1. 동물용의약품 학술정보
덕성여자대학교
약학대학
이용수 교수

2. CONTENTS INTRODUCTION EXTRA-LABEL DRUG USE PHARMACOLOGY: PK & PD
SPECIES DIFFERENCES IN PHARMACOLOGY
TOXICOLOGY OF ANIMAL DRUGS

3. INTRODUCTION

4. Animal Drugs

5. Domestic Sales of Animal Drugs

6. The Number of Animal Pharmacy in Korea
약 2,000개

7. Best Selling Items of Animal Drugs

8. EXTRA-LABEL DRUG USE

9. Extra-Label Drug Use
√ Actual use or intended use of a drug in an animal in a manner that is not in accordance with the approved labeling
▪ Use in species not listed in the labeling
▪ Use for indications (disease and other conditions) not listed in the labeling
▪ Use at dosage levels, frequencies, or routes of administration other than those stated in the labeling
▪ Deviation from labeled withdrawal time based on these different uses

10. AMDUCA √ Animal Medicinal Drug Use Clarification Act of 1994 (AMDUCA)
▪ Prescribing extra-label uses of animal drugs and human drugs for animals
▪ Not allowed for drugs intended for production use (food animals)
▪ Not permitted if it results in violative food residues or any residues that may present a risk to public health
▪ Not allowed if specifically prohibited by the FDA

11. Drugs Prohibited for Extra-Label Use
√ Chloramphenicol
√ Clenbuterol
√ Diethylstilbestrol (DES)
√ Dimetridazole, ipronidazole & other nitroimadazoles
√ Furazolidone, nitrofurazone & other nitrofurans
√ Sulfonamide drugs
√ Fluoroquinolones & glycopeptides (vancomycin)
√ Phenylbutazone
√ Amandatine

12. Animal Drugs Derived from Human Drugs

13. Animal Drugs Derived from Human Drugs

14. Animal Drugs Derived from Human Drugs

15. Animal Drugs Derived from Human Drugs

16. Animal Drugs Derived from Human Drugs

17. Therapeutic Areas in Humans & Animals

18. PHARMACOLOGY: PK & PD

19. PD & PK
√ Pharmacodynamics(PD) vs. Pharmacokinetics(PK)
ADME

20. Dose-Response Curve
√ Potency vs. Efficacy

21. Dosage & Therapeutic Index
신생아
출생 후
6개월 1세 3세
7.5세
12세 성인
1/10－1/20
1/5
1/4
1/3
1/2
2/3 1
√ Therapeutic index > 10 : 안전한 약물
√ Aspirin: ▪ 관상동맥질환 예방(325mg) vs. 항관절염약(5g)
▪ 고농도 : 위장출혈, salicylism(이명현상)
√ 극약(LD50 < 200mg/kg) vs. 독약(LD50 < 20mg/kg)

22. Administration Routes of Drugs

23. Administration Routes of Drugs

24. Administration Routes of Drugs

25. Bioavailability & First-Pass Effect
√ 생체이용률(bioavailability, BA)
√ 생체 등가성(bioequvalence, 생물학적 동등성)

26. Distribution
Ex. Ethanol
Ex. Aminoglycosides
Ex. Heparin

27. Metabolism √ 대사체가 약리작용 보유 (Italic: prodrug) ▪ Levodopa → Dopamine
▪ Minoxidil → Minoxidil sulfate
▪ Imipramine → Desipramine
▪ Procainamide → N-Acetyl procainamide
√ 작용이 증강
▪ Codeine → Morphine → Morphine glucuronide
√ 독성이 증가
▪ Parathion → Paraoxon
√ Sulfa제: 대사되어 난용성→요로결석
√ 대사물의 독성: Isoniazid(INH)의 간독성

28. CYP Isozymes
√ Genetic variability: alter drug’s efficacy & risk of adverse events
▪ CYP2C19: PM of Clopidogrel (prodrug)  high incidence of MI
√ Inducers
▪ Rifampin ↓conc. of HIV protease inhibitors
√ Inhibitors
▪ Omeprazole → ΘCYP2C19(ΘWarfarin metabolism)
▪ Erythromycin, Ketoconazole, Ritonavir  Θseveral CYP isozymes
▪ Grapefruit juice: ΘCYP3A4  Θmetabolism of Nifedipine, Clarithromycin, Simvastatin

29. Phase II Metabolism

30. Renal Excretion √ 사구체여과율(GFR) ≒ creatinine clearance
▪ if renal clearanceGFR(분비), clearanceGFR(재흡수)
√ 신장에서 약물재흡수는 약물의 pKa값과 뇨의 pH에 따라 좌우 → 약물의 중독치료에 사용
√ Penicillin, Sulfa제는 Probenecid에 의해 혈중농도 높아지고 중조에 의해 배설 촉진
√ Prostaglandin은 신혈류량 조절 기능: (NSAIDs + 이뇨제) 병용투여는 신혈류량 감소에 의해 Na+ 배설 감소 → 이뇨제에 의한 혈압조절에 악영향(∵NSAIDs의 COX 활성억제로 prostaglandin 생성 억제)
√ Triple whammy effect: (ACEI+diuretics+NSAID)  renal failure

31. SPECIES DIFFERENCES IN PHARMACOLOGY

32. Differences in Absorption
√ In dogs
▪ Gastrointestinal length is shorter
▪ Gastric emptying time is longer
▪ Affecting the rate and extent of absorption of drugs
√ Enteric coated aspirin
▪ In human : reducing stomach irritation by delaying absorption until the drug reached the small intestine
▪ In dogs : its oral absorption was incomplete, gastric retention of tablets occurred, and partially digested tablets were found in the feces
√ Sustained release preparations
▪ In human : convenient dosing regimens such as once a day administration in people
▪ In dogs : due to pharmacokinetic differences, not having 24-hour duration of efficacy in dogs

33. Differences in Absorption
√ Immediate release (IR) tramadol
▪ Used for the control of pain in dogs
▪ Administered every 6–12 hours
√ Tramadol HCL extended release (ER) tablets
▪ In dogs : more convenient dosing regimens
▪ In human : one a day administration for management of moderate to moderately severe chronic pain
▪ In dogs : if chewing the ER formulation  rapid release of the drug  ↑potential for adverse effects
√ Oral narcotics
▪ In human : frequently prescribed to control pain associated with chronic medical conditions
▪ In dogs
- Morphine sulfate extended release tablets  poor and erratic absorption after oral administration
- Codeine and methadone : low bioavailability after oral administration
- Clinical use of oral narcotics is limited

34. Differences in Digestive Tract
√ In cats
▪ Esophagus : smooth muscle covering terminal 8% of its length and 16% for its circular muscle
▪ Prone to retain drug tablets in the distal part of the esophagus
▪ Highly acidic medications  severe irritation
√ In horses
▪ Choking : esophagus blocked in distal segment of smooth muscle
√ In monogastric species
▪ Stomach : disintegration/dissolution of drug formulations and gastric emptying
▪ Pylorus : sieving gate leading into the duodenum
√ In reticulo-rumen (RR) of ruminants
▪ Large capacity (225L in adult cattle)  leading to dilution & affecting the residence time of orally administered drugs
▪ Microflora of the rumen  inactivating drugs
▪ Cellulose-binding drugs : transit to the distal part of the gut  long delay (50–60 hours)

35. Digestive Tract of Hindgut Fermenters
▪ Cecum and colon : major sites of microbial digestion of feed
▪ Antimicrobial drug-induced enterocolitis : secondary to disruption of normal microflora leading to an overgrowth of pathogenic microorganisms like Clostridium ssp.
√ In rabbit
▪ C. spiriforme : a primary causative agent producing iota toxin  enterotoxaemia & death
▪ Antibiotics
- Oral administration : poor bioavailability
- Parenteral administration : extensively excreted in the bile (oxytetracycline) or by enterocyte efflux (doxycycline)
√ Enterocolitis-inducing antibiotics
▪ Lincomycin & clindamycin in horse
▪ Penicillins (amoxicillin, ampicillin) & cephalosporins (ceftiofur) in rabbit
▪ Irrespective of route of administration, they should be avoided in these hindgut fermenters

36. Digestive Tract of Hindgut Fermenters
√ Trimethoprim-sulfonamides & macrolides (erythromycin and spiramycin)  disruption of gut flora in horse
√ In horse : oral administration of NSAIDs (phenylbutazone, flunixin, meclofenamic acid)
▪ NSAIDs adsorbed onto the cellulose
▪ Conveyed to the cecum and proximal colon in bound form, where cellulose digestion takes place releasing the adsorbed drug
▪ Diet & schedule of drug administration relating to feeding  influence on bioavailability
▪ Local side-effects of NSAIDs on the digestive tract : erosions of distal part (colon) rather than stomach (in monogastric species)

37. Differences in Metabolism
√ Species differences in metabolism  variation in drug activity & toxicity
√ Benzodiazepines : metabolized more rapidly in dogs than humans
√ Half life of most NSAIDs : longer in cats than in dogs
√ MDR-1 gene coding for p-glycoprotein in dogs
▪ Mutations in the MDR-1 gene identified : Australian shepherd, English shepherd, Shetland sheepdog, Old English sheepdog, longhaired whippet, and silken windhound
▪ Dogs with the MDR-1 mutation
- Side effects with acepromazine, butorphanol, vincristine, doxorubicin, and digoxin
- More sensitive to the neurotoxicity side effects of avermectins (hypersalivation, mydriasis, ataxia, muscle tremors, depression, and coma)

38. Differences in Metabolism
√ Greyhounds
▪ Differences in the metabolism of thiobarbiturates, propofol, midazolam, and amikacin compared to other breeds
▪ Difference in drug disposition : attributed to a decrease in CYP mediated drug metabolism and/or differences in body composition (percent body fat, muscle mass)
▪ Requirement of dose selection and/or dose adjustment for these drugs
√ Prednisone
▪ Metabolized to prednisolone (active metabolite)
▪ In dogs : similar AUC (area under the curve) parameters for prednisone/prednisolone with oral administeration
▪ In cats : plasma concentration of prednisone is lower than that of prednisolone

39. Differences in Phase II Metabolism
√ In cats
▪ Reduced ability to conjugate drugs with glucuronic acid for some drugs (acetaminophen)
▪ A genetic analysis : a very low glucuronidation capacity due to a mutation in the UDPT (uridine-diphosphate-glucuronosyl transferase) 1A6 gene  expression of a pseudoenzyme (a non-functional protein)
√ In dogs
▪ Decreased N-acetylation activity  toxicity of some drugs (sulfonamides, procainamide, hydralazine)

40. Species Variation in Drug Metabolism
√ Cytochrome P450 enzyme (CYP450)
▪ A large superfamily of oxygenases
▪ The most important metabolizing enzymes for xenobiotics
▪ Herbivores : well-developed  rapid drug clearance by hepatic metabolism
√ In horse : fatal monensin intoxication
▪ Monensin : an ionophoric coccidiostat used in poultry
▪ High susceptibility due to inability to demethylate
▪ Lowest catalytic ability to demethylate (detoxify) monensin
√ Inter-species differences in phase I & II metabolism
▪ Cats : poor capacity to carry out glucuronidations
▪ Dogs : deficiency of acetylation reactions
▪ Pigs : low level of sulphate conjugation

41. Species Variation in Drug Metabolism
√ Lower clearance in carnivores than in herbivores with omnivores having an intermediary position
√ Half-life of salicylic acid
▪ Varies considerably between species
▪ Less than one hour in herbivores (cattle, horses)
▪ From 3 to 6 h in omnivores (man, pigs)
▪ Up to 9 h in dogs
▪ Longer (22–48 h) in cats due to a deficit in glucuronic conjugation

42. Species Variation in CYP Enzymes

43. Differences in Elimination
√ Compared to hepatic metabolism, differences in renal elimination in dogs and cats are relatively minor
√ Gabapentin
▪ A human drug : used to manage chronic pain in dogs
▪ In humans
- No biotransformation in the liver
- Primarily excreted in the urine
▪ In dogs
- Metabolized to N-methyl-gabapentin (up to 34% of the dose)
- Both parent drug & metabolite : excreted in the urine
- Up to 32% of the administered dose excreted in the feces

44. Role of Molecular Weight in Excretion
√ Molecular weight (MW) of a compound : a key factor determining the extent of biliary vs. non-biliary excretion
√ Substances with MW < 250 : urinary excretion accounts for almost all the elimination of compounds
√ Substances with MW < 300 : primarily eliminated by renal clearance (glomerular filtration) in most species
√ Substances (drug, metabolites, conjugates) with MW > 600 : typically eliminated in the bile by active carrier-mediated transport
√ Substances with MW between 300 and 600 : the highest interspecies differences
▪ Poor biliary excreters : rabbits, ginea-pigs, man
▪ Good biliary excreters : rats, chickens, dogs
▪ Intermediate species : cats, sheep

45. Interspecies Differences in Excretion
√ Differences may exist even in closely related species (between horses and donkeys)
▪ Phenylbutazone (PBZ)
- Plasma clearance : 10 times higher in donkeys than in horses
- Dose should be 10 times higher in donkeys
▪ Plasma clearance
- Higher in the donkey than in the horse for several antibiotics (benzylpenicillin, ampicillin, amoxicillin, and oxytetracycline)
- But not aminoglycosides (amikacin, gentamicin)
√ Bioavailability
▪ The greatest interspecies difference for the oral route of administration
▪ Extrapolation from man to dogs or cats  hazardous
▪ Mean bioavailabilities of 43 drugs in humans and dogs
- Mean F values : between 1.5 and 100%
- Overall correlation : r¼ 0.51
- Data derived in dogs may be inapplicable to man

46. Differences in Dosage Regimens
√ For each drug in each species
▪ Efficacious and safe dosage regimen should be determined
▪ Dosage regimen : dose level, interval of administration, and dosing duration
√ Xylazine
▪ An 2 agonist used as a sedative
▪ Dose is tenfold lower in cattle than in horses, despite similar PK profiles
√ Morphine : dose is ten-fold lower in cats than in dogs
√ Aspirin : dosage is 40 times higher in cattle than in cats
√ Suxamethonium (succinylcholine)
▪ A depolarizing neuromuscular blocker
▪ Dose in cattle is 40 times lower than in cats

47. Differences in Dosage Regimens
√ Dosage regimen : a PK/PD hybrid variable with two PK & PD components
√ ED = (Clearance x EC)/(Bioavailability)
▪ ED: an efficacious dose
▪ Clearance: a pharmacokinetic parameter expressing the overall capacity of the body to eliminate the drug
▪ Bioavailability: a PK variable expressing the percentage of drug that actually reaches the systemic circulation after administration by an extravascular route
▪ EC: the efficacious plasma concentration; the PD parameter expressing drug potency

48. Differences in Dosage Regimens
√ Interspecies variability
▪ PK origin : as for aspirin or suxamethonium
▪ PD origin : as for xylazine
√ 3 Factors determining a dose
▪ Hybrid parameters of clearance, bioavailability & EC
▪ Recognizing their biological determinants helps to identify the different anatomical, physiological, and/or behavioral sources of interspecies differences

49. TOXICOLOGY OF ANIMAL DRUGS

50. Acetaminophen √ Poisonous to: cats, dogs
√ Level of toxicity: generally moderate to severe
√ Common signs to watch for: lethargy, swelling of the face/paws, difficulty breathing, brown/blue gums, vomiting, inappetance/anorexia, black-tarry stool, jaundice
√ Cyclooxygenase (COX)-3 inhibitor
√ In cats an altered liver metabolism (glucuronidation) : a decreased ability to metabolize  much more susceptible to poisoning
√ In dogs keratoconjunctivitis sicca (dry eye), liver failure, and RBC injury
√ Treatment
▪ Decontamination, fluid therapy, provision of a glutathione source (S-adenosyl-methionine or SAMe), and the antidote, N-acetylcysteine
▪ Monitor for RBC injury or liver failure

51. ACE Inhibitors √ Poisonous to: cats, dogs
√ Level of toxicity: generally mild to moderate, depending on the dose ingested
√ Common signs to watch for: dizziness, weakness, excessive drinking or urination, collapse
√ Angiotensin-converting enzyme inhibitors (ACEI) : common cardiac medications to treat underlying heart disease or hypertension
√ When accidentally ingested in poisonous amounts  hypotension, dizziness, and weakness
√ Ingesting small amounts of ACEI  monitored at home, unless they have underlying medical problems (kidney failure, cardiac disease, etc.)
√ Treatment : decontamination, blood pressure monitoring, aggressive IV fluid therapy if hypotension is detected, and blood work monitoring

52. Anthelmintics Ivermectin √ Poisonous to: Cats, Dogs
√ Level of toxicity: Generally moderate to severe/life-threatening
√ Common signs to watch for: drooling, dilated pupils, tremors, seizures, coma, inability to breath, death
√ A class of drugs commonly used : ivermectin, milbemycin, moxidectin
√ Anthelmintics (drugs kill parasites) : commonly used as an active ingredient for monthly heartworm preventatives
√ Dogs (collies, Border collies, Australian shepherds, Old English sheepdogs, etc.) with a multidrug resistant (MDR) gene mutation : extremely sensitive to this class of drugs
√ Dogs accidentally ingest horse dewormer, containing large amounts of ivermectin; ingesting feces from horses that were recently dewormed
√ Without aggressive treatment, ivermectin poisoning can be deadly

53. Antibiotics √ Poisonous to: cats, dogs
√ Level of toxicity: generally mild to severe
√ Common signs to watch for: drooling, inappetance, vomiting, diarrhea, discolored teeth, inappropriate drinking or urinating, skin lesions, tremors, seizures, death
√ Ingested in toxic amounts  mild to severe signs ranging from GI signs (drooling, vomiting, diarrhea, inappetance, discolored teeth), metabolic signs (skin lesions, liver failure, kidney failure, etc.) to CNS signs (tremors, seizures, death)
√ Isoniazid
▪ Used for tuberculosis in human
▪ Ingested in dogs and cats  severe tremors, seizures, and death

54. Antidepressants √ Poisonous to: cats, dogs
√ Level of toxicity: generally moderate to severe
√ Common signs to watch for: agitation, aggression, panting, sedation, elevated heart rate, drooling, vomiting, diarrhea, tremors, seizures
√ Antidepressants : the top accidental poisonings in dogs
√ Selective serotonin re-uptake inhibitors (SSRIs)
▪ With accidental poisoning or ingestion  sedation or CNS stimulation, anorexia, and lethargy
▪ With larger poisonings  serotonin syndrome (CNS sedation or stimulation, vomiting, tremoring, seizures, hyperthermia, diarrhea, abdominal pain, and dilated pupils)
√ Treatment
▪ Decontamination; sedation; thermoregulation; IV fluid therapy; blood pressure and electrocardiogram monitoring; and supportive and symptomatic care
▪ Immediate veterinary attention is necessary!

55. Antihistamines √ Poisonous to: cats, dogs
√ Level of toxicity: generally mild to severe
√ Common signs to watch for: agitation, lethargy, sedation, aggression, abnormal heart rate, hypertension, vomiting, diarrhea, inappetance, seizures, respiratory depression, death
√ Antihistamines : used commonly in both human and veterinary medicine for allergies, hay fever, skin disease, etc.

56. Aspirin √ Poisonous to: cats, dogs
√ Level of toxicity: generally moderate to severe
√ Common signs to watch for: vomiting, diarrhea, bloody vomit, black-tarry stool, respiratory changes, hyperthermia, change in thirst or urination, collapse, weakness, tremors, seizures, death
√ Aspirin (acetylsalicylic acid, ASA) : NSAID, at appropriate doses in pets, used for pain management for osteoarthritis to clot prevention
√ Inappropriately ingested  severe poisoning in dogs and cats; Cats are much more sensitive to aspirin poisoning than dogs
√ Aggressive treatment is necessary with toxic amounts
▪ Decontamination, gastrointestinal protectants, symptomatic and supportive care, IV fluids, and blood work monitoring

57. Baclofen √ Poisonous to: cats, dogs
√ Level of toxicity: generally moderate to severe
√ Common signs to watch for: vocalization, walking drunk, severe sedation, agitation, slow heart rate, low blood pressure, tremors, seizures, difficulty breathing, death
√ Baclofen : a human medication used as a skeletal muscle relaxant; commonly used for patients with MS, diseases of the spinal cord, Parkinson’s disease, and Huntington’s chorea
√ In dogs and cats, it can be deadly, as it has a narrow margin of safety
√ Treatment
▪ Immediate veterinary attention is necessary
▪ Decontamination, IV fluids, intravenous lipid emulsion (an antidote for fat-soluble poisons), a mechanical ventilator (in severe cases), anti-seizure medications, and aggressive symptomatic and supportive care

58. Benzodiazepines √ Poisonous to: cats, dogs
√ Level of toxicity: generally mild to severe
√ Common signs to watch for: severe sedation, walking drunk, aggression, agitation, nausea, vomiting, respiratory depression, cardiovascular depression
√ Benzodiazepines : a class of drugs used in both human and veterinary medicine as sedatives/hypnotics, anti-anxiety medications, anti-convulsants (e.g., anti-seizure drugs), and as muscle relaxants
√ Action mechanism : inhibiting neurotransmitter gamma-aminobutyric acid, with the opening of chloride channels

59. Beta-blockers √ Poisonous to: cats, dogs
√ Level of toxicity: generally moderate to severe
√ Common signs to watch for: nausea, vomiting, weakness, collapse, slowed heart rate, lethargy
√ Beta-blockers : used in both human and veterinary medicine for heart disease and for blood pressure regulation
√ In cats and dogs, accidental overdose  severe, life-threatening poisoning due to the drug’s narrow margin of safety; heart failure, a very slowed heart rate, severe hypotension, and secondary acute kidney failure
√ Aggressive and immediate treatment must be initiated
▪ Decontamination, heart and blood pressure monitoring, aggressive IV fluids, blood work monitoring, and symptomatic supportive care
▪ With severe toxicosis, the use of high-dose insulin therapy or intravenous lipid emulsion can be used

60. Calcipotriene √ Poisonous to: cats, dogs
√ Level of toxicity: generally severe
√ Common signs to watch for: lethargy, vomiting, inappetance, diarrhea, excessive thirst and urination, weakness, seizures, death
√ Calcipotriene : a source of Vitamin D, an ingredient commonly found in a topical human medication for psoriasis
√ Ingestion of topical creams
▪ Can be deadly, and costly to dogs and cats
▪ A life-threateningly high calcium level in the body
▪ Acute kidney failure and potentially chronic renal failure in dogs and cats

61. Calcium Channel Blockers
√ Poisonous to: cats, dogs
√ Level of toxicity: generally moderate to severe
√ Common signs to watch for: nausea, vomiting, weakness, collapse, slowed heart rate, lethargy
√ Calcium channel blockers : used in both human and veterinary medicine for heart disease and for blood pressure regulation
√ Accidental overdose  severe, life-threatening poisoning due to the drug’s narrow margin of safety; heart failure, a very slowed heart rate, severe hypotension, and secondary acute kidney failure
√ Aggressive and immediate treatment must be initiated
▪ Decontamination, heart and blood pressure monitoring, aggressive IV fluids, blood work monitoring, and symptomatic supportive care
▪ With severe toxicosis, the use of calcium, glucagon, high-dose insulin therapy or intravenous lipid emulsion can be used

62. Corticosteroids √ Poisonous to: cats, dogs
√ Level of toxicity: generally mild to severe
√ Common signs to watch for: vomiting, bloody vomit, black-tarry stool, diarrhea (+/- blood), inappetance, abdominal pain, increased thirst, urination, excessive panting
√ Topical steroid creams or ointments
▪ Ingredients : betamethasone, hydrocortisone, and triamcinolone  a wide margin of safety when ingested
√ Accidental ingestion in dogs and cats  mild signs of gastrointestinal distress (vomiting, diarrhea); typically secondary to the petroleum-based carrier in the topical form
√ Topical creams containing more dangerous active ingredients (calcipotriene, 5-FU, diclofenac, etc.)  fatal when ingested
√ For the oral form of corticosteroids : toxic ingestions  stomach ulcers, gastroenteritis, and rarely, stomach rupture

63. Decongestants √ Poisonous to: cats, dogs
√ Level of toxicity: generally moderate to severe
√ Common signs to watch for: vomiting, dilated pupils, severe blood pressure changes, elevated or really slow heart rate, tremors, seizures, acute death
√ Decongestants : designed to prevent post-nasal drip, work by constricting the blood vessels in the nose; pseudoephedrine and phenylephrine; commonly found in cold, flu and allergy medications
√ Accidentally ingested by dogs and cats  deadly; vomiting, dilated pupils, severe blood pressure changes (hypertension), abnormal heart rhythms and rates, tremors, and seizures
√ Immediate treatment is necessary to prevent potentially life-threatening signs
▪ Decontamination, blood pressure monitoring, medications to lower the blood pressure, and aggressive symptomatic supportive care

64. Diuretics √ Poisonous to: cats, dogs, horses, cows, birds
√ Level of toxicity: generally moderate, depending on the amount ingested and the health of the animal
√ Common signs to watch for: severe dehydration, excessive thirst and urination, lethargy, acute kidney failure (rare)
√ Diuertics : commonly used in both veterinary and human medicine for cardiac disease or hypertension
√ Ingested in toxic amounts  severe dehydration, excessive thirst and urination, and rarely, even kidney failure
√ Immediate veterinary attention is generally required, depending on the amount ingested

65. Flea & Tick Medications
√ Poisonous to: cats, dogs
√ Level of toxicity: generally mild to severe, life-threatening
√ Common signs to watch for: profuse drooling, vomiting, tremoring, hyperexcitability, agitation, seizures, weakness, difficulty breathing
√ Flea and tick medications : topical drugs applied to the skin over the neck/back; pyrethrins (derived from the Chrysanthemum flower/plant) or pyrethroids (synthetic derivatives)
√ In cats, untreated, poisoning can be fatal; rarely seen in dogs
√ Treatment
▪ Prompt removal of the product by bathing with a liquid dish soap to get the greasy substance off

66. Ibuprofen √ Poisonous to: cats, dogs
√ Level of toxicity: generally moderate to severe, life-threatening
√ Common signs to watch for: vomiting, bloody vomitus diarrhea, black-tarry stool, weakness, pale gums (anemia), abdominal pain, lethargy, loss of appetite, halitosis (secondary to kidney failure), seizures, death
√ NSAID : commonly used in people and animals for the relief of pain and inflammation associated with arthritis, headaches, cramps and for the relief of mild fevers
√ There are no NSAIDs designed for long term use in cats; poorly tolerated  severe kidney failure with overdose, poisoning, or repeated doses
√ Small overdoses of an NSAID  severe stomach ulcers, vomiting, bloody vomitus, diarrhea, black-tarry stool, weakness, pale gums (anemia), abdominal pain, lethargy, and loss of appetite
√ Larger ingestions  halitosis, kidney failure, liver failure and neurological problems (tremors, seizures)

67. Long Acting Anticoagurants
√ Poisonous to: cats, dogs
√ Level of toxicity: generally mild to severe; depending on the amount and time of ingestion, active ingredient, and concentration of the product
√ Common signs to watch for: lethargy, exercise intolerance, coughing, difficulty breathing, weakness, pale gums, collapse, vomiting, diarrhea (+/- blood), nose bleeds, bruising, bloody urine, swollen joints, inappetance, bleeding from the gums
√ It typically takes 3-5 days before signs of poisoning are visible
√ Antidote : vitamin K1 (treated for 30 days); two days after the last dose of vitamin K1, a blood clotting test (a prothrombin time) should be checked
√ Sensitivity to poisoning
▪ Animals (liver/gastrointestinal disease, very young/old)  more at risk
▪ Cats : more resistant and rarely suffer poisoning
▪ Dogs : sensitive and often require veterinary intervention

68. Methylphenidate √ Poisonous to: cats, dogs
√ Common signs to watch for: agitation, aggression, panting, sedation, elevated heart rate, hypertension, drooling, vomiting, diarrhea, tremors, seizures, death
√ Methylphenidate : a CNS stimulant used in human for attention deficit hyperactivity disorder (ADHD); used in animal for narcolepsy, cataplexy, and hyperkinesis-hyperactivity
√ Amphetamine poisoning in dogs and cats  CNS (agitation, dilated pupils, tremors, seizures), CV (elevated heart rate, high blood pressure), GI (drooling, vomiting, diarrhea), and respiratory (panting)
√ Aggressive treatment : decontamination (if appropriate), IV fluids, sedation, thermoregulation (and cooling measures, if needed), electrocardiogram/blood pressure monitoring, and symptomatic/supportive care

69. Opioids √ Poisonous to: cats, dogs
√ Common signs to watch for: walking drunk, vomiting, pinpoint pupils (dogs), dilated pupils (cats), severe sedation, slowed respiratory rate, slowed heart rate, coma, respiratory arrest (stopped breathing)
√ Opioids and opiates : designed to provide pain relief for both animals and humans
√ Accidentally ingested by pets in either the oral or patch form  severe poisoning as opioids are rapidly absorbed by all routes of administration
√ Treatment
▪ Rapid decontamination, blood pressure and heart monitoring, and the reversal agent, naloxone
▪ Without treatment, animals can die from severe sedation and respiratory arrest

70. Phenylpropanolamine √ Poisonous to: cats, dogs
√ Common signs to watch for: agitation, hypertension, abnormal heart rate, tremors, seizures, dilated pupils
√ Phenylpropanolamin (PPA) : a stimulant used in veterinary medicine to treat urinary incontinence in dogs (typically female, spayed, large breed dogs)
√ At therapeutic doses  safe
√ Accidentally ingested in large amounts of chewable form  severe poisoning

71. Sleep Aids √ Poisonous to: cats, dogs
√ Level of toxicity: generally mild to moderate
√ Common signs to watch for: severe sedation, severe agitation, hyperactivity, aggression, panting, vomiting, diarrhea, drooling, tremors, hyperthermia, walking drunk, respiratory or cardiovascular depression
√ Sleep aids : benzodiazepines or non-benzodiazepine hypnotics; causing sleep and sedation in humans, but the opposite effects in dogs and cats
√ In cats, some benzodiazepines  causing liver failure when ingested

72. Thyroid Hormone √ Poisonous to: cats, dogs
√ Level of toxicity: generally mild to moderate
√ Common signs to watch for: nervousness, panting, vomiting, elevated heart rate, aggression, muscle tremors
√ Pets (especially dogs)
▪ Underactive thyroids too
▪ Dose of thyroid hormone needed to treat dogs is much higher than a person’s dose
▪ Accidentally get into thyroid hormones at home  rarely problematic
▪ Large acute overdoses in cats and dogs  muscle tremors, nervousness, panting, a rapid heart rate and aggression