LATG Chapters 14 & 15 Pharmacology Anesthesia

1. LATGChapters 14 & 15PharmacologyAnesthesia

2. Pharmacology • The science that deals with origin, nature, chemistry, effects, and uses of drugs • includes pharmacokinetics, pharmacodynamics, pharmacotherapeutics, and toxicology • drugs are good, but may be only one factor

3. Modes of Drug Action • Stimulation: increases the activity of cells (doxapram) • Depression: decrease cellular activity (atropine) • Irritation: leads to stimulation of activity (fleet enemas) • Replacement: synthetic substitutes (insulin or synthroid) • Chemotherapy: kill malignant tumor cells (Taxol or Doxorubicin)

4. Drug Classification • Classification systems: primary effect & site of action • Primary effect: unknown cause, but drug may relieve clinical signs • Site of action: organ specific drugs

5. Routes of Administration • Enteral: drugs are delivered directly into GI tract; slower absorption; wider safety margin • Oral & Rectal • Oral: tablets, capsules, powders, solutions, caplets, suspensions • powders, solutions, or suspensions: mix with food or require administration via stomach tube • Rectal: suppositories or enemas

6. Routes of Administration • Parenteral: without or around (par) the intestines (enteral) • IV, SC, ID, IM, IP, IC • quickest route to get drug into animal & to site of action • other routes: Intra-articular; Subarachnoid or Intrathecal, subconjunctival • drugs given should be sterile, nonirritating, and pyrogen-free

7. Routes of Administration • Inhalation: directly into respiratory tract • gas, vapor, fine mist or powder • particles or droplets must be less than 5um • most commonly used for anesthetic gases (i.e. isoflurane) • advantages: rapid absorption and elimination • disadvantages: intubation, mask, or inhalation chamber

8. Routes of Administration • Topical: application to skin or external membranes • lotions, ointments, pastes, and suspensions • slowest rate of absorption • advantages: high doses to local area without systemic toxicity • disadvantages: fur, dirt, bedding, licking

9. Dosage Forms • Enteral forms: solutions, suspensions, capsules, or tablets • Solutions: water based, tinctures, spirits, fluid extractions • Suspensions: insoluble drugs • Capsules: soluble in stomach or intestine (time-release) • Tablets: solid preparations (enteric coating)

10. Dosage Forms • Parenteral forms: mixed or dissolved in a sterile, pyrogen-free medium • IV, IA, IC drugs: dissolved in water, isotonic saline, or saline-dextrose • Depot effect: drug dissolve slowly gives a constant drug level

11. Therapeutic Use of Drugs • Tolerance: decrease in response to normal dose (e.g., NHP to ketamine) • Sensitization: increase in response (e.g., allergic reactions) • Synergistic: two or more drug which give an enhanced response (e.g., antibiotics) • Potentiation: increased action by one drug produced by another drug with nonrelated action

12. Therapeutic Use of Drugs • All drugs have a toxic effect if given in excess • Therapeutic Index or Margin of Safety • TI = Toxic dose/Effective dose

13. Distribution and Elimination • Distribution of drugs within the body varies considerably • Most drugs are inactivated by normal metabolic processes • Kidneys: primary route of excretion • Other routes: bile, respiratory • Metabolism: mostly occurs in the liver

14. Controlled Drugs • Schedule III-V: less potential for abuse (ketamine, butorphanol) • Requires federal and state licenses • Detailed records showing usage • Facilities which use controlled drugs may be inspected by DEA • Must be stored behind at least two locked doors

15. Controlled Drugs • Potential for being abused or addictive • Comprehensive Drug Abuse and Control Act: lists control drugs and 5 schedules • Schedule I: high potential for abuse; no medical treatment, no safety (LSD, heroin) • Schedule II: high potential for abuse, but have medical uses (codeine, opium derivatives, pentobarbital)

16. Dogs • Parvovirus: • acute disease of young dogs • bloody diarrhea and severe panleukopenia • Otitis Externa: • bacteria, yeast, ear mites (Otodectes cynotis) • factors: dirt, trauma, hair, foreign bodies • excess head shaking and odor • Heartworms: • Dirofilaria immitis; spread by mosquitos • adults live in pulmonary artery, right artium, and right ventricle

17. ANESTHESIA Review dosage calculations using ratios and cross multiplication Review the stages and planes of anesthesia Stage 1 - narcosis, sedation, analgesia Stage 2 - uninhibited response, delirium, excitement Stage 3 - surgical stage Plane 1 - loss of pain response Plane 2 - surgical plane Plane 3 - beginning of respiratory paralysis/pupil dilation Plane 4 - cyanosis, non-responsive pupils Stage 4 - paralysis of brain respiratory centers

18. • Respiratory Pattern - rate, depth and character of the respirations Shallow, thoracic pattern = lightly anesthetized Deep, abdominal pattern = deeply anesthetized Pattern should be regular ANESTHESIA Monitoring General Anesthesia • Monitored by observing flow valves, rebreathing bag, observing chest movement, in-line flow meter

19. Mucous membrane color - The gums, lips, rectum/vulva remain pink if the animal is receiving enough oxygen. They turn blue if there is a lack of oxygen. ANESTHESIA Monitoring General Anesthesia Capillary refill time - Measured by pressing on the gum line until the color blanches and timing its return to normal color when pressure is released. Normal is 2 seconds or less. Longer times indicate a perfusion problem from lowered cardiac output, increased vascular resistance, or hypovolemia.

20. Pulse evaluation - Done on the femoral or mandibular artery or the heart itself. The strength and character of the pulse vary with anesthetic depth and blood pressure. ANESTHESIA Monitoring General Anesthesia Blood pressure - Blood pressure can be measured indirectly using a pressure cuff on the tail or leg and an ultrasonic doppler flow detector. An arterial catheter can be used for direct BP.

21. Body temperature - Anesthesia affects the brain’s heat regulatory center, lowering the patient’s temperature. Loss is minimized by using a heating pad, warm fluids, and a heat lamp during recovery. Cooler temperatures slow the metabolism of the anesthetic. ANESTHESIA Monitoring General Anesthesia Eyes - Presence or absence of reflexes or nystagmus, and size of the pupil indicate the level of anesthesia

22. ANESTHESIA Muscle tone - varies with type of anesthesia used. Ketamine results in stiff, rigid muscles. Most other anesthetics result in some degree of relaxation which is easily observed in the larger species using jaw tone. Monitoring General Anesthesia Reflexes - most common is the pedal or withdrawal reflex, anal reflex also used. Both disappear as surgical plane reached. Laryngeal reflex used to determine time to remove endotracheal tube

23. ANESTHESIAPreanesthetics • Preanesthetics include tranquilizers, analgesics, and anticholinergics • Tranquilizers - lower the animals apprehension and aid in restraint for anesthetic induction • Analgesics - work with the tranquilizer to lower the amount of general anesthetic needed, increasing the safety margin. CAN MASK THE ANESTHETIC STAGES. • Anticholinergics - reduce secretions and raise heart rate

24. ANESTHESIAPreanesthetics • Anticholinergics -Atropine blocks acetylcholine resulting in decreased secretions from salivary and respiratory glands; blocks the vagal tone on the heart, increasing the heart rate • Tranquilizers - Phenothiazines reduce anxiety and cause muscular relaxation. Note: These agents cause peripheral vasodilation and hypotension. • -Analgesics - Medetomidine, Xylazine provides some anesthesia as well as analgesia and sedation. Often used with ketamine.

25. ANESTHESIAInjectable Anesthetics • Pentobarbital - Not to be confused with Phenobarbital. Long acting anesthetic that can be given IV or IP. For IV administration, half the dose is given quickly then titrated to the desired effect. No reversal agent. Must be very deep for analgesia. • Thiamylal, thiopental, methohexital - Ultrashort acting (about 15 minutes) agents commonly used for general gas anesthetic induction.

26. ANESTHESIAInjectable Anesthetics • Chloral hydrate - Used primarily as a sedative/hypnotic due to poor analgesic properties. Can cause profound depression of cardiovascular and respiratory systems. • Alpha-Chloralose - Poor analgesia and slow onset. Used in physiological studies since there is little effect on the cardiovascular and respiratory systems. Primarily used as a sedative.

27. ANESTHESIAInjectable Anesthetics • Urethane (Ethyl Carbamate) - Long lasting anesthetic. Has been associated with increased tumor formation. Can cause intestinal irritation if given IP. Usually used for long, terminal experiments. • Tricaine Methanesulfonate (MS-222) - A water soluble anesthetic frequently used for fishes and amphibians. • Fentanyl/Droperidol (Innovar-Vet) - An opioid and tranquilizer. Used for minor painful procedures.

28. ANESTHESIAInjectable Anesthetics • Ketamine HCl - A dissociative anesthetic. Administration results in excessive muscular tone, very mild respiratory depression, mild cardiac stimulation, salivation, adequate somatic but poor visceral analgesia. May produce seizures in some animals. Often used with xylazine for muscle relaxation and additional analgesia.

29. ANESTHESIAInhalant Anesthetics • Delivery and elimination occurs via the lungs = easy to adjust level of anesthesia being administered. • Supplied as a liquid that slowly evaporates at room temperature. • Carrier gases (oxygen +/- nitrous oxide) enter vaporizer where anesthetic gas vapor is added. • Unused anesthetic gas and exhaled CO2 must be removed.

30. ANESTHESIAInhalant Anesthetics - Delivery Systems • Chamber system - Clear plastic or glass container with cotton soaked in anesthetic placed in bottom and covered by mesh or perforated floor. Animal placed on floor and lid put on container. Anesthetic induction can be observed through the container wall. Once animal is removed, recovery begins. • Open Drop system - Nose cone with anesthetic soaked cotton used to maintain animals induced above. • Both systems must be used in a fume hood.

31. ANESTHESIAInhalant Anesthetics - Delivery Systems • Rebreathing systems allows recirculation of carrier and anesthetic gas and consist of a number of components

32. ANESTHESIAInhalant Anesthetics - Delivery Systems • Vaporizer • - Precision vaporizers are the most accurate and most commonly used type today. It automatically compensates for changes in vapor pressure due to temperature. • Copper kettle - older style that requires user to adjust for temperature variations • Wick-type - Used only with methoxyflurane since delivery concentration determined by liquid’s vapor pressure

33. ANESTHESIAInhalant Anesthetics - Delivery Systems • Lime Canister - Soda lime (calcium hydroxide or barium hydroxide) used to absorb the carbon dioxide in the expired air. A chemical indicator changes color when the soda lime should be replaced. • Compressed Oxygen - Supplied in tanks available in a variety of sizes, green color code, full tanks ~2200 psi indicated on regulator pressure gauge, delivery controlled by flowmeter (measured in l/m).

34. ANESTHESIAInhalant Anesthetics - Delivery Systems • Tubing and rebreathing bag - Allow for the one-way system to function. Rebreathing bag expands/contracts with each breath, should have a capacity of about 6 times the patient’s tidal volume. • Pressure relief (Pop-off) valve - Adjustable, used to fine-tune flow rate so that the rebreathing bag stays about 2/3 full.

35. ANESTHESIAInhalant Anesthetics - Delivery Systems • Scavenger systems - Used to remove the excess exhaled gases = Waste Anesthetic Gas or WAG • Most effective is direct exhaust to the outside via central vacuum • Activated charcoal canisters used on portable setups • Leakage of anesthetic around tubing connections, around endotracheal tube, and at machine connections can occur and frequent equipment inspections should be performed.

36. ANESTHESIAInhalant Anesthetics - Delivery Systems • Non-rebreathing systems - used for animals weighing ~ 7kg or less. Their tidal volume is too small to use the rebreathing systems so they use equipment that provides linear flow through the animal and then out to the scavenging device. This set-up produces large amounts of WAG.

37. ANESTHESIAInhalant Anesthetics • Vapor pressure - the higher the vapor pressure of a liquid, the quicker it will evaporate at a given temperature. The reason halothane and isoflurane can’t be used in the open drop system but methoxyflurane can is due to the differences in vapor pressure. • Tissue solubility - the greater the solubility of the gas in tissue, the slower the induction and the longer the recovery. Less soluble anesthetics are more potent.

38. ANESTHESIAInhalant Anesthetics • Diethyl Ether - highly flammable and explosive and must be used in explosion proof hoods. High tissue solubility = slow induction and recovery • Chloroform - NOT TO BE USED IN ANIMAL FACILITIES. Can be highly toxic to mice, has low margin of safety, is a known carcinogen.

39. ANESTHESIAInhalant Anesthetics • Methoxyflurane - Low vapor pressure and high tissue solubility = safe. Can use wick-type vaporizers. Provides some analgesia after anesthetic recovery • Halothane - Common veterinary inhalant anesthetic. High vapor pressure and low tissue solubility - use only precision vaporizers. Has been associated with cardiac arrhythmias. • Isoflurane - Similar to halothane but no cardiac problems.

40. ANESTHESIAInhalant Anesthetics • Nitrous Oxide - Like oxygen, nitrous exists in a gaseous state at room temperature and is supplied in (blue) tanks. Under pressure it becomes a liquid. Tank pressure remains even (~800 psi) until there is no more liquid, then it decreases as the remaining gas is used. • Nitrous is combined with oxygen and should make up 50-80% of the carrier gas combination to be effective. Low tissue solubility = rapid onset and recovery. • Discontinue nitrous several minutes before oxygen

41. ANESTHESIANeuromuscular Blockers • ALWAYS USED IN CONJUCTION WITH GENERAL ANESTHESIA AND APPROPRIATE MONITORING • gallamine, pancuronium, succinylcholine • These agents cause paralysis of the voluntary skeletal muscles and, at higher doses, the diaphragm. Usually used with a ventilator. They provide NO analgesia. • Indications: fractures, dislocations, laparotomies • Use BP, HR, mucous membrane color and capillary refill time to monitor anesthetic depth

42. Analgesics • NSAIDs - act by inhibiting prostaglandin synthesis, good for inflammation but not good for pain. Oral delivery. -Aspirin and Acetaminophen have limited use. - flunixin, ketoprofen, and carprofen • Opioids • Morphine provides sedation and analgesia. May also cause vomiting and defecation, cardiac and respiratory depression. Can see tremors/convulsions in mice and cats. • Meperidine, Oxymorphone, Pentazocine, Buprenorphine

43. Drugs to keep on hand for emergencies: Apomorphine - induces vomiting Atropine sulfate - increases heart rate Calcium gluconate - strengthens myocardium contractions Chlorpromazine - tranquilizer Dexamethasone - steroid for shock/anaphylaxis Doxapram - stimulates breathing Epinephrine HCl - for asystole Heparin - dissolves blood clots Lactated Ringer’s - increases blood volume Morphine HCl - analgesia Pentobarbital - anesthesia Pitocin - stimulates uterus Sodium bicarbonate - acidosis Normal saline - increases blood volume Isoproterenol - stimulates heart Postanesthesia and Emergency Care

44. Postanesthesia and Emergency Care • Evaluation of patients should include behavioral observations and a complete physical examination • Emergencies can usually be prevented by careful attention to the patient before, during, and after the anesthetic administration • Technicians should work with the veterinarians both to avoid problems from occurring and to learn from those that do occur to prevent them from happening again.