Veterinary Pharmacology Part 2

Question 1

Clomipramine

Amitriptyline

Answer 1

TCA (antidepressants)
NE and serotonin reuptake inhibitor
Sole tx (or combined with anxiolytics) for anxieties/stereotypies
Takes 4-6 weeks before full therapeutic effect
Mild sedation, dry mouth, tachycardia, urinary retention,, constipation, hypotension, arrhythmias, +/- V/D

Question 2

Fluoxetine, paroxetine, sertraline

Answer 2

SSRI (antidepressants)
Serotonin reuptake inhibitor
Sole tx (or combined with anxiolytics) for anxieties/stereotypies
Takes 4-6 weeks before full therapeutic effect
Mild sedation, GI irritation (V/D, inappetance), excessive vocalization, seizures

Question 3

Trazodone

Answer 3

SARI (antidepressant)
Serotonin reuptake inhibitor, antagonist at 5HT2, H1 and a1 receptor (low doses), agonist at 5H1 and impacts GABAr
Generally safe in combination with SSRI and TCAs in dogs
3h half life in dogs, 85% bioavailability

Question 4

Selegiline

Answer 4

MAOi (antidepressant)

Question 5

Diazepam (and other benzodiazepines)

Answer 5

Benzodiazepines (anxiolytics)
Stabilize/inhibit GABA receptors
Sole tx (or in combination w/ antidepressants) of anxiety
Sedation, ataxia, polyphagia, increased friendliness, excitation, hepatic necrosis
Can interfere with learning/memory
Don’t store in plastic or in light

Question 6

Buspirone

Answer 6

Azapirones (anxiolytic)
5HT1 partial agonist, dopaminergic effects
Usually sole tx of anxiety, urine spraying - not approved
Multi-cat households
Not sedating, no effect on learning, not CYP mediated
Requires frequent dosing
Decreased inhibition (–> aggression), +/- V, increased affection towards owner, tachycardia

Question 7

Acepromazine, chlorpromazine, chlorpromazine

Answer 7

Phenothiazines (antipsychotics and anti-emetics)
Dopamine antagonism - inhibits CTZ and/or emetic center
For on-specific sedation, motion sickness?
Poor oral efficacy
Potent, long-acting; hypotension, extrapyramidal signs, mm. rigidity, penile prolapse in horses, ataxia, prolapsed 3rd eyelid, CYP-mediated

Question 8

Mirtazepine

Answer 8

NaSSA (antidepressant and appetite stimulant)
NE and 5HT1 stimulant
Antagonist of 5HT2 (appetite stimulant) + 5HT3 (anti-nausea/anti-emetic effects), H1 receptors (sedation)
Increased neediness (vocalization/interaction)
Transdermal form
Hepatic metabolism and renal excretion (accumulation?)
Polyphagia within 8-36 hours

Question 9

Dextromethorphan

Answer 9

NMDA receptor antagonist
Decreased glutamate
Activates sigma receptors (5HT), activates AMPA
Excitatory effects

Question 10

Reserpine

Answer 10

NE reuptake inhibitor –> NE depletion
Drug of abuse in horses
Significant hypotension
Potentially fatal interactions with other hypotensive drugs (ex. ace)

Question 11

Dirlotapide

Answer 11

Microsomal triglyceride transfer protein inhibitor
Decreased lipoprotein/chylomicron assembly
More lipid in enterocyte –> satiety signal
Steatorrhea, anorexia, emesis, increase liver enzymes, hepatic lipidosis in cats

Question 12

Orlistat

Answer 12

Pancreatic lipase inhibitor
Decreased fat digestion/absorption
Like osestra –> diarrhea

Question 13

Testosterone

Answer 13

Appetite stimulant

Only anabolic steroid approved in vet med

Question 14

Diazepam

Answer 14

GABA agonist; inhibits satiety center in hypotahlamus
Used in cats
Not terribly effective

Question 15

Cyproheptadine

Answer 15

Antihistamine + 5HT2 blocker - control satiety
Appetite stimulant in cats
Hit or miss

Question 16

Megesterol acetate

Answer 16

Synthetic progestin as an appetite stimulant

Significant side-effects (better options out there)

Question 17

Glucocorticoids (for appetite stimulation)

Answer 17

Transient polyphagia
For palliative cases (ex. oncology)
Inherent activity or “perking up?”

Question 18

Apomorphine

Answer 18

Emetic in dogs

Give via conjunctiva or IV

Question 19

Alpha-2-agonists (ex. Dexmedetomidine)

Answer 19

Emetic in cats

Give via IM

Question 20

Syrup of Ipecac

Answer 20

GI irritaiton –> emesis

Not very effective in vet med

Question 21

Hydrogen peroxide

Answer 21

Emetic in dogs
Irritation of throat/glossopharyngeal nerve
Not very effective (useful for clients at home)

Question 22

Antihistamines (as anti-emetics)

Answer 22

Block cholinergic (cats) and histaminic (dogs) nerve transmission responsible for transmission of vestibular stimuli to emetic center
Mild sedation

Question 23

Metaclopromide

Answer 23

Inhibit dopamine in CNS and 5HT3 receptors in CRTZ
Variable PK in small animals but reasonably effective
Peripheral prokinetic effect - increased gastric and upper duodenal emptying + increased GE sphincter tone, through stimulation of 5HT4, dopamine (D2) antagonism
Used for mega-esophagus postop GDV - poor evidence
Extrapyramidal effects (esp. with ace)

Question 24

Ondansetron

Answer 24

Potent anti-emetics
Serotonin (5HT3) antagonist
Very expensive
Useful during chemotherapy (cytotoxic drugs release serotonin from endochromaffin cells in SI - not as useful for motion sickness-induced vomiting)

Question 25

Maropitant

Answer 25

Neurokinin (NK1) receptor antagonist: blocks binding of substance P in emetic center - works against SoI and apo For acute vomiting and motion sickness in dogs Bone marrow hypoplasia in puppies (<16 weeks) Can use in cats

Question 26

Omeprazole

Answer 26

Irreversible inhibition of gastric proton pumps Very effective for ulcer treatment/prevention - relapse when off therapy Can lead to hypergastrinemia --> hyperplasia/hypertrophy and carcinoids CYP enzyme inhibitor Wean off after prolonged use (>3-4 weeks) - risk of hyperacid rebound syndrome)

Question 27

Cimetidine, famotidine, ranitidine

Answer 27

H2 receptor antagonists Limited evidence of efficacy in dogs/cats (Omeprazole is better) - none licensed for vet use Ranitidine and cimetidine may be prokinetic Low bioavailability in horses/ruminants; lipid-soluble Cimetidine inhibits CYP enzymes

Question 28

Antacids

Answer 28

Neutralize stomach acid to form water and salt | Short-term fix, cheap

Question 29

Sucralfate

Answer 29

Dissociates to sucrose octasulfate (coats ulcer) and aluminum oxide Increases mucosal PGE synthesis Few ADRs, cheap, easy to administer No good evidence

Question 30

Misoprostal

Answer 30

Synthetic PGE analogue - stimulates bicarb and mucus secretion, increases blood flow, decreases vascular permeability, increases cell proliferation/migration Use as preventative for NSAID or steroid-induced ulcers in dogs Few ADR, but limited evidence of efficacy

Question 31

Domperidone

Answer 31

Poor GI prokinetic effect Dopamine antagonist (like metaclopramide) No CNS reactions Treatment of agalactia (stimulate prolactin secretion)

Question 32

Cisapride

Answer 32

``` 5HT4 agonist (increased ACh in myenteric neurons) and 5HT3 antagonist (like metaclopramide) More effective than metaclopramide Increase smooth muscle motility in stomach, small intestine and colon - used for megacolon in cats, for dogs throughout GIT, and for horses to treat postop ileus Shorter half-life in dogs and cats than horses/ruminants Arrhythmias and CYP interactions in humans ```

Question 33

Erythromycin

Answer 33

Macrolide antimicrobial Activates motilin receptors in stomach and proximal SI Can cause vomiting and regurgitation (direct irritation?) Can cause diarrhea in horses (GI flora disturbance)

Question 34

Lidocaine

Answer 34

Reduce postop ileus in horses when given as an IV infusion (expensive!) Many possible mechanisms of action ADRs: muscle fasciculations, ataxia, seizures

Question 35

Kaolin pectin, activated charcoal, bismuth subsalicylate

Answer 35

Anti-diarrheal drugs (protectants and dsorbents) Safe even if worried about delayed transit through GIT Don't solve the issue but may make a person feel better

Question 36

Anticholinergic drugs (anti-diarrheal use)

Answer 36

Significantly decease intestinal motility and secretions Few cases of diarrhea are due to hypermotility - may actually worsen diarrhea Systemic side-effects (tachycardia)

Question 37

Hyoscine butylbromide (Buscopan)

Answer 37

Antispasmodic and anticholinergic for horses with "intestinal pain in non-surgical colic" May cause tachycardia and decreased gut sounds Not efficacious as an antidiarrheal

Question 38

Loperamide

Answer 38

Opioid; anti-secretory, anti-motility effects - increased segmentation = overall constipating effect; increased tone of GI sphincters, stimulate absorption of fluid/electrolytes Doesn't cross BBB (b/c of P-gp) Don't use with infectious diarrhea or ABCB1 mutant dogs

Question 39

Antimicrobials for diarrhea

Answer 39

Only for KNOWN bacterial causes Abx frequently cause diarrhea (esp. in hindgut fermenters) Prophylaxis to reduce septicemia (ex. parvo)? May result in carrier animals d/t resistance

Question 40

NSAIDs for diarrhea

Answer 40

Meloxicam has label claim for calf diarrhea; flunixin (if blood present in feces) Risk of adverse events with concurrent dehydration Actually decreasing diarrhea (decreased inflammation/secretion) Or just feeling better (antipyretic/central analgesia?)

Question 41

Lubricants for constipation

Answer 41

``` Mineral oil (1st choice), white petroleum Safe, cheap, generally effective; may not help ```

Question 42

Motility modifying drugs for constipation

Answer 42

Cisapride, erythromycin, metaclopromide, cimetidine, ranitidine... NO

Question 43

Stimulant laxatives

Answer 43

Irritate mucosa or intrinsic nerves, causing motility Phenolphthalein (too potent), Senna (new ExLax), Bisacodyl (Dulcolax - human drug) Can cause excess fluid loss and electrolyte loss

Question 44

Hyperosmotic laxatives

Answer 44

Draw fluid into GI lumen to stimulate motility Don't use sodium phosphate enemas in cats (hyperphosphatemia) Lactulose Polyethylene glycol (effective and potent - cleans out)

Question 45

Bulk laxatives

Answer 45

Non-absorbed cellulose material increases bulk of fecal material Metamucil (hydrophilic colloids), prunes/pumpkin (fiber) Doesn't work immediately (if at all), but safe and easy; use for chronic constipation

Question 46

Stool softeners

Answer 46

Increase water accumulation in feces | Dioctyl sodium sulfosuccinate, dioctyl calcium sulfosuccinate

Question 47

Probiotics

Answer 47

Change flora? Specific nutrient production? Stimulates enteric immune system? Safe, relatively cost-effective (can be expensive); routine administration of the right combinations Inefficacy

Question 48

5-amino-salicylic acid

Answer 48

Treatment of chronic colitis in dogs NSAID effects - poor GIT absorption Still risky in cats

Question 49

Sulfasalazine

Answer 49

Treatment of chronic colitis Cytoprotective - blocks formation of ROS Sulfapyridine component (sulfa) Anti-inflammatory effects

Question 50

Metronidazole

Answer 50

Treatment of Giardia, aerobes (clostridia) | For some types of colitis it's effective, others not at all

Question 51

Tylosin

Answer 51

Macrolide antibiotic Antimicrobial/anti-inflammatory/motility effects? Hit or miss - depends on pathogenesis of colitis

Question 52

Glucocorticoids (for colitis)

Answer 52

Prednisone/prednisolone and budesonide (potent - don't want it absorbed from GI - for human use) Decreased inflammation

Question 53

Azathioprine

Answer 53

Immunosuppressive drug

Question 54

Chlorambucil

Answer 54

Immunosuppressive drug

Question 55

Cyclosprorine

Answer 55

Immunosuppressive drug | Works for IBD

Question 56

Pancrelipase

Answer 56

Exocrine pancreas enzymes To treat EPI in dogs (not cheap but it works) Mix with food 20 mins before feeding - H2 receptor antagonists may increase amount that reaches duodenum

Question 57

Octreotide

Answer 57

Pancreatitis treatment... Synthetic analog of somatostatin (GHIH) - human drug Inhibits gastrin, secretin, VIP, motilin, glucagon, and insulin secretion --> decreased acid, pepsin production, intestinal motility and GI blood flow - shuts down GIT Not a viable therapy - no clinical studies

Question 58

Hepatitis drugs

Answer 58

Glucocorticoids (metabolism?), ursodiol (bile acid - for cholestatic disease; aids in clearing gallstones), SAMe (increases antioxidants glutathione in hepatocytes), colchicine, penicillamine/trientine/zinc (copper chelators) antioxidants, milk thistle (approved neutraceutical) Not good evidence for any; anecdotal

Question 59

Cyclophosphamide

Answer 59

Nitrogen Mustard (cross-link DNA strands) Cell cycle nonspecific Myelosuppression (neutropenia) - delayed in cats Prodrug - forms Acrolein (sterile cystitits/bladder irritation - furosemide and fluids) Vomiting, diarrhea, alopecia For carcinomas, sarcomas

Question 60

Chlorambucil

Answer 60

Nitrogen Mustard (cross-link DNA strands) Cell cycle nonspecific Myelosuppression and vomiting (Fanconi's syndrome + neuro signs rare) Less potent and less toxic Expensive - used in cats and small dogs Immunosuppressive drug of choice in cats - chronic, immune-mediated derm protocols Steroid sparing

Question 61

CCNU (Lomustine)

Answer 61

Nitrosurea (cross-link DNA strands) Lipid-soluble - brain tumors? lymphoma, MCT, etc. Leukopenia - can cause thrombocytopenia

Question 62

Streptozocin

Answer 62

Nitrosurea (cross-link DNA strands) Toxic to pancreatic B-cells - for insulinoma Causes renal tubular necrosis - use with IV fluid diuresis Can result in type I diabetes Vomiting common in dogs

Question 63

Cisplatin

Answer 63

``` Cross-linking DNA around platinum ion Inhibits DNA synthesis (S-phase) For osteosarcoma, carcinomas, MCT (solid tumors), sarcoids in horses Nephrotoxicity - IV diuresis Fatal pulmonary edema in cats V/D; some myelosuppression ```

Question 64

Carboplatin

Answer 64

Second generation platinum derivative Less nephrotoxic than cisplatin Causes thrombocytopenia Can be used in cats

Question 65

Pamidronate

Answer 65

Inhibits osteoclasts, decreases bone resorption Not chemotherapy - may be analgesic for dogs with osteosarcoma Used to treat hypercalcemia of malignancy Can cause nephropathy

Question 66

5-Fluorouracil

Answer 66

Inhibit nucleic acid synthesis - thymine synthesis Active in S-phase Neurotoxicity (and hepatotoxicity in cats) SSC in horses

Question 67

Rabacfosadine

Answer 67

``` Prodrug converted to active forms - multimodal action Lymphoma in dogs IV infusion over 30 minutes Fatal pulmonary fibrosis in WHWT Typical chemo ADE ```

Question 68

L-asparaginase

Answer 68

Made by E. coli Breaks down asparagine to aspartic acid - interferes with tumor protein synthesis - G1 lymphoma, melanoma, MCT Hypersensitivity (allergic) reactions occur (diphenhydramine) - minimal myelosuppression Expensive

Question 69

Toceranib

Answer 69

Cutaneous MCT in dogs Anti-tumor and anti-angiogenic Decreased proliferation of endothelial cells in vitro Oral - many adverse events

Question 70

Vincristine

Answer 70

Vinca Alkaloids Interferes with microtubules needed for mitosis Lymphoma protocols Tissue necrosis if given perivascular; peripheral neuropathy; constipation; not too bad for neutropenia Therapy for immune-mediated thrombocytopenia

Question 71

Doxorubicin

Answer 71

Variety of mechanisms S-phase; intercalates between bases; alters ion transport in cell; generates free oxygen radicals Lymphosarcoma, osteosarcoma, mammary carcinomas Slow IV infusion every 21 days Metabolized by liver, excreted in bile Severe tissue necrosis, bone marrow suppression, cardiotoxicity (Fe buildup) - related to cumulative dose

Question 72

Paclitaxel

Answer 72

Stops M phase by inhibiting microtubular network Hypersensitivity reactions - carrier causes pruritus, anaphylaxis, hypotension and peripheral edema Pretreat with steroids, cimetidine, antihistamine Extremely myelosuppressive P-gp substrate

Question 73

Piroxicam

Answer 73

Inflammation of transitional cell carcinoma

Question 74

Azathioprine

Answer 74

Purine anti-metabolite - Immunosuppressive in dogs Metabolized in liver to active (6-mercaptopurine) and inactive metabolites Not used in cats - more prone to bone marrow suppression Rebound hyper-immune response - taper slowly

Question 75

Cyclosporine

Answer 75

Immune modulating Inhibits calcineurin phosphatase - prevents induction of genes coding for IL2 production --> inhibition of T-cell activation/chemotaxis, APCs, MC and eosinophil infiltration For dogs (capsules) and cats (solution) - also topical for KCS/CSK in dogs Bioavailability is formulation-dependent V/D/GI disorder, gingival hyperplasia, secondary infections, P-gp/CYP

Question 76

Leflunomide

Answer 76

Not typically recommended in vet med Rheumatoid arthritis in humans Prodrug (active = teriflunomoide) - inhibits pyrimidines

Question 77

Mycophenolate Mofetil

Answer 77

Purine synthesis inhibitor | Raging, horrible diarrhea in dogs

Question 78

Tacrolimus

Answer 78

Calcineurin/T-cell inhibitor | Expensive

Question 79

Apoquel (Oclacitinib)

Answer 79

Janus kinase inhibitor - blocks intracellular communication and inhibits IL-31 (pruritogenic/proinflammatory cytokine) Pruritus associated with allergic dermatitis/control of atopic dermatitis Rapid effect (within days) Not often see immunosuppression, low incidence V/D

Question 80

Cytopoint

Answer 80

Canine monoclonal antibody against IL-31 Doesn't solve allergy problem, but minimize epithelial damage d/t itching SC injection, long duration of effect (>30 days)

Question 81

Pegbovigrastim (Imrestor)

Answer 81

G-CSF - immune stimulant to increase neutrophil counts/function (phagocytosis) Peg = polyethylene glycol (decrease rate of protein clearance) Reduce clinical mastitis in first 30 days of lactation SC injection 7 days prior to calving, at calving Rare but fatal idiosyncratic "hypersensitivity" reactions

Question 82

Erythropoietin

Answer 82

Injectable forms only (it's a protein) Used for anemia d/t chronic kidney disease, myelodysplasia, or as a drug of abuse (performance enhancing) Darbopoietin-a = longer-lasting version

Question 83

Pentoxifylline

Answer 83

Oral methylxanthine derivative | Supposedly lowers blood viscosity/improves RBC deformability