Veterinary Pharmacology - Collaboration between IMAKAHI and ISMAFARMASI

ANIMAL DRUGS Veterinary Pharmacology - Collaboration between IMAKAHI and ISMAFARMASI

Introduction Animal health or veterinary drug products are the materials intended for animals other than humans, including drugs used in animal feeds.

These drugs may be the same as the human drug approved through the NDA, but approval of a new animal drugs application (NADA) is required for marketing.

Additional requirements for “animals for food” include environmental impacts, human toxicology, and residue levels in meat for food consumption.

Because most dosage forms for animals are similar to those for the human product, the preformulation study should be the same or should be modified slightly if problems such as mixing homogeneity or instability of “premix” occur.

common drugs for animal antibiotic non steroidal anti-inflammatories opioid pain relievers/ analgesics steroid antiparasitics

common drugs for animal behavior-modifying drugs and sedatives hormones and other medications used to treat specific conditions chemotherapeutics gastrointestinal cardiac/blood pressure

Antibiotics These are drugs that kill microbes, such as bacteria and yeast, and are used to treat infections. They don’t kill viruses, but they are sometimes prescribed to treat secondary bacterial infections that can occur when an animal is ill from a viral infection.

The example are: • Gentamicin  aminoglycoside, can be renal-toxic • Clindamycin  lincosamide • Amoxicillin  aminopenicillin • Enrofloxacin  fluoroquinolone (oxacin suffix), may cause cartilage defects in young dogs, or blindness in cats

Antibiotics • Cephalexin  1st generation cephalosporin (oral) • Cefazolin  1st generation cephalosporin (injectable) • Cefpodoxime  3rd generation cephalosporin (oral)

• Cefovecin (Convenia)  3rd generation cephalosporin (injectable) • Trimethoprim-Sulfa (TMS)  sulfonamide, may cause dry-eye

Antibiotics • Doxycycline  tetracycline antibiotic (Doxy doesn’t typically cause bone and teeth abnormalities or discoloration in young animals but tetracyclines in general may cause this side effect). Should not be given as a dry pill to cats, as esophageal strictures may occur.

• Metronidazole  used commonly to treat diarrhea or colitis, can rarely cause a neurotoxicity which treatment for is diazepam.

May be used to treat Giardia.

Non-steroidal anti-inflammatory These common drugs reduce, inflammation, swelling, pain and lameness. All NSAIDS cause increased risk of GI ulceration and may have effects on the liver and kidneys, labwork should be monitored.

The example are:

• Carprofen (Rimadyl)  COX-2 inhibitor; rarely may cause liver failure, most commonly used post-operatively for analgesia and for arthritis management or acute orthopedic injury • Firocoxib (Previcox)  COX-2 inhibitor

Non-steroidal anti-inflammatory • Deracoxib (Deramaxx)  COX-2 inhibitor (may have some COX-1 effects at higher doses) • Meloxicam (Metacam)  may enhance risk of nephrotoxicity, mostly COX-2 inhibitor

• Flunixin Meglumine (Banamine)  used mostly in horses • Phenylbutazone (“Bute”)  used mostly in horses • Ketoprofen (Ketofen)  used most frequently as a fever reducer

Opioid pain relievers/analgesics These medications are generally derived from morphine and can be potent pain relievers.

Examples include oxycodone, hydromorphone, butorphanol, morphine, buprenorphine, tramadol, meperidine and fentanyl. Most of these drugs are controlled substances because of their addictive potential.

Steroids Steroids have many different uses. They can be potent anti-inflammatories and are frequently used to reduce allergic and anaphylactic reactions. They are also used at high doses to suppress the immune system. Examples include prednisone, prednisolone, triamcinolone, methylprednisolone and dexamethasone.

Antiparasitics These products are intended to prevent, repel or kill internal or external parasites such as intestinal worms, intestinal protozoans (Giardia, etc.), heartworms, fleas and ticks. Examples: • Pyrantel  used primarily for ascarids

• Sulfadimethoxine (Albon)  treats coccidian • Fenbendazole (Panacur)  general anthelmentic, also commonly used to treat Giardia • Praziquantel, Pyrantel, and Febantel (Drontal plus) dewormer for canine or feline

Antiparasitics • Selamectin (Revolution) • Ivermectin (Heartgard or  opical parasite injectable  heartworm prevention (ear mite tx, prevention, hooks, rounds, flea control, hooks, demodex treatment with rounds, heartworm injectable, contraindicated prevention), treatment for in Collie type breeds Sarcoptes

Behavior-modifying drugs and sedatives These drugs are used to quiet anxious pets or help in reducing anxiety associated with various behavioral issues in pets, prepare pets for anesthesia, and to reduce pet movement during delicate procedures.

Injectables: • Ketamine  dissociative anesthetic, causes muscle rigidity (used with diazepam because of this) • Tiletamine  dissociative anesthetic, part of Telazol (along with zolazepam) • Valium  benzodiazepine (end in the suffix –pam), causes skeletal muscle relaxation and sedation by enhancing GABA

Behavior-modifying drugs and sedatives Injectables: • Lidocane/Bupivicaine (local anesthetics, Lidocaine also given as anti-arrhythmic) • Dexmedetomidine (Dexdomitor)  alpha-2 adrenergic agonist, reversed with atipamezole (Antesedan-an alpha-2 adrenergic antagonist), should not be used in pets with cardiac disease or that are debilitated • Xylazine  alpha-2 adrenergic agonist, reversed with yohimbine-an alpha-2 adrenergic antagonist)

Behavior-modifying drugs and sedatives Injectables: • Acepromazine  phenothiazine tranquilizer, may lower seizure threshold (this is controversial but could be asked on boards) • Apomorphine  used to cause vomiting (emetic), injectable or comes in a tablet which can be placed in the conjunctival sac in the eye, opioid • Thiopental  short acting thiobarbiturate, not recommended for greyhounds or other sighthounds due to slow metabolism of this drug

Behavior-modifying drugs and sedatives Inhalants: most common side effect of inhalants is hypotension • Isoflurane • Sevoflurane • Halothane (not widely used due to side effects, especially cardiac)

Hormones and other medications used to treat spesific conditions Examples include insulin used for diabetes treatment, methimazole or levothyroxine for abnormal thyroid hormone levels, and heart medications such as atenolol, digoxin, and pimobendan.

Chemotherapeutics These drugs are used to treat tumors and cancer. Examples include cisplatin, vincristine, doxorubicin and cyclophosphamide.

Gastrointestinals • Famotidine (Pepcid AC) - H2 receptor blocker • Carafate (Sucralfate)  gastroprotectant, also known as a “band-aid” for the GI tract, may impair absorption of some oral medications • Maropitant (Cerenia)  antinausea/anti-vomiting agent

• Metoclopramide (Reglan)  upper GI pro-kinetic agent, may cause excitement or hyperactivity in cats, antiemetic- prevents nausea by blocking dopamine in the chemo-receptor trigger zone (CRTZ)

Gastrointestinals • Cisapride  pro-motility agent for upper and lower GI, used in cats with megacolon (not commercially available, must get compounded) • Omeperazole (Prilosec)  proton pump inhibitor, used for treating and preventing GI ulcers • Misoprostol  prostaglandin E1 analog, used to prevent gastric ulceration

Cardiac/ blood pressure • Furosemide (Lasix)  Loop diuretic most often used in congestive heart failure • Enalapril/Benazapril  ace-inhibitors (end in suffix–pril), used in treating heart failure and hypertension, sometimes used in chronic renal failure, causes vasodilation • Pimobendan (Vetmedin)  inodilator, used in treating congestive heart failure

• Spironolactone (potassium sparing diuretic) • Amlodipine (decreases blood pressure, choice antihypertensive for cats) • Atropine  anticholinergic, used to increase heart rate; used in CPCR and also during anesthesia to treat bradycardia

Important notes on animal medicine drug withdrawal periods extra-label drug use

Drug withdrawal periods Veterinary drugs contain substances, which are potentially toxic and harmful to humans. After giving a drug to an animal these substances remain in the animals' body for some time until they have been completely excreted.

While these toxic substances remain in the body they can be found in the muscle (meat) and also in the udder (milk).

Drug withdrawal periods A person consuming meat or milk from an animal that still has drug substances in its body will ingest harmful and toxic substances. To prevent this from happening drug manufacturers provide a withdrawal period for each drug. The withdrawal period is the time until all toxic and harmful substances have

been cleared from the body (including from meat and milk) of the treated animal.

• Do not slaughter for 5 days after last dose • Discard milk for 36 hours after last dose • Discard eggs for 14 days after last dose

Extra-label drugs use This includes not limited to a different dosage, interval, route, indication, or species.

Decisions to use ELDU may include a potential lack of efficacy of approved products, lack of approved products to address specific needs and economic considerations.

There are possible human health risks relating to ELDU in animals including: • Development of antimicrobial resistance (AMR); • Presence of drug residues in foods derived from treated animals and in the environment

Extra-label drugs use One of the following general conditions must be met before a veterinarian can legally prescribe an approved human or animal drug for an extra-label use: • There is no animal drug approved for the intended use; or • There is an animal drug approved for the intended use, but the approved drug does not contain the active ingredient you need to use; or

Extra-label drugs use • There is an animal drug approved for the intended use, but the approved drug is not in the required dosage form (for example, you need a liquid dosage form, but the approved drug is only available as a tablet dosage form); or • There is an animal drug approved for the intended use, but the approved drug is not in the required concentration (for example, you need 5 mg, but the approved drug is only available at 50 mg); or • Veterinarian has found, in the context of a valid veterinarian-clientpatient relationship, that the approved drug is clinically ineffective when used as labeled.

Extra-label drugs use Drugs Prohibited from Extra-Label Uses in Animals Under the AMDUCA provisions, FDA has the right to prohibit extra-label uses of certain drugs in animals. The following drugs (both human and animal), families of drugs, and substances are prohibited from extra-label uses in all foodproducing animals, including horses intended for human food: o Chloramphenicol o Clenbuterol

Extra-label drugs use • Sulfonamide drugs in lactating dairy cattle, except for the approved use of sulfadimethoxine, sulfabromomethazine, and sulfaethoxypyridazine • Phenylbutazone in female dairy cattle 20 months of age or older • Cephalosporins (not including cephapirin) in cattle, swine, chickens, or turkeys

• Diethylstilbestrol (DES) • Dimetridazole • Ipronidazole and other nitroimidazoles • Furazolidone and nitrofurazone • Fluoroquinolones • Glycopeptides

Extra-label drugs use For disease prevention purposes; • At unnaproved doses, frequencies, duration, or routes of administration; or • If the drug is not approved for that species and production class.

Currently, no approved drugs are prohibited from extra-label uses in companion animals.

The following drugs, or classes of drugs, that are approved for treating or preventing influenza A are prohibited from extra-label uses in chickens, turkeys, and ducks: adamantane and neuraminidase inhibitors.