Anesthetic and Analgesic Agents Tessa Bowers, LVT

What do you really know about the drugs you use? Name Strength Dosage ranges (species specific) Common uses Systemic effects Reversibility Routes

Drug “Categories” Inhalant Benzodiazepine Pure Opioid and partial agonist/antagonist Dissociative Tranquilizer/Alpha-2 Agonist Hypnotic Non-barbiturate Anticholinergic Local Non-steroidal Anti-inflammatories (NSAID) Agonists

Cookie cutter drug protocols It is imperative to limit the use of “cookie cutter” dosage protocols. Every patient is different. Drugs along with their dosages should be adjusted base on their species, age, PE, blood work, past anesthetic experiences, and procedure.

Inhalants Isoflurane Allows for rapid changes in induction, depth transition, and recovery Causes respiratory depression, depression of cardiac contractility, vasodilatation, increases ICP Contraindicated for pets in shock or history of malignant hyperthermia MAC 1.3% in dogs and 1.6% in cats, surgical plane 1 – 1.5x MAC

Sevoflurane Allows for very rapid changes in induction, depth transition, and recovery Causes respiratory depression, depression of cardiac contractility, vasodilation, increase ICP Contraindicated in animals in shock or history of malignant hyperthermia MAC 2.4% in dogs and 2.6% in cats, surgical plane 1 – 1.5x MAC Does not cause larynospasm

Benzodiazepines Diazepam Anticonvulsant Excellent muscle relaxant Minimal CV depression Minimal respiratory depression Reduces ICP When used in conjunction with other medications, reduces required doses necessary

Diazepam Causes Delayed recovery in pets with hepatic dysfunction Excitation in young, health patients Potentates respiratory depression of opioids Occasional PVC after IV dose (due to propylene glycol solvent) Significant thrombophelbitis with rapid IV False urine glucose

Diazepam Uses IM administration is accompanied by poor and erratic absorption Non water soluble, will sting if given IM Crosses the blood brain barrier Metabolized in the liver, eliminated primarily in the urine. Reversible by Flumazenil (0.1 mg/kg IV) Dosage 0.1 – 0.2 mg/kg IV May be used as a CRI but binds to plastic and should be protected by light

Midazolam Delayed recovery in pets with hepatic dysfunction Highly protein bound Excitation in young, health patients Potentates respiratory depression of opioids Nearly 3x times as potent as diazepam Crosses the blood brain barrier

Midazolam Uses Well absorbed after SC and IM injections Water soluble, does not sting after IM injections Shorter duration than Diazepam Metabolized in the liver Reversible by Flumazenil (0.1 mg/kg IV) Dosage 0.1 – 0.3 mg/kg IV, IM, SC CRI 0.3 mg/kg/hr, protect from light

Butorphanol Synthetic partial agonist/antagonist opioid Minimal organ toxicity More rapid onset then morphine Does not cause histamine release Does not induce vomiting Minimal respiratory depression then other opioid agonists Antitussive Antiemetic

Butorphanol Undesirable Effects At high doses will cause dysphoria, nystagmus, salivation, hyperthermia, and decrease GI motility Ceiling effect to analgesic action Analgesic and sedation effects are short lived due to drug duration Unless frequent dosing, does not provide aid in inhalant reduction needs

Butorphanol Uses Parenteral analgesia for mild pain in dogs and cats Opioid partial antagonist or reversal agent Onset of action approximately 5 minutes Peak analgesic and sedation effects 15 – 30 minutes Reversible by Naloxone (0.04 – 0.1 mg/kg IV/IM) Dosage 0.1 – 0.5 mg/kg IV, IM, SC (alone) Sedation effects prolonged when combined with other drugs

Morphine Agonist at mu opiate receptor Minimal organ toxicity Histamine release with IV injection, sometimes causing pronounced vasodilation/hypotension Induces vomiting with IM or SC injection Antitussive

Undesirable effects from Morphine Slow onset of action Induces bradycardia (or tachycardia due to coronary vasoconstriction) Miosis in dogs Decreased GI motility (may have immediate defecation, then GI slows) Respiratory depression Dysphoria at high doses in cats Constipation Bronchoconstriction Hyperthermia in cats and hypothermia in dogs

Wait there’s more.... Morphine causes a decrease in sympathetic nervous tone, which can lead to decreased venous tone, decreased CO, pooling of blood, decreased arterial pressure secondary to decrease return GI side effects include nausea, vomiting, decreased intestinal peristalis

Morphine Uses Parenteral analgesia for moderate pain Epidural analgesia for abdominal and hind body surgical procedures (exploratory, PU, orthopedic are some examples) Contraindicated in head trauma, respiratory disease or acute respiratory dysfunction Crosses the placenta Provides better sedation THEN analgesia

Sedation does not = pain control Morphine needs to be protected from light Incompatible with heparin Increase Amylase and Lipase upto 24 hours following administration Reversed by naloxone Dogs: 0.1 – 1 mg/kg IM, SC (IV 10% of this) Cats: 0.05 – 0.2 mg/kg IM, SC Epidural: 0.1 mg/kg, duration 12 to 24 hours

Hydromorphone Agonist at mu opiate receptor Minimal organ toxicity 5x more potent then morphine Mild histamine release with IV injection More rapid onset then morphine Induces vomiting with IM or SC injection Antitussive

Undesirable effects of Hydro Dose dependant respiratory depression Dysphoria at high doses, use a tranquilzer with Side effects include: sedation, bradycardia, slight decrease in cardiac contractility and blood pressure, panting Do not use with patients that have head trauma, increased ICP, acute abdomen, respiratory disease Do not use with patients that are bradycardic Be careful with GDV and other obstructive disease

Hydromorphone Uses Use for analgesia for moderate to severe pain in dogs and cats Epidural analgesia for abdominal and hindlimb body surgical procedures Increase Amylase and lipase up to 24 hours

Hydromorphone Dosage Sedation onset (route dependant) 5 – 10 minutes Analgesic onset (route dependant) 15 – 30 minutes Metabolized in the liver, excreted by the kidneys Reversible by naloxone Dogs 0.05 mg – 0.4 mg/kg IV, IM, SC q 2 -4 Cats 0.02 mg – 0.2 mg/kg IV, IM, SC q 2 – 6 CRI

Fentanyl Pure mu opioid agonist Extremely rapid onset with extremely short duration Neuroleptanalgesia in dogs when combined with a benzodiazepine or acepromazine Reversible by naloxone, but normally not necessary due to it’s short duration

Fentanyl effects Excitatory at high doses or alone in young/healthy dogs or cats Respiratory depression Dose related bradycardia Urine retention, possible constipation, possible ileus Increase Amylase/Lipase up to 24 hours Dosage 2 – 10 mcg/kg IV as bolus, then CRI Recent studies with patches show 18 hours till effect

Buprenorphine A partial opiate agonist Because of the above may not provide appropriate analgesia for moderate to severe pain. (thoracotomy and orthopedic procedures) Slower onset of action (30 min – 1 hour) Do not give SC, poor erratic absorption IV, IM, SL every 4 to 8 hours, BUT does have a ceiling effect.

Buprenorphine Effects Incompatible with diazepam Side effects include decrease blood pressure, HR, and rarely respiratory rate Highly plasma protein bound (not albumin) Crosses the placenta Dogs 0.005 – 0.02 mg/kg Cats 0.005 – 0.01 mg/kg

Dissociative Ketamine can be used SC, IM, IV for anesthesia/chemical restraint Inhibits NMDA receptors for adjunct use to control pain Inhibits GABA and may block serotonin, norepiniephrine, and dopamine Superficial analgesia Rapid onset of effects, no matter the route Sympathetic stimulation

Ketamine effects Muscle rigidity if given alone Seizures in 20% of cats Increase ICP, IOP, BP, salivation, temperature Increase CO = increase in HR, increase in MAP and in CVP Eyes remain open, mild jaw tone once induced Pain with IM injections Sensitive to noise during induction/recovery

Ketamine Use Do not use in patients with shock, renal/liver impairment, alone, hypertension, ICP, hyperthyroidism Decreases airway resistance. Do not use for airway procedures Good for patients in wind up. Low dose CRI. Dogs and Cats 10 mg/kg IV CRI 0.1 – 0.6 mg/kg/min

Tranquilizer Acepromazine antiarrhythmic, antiemetic, antihistamine slow onset, even in IV (up to 15 minutes) duration (12 – 24 hours) Occasional bradycardia (or reflex tachycardia) Lower dosage in giant breeds and greyhounds Incompatible with diazepam and glycopyrrolate dogs and cats 0.025 – 0.5 mg/kg IV 0.025 – 0.1 mg/kg IM/SC

Alpha 2 Domitor (medetomidine) Primary use for restraint and quick procedures at regular veterinarians Beneficial for wind up patients At bottle dosage causes cardiac depression, decrease BP (or hypertension caused by vasoconstriction) At much lower dosage plus and opiod, decreases these side effects Reversible with atipamazole (IM only)

Hypnotic Propofol Rapid and short acting Reduces ICP, IOP Transient apnea (worsened by other drugs) Hypotension and bradycardia Repeated doses in cats may cause increase Heinz body production, slow recoveries, anorexia, lethargy, diarrhea Repeated doses in dogs may cause autoimmune problems

Propofol uses Do not use with patients that are anemic, dehydrated, hypovolemic, shock, hypoproteinemia Onset within 1 minute, duration 2-5 minutes Dosage 4 – 6 mg/kg IV, give over 60 – 90 seconds. CRI intra-op 0.4 mg/kg IV Side effects may be less if given while administering crystalloid therapy

Non-Barbiturate: Etomidate IV anesthetic agent useful in patients with pre-existing cardiac dysfunction or the critically ill Little effect on CV system, RR, decreases cerebral blood flow and O2 consumption Do not use with hypoproteinemic patients Pain at IV site, retching, transient hemolysis Pre-treating with diazepam and/or opioid reduces the above effects along with dosage

Etomidate Give via rapid IV injection, via an IV line to reduce pain and chance of hemolysis Protect from light at room temperature Duration of hypnosis 3 -5 minutes Recovery slower then propofol Onset 15 to 30 seconds Duration 5 to 15 minutes Etomidate alone: 1 -3 mg/kg IV Etomidate 1 mg/kg IV + diazepam 0.5 mg/kg IV

Anticholinergic Atropine Glycopyrrolate Protects the heart from bradycardia of reflex vagal stimulation and bradycardia induced by the effects of drugs Glycopyrrolate Anticholinergic of choice for patients with hyperthryoidism and HCM Incompatible with dex sp and diazepam (+ others)

Glycopyrrolate and Atropine Will not cross blood brain barrier Marginally crosses Tachycardia (some) IV peak 1 – 5 minutes IM, SC peak 30-40 min Vagalytic effects 2 -3 hr 0.005-0.01mg/kg IV 0.01-0.02 mg/kg IM, SC Atropine Crosses the blood brain barrier Crosses the placenta Tachycardia (raging) IV peak 3-4 minutes Antihistamines may enhance effects 0.01-0.02 mg/kg IV 0.02–0.04 mg/kg IM, SC

Local anesthetics Lidocaine Bupivacaine Rapid onset Duration 60 – 120 min Quickly absorbed Given IV to fast may cause rapid pressure drop Decrease general anesthetic needs Local and systemic use Bupivacaine 4x more potent then lidocaine Used for regional & epidural nerve blocks Onset slow to intermediate Duration 3-10 hours Cardiac toxicity higher

NSAIDs These drugs as a class share common therapeutic actions: anti-inflammatory analgesic effects antipyretic effects Are effective to both acute and chronic pain with minimal side effects COX-1 inhibitors are more commonly known for their side effects. (ie: piroxacam) COX-2 inhibitors oral longer acting, less SE. Do not alter the patients CNS, respiratory, CV system

General Info The use of NSAIDs predisposes animals to gastric erosions and ulceration, especially those the GI disease. On the ER side of things we see worst case scenario...... PO SID: Rimadyl, Etogesic, Metacam, Deramaxx, Previcox IV SID: Rimadyl, Metacam Do not change from one to another w/out waiting a minimum of 48 to 72 hours.

Antagonists Flumazenil Benzodiazepine antagonist Antagonizes the sedative and amnestic qualities May benefit treating encephalopathy with severe hepatic failure May cause vomiting, cutaneous vasodilation, vertigo, ataxia, blurred vision Discard once in syringe after 24 hours Antagonist: 0.01 mg/kg IV

Naloxone Pure opioid antagonist, reverse apomorphone Reversal of CNS and respiratory depressant Being investigated to treat septic, hypovolemic, or cardiogenic shock At high doses increases dopamine levels and seizures may be seen Sudden reversal can cause a catecholamine surge, resulting in tachycardia, hypertension, dysrhythmias, and pulmonary edema

Use of Naloxone Crosses the placenta IV onset is 1-2 minutes, duration 20-40min IM onset w/in 5 min, duration 40-70 min Duration of reversal is normally shorter then the drug you are reversing IV 0.01 mg/kg and IM 0.04 mg/kg Protect from light

Questions?