenothiazines, such as Acepromazine (ACP). |
NON-SELECTIVE, DOPAMINE ANTAGONISTS - activity in basal ganglia/limbic system and act by inhibiting adenylate cyclase - Most affect other receptor systems as well (alpha-1 adrenoreceptors, 5-HT1, H1, muscarinic) |
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Briefly describe each pharmacodynamic effect of phenothiazine. |
1. CNS = Tranquilizer 2. CVS = Arterial hypotension (10-20% dec in ABP) 3. Respiratory = minimal effects except in dyspnoeic animals 4. GIT/Anti-emetic = dec sm muscle activity (anti-muscarinic activity) delaying emptying; dopamine antagonism at chemoreceptor trigger zone (CTZ) effective anti-emetic 5. Antihistamine = promethazine is the most potent 6. Hypothermia = PHERIPHERAL VASODILATION 7. Others = penile prolapse & priapism in stallions, Dec PCV (uptake of RBCs into spleen) & potentiates the effects of other drugs. |
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Describe the effects of Phenothiazines on the Cardiovascular system. |
1. ARTERIAL HYPOTENSION (10-20% dec in arterial BP) - Peripheral vasodilation (alpha-adrenergic blockade) - Direct action on vascular smooth muscle - Central actions on medulla causing dec sympathetic outflow = dec vasoconstriction 2. MILD TACHYCARDIA - Response to hypotension - Anti-muscarinic effect 3. ANTI-ARRHYTHMIC ACTION - Raises threshold to adrenaline = induced arrhythmias |
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Describe the effects of Phenothiazines on the Respiratory system. |
Generally minimal . . - Sedation may worsen degree of respiratory distress in dyspnoeic patients |
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Describe the effects of Phenothiazines on the GIT and Anti-emetic properties. |
GI EFFECTS: - Dec GI smooth muscle activity (anti-muscarinic action) - Delayed gastric emptying - Dec gastro-esophageal sphincter tone - Anti-sialagogue ANTI-EMETIC AGENTS: - Act centrally via domine antagonism, thus inhibiting the Chemoreceptor Trigger Zone for emesis |
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Promethazine has the most potent antihistaminic action of all the phenothiazines.
True or False? |
TRUE |
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Phenothiazines have hypothermic effects due to . . . |
PHERIPHERAL VASODILATION = inc heat loss |
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Describe the other random effects that can result from phenothiazine use, aside from CNS, CVS, Respiratory, GIT/Anti-emetic, Antihistaminic and hypothermic effects. |
1. Penile prolapse - Correlates with onset and duration of sedation - Priapism (persistent erection) in stallions 2. Decreased PCV - Uptake of RBCs into spleen 3. Potentiate the effects of other drugs - Reduce induction and maintenance anesthetic requirements! |
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Butyrophenones are chemically unrelated to phenothiazines.
True or False? |
TRUE - Although they are both tranquilizers, they are chemically UNRELATED! |
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Describe the general pharmacological effects of Butyrophenones. |
1. CNS - sedative action, antiemetic properties 2. CVS - some vasodilation & hypotension (alpha-1 adrenergic antagonism)
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Describe the main CLINICAL USES of Phenothiazines. |
1. Premedication prior to G/A - By themselves or - Mixed with opioids (neuroleptanalgesia) 2. Sedation for minor procedures (radiography, ultrasound, etc) 3. Control of motion sickness 4. Calming (fireworks, etc) |
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What is the only Phenothiazine used in vet med? |
Acepromazine (ACP) - licensed in dog, cat and horse, with high therapeutic index meaning it's a rather safe drug; requires massive overdose to do harm. - poor dose-response relationship; sedation effect can be quite unpredictable so only for minor procedures - lowers mortality rate in horses quite dramatically when used as premedication before surgeries; mechanism unknown |
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When sedating with acepromazine (ACP), if the animal doesn't seem to be sedated enough after initial dose, you can simply top up the amount with additional dosing to reach desired effect.
True or False? |
FALSE - ACP has a poor dose-response relationship = little correlation between plasma levels and clinical effect. - Can't just give more because this will only prolong the sedation and increase the risk of side effects, not sedate the animal anymore. |
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What is the percent of oral bioavailability of acepromazine? What is the preferred route of administration? Other route options? Duration? Metabolized by? |
- ORAL BIOAVAILABILITY = 20-55% reaches systemic circulation; rest isn't absorbed/broken down by liver and excreted in urine - PREFERRED ROUTE: IM - OTHER ROUTES: SC, IV - DURATION: 4-6 hours (dose-dependent) - METABOLISM: Liver |
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Contraindications of Phenothiazines? |
1. Breeding stallions & bulls: - Priapism of the penis can lead to damage/necrosis 2. Hypovolemic (dehydrated) animals - Hypotension can be precipitous - If animal falls flat during sedation, check BP and give fluids immediately; probably dehydrated. 3. Care with specific breeds: - Boxers tend to faint, but still safe; give lower dose - Giant breeds are more sensitive; again lower dose 4. Kidney-damaged animals - Hepatic metabolism is main source of breakdown of acepromazine. |
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Vet clinical uses of BUTYROPHENONES. |
Azaperone (Strensil) - Used to sedate/modify behavior in pigs during surgical procedure or when introducing new herds of pigs together to deter fighting Fluanisone + fentanyl = HYPNORM - Licensed for use in small furies for tranquilizing - Combined with full opioid agonist = POTENT |
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Describe the pharmacokinetic aspects of Azaperone (stresnil) wrt: - Preferred route? - Duration? |
PREFERRED ROUTE: Deep IM injection - IV is difficult and doesn't absorb well. - Leave animal undisturbed for 30 mins, otherwise stress may fight effects DURATION: 2-3 hours |
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Azaperone is considered a dose-related sedation and results in slight fall in blood pressure.
True or False? |
TRUE |
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Side effects of Azaperone? |
Similar to ACP: - Mild hypotension - Hypothermia - Priapism of penis - Minimal respiratory effects |
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Tranquilizer (neuroleptanalgesia) licensed for use in small furies and mixed with a full opioid agonist, Fentanyl. |
HYPNORM - Fluanisone + Fentanyl - 100x more potent than morphine - Profound sedation! |
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Sedative drugs which have central effects as well as effects out in the periphery? |
ALPHA-2 ADRENORECEPTOR AGONISTS - Alpha-2 receptors widespread throughout the body (sympathetic NS, vascular endothelium, CNS, platelets, uterus, & gut) |
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Describe the functions of the alpha2-adrenoreceptors throughout the body. |
Inhibit adenylate cyclase, thus decreasing cAMP & inhibit voltage-gated Ca2+ channels & activate Ca dependent K+ channels. - Located prejunctionally at synapses and inhibit NT release (NA stimulates alpha2 receptor -> inhibits adenylate cyclase -> inhibits cAMP -> inhibits further NT release) - Located post-junctionally in vascular smooth muscle = vasoconstriction/contraction - CNS mediate sedation and analgesia |
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Effects of alpha2-adrenoreceptor agonists in the Central Nervous System? |
Effects on Function: - Sedative, analgesic & muscle relaxant * Mediated by central alpha-2 receptors * Presynaptic dec NA release * Depression of neurons in locus ceruleus (conducts signals from low brain stem to upper brain = sedative effect) - Decrease in sympathetic drive (predominance of vagal tone) |
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Which alpha-2 adrenoreceptor agonist has the greatest specificity? |
MEDETOMIDINE Ratio of a2:a1 selectivity = 1620:1
Than, Detomidine > Xylazine |
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What are the two alpha-2 receptor subtypes? Where are each most important within the body? |
1. Alpha-2A = most imp PRESYNAPTICALLY
2. Alpha-2B = most imp POSTSYNAPTICALLY |
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Effects of alpha-2 adrenoreceptor agonists on blood pressure? |
1. Dec in Sympathetic Vascular Tone: - Initial, peripheral, postsynaptic vasoconstriction = hypertension (inc BP) - Followed by, Peripheral & central presynaptic vasodilation = normalization 2. Bradycardia (slowing of heart) - Partly reflexive baroreceptor response to vasoconstriction - Partly due to central dec in sympathetic drive |
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What can be done to offset the effects of bradycardia (dec HR) caused by alpha2-adrenoreceptor agonist sedatives? |
Use an alpha2-adrenoreceptor ANTAGONIST * Beware, because this reverses sedation AND ANALGESIA. |
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Describe the sedative effects of alpha2-adrenoreceptor agonists (alpha2s). Licensed? |
Mild to deep sedation - Dose-dependent
Licensed in dogs, cats, horses and cattle. |
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Describe the analgesic effects of alpha2s. |
POTENT analgesic action - Central action (spinal & supraspinal) - Dose dependent and shorter than sedation |
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Cardiovascular effects of alpha2s? |
HYPERTENSION => Hypotension/normotension - Marked bradycardia (dec HR) |
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Respiratory effects of alpha2s? |
Mild to moderate depression in dogs, cats & horses * RUMINANTS = arterial hypoxemia (can be very severe in sheep) |
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GIT effects of alpha2s? |
* Vomiting in some species - Zylasine given IM in cats to induce emesis.
* GIT motility is depressed (dec Ach release) |
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Endocrine effects of alpha2s? |
- Inhibition of ADH = diuresis - Inhibition of insulin release (alpha2s in pancreas) = hyperglycemia |
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Urogenital effects of alpha2s? |
Uterine contraction |
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Veterinary clinical uses of alpha2s? |
- Sedation/premedication - Offset muscle hypertonicity caused by pre-anesthesia drugs like ketamine (which inc muscle tone) - Analgesia = horses with colic; during anesthesia |
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Routes of administration for alpha2s? |
IM, IV, SC & Epidural routes common. * Oral route = high 1st pass metabolism! |
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What are the main alpha2-adrenoreceptor agonists used in veterinary medicine? |
1. Xylazine (not specific) 2. Detomidine (semi-specific) 3. Romifidine 4. Medetomidine (most specific) 5. Dexmedetomidine (also used in humans) |
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What is the dirtiest alpha2-agonist drug, licensed for dogs, cats, horses and cattle, which isn't used in the UK as much anymore, but is still used on small animals in N. America? |
XYLAZINE (Rompun) - "Dirty" because has very low selectivity for alpha2 receptors, which causes inc side effects - Administered via IM & IV routes - Duration is short and varies depending on the species, route & dose of drug. - Metabolized to multiple products that are excreted in urine - Species differences in sensitivity: Ruminants > Horse/dog > Pig |
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Describe the following pharmacokinetic aspects of XYLAZINE: - Route of admin - Duration - Metabolism - Selectivity - Species differences? |
ROUTES: IM or IV DURATION: Short - spp, route & dose-dependent METABOLIZED: to multiple products that are excreted in urine SELECTIVITY: Very low for alpha2 rec = increased side effects SPECIES DIFFERENCES: Ruminant (very sensitive)> horse/dog > Pig |
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Describe the pharmacological effects of Xylazine. |
Typical alpha2-agonist used in small & large animals CVS: Arrhythmogenic Urogenital: contraction of uterine smooth muscle |
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________________ used in horses and recently licensed in cattle for standing sedation. |
DETOMIDINE (Domosedan) - Imidazole derivative; typical alpha2-agonist |
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Describe the pharmacokinetic aspects of detomidine. |
- Administered IM or IV - Longer duration of action than xylazine (1-2 hours in horse) - Equipotent in horses and cattle (standing sedation) |
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Clinical use of detomidine in vet med? |
Alpha2-adrenoreceptor agonist - used for "standing" sedation in horses and cattle. |
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Alpha2-adrenoreceptor agonist used in horses that provides the longest duration of sedation (up to 3 hours)? |
ROMIFIDINE (Sedivet) - Causes less ataxia in horses |
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______________ - Cleaner alpha2-agonist, used mainly in dogs, cats, and exotic species, which is very potent & very selective for alpha2 receptors (a2:a1 ratio = 1620:1) |
MEDETOMIDINE (Domitor) |
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Describe the pharmacokinetic aspects of Medetomidine. |
- Administered IM, IV, or SC - Rapid onset & duration up to 3 hours - Very potent & very selective for alpha2s - Sedation may be profound |
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Pharmacological effects of Medetomidine? |
Typical Alpha2-Adrenoreceptor Agonist CVS: may be antiarrhythmic - Vomiting in some patients, but less than xylazine. |
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Medetomidine is a racemic mixture of levomedetomidine and dexmedetomidine. Which is the active isomer? |
DEXMEDOTOMIDINE = active isomer
Levomedetomidine = inactive - Reduces activity of dexmedotomidine - Delays metabolism of other hepatically metabolized drugs (e.g. ketamine) = "hangover" effects |
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What is the main alpha2-adrenoreceptor ANTAGONIST used in vet med? |
ATIPAMEZOLE (Antisedan) - Specific for alpha2 receptors - Antagonizes alpha2 agonists awakening the animal from sedation - Reverses analgesia also - Licensed for dogs and cats via IM route |
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Benzodiazepines (BZPs) are considered a ____________ class of drug. |
HYPNOTIC |
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Clinical uses of Benzodiazepines (BZPs) in Vet Med? |
- Sedative/Premedicant - Anticonvulsant
* Few side effects which makes it good for use in very young, very old, or very ill animals. |
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What is the main inhibitory neurotransmitter in the CNS? |
GABA Two receptor types: 1. GABAa - Receptor for ligand gated Cl- channels, which mediate fast inhibitory synaptic responses - Drugs mostly target these GABAa 2. GABAb |
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Describe the mechanism of action of Benzodiazepines (BZPs). |
BZPs potentiate GABA (inhibitory action on CNS) - Facilitate the opening of GABA activated chloride channels - BZP binding site is distinct from GABAa site & increases affinity of GABA for its receptor (enhanced agonist effect) |
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Describe the general pharmacological effects of Benzodiazepines (BZP). |
- CNS - primarily anxiolytic action (muscle relaxation & anticonvulsant properties) - CVS/RESP - minimal depression |
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Describe the pharmacokinetics of benzodiazepines. |
- Well absorbed orally = good bioavailability - Highly plasma protein bound - Lipid soluble = high = inc distribution = accumulation within tissues likely - Metabolism = glucuronidation |
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Side effects of Benzodiazepines? |
Acute - less dangerous than other hypnotics - Little CVS/respiratory effects - Paradoxical excitement in healthy patients, rather than sedation... |
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Clinical use of Benzodiazepines? |
- Excellent anxiolytics (anxiety inhibitors) - Minimal CV & respiratory effects - Good sedation in sicker patients (CNS system depressed)
* Would seem to be ideal agents for sedation/premedication, EXCEPT FOR THE PARADOXICAL EXCITEMENT IN HEALTHY PATIENTS; so not used with healthy patients |
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What are the two main types of benzodiazepines? |
1. DIAZEPAM 2. MIDAZOLAM (Hypnovel) |
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Describe the pharmacokinetic aspects of DIAZEPAM. |
- Administered via IV, orally, or rectally for epileptic animals - Rapid onset & short duration (IV) - Liver metabolism - Excreted in urine - Insoluble in Water |
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What are the two DIAZEPAM preparations available? |
1. "Valium" = formulated in propylene glycol - May induce thrombophlebitis 2. "Diazemuls" = lipid emulsion formulation - Better for veins (no thrombosis) - BUT decreased bioavailability. |
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Water soluble benzodiazepine, which undergoes conformational change at physiological pH to become lipid soluble. |
MIDAZOLAM (Hypnovel) |
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Describe the pharmacokinetic aspects of MIDAZOLAM. |
- Administered IV, IM, or orally - Rapidly metabolized; short duration
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Describe the pharmacological effects of MIDAZOLAM. |
Similar to Diazepam, but twice the potency - Less likely to accumulate because requires only have the dose & is metabolized much faster. |
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Clinical uses of Benzodiazepines? |
1. Neuroleptanalgesia (a state of quiescence, altered awareness, and analgesia) 2. Premed/hypnosis of 'sick' animals 3. Control seizures 4. Pre-empt seizures 5. Induce eating (cats) 6. Occasionally, to alter behavior 7. Muscle relaxation (often combined w/ ketamine) * NONE OF BZPs ARE LICENSED IN ANIMALS! |
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None of the benzodiazepines are licensed for use in animals.
True or False? |
TRUE |
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A condition in which the patient, though not entirely unconscious, is insensitive to painful stimuli. |
NEUROLEPTANALGESIA
Neuroleptic = "nerve seizing" |
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________________ is produced by the combination of neuroleptic (e.g. phenothiazines, butyrophenones) & opioid analgesic. |
NEUROLEPTANALGESIA - Definition in vet med extended to include combinations of sedative or hypnotic (alpha-2 agonists, benzodiazepine) and an opioid analgesic. |
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Licensed neuroleptanalgesia for small furies. |
HYPNORM - Fluanisone + fentanyl (full opioid agonist) - Usually given IM or IP - Long duration of action - Can be antagonized by "sequential analgesia" (partial opioid antagonist to wake up the animal, but still providing some analgesia) |
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Give two examples of "homemade" neuroleptanalgesia preparations. |
1. ACP + pethidine 2. alpha2 agonist + butorphanol |