Pre-Anesthetic Drugs

Medetomidine HCl

Alpha-2 agonist Approved in DOGS (sometimes used in cats too) Dose dependent CNS depression; can get sedation to immobilization More lipophilic, selective, potent and efficacious than xylazine or detomidine (and shorter elimination half life) Vomiting in 10-20% of dogs and 50-65% of cats Deep sedation with recumbency; can be aroused and walk around; once sedated, not responsive to sound Use for diagnostic procedures with deep sedation but don't need general anesthesia; no species variation NOT for use in horses b/c severe ataxia can cause brief intrauterine contraction at high doses but no premature parturition reported Lumbosacral or intercoccygeal epidural injection for perineal analgesia for 4-7 hours in cattle, 4 hours in cats Combined with ketamine-can use for short term anesthesia in small animal and zoo/wild animals, llamas and calves

Tolazoline

Alpha-2 A ANTAGONIST Least selective for alpha-2's Side effects -sympathomimetic, anti-hypertensive, histamine-like effect that causes cardiac stimulation, tachycardia, increased CO, vasodilation, hypotension, coronary vasodilation -Ach-like effect: cardiac slowing, stimulation of GI musculature -Tachycardia and GI distress are two major ones, especially with rapid IV injection -In humans, abdominal pain, nausea, diarrhea, exacerbation of ulcers, and GI bleeding after chronic use Ruminants and camelids more sensitive (low dose, slow injection)

Atipamezole (Antisedan)

Alpha-2 ANTAGONIST Antagonism of medetomidine, also effective for others 100x greater affinity for alpha-2's, 200-300x greater a2:a1 selectivity than yohimbine Rapid reversal of CNS depression induced by medetomidine Excitement may follow rapid IV injection

Yohimbine

Alpha-2 ANTAGONIST a2:a1 selectivity = 60:1 Antagonism of alpha-2 agonist induced CNS depression by enhancing the release of NE and replacing alpha-2 agonists from the receptor sites Increased BP, HR, and arousal by increased central sympathetic outflow Antagonism of side effects, treatment of accidental overdosing Shortens recovery time

When to use caution with xylazine

Cardiac aberration Hypotension/shock Hepatic or renal dysfunction Pregnancy (esp. last trimester in ruminants) Urethral obstruction Wobbler's (ataxia) Kick

Tolazoline toxicity

Generalized weakness, anxiety, trembling, hyperesthesia of head and neck Profuse salivation and sweating Tachypnea with episodes of dyspnea Convulsion, seizure activity (treat with diazepam) Weak pulse, hypotension (treat with phenylephrine) Profuse diarrhea Severe dyspnea, collapse (upper airway obstruction due to nasal edema) -histamine release, increased respiratory effort, lowered head position -phenylephrine nasal spray, tracheotomy, 100% O2 Camels: weakness, abdominal pain, colic

Benzodiazepines

Minor tranquilizers CNS depression: stimulation of benzodiazepine receptors and potentiation of GABA, increased chloride inflow into the cell, hyperpolarizing the cell (makes it harder to stimulate) Anticonvulsant Anxiolytic effect (depression of limbic system) Central muscle relaxation: inhiition of internuncial neurons at the spinal cord PO, IV, or IM, high oral bioavailability

Species variation: Xylazine

Ruminants are 10x more sensitive than horses Pigs are the least sensitive Pigs > Horses > Dogs > Cats > Ruminants Less effective in animals with high circulating catecholamines (excitement, fear, stress, pain; cause of sudden death in horses) Intracarotid injection can cause violent seizures by stimulating central alpha-1 receptors (put under general anesthesia to correct it)

Butyrophenone Derivatives

Similar to phenothiazines CNS depression by prevention of binding central catecholamines to their receptors -Tranquilization -Antiarrhythmic -Most potent antiemetic Extrapyrimidal effects -low doses, inhibition; high doses, stimulation -muscle tremors, spasticity, hyperirritability Lack analgesic effect, potentiate opiate analgesia

Chloral hydrate + Magnesium sulfate

12% chloral hydrate, 6% magnesium sulfate Sedation and anesthesia in large animals Improved muscle relaxation by neuromuscular blocking effect of magnesium sulfate

Fluphenazine

A phenothiazine derivative used in zoo animals (similar to ace)

Xylazine HCl

Alpha-2 agonist Approved in dogs, cats, horses, deer, and elk IV: sedation in 3-5 minutes, duration 30-40 minutes Rapid hepatic metabolism, less than 1% unchanged in urine within 2 hours Stimulation of CTZ, vomiting more frequently in cats, occasionally in dogs PAY ATTENTION TO THE CONCENTRATION-THERE ARE 2 Wide margin of safety -10x recommended dose is "safe" in dogs, cats, and horses, but will cause muscle tremors, bradycardia with AV block, and decreased RR

Romifidine

Alpha-2 agonist NEW Less ataxia and sedation, horses maintain higher head position Sedative ONLY, lack of analgesia Use with butorphanol for standing sedation, with ketamine for short-term anesthesia

Dexmedetomidine (Dexdomitor)

Alpha-2 agonist Racemic compound of medetomidine 2x potency of medetomidine Analgesia only with high doses Measured in micrograms/kg! Uses: chemical restraint, pre-anesthetic, epidural analgesia, CRI Can cause dark red/bluish tongue, low SaO2 but NR PaO2

Azaperone

Another butyrophenones Marketed for use in PIGS (only one that works really well on pigs at a low dose) -effective, dose-dependent tranquilization Slight decrease in blood pressure, but stable RR Excitement if disturbed within 20 minutes after IM IV results in vigorous excitement Avoid in horses Metabolized and eliminated within 16 hours Clinical uses: preanesthetic tranquilization, before transportation, prevent fighting before mixing

Anticholinergics

Antimuscarinic effects Prevent binding of Ach Competitive antagonism Pharmacological effects include inhibition of vagal stimulation, prevention of bradycardia, reduction of airway secretion and salivation, and mydriasis

Glycopyrrolate (anticholinergic)

Antimuscarinic effects Quaternary nitrogen, large molecular size; cannot penetrate BBB easily, lack of central vagal effect Fewer side effects: decreased tachycardia and arrhythmias Onset of action in 5-10 minutes IV, or 30-45 minutes IM/SC

Detomidine HCl (alpha-2 agonist)

Approved for use in HORSES ONLY Greater potency than xylazine (20-30x) Higher selectivity for alpha-2 receptors More profound and longer duration of sedation, analgesia, and muscle relaxation Severe bradycardia (HR of 12 bpm in horses) Visceral analgesia for 45 minutes vs. 20 with xylazine No species variation or dose requirement (ONLY HORSES) Epidural or intrathecal analgesia of >3 hours Increased intrauterine pressure and contraction, but it is less severe and premature parturition has not been reported

Clinical Uses of Diazepam (Valium)

Behavioral modifier Anticonvulsant Preanesthetic tranquilizer (anxiolytic) Anesthetic adjunct, especially in critical cases Anesthetic adjunct for muscle relaxation Appetite stimulant

Diazepam (Valium)

Benzodiazepine Controlled substance Not water soluble (40% propylene glycol), precipitates if mixed with water soluble drug Plasma half life in dogs is 125-160 minutes Active metabolites (2 of 3): nordiazepam and oxazepam, equipotent on the CNS Minimal cardiovascular effects High dose and rapid injection can cause transient hypotension (most likely due to the propylene glycol) Dogs occasionally get excitation, cats have aberrant behavior Horses: doses greater than 0.2 mg/kg may induce profound muscle relaxation and recumbency Respiratory depression LACK ANALGESIC EFFECT

Zolazepam

Benzodiazepine Similar to diazepam, midazolam Tiletamine + Zolazepam = Telazol Minimal CV effects Central muscle relaxation Longer duration Cats: aberrant behavior

Midazolam

Benzodiazepine Water soluble with pH of 3.5, no tissue irritation Shorter duration and more rapid elimination half-life Occasional behavioral changes in dogs and cats -restless, difficult to approach, pace, and vocalization in cats Minimal CV effects, similar to diazepam

Flumazenil

Benzodiazepine ANTAGONIST Only benzodiazepine antagonist available High affinity and specificity for benzodiazepine receptors Minimal intrinsic effect Onset of reversal within 2-4 minutes Duration of 60 minutes, may have to repeat dose No side effects

Droperidol

Butyrophenone used most often in vet med Therapeutic dose (0.5 mg/kg IV): decreased blood pressure, PVR, HR due to alpha-1 blockade, no change in cardiac output High dose (4 mg/kg): decreased RR, HR, CO, blood pressure, myocardial contractility Animals with severe cardiovascular disturbance -severe hypotension and cardiovascular collapse Epinephrine is contraindicated in droperidol-induced hypotension Less hypotension and hypothermia than phenothiazines Shorter duration of action (2hrs) and wider margin of safety than other butyrophenones -Haloperidol Sedation, analgesia, antiemetic

Cardiovascular effects of Xylazine

CV effects -Biphasic blood pressure: hypertension (stimulation of peripheral alpha-2 receptors) then hypotension (stimulation of central alpha-2 receptors); decreased central sympathetic outflow and depression of vasomotor center -Decrease in HR and CO: decreased central sympathetic outflow, increase in parasympathetic activity, decreased myocardial contractility (can give anticholinergic like atropine to counteract) -Arrhythmogenicity to epinephrine (SA block, AV block, AV dissociation and third degree block, sinus arrhythmia, bradycardia)

Contraindications of Acepromazine

Change in behaviors (can cause aggressiveness) Pre-existing seizure activity or procedures that cause seizures Head trauma with space-occupying lesion Hypovolemic, low CO and debilitated animals Sudden collapse in dogs Syncope in brachycephalic small animals (esp. Boxers)-vasovagal syncope Potential penile prolapse or paralysis in stallions Prolonged residues in food animals

Atropine (anticholinergic)

Comes from the belladonna plant (deadly nightshade) Antimuscarinic effect Easily penetrates the BBB because of small molecular weight Central vagal stimulation, initial slowing and then increasing of HR IV: onset of action in 1-2 minutes, with a duration of 30 minutes Can cause tachycardia, 2nd degree AV block, unifocal PVC, ventricular bigeminy (BP is unchanged) Increases RR and MV, relaxes bronchial muscles (increases dead space and bronchial secretion) Decrease in GI and ruminal motility, inappetence, ruminal stasis, colic Mydriasis, cycloplegia, sensitive to bright light, panic in cats and horses, blindness Carnivores more likely to develop toxicity; pigs are least resistant of all; horses, cattle and goats resistant when PO vs IV

Side effects of chloral hydrate

Decreased arterial blood pressure due to depression of the vasomotor center at anesthetic doses Mild respiratory depression during hypnosis, severe at anesthetic dose Death can result from progressive depression of the respiratory center Sudden death in high-strung horses (high circulating catecholamines, v-fib)

"InnovarVet"

Droperidol (20mg/ml) + fentanyl (0.4 mg/ml) Neuroleptanalgesic

Clinical signs of atropine toxicity

Dry mouth, thirst, dysphagia Constipation Mydriasis Tachycardia Hyperpnea Ataxia, muscle tremors Restlessness, delirium Convulsions Respiratory depression and failure Death

Alpha-2 agonists: CNS

Function: Decreased NE turnover, cardiovascular depression, sedation

Alpha-2 agonists: cholinergic neurons

Function: Inhibition

Alpha-2 agonists: platelets

Function: cause aggregation

Alpha-2 agonists: Smooth muscle

Function: contraction

Alpha-2 agonists: terminal adrenergic axons

Function: inhibition of NE release

Alpha-2 agonists: fat cells

Function: inhibition of lipolysis

Alpha-2 agonists: cell bodies of NE neurons

Hyperpolarization, inhibition of firing

Alpha-2 agonists: pancreatic islets

Inhibition of insulin release

Alpha-2 agonists in order of selectivity for a2 vs a1 receptors

Least => Greatest Xylazine Clonidine Detomidine Romifidine Medetomidine/Dexmedetomidine

Sublingual Detomidine gel

Oral bioavailability 22% Peak plasma concentration only 40% of what IM plasma concentration would be Used only sublingually, not meant for swallowing Leave horse in a quiet area for 30-40 minutes Duration: 90-180 minutes Signs of sedation: lowering head, front legs placed in a firm stance, mild ataxia, sweating IMPORTANT: LACK OF ANALGESIC EFFECT (vs. IV, which does have analgesic effect) Good for foot trimming, teeth floating, placement of stomach tube, endoscope, radiography, grooming, or other procedures where you need mild sedation and pain shouldn't be an issue Need impermeable gloves for administration Rinse well if contacts your sin Potential for abuse!

Acepromazine (tranquilizer)

Phenothiazine derivative CNS effects: Depression of brainstem and connections to cerebral cortex; antidopaminergic effects, increased turnover rate Good calming, not profound tranquilization Popular for dogs and cats Has extrapyrimidal effects at high doses: excitement, muscle rigidity, tremors, akinesia, cataleptic symptoms (due to increased concentration of dopamine metabolites, homovanillic acid, in the caudate nucleus) Alpha-1 adrenoreceptor blockage: Vasodilation, hypotension, not dose dependent, anti-epinephrine effect Epinephrine reversal: more severe hypotension in excited animals Can treat with alpha-1 adrenoceptor agonists (phenylephrine, methoxamine) HR and CO unchanged, significant decrease in RR Hypothermia (depletion of catecholamines in hypothalamus, thermoregulatory center, peripheral vasodilation) Prevent malignant hyperthermia in pigs Antiemetic effect; inhibits dopamine interaction in the CTZ in the medulla, effective against opiod-induced vomiting Antihistaminic effect, antiarrhythmic effect on the heart Splenic sequestration of red blood cells, decrease in PCV Lack of analgesic effect! -potentiates the analgesic effect of other drugs Spasomolytic effect on the intestinal smooth muscle (treatment for spasmodic colic) Oral, SC, IM, or IV (onset of action in 10-20 minutes and lasts for 2-3 hours)

GI effects of xylazine

Prolonged GI transit time -In non-fasted ruminants, can cause ruminal tympany and bloat Increased salivation and drooling Decreased swallowing

Chloral hydrate

Rauwolfia derivative Controlled substance, Schedule IV 1st CNS depressant used in animals CNS depression caused by depression of the cerebrum with loss of reflex excitability General anesthetic Poor analgesia and muscle relaxation; motor and sensory nerves not affected, subanesthetic dose Good hypotic but poor anesthetic (narrow margin of safety) Sedative/hypnotic in large animals Reliable sedation in horses when others fail Onset of hypnosis in 10-20 minutes Colorless, translucent, volatilize on exposure to air with aromatic, penetrating odor Active metabolite: trichloroethanol PO: irritates GI mucosa if not diluted in water; bitter and caustic tasting Perivascular injection causes severe pain, swelling, and tissue necrosis Usually administered IV Difficult to assess anesthetic depth b/c slow appearing depressent effect; continues several minutes after stopping administration Trichloroehtanol is further metabolized in the liver and excreted in the urine Chloral hydrate and tricholorethanol are secreted into saliva of the horse

Reserpine

Rauwolfia derivative Sedation by depletion of central catecholamines Approved in dogs Use in extremely high-strung, excitable horses on rare occasion No analgesic effects Not often used

Respiratory effects of Xylazine

Respiratory effects Decreased RR, increased tidal volume slight change in PaO2, PaCO2 Hypoxemia in sheep and calves -Very decreased PaO2 -increased resonant frequency, airway pressure and resistance -sheep: decreased PaO2 in conscious, recumbent state

Effects of alpha-2 agonists

Sedation, analgesia, muscle relaxation -sedation: locus ceruleus -analgesia: postsynamptic alpha-2 receptor in the substantia gelatinosa -central muscle relaxation: inhibition of polysynaptic reflexes in internuncial neurons Hyperclygemica, hypoinsulinemia -decreased insulin release, increased hepatic glucose production Increased urine output -decreased ADH secretion, esp. in ruminants Increased intrauterine contraction and pressure -premature parturition especially in ruminants

Alpha-2 adrenoreceptor Agonists

Sedative/analgesic Alpha-2 agonist + Alpha-2 receptor: activates G-protein -opens K+ channels in the neuronal membrane -lose K+ to extracellular space -membrane is hyperpolarized -cells are unresponsive to excitatory input

Xylazine: Epidural analgesia

Stimulation of alpha-2 receptors in pain pathways in supraspinal and spinal levels Brainstem, dorsal horn Injection site at L5-S1, or Co1-Co2 Slow onset of analgesia (15-30 minutes) and is long lasting (3-4 hours) Less motor function disruption CNS depression, sedation Reversible by IV alpha-2 antagonist

Intracarotid arterial injection in horses

Violent excitation Muscle tremors Stertorous respiration Pupillary dilation Recumbency Convulsion Cardiovascular collapse Avoid by doing injection on the upper half of the neck, because there is more separation between the jugular vein and carotid artery