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Anesthetic and Analgesic Agents Tessa Bowers, LVT.

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1 Anesthetic and Analgesic Agents Tessa Bowers, LVT

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

17 Wait theres 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 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 GI side effects include nausea, vomiting, decreased intestinal peristalis

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

35 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 Little effect on CV system, RR, decreases cerebral blood flow and O2 consumption Do not use with hypoproteinemic patients Do not use with hypoproteinemic patients Pain at IV site, retching, transient hemolysis Pain at IV site, retching, transient hemolysis Pre-treating with diazepam and/or opioid reduces the above effects along with dosage Pre-treating with diazepam and/or opioid reduces the above effects along with dosage

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

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

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

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

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

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

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

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

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

45 Questions? Questions?


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