Veterinary Pharmacology Part 2 Flashcards
Clomipramine
Amitriptyline
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
Fluoxetine, paroxetine, sertraline
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
Trazodone
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
Selegiline
MAOi (antidepressant)
Diazepam (and other benzodiazepines)
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
Buspirone
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
Acepromazine, chlorpromazine, chlorpromazine
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
Mirtazepine
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
Dextromethorphan
NMDA receptor antagonist
Decreased glutamate
Activates sigma receptors (5HT), activates AMPA
Excitatory effects
Reserpine
NE reuptake inhibitor –> NE depletion
Drug of abuse in horses
Significant hypotension
Potentially fatal interactions with other hypotensive drugs (ex. ace)
Dirlotapide
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
Orlistat
Pancreatic lipase inhibitor
Decreased fat digestion/absorption
Like osestra –> diarrhea
Testosterone
Appetite stimulant
Only anabolic steroid approved in vet med
Diazepam
GABA agonist; inhibits satiety center in hypotahlamus
Used in cats
Not terribly effective
Cyproheptadine
Antihistamine + 5HT2 blocker - control satiety
Appetite stimulant in cats
Hit or miss
Megesterol acetate
Synthetic progestin as an appetite stimulant
Significant side-effects (better options out there)
Glucocorticoids (for appetite stimulation)
Transient polyphagia
For palliative cases (ex. oncology)
Inherent activity or “perking up?”
Apomorphine
Emetic in dogs
Give via conjunctiva or IV
Alpha-2-agonists (ex. Dexmedetomidine)
Emetic in cats
Give via IM
Syrup of Ipecac
GI irritaiton –> emesis
Not very effective in vet med
Hydrogen peroxide
Emetic in dogs
Irritation of throat/glossopharyngeal nerve
Not very effective (useful for clients at home)
Antihistamines (as anti-emetics)
Block cholinergic (cats) and histaminic (dogs) nerve transmission responsible for transmission of vestibular stimuli to emetic center Mild sedation
Metaclopromide
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)
Ondansetron
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)
Maropitant
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
Omeprazole
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)
Cimetidine, famotidine, ranitidine
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
Antacids
Neutralize stomach acid to form water and salt
Short-term fix, cheap
Sucralfate
Dissociates to sucrose octasulfate (coats ulcer) and aluminum oxide
Increases mucosal PGE synthesis
Few ADRs, cheap, easy to administer
No good evidence
Misoprostal
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
Domperidone
Poor GI prokinetic effect
Dopamine antagonist (like metaclopramide)
No CNS reactions
Treatment of agalactia (stimulate prolactin secretion)
Cisapride
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
Erythromycin
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)
Lidocaine
Reduce postop ileus in horses when given as an IV infusion (expensive!)
Many possible mechanisms of action
ADRs: muscle fasciculations, ataxia, seizures
Kaolin pectin, activated charcoal, bismuth subsalicylate
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
Anticholinergic drugs (anti-diarrheal use)
Significantly decease intestinal motility and secretions
Few cases of diarrhea are due to hypermotility - may actually worsen diarrhea
Systemic side-effects (tachycardia)
Hyoscine butylbromide (Buscopan)
Antispasmodic and anticholinergic for horses with “intestinal pain in non-surgical colic”
May cause tachycardia and decreased gut sounds
Not efficacious as an antidiarrheal
Loperamide
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
Antimicrobials for diarrhea
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
NSAIDs for diarrhea
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?)
Lubricants for constipation
Mineral oil (1st choice), white petroleum Safe, cheap, generally effective; may not help
Motility modifying drugs for constipation
Cisapride, erythromycin, metaclopromide, cimetidine, ranitidine…
NO
Stimulant laxatives
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
Hyperosmotic laxatives
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)
Bulk laxatives
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
Stool softeners
Increase water accumulation in feces
Dioctyl sodium sulfosuccinate, dioctyl calcium sulfosuccinate
Probiotics
Change flora? Specific nutrient production? Stimulates enteric immune system?
Safe, relatively cost-effective (can be expensive); routine administration of the right combinations
Inefficacy
5-amino-salicylic acid
Treatment of chronic colitis in dogs
NSAID effects - poor GIT absorption
Still risky in cats
Sulfasalazine
Treatment of chronic colitis
Cytoprotective - blocks formation of ROS
Sulfapyridine component (sulfa)
Anti-inflammatory effects
Metronidazole
Treatment of Giardia, aerobes (clostridia)
For some types of colitis it’s effective, others not at all
Tylosin
Macrolide antibiotic
Antimicrobial/anti-inflammatory/motility effects?
Hit or miss - depends on pathogenesis of colitis
Glucocorticoids (for colitis)
Prednisone/prednisolone and budesonide (potent - don’t want it absorbed from GI - for human use)
Decreased inflammation
Azathioprine
Immunosuppressive drug
Chlorambucil
Immunosuppressive drug
Cyclosprorine
Immunosuppressive drug
Works for IBD
Pancrelipase
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
Octreotide
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
Hepatitis drugs
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
Cyclophosphamide
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
Chlorambucil
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
CCNU (Lomustine)
Nitrosurea (cross-link DNA strands)
Lipid-soluble - brain tumors? lymphoma, MCT, etc.
Leukopenia - can cause thrombocytopenia
Streptozocin
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
Cisplatin
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
Carboplatin
Second generation platinum derivative
Less nephrotoxic than cisplatin
Causes thrombocytopenia
Can be used in cats
Pamidronate
Inhibits osteoclasts, decreases bone resorption
Not chemotherapy - may be analgesic for dogs with osteosarcoma
Used to treat hypercalcemia of malignancy
Can cause nephropathy
5-Fluorouracil
Inhibit nucleic acid synthesis - thymine synthesis
Active in S-phase
Neurotoxicity (and hepatotoxicity in cats)
SSC in horses
Rabacfosadine
Prodrug converted to active forms - multimodal action Lymphoma in dogs IV infusion over 30 minutes Fatal pulmonary fibrosis in WHWT Typical chemo ADE
L-asparaginase
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
Toceranib
Cutaneous MCT in dogs
Anti-tumor and anti-angiogenic
Decreased proliferation of endothelial cells in vitro
Oral - many adverse events
Vincristine
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
Doxorubicin
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
Paclitaxel
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
Piroxicam
Inflammation of transitional cell carcinoma
Azathioprine
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
Cyclosporine
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
Leflunomide
Not typically recommended in vet med
Rheumatoid arthritis in humans
Prodrug (active = teriflunomoide) - inhibits pyrimidines
Mycophenolate Mofetil
Purine synthesis inhibitor
Raging, horrible diarrhea in dogs
Tacrolimus
Calcineurin/T-cell inhibitor
Expensive
Apoquel (Oclacitinib)
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
Cytopoint
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)
Pegbovigrastim (Imrestor)
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
Erythropoietin
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
Pentoxifylline
Oral methylxanthine derivative
Supposedly lowers blood viscosity/improves RBC deformability
