PRE-ANESTHETIC AGENTS

INTRODUCTION TO ANESTHESIA & PRE-ANESTHETIC AGENTSCHAPTERS 1 & 3TERMINOLOGY OF ANESTHESIAAnesthesia may be defined as loss of sensation, but this only describes one of its effects.It is used daily in most veterinary practices to provide sedation, tranquilization, immobility, muscle relaxation, unconsciousness, and pain control for a diverse range of indications including surgery, dentistry, grooming, diagnostic imaging, wound care, and capture/transport of wild animalsTERMINOLOGY OF ANESTHESIASedation refers to drug-induced CNS depression and drowsiness that vary in intensity from light to deep.Patient can be aroused by noxious stimuliTranquilizaion is a drug-induced state of calm in which the patient is reluctant to move and is aware of but unconcerned about its surroundings.Often used interchangeable with sedationTERMINOLOGY OF ANESTHESIAHypnosis is a sleeplike state from which the patient can be aroused with sufficient stimulation.

Narcosis refers to a drug-induced sleep from which the patient is not easily aroused and that is most often associated with the administration of narcotics.TERMINOLOGY OF ANESTHESIAGeneral anesthesia may be defined as a reversible state of unconsciousness, immobility, muscle relaxation, and loss of sensation throughout the entire body produced by administration of one or more anesthetic agents.Surgical anesthesia is a specific stage of general anesthesia in which there is sufficient degree of analgesia(loss of sensitivity to pain) and muscle relaxation to allow surgery to be performed without patient pain or movement.AwakeLight sedationModerate sedationDeep sedationHypnosisNarcosisLight surgical anesthesiaModerate surgical anesthesiaDeep surgical anesthesiaAnesthetic overdoseSedationGeneralanesthesiaFully consciousBorder between Consciousness and unconsciousnessUnconsciousTERMINOLOGY OF ANESTHESIALocal anesthesia refers to loss of sensation in a small area of the body produced by administration of a local anesthetic agent in proximity to the area of interest.Topical anesthesia is the loss of sensation of a localized area produced by administration of a local anesthetic directly to a body surface or to a wound.Regional anesthesia refers to a loss of sensation in a limited area (larger area than with local anesthetics)of the body produced by administration of local anesthetic agent in proximity to sensory nerves.

TERMINOLOGY OF ANESTHESIABalanced anesthesia refers to the practice of administering multiple drugs concurrently in smaller quantities than would be required if each were given alone.Maximizes benefits of each drugMinimizes adverse effectsAllows anesthetist to produce CNS depression, immobilization, and pain relief that is appropriate for the patient and the procedure.PRE-ANESTHETIC AGENTS & ADJUNCTSANESTHETIC AGENT: any drug used to induce a loss of sensation with or without unconsciousness.ADJUNCTS: a drug that is not a true anesthetic but that is used during anesthesia to produce other desired effects such as sedation, muscle relaxation, analgesia, reversal, neuromuscular blockade, or parasympathetic blockadeEx: muscle relaxants, neuromuscular blockers, reversal agentsPRE-ANESTHETIC AGENTS & ADJUNCTSCHOOSING THE APPROPRIATE AGENTSAVAILABILITY: most clinics will not have the option of choosing from every drug on the market.FAMILIARITY: drugs are often chosen based on the veterinarians familiarityPROCEDURE: drugs that are appropriate for one procedure may not be appropriate for another Some drugs are short-acting and would not be appropriate for long surgeriesSome drugs may be appropriate for a spay but not a c-sectionPRE-ANESTHETIC AGENTSCOST: It is ok to use a cheaper anesthetic as long as it is just as safe as the more expensive one.TIME TO ONSET OF ACTION: in emergency situations, fast-acting drugs may be necessary

The anesthetic protocol, dose, and route are chosen by the veterinarianMany clinics have a routine protocol, but is important to consider all aspects of the patients minimum databasePRE-ANESTHETIC AGENTSDrugs that are administered to an animal prior to general anesthesiaMay be a single drug or combination of drugsDo not mix two or more drugs unless you have reliable evidence that it is safe to do so.REASONS TO ADMINISTER PRE-ANESTHETIC AGENTSTo calm or sedate an excited or fractious animal

PRE-ANESTHETIC AGENTSREASONS TO ADMINISTER PRE-ANESTHETIC AGENTSTo counteract the effects of other injectable or inhalant anestheticsEx: some anesthetic agents cause hypersalivation, we can use atropine or glycopyrrolate to counteract this effect. To reduce the amount of general anesthetic agents requiredIf the patient is already sedated, it takes less drug to bring them into the unconscious state. This is a safer practice than using large amounts of drugsUsing smaller amount of both pre-anesthetics and anesthetic agents in combination is known as balanced anesthesia.PRE-ANESTHETIC AGENTSREASONS TO GIVE PRE-ANESTHETIC AGENTSTo reduce pain & discomfort: some pre-anesthetic agents last long enough to be effective post-operatively

ANTICHOLINERGICS

TRANQUILIZERS and SEDATIVESPhenothiazinesBenzodiazepinesAlpha-2 agonists

OPIODSAgonistsPartial agonistsAgonist-antagonistsantagonistsCLASSES OF PREANESTHETIC AGENTSANTICHOLINERGICSaka parasympatholytics or sympathomimeticsThe vagus nerve provides parasympathetic innervation to numerous target organ such as:HeartLungsGI tract (viscerovagal reflex)Secretory glandsIris(oculovagal reflex)When the vagus nerve is stimulated by endotracheal intubation, GI traction, or manipulation of the eye, what effect does it have on the organs above?

ANESTHETIC & SURGICAL TECHNIQUES MAY STIMULATE THE VAGUS NERVEANTICHOLINERGICSAcetylcholine is the primary neurotransmitter in the PNS responsible for parasympathetic effects (cholinergic effects)

AchAchThese drugs are given to counteract the effects caused by vagal stimulation

EXAMPLES: Atropine, GlycopyrrolateANTICHOLINERGICSANTICHOLINERGICS

ANTICHOLINERGICS ONLY AFFECT MUSCARINIC RECEPTORS ON THE TARGET ORGANSAchAchWHAT EFFECT DO ANTICHOLINERGICS HAVE ON THE VARIOUS BODY SYSTEMS?

EFFECTS:ADVERSE EFFECTS:WHAT EFFECT DO ANTICHOLINERGICS HAVE ON THE VARIOUS BODY SYSTEMS?

EFFECTS:ADVERSE EFFECTS:WHAT EFFECT DO ANTICHOLINERGICS HAVE ON THE VARIOUS BODY SYSTEMS?

EFFECTS:ADVERSE EFFECTS:WHAT EFFECT DO ANTICHOLINERGICS HAVE ON THE VARIOUS BODY SYSTEMS?

EFFECTS:ADVERSE EFFECTS:WHAT EFFECT DO ANTICHOLINERGICS HAVE ON THE VARIOUS BODY SYSTEMS?

WHAT EFFECT DO ANTICHOLINERGICS HAVE ON THE VARIOUS BODY SYSTEMS?

WHAT EFFECT DO ANTICHOLINERGICS HAVE ON THE VARIOUS BODY SYSTEMS?

Both drugs can be given SQ or IM (preanesthetic purposes) or IV (emergency treatment of bradycardia/cardiac arrest)Atropine is generally preferred for emergencies due to the quicker onset of action Onset of Action/Duration of ActionAtropine IM: 5min, peak @ 10-20min, duration 60-90minAtropine IV: 1 min, peak @ 3-4 min, duration several minutesGlycopyrrolate IM: similar onset time to atropine, peak @ 30-45min, duration 2-3 hrsATROPINE vs. GLYCOPYRROLATE: A COMPARISONGlycopyrrolate causes less tachycardiaGlycopyrrolate is better at decreasing salivation

TOXICITYWith overdoses drowsiness, excitement, dry mouth, ataxia, muscle tremors, dilated pupils, hyperthermia, and tachycardia may be seenREVERSED with PHYSOSTIGMINEReversal is uncommonANTICHOLINERGICS ARE NOT CONTROLLEDATROPINE vs GLYCOPYRROLATE: A COMPARISONTRANQUILIZERS and SEDATIVESPHENOTHIAZINESBENZODIAZEPINESALPHA-2 AGONISTSTranquilizers reduce anxiety, but may not decrease awarenessSedatives reduce mental activity and awareness and induce sleepiness

These terms are often used interchangeably

Patients that have received a tranquilizer/sedative may still be easily aroused and could potentially get aggressive or injure themselvesGENERAL INFO ON TRANQUILIZERS/SEDATIVEShttp://www.youtube.com/watch?v=AkaGWwTHD5gPHENOTHIAZINESACEPROMAZINECHLORPROMAZINEThese drugs have no analgesic effectsThese drugs are not controlledThese drugs do not have a reversal agentExamples: Acepromazine, Chlorpromazine

GENERAL INFO on PHENOTHIAZINESWHAT ARE THE EFFECTS THAT PHENOTHIAZINES HAVE ON THE VARIOUS BODY SYSTEMS?

EFFECTS:ADVERSE EFFECTS:EFFECTS:ADVERSE EFFECTS:WHAT ARE THE EFFECTS THAT PHENOTHIAZINES HAVE ON THE VARIOUS BODY SYSTEMS?

EFFECTS:ADVERSE EFFECTS:EFFECTS:ADVERSE EFFECTS:ANTIHISTAMINE EFFECT

PENILE PROLAPSE

DECREASED PCV

Onset of action/duration of action 15min after IM injection, peak@ 30-60 minDuration: 4-8 hrs( could be up to 48hrs)

OTHER EFFECTS & ADVERSE EFFECTS of PHENOTHIAZINES:Sedative effects can be overridden if patient is stimulated to a sufficient degreeUse a max of 3mg in dogs and 1mg in catsBoxers and giant breed dogs by have increased sensitivityTerriers and cats are more resistant to its effectsChlorpromazine is used in veterinary medicine as an antiemetic, but not as an anesthetic adjunct.THINGS TO CONSIDER WITH PHENOTHIAZINESBENZODIAZEPINESDIAZEPAMMIDAZOLAMZOLAZEPAMBenzodiazepines depress the CNS by increasing activity of endogenous gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in the brain.These drugs are controlledThese drugs can be reversedFlumazenil is the benzodiazepine antagonist. It is rarely used due to the very low incidence of adverse effects and the high cost.These drugs provide no analgesiaThese drugs have unreliable sedative effects & could induce dysphoria, excitement, or ataxia in young, healthy animals, esp. when given alone

EXAMPLES: DIAZEPAM, MIDAZOLAM, ZOLAZEPAM

GENERAL INFO ON BENZODIAZEPINESWHATEFFECTS DO BENZODIAZEPINES HAVE ON THE VARIOUS SYSTEMS OF THE BODY?

EFFECTS:ADVERSE EFFECTS:

EFFECTS:WHAT EFFECTS DO BENZODIAZEPINES HAVE ON THE VARIOUS SYSTEMS OF THE BODY?

EFFECTS:EFFECTS:Diazepam is not water-soluble and cannot be mixed with water-soluble agents except ketamineMidazolam and zolazepam are water-soluble and can be mixed with other agentsDiazepam is is painful and poorly absorbed when administered intramuscularlyMidazolam is more readily absorbed via IM and SQ routesZolazepam is available only mixed with tiletamine to produce the combination product Telazol.Diazepam is very soluble in plastic and over time is absorbed by syringes, IV bags, and IV tubingTHINGS TO CONSIDER ABOUT BENZODIAZEPINESTHINGS TO CONSIDER ABOUT BENZODIAZEPINESDiazepam and midazolam are light-sensitiveOnset of action/duration of actionLess than or equal to 15 min after IM injectionDuration: 1-4 hoursALPHA-2 AGONISTSXYLAZINEDEXMEDETOMIDINEThese drugs are not controlledThese drugs can be reversedThese drugs do provide analgesic effects

These drugs act on alpha-2 adrenergic receptors in the CNS and PNS causing a decrease in the neurotransmitter norepinephrine

GENERAL INFO ON ALPHA-2 AGONISTSThe sedation is actually a paradoxical effect on the SNS. It decreases release of the neurotransmitter norepinephrine. The sedative effect is potent.The analgesic effects are relatively short-lived (~20 minutes) and should be supported by other agents45WHAT EFFECTS DO ALPHA-2 AGONISTS HAVE ON THE VARIOUS BODY SYSTEMS?

EFFECTS:ADVERSE EFFECTS:

EFFECTS:ADVERSE EFFECTS:CV: vasoconstriction with a reflex bradycardia leading followed by a decrease in cardiac output, hypotension, and further decrease in heart rate due to decrease in sympathetic tone.Resp: depress respirations, effects are dose-dependentMS: muscle relaxationGI:vomiting esp in cats and xylazine>dexmedetomidineOther drugs: increased effects of other anesthetic agents, reduce the amount of other drugs given46WHAT EFFECTS DO ALPHA-2 AGONISTS HAVE ON THE VARIOUS BODY SYSTEMS?

EFFECTS:ADVERSE EFFECTS:EFFECTS:ADVERSE EFFECTS:CNS:temporary behavior changes, aggression, excitementCV: pronounced bradycardia; dont use in debilitated animals or those with heart dzRESP:pronounced depression esp when given with other agents and in brachycephalic breedsOther: increased urination,gas distension of the stomach, premature labor, accidental absorption through the skin

47OTHER EFFECTS OF ALPHA-2 AGONISTSHyperglycemia: alpha-2 agonists reduce the secretion of insulin by the pancreasHypothermia: alpha-2 agonists decrease thermoregulation and shiveringPremature parturitionCan be absorbed through the skin and abrasions as little as 0.1ml of dexmedetomidine can cause hypotension and sedation in humans.THINGS TO CONSIDER ABOUT ALPHA-2 AGONISTSXylazine is largely reserved for use in large animalsCattle are sensitive and only require 1/10 of the dose used in horsesDexmedetomidine is largely used in small animals and is more potent than xylazineBoth drugs are commonly mixed with other drugs such as ketamine, and an opioid such as butorphanol or morphineAnimals can undergo minor and major surgical procedures with these combinations

These drugs can be reversed with Yohimbine (reverses xylazine) and Atipamezole (reverses dexmedetomidine)Atipamezole is sold in combination with dexmedetomidine and is given in a 1:1 ratioIt is not recommended to treat bradycardia with anticholinergics, but rather the appropriate reversal agentReversal takes only 5-10min

THINGS TO CONSIDER ABOUT ALPHA-2 AGONISTSOPIOIDSAGONISTSPARTIAL AGONISTSAGONIST-ANTAGONISTSANTAGONISTSMODE OF ACTION3 Primary receptor in the brain and spinal cordMu, kappa, delta

SEDATIONONSET OF ACTION:15min after IM administrationDURATION: 1-3 hrs for most (buprenorphine 6-8 hrs)

ANALGESIA*excellent somatic and visceral analgesia

GENERAL INFO ON OPIOIDSAgonists their effects on the mu and kappa receptors; partial agonists only partially stimulate the receptors; agonist-antagonists do not stimulate the mu, but stimulate the kappa; pure antagonists bind to but do not stimulate the mu & kappa receptor52WHAT EFFECTS DO OPIOIDS HAVE ON THE VARIOUS BODY SYSTEMS?

EFFECTS:ADVERSE EFFECTS:

EFFECTS:ADVERSE EFFECTS:CV: bradycardia, esp with other agentsRESP: minimal resp depression, panting due to effect on thermoregulatory center53WHAT EFFECT DO OPIOIDS HAVE ON THE VARIOUS BODY SYSTEMS?

EFFECTS:ADVERSE EFFECTS:EFFECTS:ADVERSE EFFECTS:Allergic reactions: morphine for example may cause facial swelling and hypotension after rapid Iv administration

Changes in body temperature: there is a resetting of the thermoregulatory center in the brain resulting in the dog panting and possibly lowering the body temperatureCats may have an elevated body temperature for unknown reasons.Miosis in dogs; mydriasis in cats

OTHER EFFECTS OF OPIOIDSCNS: anxiety, disorientation, dysphoria, increased response to noiseCV: pronounced bradycardiaRESP: dose dependent respiratory suppression, esp with other agentsGI:initally vomiting, salivation, diarrhea, flatulence, followed by prolonged constipationALLERGIES: morphine, meperidine, facial swelling, hypotension

55These are controlled substances with human abuse potential

Opioids used in combination with a tranquilizer achieve a state of profound sedation and analgesia termed neuroleptanalgesia

These drugs can be reversed with the opioid antagonist NALOXONE (works within 2 min IV and 5 min IM)Agonist-antagonists such as butorphanol can also be used to reverse the effects of pure agonists

These will be discussed further and in more detail in week 5-6

GENERAL INFO on OPIOIDS