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Pharmacology Review

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  1. Pharmacology Review

  2. Dosage forms • Tablets • Powder-compressed • Enteric-coated-protective coating • Chewable-mixed with flavorings • Sustained-release-released slowly over time • Boluses-larger powdered tablets • Capsules-loose powder in gelatin shell • Suppositories-designed for absorption through rectal wall

  3. Dosage forms • Liquids • Solutions-drug dissolved in solvent • Elixirs-sweetened alcohol based • Syrups-sweetened sugar based • Suspensions • Emulsions-oil based • Gels-drug suspended in semi-solid medium • Topicals • Ointments-petroleum based-forms barrier • Creams-liquefies at body temps • Paste-semisolid, stays solid at body temps

  4. Dosage forms • Injectables • Ampule-single use, must break container • Vials • Single dose • Multidose • Repository forms-designed for release over time from injection site • Implants-sterile hypodermic tablets

  5. Prescription Label • Vet clinic name, address and phone • Prescribing Dr. name • Patient name • Date dispensed • Dosing instructions • Medication name, strength and qty • Number of refills • Slaughter withdrawal times (if applicable) • Childproof container unless written documentation from client (decline such containers)

  6. Controlled Substances • Required by DEA due to potential for addition in humans • Capital C followed by roman numeral • CI-marijuana, LSD • CII-Morphine, pentobarb. • CIII-hydrocodone, thiopental, ketamine • CIV-phenobarb, diazepam, torb • CV-codiene syrups • Locked, immovable area with inventory log book

  7. Patient 5 Rights • Right patient • Right drug • Right route • Right dose • Right time

  8. Compounding Drugs • Compounding for economic benefit of vet not permitted • Considered not approved drug • Vets assume all risks • Can’t be sold to other practices

  9. Extra Label Use • Use of a drug in a way not defined on label • Vets have wide latitude but assume all responsibility • FDA considers legit • Dx with CP relationship • No drug specifically labeled to tx cond. • Procedures in place to ensure the identity of animals treated for purposes of monitoring • Extended withdrawal time from tx animals • Drug adequately labeled to ensure safe and proper use

  10. Pharmacokinetics • Movement of drugs or chemicals within the body • Absorption • Distribution • Biotransformation • Elimination

  11. First Pass Effect • Bioavailability • Percent of a drug that is absorbed and reaches the systemic circulation • Drugs given IV have 100% bioavail. • Drugs given orally have lowest bioavail. • Must pass through hepatic portal system first • Liver acts on drugs before they are distributed to target tissues (First pass effect) • Dosages unusually much higher to account for this

  12. Bioavailability Affected By • Absorptive surface area • Blood supply to area of administration • Solubility of drug • pKa –specific pH at which 50% of drug are ionized • Hydrophilic • Lipophilic • Distribution of drugs in body tissues • Example-for drugs to leave capillaries in brain must be lipophilic (blood brain barrier) • Biotransformation of drugs • Altering drug before it can be eliminated • Phase I-chemical transformation (oxidation, reduction, hydroloysis) Most drug metabolites are less biologically active after phase I • Phase II-enzymatic conjugation of metabolite into a hydrophilic molecule • Elimination of drugs from body tissues • Kidney and liver • Half life

  13. Pharmacodynamics • Physiological effects of drug on the body system into which it has been admin. • AKA mechanism of action • For (most) drugs to exert an effect they must bind to specific receptor • Lock and key principle • Agonist/antagonist • Nonreceptor-mediated reactions • Osmotic diuretics-active molecules that are filtered into the urine and not reabsorbed • Chelators-binds to ions or blood compounds and inactivates them • Antactids-directly reduces stomach acid

  14. Therapeutic Range/Index • Ideal range of a drug concentration within a body that provides a desired effect without signs of toxicity • Above=toxic • Below=subtherapeutic • Wider range=safer drug • Goal is to maintain levels in therapeutic range

  15. Nervous Pharmacology • Nervous System • CNS • PNS • Somatic • Autonomic • Sympathetic • Parasympathetic • Work by altering one or more of systems • Mimicking neurotransmitters • Preventing neurotransmitter release (presynaptic) • Blocking neurotransmitter binding (postsynaptic) • Inhibiting reuptake or breakdown of neurotransmitter

  16. CNS Drugs • General • Anesthesia • Analgesia • CNS excitation/stimulation • Control seizures • Cause euthanasia • Categories • Tranqs (Phenothiazines) (Benzodiasepaines) (Alpha 2 agonists) • Barbs (Long (8-12 hrs), short (45 min-1.5 hrs) and ultrashort acting) • Dissociatives (Cyclohexamines) • Opiods (Analgesia and sedation) (5 receptors-alpha, sigma, kappa, delta and epsilon unknown effects) • Neuroleptanalgesics (combines effects of opiods and tranqs) • Antisiezure • CNS stimulants (Doxapram-reversal of resp depression/apnea) • Euth agents

  17. Nervous Pharmacology Cont. • Cholinergic Agents • Stimulate acetylcholine receptors • Directly (mimicking) • Bethanechol • Pilocarpine • Metoclopramide (reglan) • Indirectly (preventing AchE) • Organophosphate compounds • edrophonium • Uses • Stimulate GI motility • Treat urinary retention • Reduce intraocular pressure • Control vomiting • Diagnosis myasthenia gravis • Adverse effects • Bradycardia • Hypotension • SLUDD (parasympathetic NS)

  18. Nervous Pharmacology Cont. • Anticholinergic agents • Block the effects of acetylcholine • Atropine • Glycopyrolate • (aminopentamide (centrine) • Usage • Preanesthetic to dry secretions and prevent bradycardia • Tx diarrhea and vomiting • Dilation of pupils for exam • Tx of bradycardia • Adverse effects • Drowsiness • Tachycardya • Constipation • anxiety

  19. Nervous Pharmacology Cont. • Adrenergic Agents • Mimic effects of epi and norepi • Epinephrine (stimulate both alpha and beta • Norepi • Isoproterenol (pure beta agonist-bronchodialator) • Dopamine (precursor to epi and norepi) • PPA • Terbutaline (Brethine) • Xylaxine (rompun-alpha agonist with sedative properties) • Medetomidine (Domitor-alpha agonist with sedative properties) • May be alpha (excitatory) or beta (inhibitory) agonists • Usage • Stimulate HR • Reverse hypotension and bronchoconstriction • Strengthen heart contractions • Treat urinary incontinence • Prolong effects of locals (vasoconstric. Reduces absorption) • Adverse effects • Hypertension • Nervousness • Cardiac arrhythmias

  20. Nervous Pharmacology Cont • Adrenergic blocking agents • Block the effects of epi and norepi • Classified • Alpha blockers • Ace (tranquilizer) • Yohimbine (reversal for xylazine) • Atipamezole (Antesedan) • Beta blockers • Propanolol • Tx hypertrophic cardiomyopathy • Adverse effects • Hypotension • Heart block

  21. Antibiotics • Spectrum of activity • The range of different bacteria affected by a given abx • Gram + vs. gram – • Mechanism of action • Bacterialcidal • Bacteristatic • C & S

  22. Penicillins • Pharmokinetics • Absorption of oral preps in stomach and duodenum • Rapid distrib. Into tissues • Excreted by kidneys • Some passage into milk • Mechanism of action • Bacterialcidal • Inhibits cell wall synthesis • Gram + bacteria have cell wall that is unprotected • Gram – bacteria have no outer membrane that protects cell wall

  23. Penicillins • Narrow spectrum • Pen G • Beta-lactamase-resistant pens • Not used in vet med (expensive) • For pen resistant bacteria • For highly resistant staph • Broad spectrum • Ampicillin • Potentiated pens • Clavamox • Wider range of bacteria

  24. Cephalosporins • Pharmokinetics • Distributed to all body except CNS • Metabolized by liver • Excreted by kidney • Mechanism of action • Bacterialcidal • Inhibits cell wall synthesis • Similar spectrum of activity as pens • Common uses • Cystitis • Skin infections • mastitis

  25. Cephalosporins Cont. • Preparations • Cephalexin (Keflex) • Most commonly used • May cause vomiting • Cefadroxil (Cefa tabs) • Cefazolin (Ancef) • Ceftiofur (Naxcel) • 2nd generation • Sefpodoxime (Simplecef) • 3rd generation • SID tx

  26. Tetracyclines • Pharmacokinetics • Rapid distribution into most body tissues • Very little metabolism occurs • Excreted by kidney in active form • Pharmacodynamics • Bacteriostatic • Inhibit bacterial cell division • Both gram + and gram – affected • Considered broad spectrum abx • Common uses • Respiratory and enteric infections

  27. Tetracyclines Cont. • Preparations • Tetracycline (panmycin) • Oxytetracycline • Chlortetracycline • Doxycycline • Most potent broad spectrum in class • Important info • May cause permanent staining of teeth enamel in young animals • Inhibited by milk, antacids and pens • Becomes toxic after exp date

  28. Aminoglycosides • Pharmacokinetics • Poorly absorbed through GI tract • Rapid distribution occurs into ECF • Doesn’t reach CSF or fetal tissues • May accumulate in renal cortical tissues • Nephrotoxic if not cleared adequately • Pharmacodymamics • Bacteriostatic • Inhibit bacterial cell division • Considered broad spectrum • Mostly effective against gram -

  29. Aminoglycosides Cont. • Common usage • Infections of resp, repro, renal, skin and ocular systems • Preparations • Neomycin • Gentamycin (Gentocin) • Amikacin (Amiglyde-V) • Important info • Highly ototoxic and nephrotoxic • Not approved for food prod. animals

  30. Fluoroquinolones • Pharmacokinetics • Good bioavailability after oral and perenter admin. • Distributed to therapeutic levels in nearly all body tissues • Metabolized by liver • Excreted by kidney and bile • Pharmacodynamics • Bacterialcidal • Inhibition of bacterial DNA-gyrase

  31. Fluoroquinolones Cont. • Considered very broad spectrum • Gram – and gram + • Usage • Skin, soft tissue, respiratory, UTI • Approved for resp dz in cattle • Approved for E coli in poultry • Preparations • Enrofloxacin (Baytril) • Orbifloxacin (Orbax) • Marbofloxacin (Zeniquin) • Difloxacin (Dicural)

  32. Fluoroquinolones Cont. • Deleterious effects to articular cartilage in young, growing animals • Inhibited by milk and antacids • Enrofloxacin induced blindness (rare)

  33. Miscellaneous Abx • Chloramphenicol • Broad spectrum, rapidly absorbed into most tissues including CNS and glands • Florfenicol (Nufuor) • Similar to chloramphenicol • Inj used for bovine resp dz • Extra label use in tx calf scours

  34. Macrolides and Lincosamides • Primary for gram + • Clindamycin is also very effective agains anaerobic bacteria • Uses resp and skin infections • Preparations • Tylosin (Tylan) • Erythromycin (Lincosin)

  35. Sulfonamides • Broad spectrum of activity • Gram + and gram – • May be potentiated by addition of trimethoprim or ormethoprim • Uses UTI, resp, coccidiosis • Preparations • Sulfadimethoxine (Albon) • Trimethoprim sulfa (Tribrissen) • Trimethoprim sulfamethozazole (Bactrim) • Ormethoprim sulf (Primor) • Important info • KCS potential side effect

  36. Antifungals • Imidazoles • Systemic and dermal fungal infections • Preparations • Ketoxonazole (Nizoral) • Miconazole (Monostat and conofite) • Clotrimazole (Lotrimin, tinactin) • Griseofulvin-superficial fungal infections (ringworm primarily) (Absorption enhanced by fatty meal)

  37. Antivirals • Acyclovir • Used in cats for herpes virus conjunctivitis • Interferon • Chronic FELV infections

  38. Parasiticides • Benzimidazoles • Broad spectrum • Usage-almost all internal parasites are susceptible to this class (except small animal tapes) • Ok to use in exotics like fish and birds • Preparations • Fenbendazole (Panacure) • Albendazole (Valbazen) • Thiabendazole (Omnizole)

  39. Parasiticides • Organophosphates • Limited use due to side effects • SLUDD • Atropine antidote • Usage • Highly effective against equine stomach bots • Effective for resistant whipworm and hookworm infections in dogs • Preparations • Trichlorphon (Combot, Equibot) • Dichlorvos (Task, Atgard)

  40. Parasiticides • Imidazothiazoles • Usage • Many parasites susceptible • Most commonly used in large animals • Preparations • Febantel • Component of Drontal Plus • Levamisole (Tramisol, Levasole)

  41. Parasiticides • Avermectins • Several OTC prods available for livestock • Usage • Effective against most parasites in large animals • Internal and External • Common HW monthly prev. • Preparations • Ivermectin (Heartgard, Ivomec, Eqvalan) • Use with caution in collies and collie mixes • Lack gene that pumps it out of the brain • Drug accumulates and causes seizures, coma etc. • Moxidectin (proheart, Quest) • Dormactin (Dectomax) • Selamectin (Revolution) • Spot on for dogs and cats

  42. Parasiticides • Tetrahydropyrimidines • Most common dewormer • OTC • Roundworm species susceptible • Not effective for whips or hooks • Preparations • Pyrantel pamoate (Nemex, Strongid-T)

  43. Parasiticides • Anticestodals • Treatment of tapeworm infections in dogs and cats • Preparations • Praziquantel (Droncit) • Epsiprantel (Cestex)

  44. Parasiticides • Antiprotozoals • For tx of coccidia and giardia • Large and small animals • Preparations • Coccidiostats • Monensin (Coban 60) poultry • Amprolium (Corid) cattle • Sulfadimethoxine (Albon) • For giardia • Metronidazole (Flagyl)

  45. Parasiticides • Heartworms • Tx involves removal of adult heartworms first then removal of juveniles (microfilaria) • Once infections have been treated should be on monthly HW prev. • Adulticides • Thiacetarsemide (Caparsolate) • Arsenical compound given IV in 4 doses • Can be hepatotoxic • Cheap • Melarsomine dihydrocholoride (immiticide) • Aresenical compound given deep IM in backless irritating to tissues • More expensive • Not hepatotoxic

  46. Parasiticides • HW Preventatives • Monthly kill retroactively • Vary in combinations • Often tx other parasites as well • Preparations • Ivermectin (Heartgard) • HG + treats and prevents rounds too • Mibemycin oxime (Interceptor, Sentinel) • Controls hooks, whips and rounds • Sentinel contans lufenuron for fleas • Moxidectin (Proheart) • Many restrictions

  47. Parasiticides • HW Preventatives • Selamectin (Revolution) • Topical • Also tx earmites, sarcoptic mange, hookworms and roundworms • Diethylcarbamazine (Filaribits) • Daily • Not commonly used anymore

  48. Parasiticides • Ectoparasites-read labels and use in caution with young, nursing or pregnant and certain species. • Monthly prev. • Fipronil (Frontline topspot) • Imidacloprid (Advantage, K9 Advantix-has 44% permethrin so don’t use in cats!) • Lufenuron (Program and Sentinal) • Oral tablets • Fleas must eat a blod meal • Permethrin (Defend, K9 Advantix) • Topical • Not for cats • Selamectin (Revolution) • Also tx earmites, sarcoptic mange, hookworms and rounds

  49. Parasiticides • Insecticides • Pyrethrins • Quick kills-fast knockdown • Safe for most animals • Very toxic to cats • Chlorinated hydrocarbons • Banned due to bald eagles • Carbamates (mycodex, sevin dust) • Organophosphates • Chylorpyfiros • Dichlorovos (Vet Kem) • Diazinon (Escort)

  50. Parasiticides • Insecticides Cont. • Neonicotinoids • Nitenpyram (Capstar) • Single oral dose kills fleas on pet within 30 mins • Formamidines • Amitraz (Mitaban, Preventic) • IGRs • Preparations • Methoprene • Fenoxycarb • Nylar