Premedication

Goals of premedication: Calm and sedate the patient Reduce stress of handling Smooth anesthetic induction, maintenance and recovery Reduce induction and maintenance drugs required Provide pre-emptive analgesia and muscle relaxation Decrease airway secretions and salivation Obtund autonomic reflexes

 Hypnosis: A depth of sedation from which the patient is not easily aroused Loss of ability to maintain a patent airway Lack of response to surgical stimuli Propofol, ketamine, thiobarbiturates, etomidate Indistinguishable from general anesthesia with volatile anesthetics

Sedative Drug that relieves anxiety Conscious sedation Drowsiness Benzodiazepines and alpha-2 agonists

 Tranquilizer: A drug with a predominant action in relieving anxiety without producing undue sedation. These drugs are also called anxiolytics or antianxiety drugs. An example of this type of drug would be diazepam and other benzodiazepines

 Competitively antagonize Ach at cholinergic postganglionic muscarinic receptors (parasympatholytic) Receptors found in: Heart Salivary glands Smooth muscles of the GIT and UT

Anti-cholinergics

Postganglionic nicotinic receptors located at the NMJ and autonomic ganglia Anticholinergics are selectively anti-muscarinic and only anti-nicotinic at toxic doses

 Atropine is an alkaloid of belladonna Semi-synthetic belladonna alkaloids (e.g., glycopyrrolate) are quaternary ammonium derivatives which are more potent Glycopyrrolate does not cross the BBB, so has no ocular or CNS effects Atropine crosses the BBB and cause sedation, excitement, and mydriasis

Potent antisialogouges Reduce salivary and bronchial secretions Mydriasis (atropine) Central Anticholinergic Syndrome (rare)

Cardiac Output = HR x SV
Parasympatholytic Competitively antagonizes Ach Sinus bradycardia, sinus at cholinergic postganglionic arrest, sinus block, 1o, muscarinic receptors 2o, and 3o AV blockade Decreases vagal tone and CPR = atropine prevents vagally induced Bronchodilation bradycardia Increases and maintains HR and improves CO

 Urinary tract Decreases tone of smooth muscles of the ureters and the urinary bladder Reduces spasm of ureters Increases tone of the bladder sphincter urinary retention

Gastrointestinal Tract Reduced motility and ileus Avoid in ruminants and horses Increased sphincter tone Decreased gastric H+ secretion Decreased tone of smooth muscles of the biliary tract

Clinical Use

Asystole = Atropine!

Included as pre-medication: Maintain heart rate and CO Offset vagal reflexes Decrease GIT, salivary and respiratory secretions To treat sinus bradycardia, sinus arrest, sinus block, and first, second, and third degree atrioventricular blockade Contraindications: Pre-existing tachycardia GI motility problems (horses, rabbits, ruminants)

Tranquilizers and Sedatives

Phenothiozines Benzodiazepines Alpha-2 agonists and antagonists

 Dopamine (D2) and alpha1 (a1) receptor antagonist (blocker) D2 receptors: CNS (arousal) Basal ganglia (coordinate motor function) CTZ (nausea and vomiting) Hypothalamus (temperature control) Alpha-1 receptors: vasoconstriction

Elimination Hepatic metabolism Elimination half-life is 3 hours; detectable in plasma > 8 hours

Acepromazine

Cardiovascular Effects - Ace

Respiratory effects Minimal effects Dose dependent decrease in blood pressure due to: Alpha1 R blockade - vasodilation Depression of CNS vasomotor centers CV collapse in patients with high SNS tone or hypovolemia Epinephrine reversal Anti-arrhythmic Decreases sensitivity to catecholamines Cardiac output and heart rate minimally affected a low dosage rates

CNS Effects of Acepromazine

Sedation (prolonged period of sedation at least 4 hours) Anxiolytic (likely not) Muscle relaxation and decreased motor activity Third eyelid prolapse Reduces required dosages of other drugs, including inhalants (MAC reduction) Anti-emesis (CTZ) Inhibits hypothalamic thermoregulation Rigidity or tremors with overdosage (Extra-pyramidal or Parkinsonian-like signs) Acepromazine has the reputation for lowering the seizure threshold, but there is little evidence to support this.

Other Effects Acepromazine

Anti-emetic (CTZ) Anti-histamine Hypothermia Penile prolapse and priapism in stallions Splenic sequestration of RBCs Prolonged sedation (4 to 8 hours or longer) Premedication prior to anesthesia Contraindicated in head trauma, increased ICP Contraindicated in neonates, elderly, shocky patients Caution in Boxers; always combine with an anticholinergic Lower dosages in larger animals Caution with aggressive animals

 Distribution & Elimination Highly protein bound (9698%) Unbound drug crosses the blood brain barrier and is active Metabolism Hepatic with renal excretion of metabolites

Mechanism of Action Receptors in cerebral cortex, hypothalamus, cerebellum, midbrain, hippocampus, medulla and spinal cord Increase GABA and glycine Sedation due to increased GABA activity in the CNS Anxiolysis & muscle relaxation due to increased glycine activity Mild analgesic effects - possibly due to increased GABA Retrograde amnesia

Benzodiazepines

CNS Effects-Benzodiazepines
Anticonvulsant Very mild sedation or even excitement when used alone in dogs, cats, horses Mild to profound sedation in sick animals Mild sedation in ruminants Muscle relaxation (spinally mediated) Analgesia (mild) Appetite stimulant

Benzodiazepines
Respiratory Minimal effects Respiratory depression when combined with opiates or other anesthetic agents Cardiovascular Minimal effects Slight increase in HR

 Diazepam (Valium) Water insoluble (dissolved in propylene glycol) Pain on injection Mixes poorly with other drugs (except ketamine) Diazepam usually given IV, but can be given orally Unreliable absorption when given IM or SQ Midazolam (Versed) Water soluble at low pH Given IM, IV or subcutaneously 2-3 xs more potent than diazepam Shorter acting than diazepam No pain on injection Can be mixed with other drugs

Benzodiazepines
Zolazepam Found only combined with Tiletamine as Telezol Only benzodiazepine licensed for use in veterinary patients Flumazenil - reversal agent for all benzodiazepines

Clinical Usage:
Rarely used alone in healthy patients as sedation is poor and excitement may occur Often combined with ketamine to induce anesthesia Administered with opiates for sedation of higher risk patients (neurolept anesthesia) Sedative affects are good in debilitated, sick patients, especially if combined with an opiate Generally used for sedation of pediatric, geriatric, and compromised patients

a2- Adrenoreceptor Agonists

Alpha2 receptors: Decreased SNS outflow: Inhibition of NE release from terminal axons Inhibition of firing of NE neurons (hyperpolarization) Decreased NE turnover in CNS

Peripheral effects: Vascular smooth muscle contraction (post-synaptic a2 R) Vasoconstriction Inhibition of insulin release from pancreas Hyperglycemia

a2- Adrenoceptor Agonists

Decreased SNS outflow in the CNS results in: Sedation (Alpha-2 receptors in the locus ceruleus) Analgesia (spinal a2 receptors) Muscle relaxation (spinal a2 receptors) Cardiovascular depression (centrally mediated) Bradycardia Decreased contractility Vasodilation Decreased CO

Cardiovascular Effects
Administration results in initial vasoconstriction, followed by reflex bradycardia, then centrally mediated SNS depression Bradycardia, vasodilation, decrease in CO, tissue perfusion Dysrhythmias Xylazine causes premature ventricular contractions (PVCs); other a-2 agonists decrease PVCs All cause sinus arrhythmias, bradycardia, sinoatrial block, 1st and 2nd degree A-V block Respiratory Mild respiratory depression More significant with opiates Hypoxemia in cattle and sheep

CNS Effects
Degree of sedation depends on: Dose rate Route of administration Mental state of patient Species and breed Physical condition (profound in debilitated or geriatric patients) Concurrent drugs (additive & synergistic effects) Hypnosis (loss of consciousness) at higher doses

Muscle relaxation centrally mediated via spinal alpha-2 receptors Anxiolytic

CNS Effects
Analgesia Comparable to opioids in efficacy for visceral pain and act synergistically with opioids Duration of analgesia is much shorter (around 1 hour) than duration of sedation Significant reduction of doses of other drugs used for anesthesia, including volatile anesthetics (MAC reduction) Reversal agents available alpha-2 antagonists

Unwanted Effects
Vomition in dogs and cats (xylazine) Decreased GI tract motility, resulting in ileus Inhibition of insulin release from pancreas resulting in hyperglycemia and osmotic diuresis Sweating and piloerection in horses Increased myometrial contractions in cattle with xylazine, which can lead to abortion in the third trimester Bradycardia -reversed with alpha-2 antagonists or atropine or glycopyrrolate only if life-threatening Indications: Young to middle-aged, healthy, exercisetolerant animals

Contraindications:
Pre-existing CNS depression Pre-existing cardiovascular disease Gastric or intestinal or urinary obstruction Diabetes mellitus Avoid xylazine in cattle in the last trimester of pregnancy In any animal that does not have normal cardiovascular and respiratory function

a2- Adrenoceptor Antagonists

Increase SNS outflow and NE release from CNS Reversibility is an advantage Specificity for a2 receptors: atipamazole > idozoxan > yohimbine > tolazoline

Neuroleptanalgesia
Goal: production of a tranquil, calm patient with some dissociation from environment and analgesI Combination of a tranquilizer or sedative with an opioid A tranquil and analgesic state due to synergism of an analgesic and a tranquilizer or sedative Better sedation results in: -- Better restraint and decreased dosages of other agents used (injectable and volatile anesthetics) Addition of the opiate allows decreased dosage of sedate Less CV depression with additional sedation More rapid elimination of drugs when differing metabolic pathways involved More rapid elimination and recovery because of lower dose