Use of Drugs in Animals PDF

2024-10-28 Use of Drugs in Animals Basic Principles for use of animal health products Nov 4, 6, and 8, 2024 Craig Wilkinson, DVM 1 Topics to be covered  Overview, and Broad types of Drugs  Context for drug use in animals  Differences between Compani...

2024-10-28 Use of Drugs in Animals Basic Principles for use of animal health products Nov 4, 6, and 8, 2024 Craig Wilkinson, DVM 1 Topics to be covered  Overview, and Broad types of Drugs  Context for drug use in animals  Differences between Companion and Food Animals  Drug selection considerations  Improper use, treatment failure  Adverse Reactions  Laws and Regulations  VCPR  Extra-Label Use 2 1  2024-10-28 “All substance are poisons, there is none which is not a poison. The right dose differentiates a poison from remedy.” (Paracelsus, 1493-1541) 3 Issues with respect to drugs  Desire: Healthy pets and livestock with good welfare  Demand: Healthy, safe food and environment  Need: Ensure drugs used in people remain effective  Concern: about drugs in food or environment  Concern: about bacteria developing resistance to antibiotics ◦ Loss of effective antibiotics – cost, risk to animals, people  Consider: Effect of use or not, on Welfare of animals  Follow: Laws and regulations  Etc. So much to consider! 4 2  2024-10-28 Why Study Principles of Drug Use in Animals?  Drugs can help improve animal health and welfare ◦ Reduce disease in animal populations ◦ Treat individual animals (pets, food animals) ◦ Reduce animal distress and pain ◦ Reduce animal losses  Provide economic benefit through ◦ Reduced treatment costs if drugs are used only when necessary and according to label directions or vet prescription ◦ Reduce inefficiency/wastage (consider costs of these in various scenarios) 5 Why Study Principles of Drug Use in Animals?  Improve food safety by ◦ Reducing the risk of drug residues and other hazards in food products  Ensure antimicrobials remain available and effective for animals and people by ◦ Reducing risk of antimicrobial resistant bacteria  Reduce need and likelihood of additional government regulation 6 3  2024-10-28 What is a “Drug”?  A substance recognized by an official pharmacopoeia or formulary - a “pharmaceutical”  A substance intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease.  A substance (other than food) intended to affect the structure or any function of the body.  A substance intended for use as a component of a medicine but not a device or a component, part or accessory of a device.  Biological products are included within this definition and are generally covered by the same laws and regulations, but differences exist regarding their manufacturing processes (chemical process versus biological process but lines are getting blurred...) 7 Examples of Categories of Drugs  Biologicals  Antimicrobials (antibiotics)  Other Pharmaceuticals (many kinds!) www.millwoodeastvet.ca 8 4  2024-10-28 Biologicals  Products (usually proteins) that are generally derived from (extracted from, synthesized by) living organisms  Examples: ◦ Includes vaccines  Particularly “traditional” vaccines ◦ Category also includes  Antibody preparations, blood or blood products, cells or tissues  Some hormones (extracted from living tissue) and growth factors  Insulin (formerly extracted from tissue, now often produced by bacteria with recombinant DNA)  Antibody/immunoglobulin products (example: colostrum replacer, various monoclonal Ab products)  Probiotics – lactobacillus, bifidobacterium, etc. https://www.who.int/health-topics/biologicals#tab=tab_1 9 Antimicrobials  Antimicrobials: Broad term for any natural or synthetic compound that kills microorganisms or suppresses their growth ◦ Includes antibiotics, ionophores, antiseptics, disinfectants  Antibiotics: Specifically – a drug (which may be derived from a substance produced by a microorganism, e.g. penicillin ) that kills or suppresses the growth of another microorganism ◦ Often used more generically for pharmaceuticals used to kill microorganisms in a host organism  To be discussed in detail by Dr. Simon Otto 10 5  2024-10-28 Other Types of Pharmaceuticals used in Animals  Many! ◦ Parasiticides ◦ Fungicides ◦ Tranquilizers and Anesthetics ◦ Analgesic (pain) medications ◦ Hormones ◦ Cardiovascular drugs ◦ Chemotherapy (of cancer) drugs ◦ Vitamins, minerals (nutritional) ◦ Many, many others… 11 Types of Pharmaceuticals used in Animals  Many used in food animals: e.g. antiparasitics, nutritional products, pain medications, anesthetics, hormones, etc.  In companion animals, all these plus a much wider variety may be used: ◦ cardiovascular drugs, ◦ respiratory drugs, ◦ gastrointestinal drugs, ◦ cancer chemotherapy, ◦ anesthetics ◦ CNS drugs (behaviour, seizure) ◦ Etc. 12 6  2024-10-28 When we use Drugs in Animals Should be in correct “context”:  Animal is receiving proper basic preventive care (or herd health)  Availability of competent diagnosis before prescribing and supportive treatments during treatment  Professionals involved have the “big picture in mind”  Consideration of ALL benefits and risks, including all animal/disease factors and also human safety, food safety, environment, etc. 13 Treatment and Control of Disease Diagnosis  Proper treatment requires accurate diagnosis, appropriate treatment Management and changes to Practices management practices: ◦ Herd Health Programs (livestock) Treatment ◦ Biosecurity ◦ Preventive health care (esp. companion animals) 14 7  2024-10-28 Food Safety – balancing act  HACCP* programs for food-safety  Categories of Hazards ◦ Biological (e.g. pathogenic bacteria, viruses, parasites) ◦ Chemical (e.g. drug residues, pesticide residues) ◦ Physical (e.g. broken needles in meat, flies or straw in milk) *Hazard Analysis Critical Control Point 15 Reasons for Drug Use in Livestock (examples)  Therapeutic ◦ Treat for infection, parasites, pain, inflammation, etc. ◦ Nutrients (vitamins, minerals) to treat deficiencies ◦ Reproductive Management (reproductive hormones)  Preventive ◦ Vaccines to prevent infection ◦ Nutrients to prevent malnutrition  Growth Promotion ◦ Antibiotics ◦ Hormones 16 8  2024-10-28 Companion Animals  Drugs used much as they are in human medicine  Includes many classes of drugs seldom or never used in food animals, such as for treatment of: ◦ Diseases in many organ systems, such as Cardiac, kidney, liver, gastrointestinal, endocrine (hormonal), and for behavioural issues, degenerative or age-related conditions ◦ Cancers ◦ Immune diseases ◦ Etc. 17 Livestock Companion Animals  Economic value of  “Members of the family” animal ◦ priceless… but on a budget  Trade domestically and  Travel with owners, internationally sometimes long distance  Treated as herd or flock  Treated as individuals  Consumption as food!  Live with and share ◦ Withdrawal or Withholding pathogens with family times (residue avoidance)  Long lifespan  Rarely become geriatric  Use of human drugs is  Most human drugs not fairly common acceptable or practical Differences between livestock and companion animals that affect drug use… What about horses? 18 9  2024-10-28 19 Rational Use of Drugs in Animals What to consider Improper drug use and failures of therapy Adverse effects and toxicity 20 10  2024-10-28 Considerations when evaluating a proposed course of treatment:  Minimum info needed to make rational decision regarding choice and use of a particular course of treatment (drug) in a particular patient  Much of this info must be explained to owner/caretaker of animal 21 So, consider the following: 1. Therapeutic Goal  What specific pathologic process do you wish to alter by using a drug from this class and this drug in particular?  Is it absolutely necessary that you use this (or any) drug? ◦ Bacterial infection? – use an antibiotic that will kill that bacterium ◦ Heart disease? – may choose a drug that will decrease blood pressure, or increase heart contractility 22 11  2024-10-28 2. Routes of administration  By what routes can the chosen drug be given? (IV, IM, Subcut, Oral, Topical, etc.)  Which do you use?  On what basis did you make this decision?  Advantages or disadvantages?  Can this owner/caretaker do it? In this animal? 23 3. Dose, Frequency, Duration  What Dose (units/kg such as mg/kg) to choose within the range for this drug?  What Interval (once a day, twice a day, three times a day, constant infusion, etc.)?  What Duration (how long)?  How do these fit the particular animal or situation? 24 12  2024-10-28 4. Is this a food animal?  Is the drug approved for use in food animals?  At certain ages/stages?  If so, what withdrawal time? (how long before animal or its eggs, milk, etc. can be eaten/consumed by people?) 25 5. Cost?  Per treatment, and then consider expected duration of therapy  Cost compared to value of animal and budget of owner?  Cost appropriate to seriousness of disease?  Include related expenses – must it be administered in-clinic? By IV line? By a technician or vet? Cost of syringes or other administration devices? 26 13  2024-10-28 6. Special precautions?  Any special considerations based on this animal, its age, other health conditions, its use, its strain, breed or species?  What contraindications for this drug? (when should it not be used?)  What adverse reactions might be expected? How do we monitor this (e.g. blood tests), and what do we do if detected? 27 7. Evaluating results  How do we tell if the drug is working, or has worked?  physical response? blood tests?  How soon do we expect response?  What follow-up procedures do we need? ◦ Re-examination? ◦ Diagnostics?  Failure to consider all these points may lead to Improper Drug Use 28 14  2024-10-28 Improper Drug Use  Consequences may include: ◦ Delay in diagnosis ◦ Failure to properly treat life-threatening but curable disease ◦ Prolonged disease state ◦ Toxicity ◦ Development of disorder to which patient would not otherwise be subject ◦ Drug Residues in food or Antibiotic Resistance in bacteria ◦ Treatment failures ◦ Increased Costs $$$! Possible Causes of Treatment Failure (of infectious disease)  Wrong diagnosis  Viral infection misdiagnosed as bacterial? Can’t use an antibiotic.  Multiple problems not all recognized  Right diagnosis but very virulent pathogen  Late initiation of treatment  Inaccessible infection (brain, joints, scar tissue, abscess)  Resistant bacteria  Maybe should have done culture/sensitivity testing of bacteria first 15  2024-10-28 Possible Causes of Treatment Failure  Ineffective medicine or use of medicine ◦ Choice of product ◦ Dose or duration inadequate ◦ Other concurrent meds interfering ◦ Expired or degraded product ◦ Resistant bacteria Adverse Effects and Toxicity  Many years ago, drug therapies used many ineffective drugs, compounds and placebos.  “Good ones” did not produce serious side effects  Some were highly toxic  Most were of little therapeutic value  With more stringent development and control of drugs came greater efficacy and safety 16  2024-10-28 Adverse Effects and Toxicity  Serious adverse effects or toxicity still occur  Anyone know someone with an allergy to an antibiotic?  What about the toxicity of some drug agents? Drug A: Broad therapeutic range = Safe ED50 = Effective dose in 50% of patients TD50 = Toxic Dose in 50% of patients Drug B: Narrow Therapeutic range = Risky! Adverse Drug Reactions  Any noxious change in a patient’s condition which a physician/veterinarian believes to be caused by a drug.  May: ◦ Require alteration or even cessation of treatment with suspected drug ◦ Require treatment of symptoms ◦ Suggest that future treatment with this drug carries an unusual or increased risk in this patient 17  2024-10-28 Drug Reactions and Toxicities - Three main categories:  Intrinsic Drug Reactions  Idiosyncratic Drug Reactions  Allergic Responses (including anaphylaxis) Intrinsic Drug Reactions  Dose-related  Predictable  Reproducible  Often identified in preclinical or clinical trials  Underlying mechanism: usually an exaggeration of desired effect  Sometimes can be alleviated by reducing the dose or frequency, so treatment can continue 18  2024-10-28 Idiosyncratic Reactions  Usually not dose-related  Not predictable, peculiar to the individual  Occurs in a small proportion of exposed animals (or people)  Associated with drug-specific, patient-specific characteristics or environmental factors  Can be related to enzyme deficiencies in the individual, or may be immune-mediated (but not “allergies” in the traditional sense  Treatment usually must be discontinued  Mechanism: not always known (“idio-”)  Example is human reactions to choramphenicol (aplastic anemia rate is 1:30,000) – so banned for use in food animals, cautious use in pets! Allergic Reactions ▫ Not dose-related ▫ Unrelated to pharmacological effects ▫ Can be severe ▫ May require treatment, even emergency care ▫ If anticipated, may be minimized or decreased by prior administration of antihistamines, corticosteroids, epinephrine 19  2024-10-28 IMG_6383.heic Allergic  Nature of reaction depends on organ specificity and Ag- Ab reaction  Includes: ◦ Immediate reaction (anaphylactic) ◦ Immune Complex Reactions (rashes) ◦ “Drug Fevers” Clinical Case: Bella  6 yr old Pomeranian- Chihuahua  Routine examination and vaccines  Facial swelling noticed one hour after vaccination  Returned to vet for treatment – antihistamines and corticosteroids  Full recovery  Future Vaccines? 20  2024-10-28 Use of Drugs in Animals Laws and Regulations VCPR Extra-Label Use 41 General Drug Laws and Regs.  Federal Laws  Provincial Laws and Regulations  Vet Profession Bylaws  Distinguish between over-the-counter (OTC) and prescription drugs  Vet-Client-Patient Relationship (VCPR) 42 21  2024-10-28 Definitions:  Prescription (Rx) : the written instructions from licensed practitioner including patient ID, specific drug info, dosing, route, frequency, etc.  Generic Name: the chemical name or common name of the drug. ◦ E.g. acetaminophen  Trade Name: the drug name used under the registered trade mark of the company that makes/markets it ◦ E.g. Tylenol 43 Federal Legislation for Drugs  Health Canada regulates the sale of all drugs in Canada through the Food and Drugs Act and Regulations, and the Controlled Drug and Substance Act.  For veterinary drugs, including antimicrobials for food animals, these legislations are administered primarily through the Veterinary Drugs Directorate (VDD) of Health Canada 44 22  2024-10-28 Health Canada’s Veterinary Drug Directorate  The VDD is responsible for licensing of veterinary drugs and protecting both human and animal health  Sets standards for human food safety relating to veterinary drugs.  Promote responsible use of drugs for pets and livestock ◦ Oversee manufacturing, quality control and packaging, Labeling, Conduct risk assessments, set Withdrawal periods, warning statements, coordinates policies with other departments, federal and international policies 45 Federal Legislation regarding Drugs  Food and Drugs Act ◦ Licensing, testing and safety ◦ Includes food, drugs, contraceptive devices, and cosmetics (also soap and toothpaste) ◦ Regulates import, export and transport across provinces ◦ Sets requirements for labeling, sale, distribution ◦ Categories: prescription; non-prescription (OTC); veterinary 46 23  2024-10-28 Federal  Controlled Drugs and Substances Act ◦ Narcotics such as morphine, oxymorphone, fentanyl and other drugs (mostly used as strong painkillers, sedatives, and anesthetics). ◦ Some substances are permitted (with strict regulations), others are banned completely (e.g. heroin, methamphetamine). ◦ Also regulates “precursors” (used to make controlled drugs) ◦ All permitted ones are by prescription and have additional prescribing requirements, documentation and security. ◦ All penalties are under the Criminal Code and may be substantial. 47 In Canada, drugs are classified into groups based on a risk management approach 1. Controlled Drugs are used for specific therapy under strict control by the practitioner. This group of drugs includes products such as stimulants, anaesthetics, sedatives and narcotics. 2. Prescription Drugs - are classified into two parts (under the Food and Drugs Act): a. Products for Human Use includes drugs that when intended for human use require a prescription from a physician or other licensed practitioner and are dispensed through a pharmacist. b. Products for Veterinary Use includes drugs that when intended for veterinary use require a prescription. …and 48 24  2024-10-28 In Canada, drugs are classified into groups based on a risk management approach 3. Non-scheduled (OTC, Over-the- Counter, or “non-prescription”) drugs are those sold without a prescription, ◦ Human examples include pain meds like Tylenol, cold medications, antihistamines, antacids, etc. ◦ Veterinary examples include some types of vaccines, some antibiotics of types that are not used in humans, anti-parasite drugs, electrolytes, vitamins and minerals, wound treatments. ◦ Licensed under Food and Drugs Act. All drugs in Canada are given a Drug Identification Number (DIN) 49 Over-the-Counter Drugs  These drugs are deemed to be low risk (in either animals or people) because: ◦ Supervision by a practitioner is not deemed essential during diagnosis, treatment or monitoring of the condition; and ◦ There is little uncertainty about the drug and its use or effects; and ◦ There is little chance of harm to human or animal health or little risk to public health  Conversely, drugs listed as prescription for animals or humans would meet the opposite criteria ◦ IE: Supervision essential; uncertainty exists; chance of harm or PH risk 50 25  2024-10-28 Since 2018 in Canada…  All antimicrobials for animals that are also medically important for humans are on the prescription list ◦ including: Penicillin, tetracycline, sulfas, bacitracin, many others.  Prescription from a vet is required for important antimicrobials used in animals by all routes, including in feed 51 Provincial Laws that apply to animal medicines or animal health (Alberta)  Pharmacy and Drug Act  Veterinary Profession Act  Animal Health Act ◦ Authorized Medicine Sales Regulation  Several others 52 26  2024-10-28 Pharmacy and Drug Act  Regulates the pharmacist profession, pharmacies and the sale of drugs in Alberta  Only pharmacists are normally allowed to sell/dispense drugs (not usually MDs, who can prescribe and administer but not dispense)  Allows registered Vets/vet clinics to sell/dispense drugs for use in animals 53 Veterinary Profession Act  Regulates the veterinary profession, confers self-governing status (as with other Profession Acts)  Defines qualifications and requirements for registration of veterinarians, scope of practice (what is veterinary medicine), who can perform vet medicine, and gives authority to prescribe and dispense drugs for animals 54 27  2024-10-28  Prescription Pr Drugs for Veterinary Use (Under the CANADA Food and Drug Act) ◦ Available only on the order (prescription) and under guidance of a licensed veterinarian ◦ May NOT be sold by non-professional staff ◦ Must be used according to manufacturer’s label, unless under guidance of vet (see VCPR) ◦ Are subject to withdrawal conditions (food animals)  Under the Vet Profession Act (AB) and ABVMA bylaws ◦ All of the above may only occur with a valid Veterinarian-Client-Patient Relationship (VCPR) 55 Requirements of a Veterinarian-Client- Patient Relationship (VCPR)  Under bylaws of the Alberta Vet Med Assoc. 1. Vet assumes responsibility for making clinical assessments and recommendations regarding the health of the animals and the need for medical treatment. 56 28  2024-10-28 Requirements of a Veterinarian-Client- Patient Relationship (VCPR) 2. Vet has sufficient knowledge of the animal(s) on which to base the assessment, diagnosis and treatment of the medical condition of the animal(s). … means that… 57 “Sufficient knowledge” means that… a. The vet must be professionally acquainted with the keeping and care of the animal, and b. Has documented relevant and timely interaction, between the veterinarian, animal owner or caretaker and animal patients, which is normally by virtue of an examination of the animal(s), by medically appropriate and timely visits to the premises where the animal(s) are kept or by both examination and visits, and c. has documented medically appropriate information and knowledge about the animal(s). 58 29  2024-10-28 Requirements of a Veterinarian-Client- Patient Relationship (VCPR) 3. Client agrees to follow the vet’s recommendations and prescription 59 Requirements of a Veterinarian-Client- Patient Relationship (VCPR) 4. Vet is available or has arranged for follow-up evaluation or emergency coverage in event of adverse reaction or treatment failure 60 30  2024-10-28 Producers  Should ensure: ◦ Biosecurity and herd-health program ◦ On-Farm Food Safety  Responsible for: ◦ Work with vet to ensure valid VCPR ◦ Record-keeping ◦ Animal ID ◦ Proper disposal of products, ◦ Disposal of dead animals (drug residues, disease) ◦ Etc.! 61 Veterinarians  Diagnosis and treatment planning  Establish VCPR and may not dispense drugs outside this relationship  Prescription (Rx) of drugs and medicated feeds  Vaccine prescription where needed  Education of Producer – e.g. Withdrawal or withholding time  Report adverse reactions  Continuing education (legislated requirement) 62 31  2024-10-28 Summary of VCPR:  What conditions must be met? ◦ Vet is responsible for clinical judgments re animal’s health and treatment and Client agrees to follow vet instructions ◦ Vet has sufficient knowledge of animals to have general Dx of condition ◦ Vet has recently seen animal, personally acquainted with circumstances ◦ Vet is available for followup and emergencies 63 64 32  2024-10-28 Extra-Label Drug Use in Animals Extra-Label Use (ELU) of Drugs 1. Using the pharmaceutical product in a way not in accordance with Health Canada’s approved label or package insert ◦ (even if approved in other countries) 2. Any approved drug that is administered in a manner not explicitly stated on the approved label with regard to indication, dosage regimen, route or frequency of administration, duration of treatment, or target species. 3. Any drug approved for human but not veterinary use, active pharmaceutical ingredients (APIs), and compounded drugs. 66 33  2024-10-28 CVMA Position Statement  Extra-Label Drug Use (ELDU) in Veterinary Medicine is an important and legally-acceptable strategy for the effective treatment of animals only by a licensed veterinarian within the confines of a valid veterinary-client-patient relationship (VCPR) and only in circumstances where an approved veterinary product is not available or is not suitable. 67 Examples of ELU? A. Administration of drug to a species for which there is no specific approval ◦ rabbits, birds, reptiles, other exotic/pocket pets, llamas, ranched wildlife, often sheep and goats, zoo animals B. Admin. by a non-approved route ◦ A drug may be approved for IV use in a species but may be used by vets by other routes such as: IM, SC, topical 68 34  2024-10-28 Examples of ELU? C. Admin of a non-approved dose or frequency ◦ Situation common in Canada because for many drugs only a single dose or frequency is on label. ◦ After approval, additional use in clinical practice indicated higher dose or frequency is effective and safe ◦ E.g. Trimethoprim/sulfadiazine (Trimidox) is approved for once daily use. Many references recommend twice daily, so vets may prescribe that way. 69 Examples of ELU? 4. Admin of a drug for a disease not listed on the label This is really common practice!  Pharma companies just can’t test drug in every possible disease situation  Veterinarians do this all the time, usually with good background knowledge of pros/cons, testing in academic settings and specialist recommendations.  Producers probably do it without realizing it. 70 35  2024-10-28 Depocillin antibiotic (Merck Animal Health) *Benzylpenicillin Procaine Injectable Suspension. 71 Depocillin antibiotic (Merck Animal Health) *Benzylpenicillin Procaine Injectable Suspension DEPOCILLIN is indicated for the treatment of infections caused by bacteria susceptible to penicillin in cattle, swine, horses and sheep:  Cattle: Bacterial pneumonia; calf diphtheria; footrot; metritis; wound infections.  Swine: Bacterial pneumonia; erysipelas; wound infections.  Horses: Bacterial pneumonia; metritis; strangles; wound infections.  Sheep: Bacterial pneumonia; metritis; wound infections. So: Treatment of any other condition in these or any other species with this drug is technically Extra-Label Use (ELU) 72 36  2024-10-28 What constitutes ELU? E. Admin of human-label drugs to animals  Not too common in food animals  Very common in companion animals if no vet drug is available : ◦ Many ophthalmic (eye) medications ◦ Insulin ◦ Many cardiac medications ◦ A number of antibiotics ◦ Drugs for gastrointestinal function ◦ Chemotherapy for cancer ◦ Many anesthetics  Equivalent human drugs (e.g. thyroid meds) more available, cheaper, etc.  More complicated problem in horses that may become food animals (companion animals that may be eaten) 73 ELU – What’s the problem?  More of a concern in food animals  Most On-farm food safety assurance programs (OFFSAPs) have banned ELU of drugs  Can result in drug residues in food products, and liability  Concern about antimicrobial resistance (Dr. Otto will talk about this)  In companion animals, ELU of important antibiotics can result in resistant bacteria in animals we live closely with 74 37  2024-10-28 Why not just ban ELU completely?  Impossible to practice state-of-the-art vet medicine  Poor welfare – may result in excessive animal suffering (what about minor species?)  Angry clients – increased cost for vet Rx  Liability – if vet can not follow most effective therapeutic regimens?  Labeling (follows testing) can’t keep up with research and empirical success  Economic disincentive for manufacturers to test and label for minor species or for off-patent drugs 75 Is there any drug that can be used effectively and safely in all species? Atlantic Veterinary College, University of PEI 76 38