Exam 2 Flashcards
Define; Ionotropy, Chronotropy, Preload, Afterload, Congestive Heart Failure (CHF)
Inotropy
- Intrinsic property of sarcomere to shorten (Actin-Myosin interaction) or to contract
Chronotropy
- affecting the heart rate. Constant flux between sympathetic and parasympathetic tone. Congestive heart failure increases sympathetic tone
Preload
- pressure that stretches the right or left ventricles prior to contraction (systole). Both pressure and volume dependent. Increased Preload elicits the Frank-Starling mechanism (increases force of contraction)
Afterload
- force that opposes ventricular ejection. Afterload ≠ Blood pressure. But we often use as clinical surrogate. Afterload can also be “fixed” as in an obstruction such as pulmonic stenosis.
Congestive heart failure
- fluid accumulation in tissues (lungs or cavities) as decompensation from the blood volume augmenting affects of the RAAS system trying to maintain C.O. Often referred to as backward failure
How to achieve Positive Ionotropy, & drugs
How
○ Increase quantity of intracellular Ca
○ Increase sensitivity of contractile proteins to Ca
○ OR both
Positive Ionotropes
○ Pimobendan
○ Digoxin
Pimobendan MOA, dose, use in dogs, use in cats
MOA
■ Phosphodiesterase inhibitor ->
■ decrease degradation of cAMP ->
■ Increases intracellular Ca+
■ Ca sensitizer
■ PDE III inhibitor -> vasodilation
Dose
■ 0.25 - 0.3mg/kg PO BID
Uses in dogs
■ Systolic dysfunction
■ CHF
■ Pre-clinical valve dz w/ cardiomegaly
Use in Cats
■ Not usually used for HCM
■ May use end stage HCM or refractory CHF
■ Use for dilated & restrictive cardiomyopathy
Pimobendan Cautions, Adverse Effects
Cautions
■ Contraindicated in ventricular hypertrophy or obstruction
■ Not stable as liquid compound
Adverse Effects
■ GI
■ Hypotension w/ tachycardia
■ CNS stimulation
Mitral Valve Endocardiosis Staging & Therapy
A
■ Breeds at risk w/ no murmur
■ Monitor yearly
B1
■ Minimal to no atrial enlargement
■ Monitor q6-12mo
B2
■ Moderate-severe atrial enlargement
■ Pimobendan +/- enalapril
C
■ Severe cardiomegaly and/or CHF
■ Pimobendan + enalapril + Furosemide + diet
D
■ Refractory CHF
■ Pimobendan + enalapril + Furosemide + diet + additional diuretics
Digoxin MOA, Dose, Use, Caution, Adverse Effects
MOA
■ Inhibits Na/K ATPase ->
■ Increase cellular Na ->
■ Decrease activity of Na/Ca exchanger ->
■ Increase Ca in cell
■ Decrease sympathetic tone
■ Decrease ALD
Dose
■ 0.0025 - 0.005 mg/kg PO BID
Uses
■ DCM
■ A fib (to slow heartrate)
Caution
■ VERY narrow therapeutic window
■ Pro-arrhythmic effect
■ Renal excretion
Adverse Effects
■ GI
■ CNS
■ Arrhythmias
What increases Pre-load & drugs to decrease preload
What Increases Preload
○ Fluid therapy
○ anemia
○ hyperthyroidism
○ Heart dz leading to fluid volume retention
Preload Reducers
○ Furosemide
○ Spironolactone
Spironolactone MOA
■ Antagonize ALD
■ K sparing
■ Slows myocardial fibrosis
What increases Afterload & drugs to decrease afterload
What increases Afterload
○ Systemic hypertension
○ Systemic vasoconstriction w/ RAAS & CHF
○ Pulmonary hypertension
○ Pulmonic stenosis
○ Subaortic stenosis
○ L ventricular outflow obstruction
Afterload Reducers
○ ACE Inhibitors
○ Amlodipine
○ Pimobendan
Ace Inhibitors; Drugs, Dose, Use, Adverse Effects, Interactions
Enalapril, Benazepril
Dose
■ 0.25-0.5 mg/kg PO BID
Use
■ Pre CHF & CHF
■ Systemic hypertension
■ Glomerular hypertension
Adverse Effects
■ Dehydration & azotemia
■ Hyperkalemia
■ Hyponatremia
■ GI
■ Renal injury
Drug Interactions
■ NSAIDs
■ Cisplatin
■ Aminoglycoside
Amlodipine; MOA, Dose, Use, Adverse Effects
MOA
■ Dihydropyridine Ca channel Blocker
Dose
■ 0.1-0.2 mg/kg PO SID-BID
Use
■ Systemic hypertension
Adverse Effects
■ Dehydration
■ GI
■ Hypotension
■ Gingival hyperplasia
Nitrates / Nitroglycerin
○ Increase nitric oxide production
○ Venodilator -> preload reducer
Class 1 (1a) Antiarrhythmic; Drugs, MOA, Use
Drugs
● quinidine (usually large animal)
MOA
■ Na channel blocker
■ Mb stabilizers
■ Slows conduction
■ 1a - Decrease upstroke & prolong AP
Use
● atrial & ventricular arrhythmias
● EQ atrial fibrilation
Class 1 (1b) Antiarrhythmic; Drugs, MOA, Use
Drugs
● lidocaine
● mexiletine
MOA
■ Na channel blocker
■ Mb stabilizers
■ Slows conduction
■ 1b - shortens AP
Use
● ventricular arrhythmias
Class 2 Antiarrhythmic; Drugs, MOA, Use
Drugs
■ Atenolol
MOA
■ Beta-blocker
■ Slows SA & AV node
■ Slows conduction of
ectopic beats
■ Depresses contractility
Use
■ Atrial & ventricular arrhythmias
■ Diastolic dysfunction (hypertrophy)
■ Slow HR & promote ventricular filling
Class 3 Antiarrhythmic; Drugs, MOA, Use
Drugs
■ Sotalol
MOA
■ K+ channel blocker
■ Prolongs AP
■ Decrease excitability
■ Multimodal class
Use
■ Atrial & ventricular arrhythmias (esp. severe/refractory)
■ multimodal
Class 4 Antiarrhythmic; Drugs, MOA, Use
Drugs
■ Diltiazem
MOA
■ Ca channel blocker
■ Inhibit L- Ca++
■ Decrease SA node firing
■ Slows AV conduct
■ Mild decrease in contractility
Use
■ Atrial arrhythmia
■ Atrial fib
■ Promote filling in diastolic dz
Quinidine Adverse Effects
○ GI
○ Arrhythmia
○ Hypotension
○ CNS excitation
○ Dose 3-4 times per day
Lidocaine Adverse Effects
○ Very short T1/2
○ CNS excitation
○ Cats very sensitive (use 1/10th dose)
Mexiletine Adverse Effects
○ Very long T1/2 must give 3x per day
○ GI
Atenolol Adverse Effects
○ Destabilize patients w/ poorly controlled DCM or CHF
○ bronchiol constriction
○ Bradycardia / hypotension
○ GI
Sotalol Adverse Effects
○ Arrhythmias
Diltiazem Adverse Effects
○ Bradycardia / hypotension
○ GI
Indications for Anti-hemostatic Drugs
Prevention of feline aortic thromboembolism
• HCM
• restrictive cardiomyopathy
Treatment of feline aortic thromboembolism
Prevention of pulmonary thromboembolism
• Hyperadrenocorticism
• IMHA
• DIC
• Protein losing enteropathy/nephropathy
• Heartworm dz
Types of Anti-hemostatic Drugs
Anticoagulants
• Interfere with clotting cascade to prevent clotting
Thrombolytics
• Breakdown thrombi that have already formed
Antithrombotics
• Interfere with platelet activation/aggregation
Heparin MOA, Caution, Monitor
MOA
• Works w/ antithrombin III
• Inhibits thrombin & some Xa
Caution
• High dose need to be effective
• Can cause excessive bleeding
Monitor
• ACT
• aPTT
Low-molecular weight heparin (LMWH) MOA, Better than?
MOA
• Higher affinity for antithrombin III than heparin
• Inactivate Xa but not thrombin
Better than Heparin?
• Tendancy for bleeding less than heparin
• No monitoring necessary
Aspirine, MOA, Caution
MOA
• Irreversibly inhibits COX enzymes ->
• Platelets can’t synthesize more COX
->
• Blocks TXA2 production for life of platelet
Caution
• Exacerbate GI & renal dz
Clopidigrel; MOA, Better than?
MOA
• ADP Antagonist, cant bind to P2Y12 receptor
• Activation of platelet is inhibited
Better than aspirin?
• More effective & less side effects
Thrombolytics; MOA, Drugs, Indications
MOA
• Conversion of plasminogen to plasmin ->
• Plasmin cleaves fibrin, breaks clot
Drugs:
• Tissue plasminogen activator
• Urokinase
• Streptokinase
Indications:
• Acute clotting, coronary artery disease
• Not good for chronic, large clots (most veterinary patients)
Drugs for Ruminat Esophageal Obstruction
o Acepromazine
o Xylazine or detomidine
Drugs for Ruminotorics
o Mineral oil
o Dioctyl sodium sulfosuccinate
Antifoaming Agents in Ruminants
o Poloxalene
o Polymerized methyl silicone
Modulators of Ruminoreticular Motility
o Neostigmine and bethanechol
o N-butylscopolammonium bromide
o Atropine
o Xylazine
o Metoclopramide
o Erythromycin lactobionate
Proton Pump Inhibitors for Large Animals; Drugs, MOA, Indications, Toxicity
o Omeprazole
o Gastroguard & Ulcerguard FDA approved for horses
MOA
• prodrug activated in acidic environment ->
• binds irreversibly to the proton pump. ->
• acid production resumes only after the new proton pumps are synthetized in the parietal cells.
• 30% of maximal effect within the first 24 hs
• maximal effect 2-4 days.
Indications
• Prevention of ulcers in horses (give 1 hr prior to meal)
Toxicity
• Rebound hyperacidity
• Chronic use -> bacterial overgrowth
• Can alter absorption of antifungals & mycophenolate
• Metabolized by P450
Prokinetic Cholinergic – NEOSTIGMINE in large animals; Clinical Use, Adverse Effects,
Clinical Use
• Enhance cecal emptying in healthy ponies
• Promote passage of gas in foals w/ abdominal distension
• Enhance gastric emptying in horses
Adverse Effects
• SLUD
• Bradycardia
• Colic
• Increased gastric acid secretion
When to Use Appetite Stimulants in Small Animals
• When a feeding tube cannot be placed
• When the underlying cause of anorexia/hyporexia has been removed but patient is still not eating
• Short term during diagnostic phase
• When secondary to behavioral or environmental factors
• To overcome food aversion
• In chronically ill or palliative cases when a feeding tube cannot be placed
Cyproheptadine; MOA, Use, Adverse Effects
MOA
• 5HT3 antagonist
• decrease serotonin -> increase opiates -> stimulate apetite
Use
• appetite stimulant for cats
Adverse Effects
• Sedation
• Dry mucous membranes
Mirtazapine; MOA, Use, Adverse Effects
MOA
• 5HT3 antagonist decrease serotonin -> increase opiates -> stimulate apetite
• alpha adrenergic receptor antagonist
• histamine receptor antagonist
Use
• Appetite stimulant for dogs PO
• Appetite stimulant cats PO or pinna
Adverse Effects
• Sedation
• Behaviior changes
• GI upset
• Pinna irritation
Capromorelin; MOA, Use, Adverse Effects
MOA
• Ghrenlin receptor agonist
• Signals hypothalamus
Use
• Appetite stimulant for dogs & cats PO
Adverse Effects
• Increased salivation
• GI upset
Diazepam; MOA, Use
MOA
• GABAminergic inhibition of satiety center
Use
• Short term appetite stimulant in cats IV
Apomorphine; MOA, Use, Adverse Effects
MOA
• Stimulates D2 dopamine receptor in CRTZ
Use
• Emetic of choice for dogs
Adverse Effects
• Ocular irritation
• Lethargy
• Prolonged nausea/vomiting
Ropinerole; MOA, Use, Adverse Effects
MOA
• Stimulates D2 dopamine receptor in CRTZ
Use
• Emetic for dogs given opthalmic
Adverse Effects
• Inhibits prolactin -> don’t use during pregancy/lactation
• Ocular irritation
• Prolonged nausea/vomiting
Xylazine; MOA, Use, Adverse Effects
MOA
• Alpha-2 agonist
Use
• Previous emetic of choice for cats (IM or IV)
Adverse Effects
• Sedation
• Reveresed w/ yohimbine
Dexmedetomidine; MOA, Use, Adverse Effects
MOA
• Alpha-2 agonist
Use
• Emetic of choice for cats (IM or IV)
Adverse Effects
• Sedation
• Reveresed w/ atipamezole
Hydrogen Peroxide; MOA, Use, Adverse Effects
MOA
• Generates water & gas ->
• Expansion of stomach ->
• Stimulate GI nerve endings
Use
• Last shot emetic in dogs
Adverse Effects
• Do not give more than 45ml
• Gastritis, esophagitis
• GI ulceration / perforation
Metoclopramide; MOA, Use, Adverse Effects
MOA
• Serotonin antagonist
• Antidopaminergic
• enhances ACh release
Use
• Antiemetic in dogs
• prokinetic in proximal GI
• ileus
• GDV
• delayed gastric emptying
• gastroesophageal reflux
• Treat postoperative ileus, gastric dilatation-volvulus, idiopathic gastroparesis in LA
• Relax pyloric sphincter to promote gastric emptying in LA
Adverse Effects
• Change in mentation
• Do not use in gi obstruction or perforation
• Constipation
Maropitant; MOA, Use, Adverse Effects
MOA
• Neurokinin-1 receptor antagonist
Use
• Antiemetic for cats & dogs
Adverse Effects
• Few
• Pain at site of injection
Ondanestron or Dolasetron; MOA, Use, Adverse Effects
MOA
• Serotonin antagonist
Use
• Antiemetic for chemo induced nausea
Adverse Effects
• May cause neuro issue is MDR1 mutation dogs
Antacids; Drug, MOA, Considerations
Drugs
o Aluminum Hydroxide
o Mg Hydroxide
o Ca carbonate
MOA
o Neutralize acid
Considerations
o Super sort-term
o Not palatable
H2 Antagonists; Drugs, MOA, Use
• Famotidine (bradycardia; hemolysis in cats)
• Ranitidine (No longer available)
• Nizatidine
MOA
o Inhibition of acetylcholinesterase activity
Use
o Uremia
o Mast cell tumors
o ileus
o gastroesophageal reflux
o delayed gastric emptying
o constipation
Erythromycin in LAs; MOA, Use, Adverse Effects
MOA
• Stimulates motilin receptor ->
• Promotes gastric & proximal intestinal motility
Use
• 2nd choice prokinetic after lidocaine
• cecal impactions
• given IV
Adverse Effects
• CRI high doses decreases motilin
• GI dz may decrease efficacy
Lidocaine as Prokinetic in LAs; MOA, Use, Adverse Effects
MOA
• Prevents inhibition of bowel motility
Use
• Prophylactically avoid post operative ileus
• Bolus dose followed by CRI
Adverse Effects
• Cardiac arrhythmia
• Muscle fasciculations
• Ataxia seizures
Hyoscine butylbromide; Use, Adverse Effects
Use
o Equine colic
o Calf scours
Adverse Effects
o Dry mouth
o Constipation
o Urinary retention
o Tachycardia
Opioids in LAs; Drugs, Use,
Loperamide
o Slow marker passage
o Decrease fecal water/weight
o Anti-diarrheal in foals
Butorphanol
• Combined w/ Xylazine, suppress duodenal motility in horses
Alpha-2 Agonists in LAs; Drugs, Use
Xylazine & Detomidine
Use
• Disrupt blood flow & motility on equine pelvic flexure
• Reduce motility in cecal muscle
• Decrease cecal blood flow
Phenoxybenzamine in LAs; Use
• Treat severe nonresponsive Ds in horses
Protectants & Absorbents in LAs; Drugs, Precautions
o Mg Sulfate
o Bismuth
o Activated Charcoal
Precautions
• Bismuth should not be given to patients on NSAIDs
Laxatives in LAs; Drugs, use
Mineral oil
Surfactants (DSS)
• Questionable efficacy
• Can cause colic & severe Ds in horses
Psyllium Hydrophilic Mucilloid
• May be useful for sand impaction in horses
Cathartic in LAs; Drug, Use
Lactulose
• Stimulates deffication
Using Motility Modulators in Cows
o Controversial
o Little efficacy
o Correct underlying issue instead
Treatment of Neonatal Ds in Ruminants
o Parenteral admin of antimicrobials
o Meloxican & flunixin meglumine
o Do not use probitics, protectants, absorbants, motility modifiers
Proton Pump Inhibitors Drugs, MOA, Adverse Effects
o Omeprazole
o Pantoprazole (drug of choice)
MOA
o Inhibit gastic H-K-ATPase pump ->
o Reduce gastric acid secretion
Adverse Effects
o Increase gastrin levelse & rebound hyperacidity
o Inhibits CYP 450 (not Pantoprozole)
Misoprostol; MOA, Use, Adverse Effects
MOA
o Prostaglandin E1 analog
o Inhibit gastric acid secretion
o Increase bicarbonate & mucus secretion
o Increase gastric blood flow
Use
o Treatment and prevention of aspirin (and maybe other NSAID) induced ulcers
• NSAID associated R dorsal colitis in horses
Adverse Effects
o GI distress
o Uterine contractions (abortion)
Sucralfate; MOA
• Combined with acid -> sucrose octasulfate+aluminum hydroxide
• Coats cells & protects
• Doesn’t work great, use PPIs instead
Insulin Similar to Endogenous Canine and Feline Insulin
Canine Insulin
o Same as porcine insulin
o 1 amino acid from human
o 3 amino acids from bovine
Feline Insulin
o 1 amino acid from bovine
o 3 amino acids from porcine
o 4 amino acids from human
5 Insulin Formulations
Regular
• Recombinant human insulin
• Onset & duration same as endogenous
• IV, IM, SQ
NPH
• Combined w/ protamine to delay absorption
• SQ only
PZI
• Combined w/ protamine & zinc
• Greater delay in absorption than NPH
• SQ only
Lente/Ultralente
• Molucules into crystals
• Small crystals – short delay in absorption
• Large crystals – ong delay in absorption
• SQ only
Synthetic/Analogs
• Chemical modification of human insulin
• Amino acids added
• Slow absorption & degredation
Humulin R & Novalin R; basics, syringe size
o Recombinant human insulin
o Insulin of choice for DKA, hyperkalemia
o Shortest acting (1-2 hours)
o Used in dogs and cats
o Must refrigerate
Syringe
• U-100
Vetsulin; basics, syringe size
o Porcine lente insulin
o best for dogs
o also approved for cats
o Must refrigerate
Syringe
• U-40
Novalin-N & Humulin-N; basics, syringe size
o NPH inslulin from human
o Often used in dogs
o Refrigerate & Do Not shake
Syringe
• U-100
Detemir; basics, syringe size
o Human recombinant/analog
o Used in dogs
o More potent
o DO not shake
Syringe
• U-100
Glargine; basics, syringe size
o Human recombinant/analog
o Used in cats
o Long-acting
o Refrigerate & Do Not shake
o Pens can last 1mo out of fridge
Syringe
• U-100
Prozinc; basics, syringe size
o PZI human insulin
o Approved for cats
o Intermediate duration
o Refrigerate & Do Not shake
Syringe
• U-40
Acarbose; MOA, Use, Adverse Effects
MOA
• Alpha-glucosidase inhibitor ->
• Inhibitis intestinal enzymes that convert starches to simple sugars ->
• Slows digestion of carbs and delays glucose absorption.
Use
• Dogs w/ poor glycemic control w/ no cause
• Maybe in cats that won’t eat a low carb diet
Adverse Effects
• GI signs
• Hypoglycemia
• Must give immediately before meal
Glipizide MOA, Use, Adverse Effects
MOA
• Sulfonylurea antidiabetic agent ->
• Stimulates beta cell secretion of insulin
• May take 1-2 mo to see effects
Use
• Cats w/ non-insulin dependent diabetes
• If insulin can’t be given or if only small amount of nsulin needed to control DM
Adverse Effects
• GI signs
• Elevated liver enzymes & jaundice
• Hypoglycemia (rare)
• Increased amyloid deposition
Cisapride; MOA, Use, Adverse Effects
MOA
• Enhances acetylcholine release
Use
• Targets smooth msucle from esophagus thru colon
• Megaesophagus & megacolon in cats
• Gastroesophageal reflux
• Delayed gastric emptying
• Ileus
Adverse Effects
• Metabolized by CYP 450 so affected by drugs that inhibit this enzyme
• Minimal; maybe V/D
Erythromycin; ; MOA, Use, Adverse Effects
MOA
• Macrolide Ab w/ motilin like activity
Use
• Delayed gastric emptying
• Gastroesophageal reflux
• Decreased colonic motility in dogs
Adverse Effects
• Inhibits CYP 450
• MDR1 mutants may react
Bethanechol; MOA, Use, Adverse Effects
MOA
• Cholinergic
Use
• Usually to improve bladder contractility
• May use to increase LES tone in megaesophagus
• Treat delayed gastric emptying in LA
• Increase contraction of cecum & R ventral colon in LA
Adverse Effects
• SLUD
• Bradycardia
• Increased gastric acid & pancreatic secretion
Diphenoxylate; MOA, Use, Adverse Effects
MOA
• Opioid binds to enteric opioid receptors & inhibits GI motility
Use
• Anti-diarrheal
Adverse effects
• Constipation, bloat, sedation in dogs
• Excitatory to cats (not recommended)
Loperamide; MOA, Use, Adverse Effects
MOA
• Opioid binds to enteric opioid receptors & inhibits GI motility
Use
• Anti-diarrheal
Adverse Effects
• Constipation, bloat, sedation in dogs
• Excitatory to cats (not recommended)
• Reaction in MDR1 mutants
Kaolin/Pectin; MOA, Use, Adverse Effects
MOA
• Demulcent/Protectant
• Adsorbs some potential toxicants (Poor efficacy)
Use
• Relieves irritation during Ds by lining mucosal surface
Adverse Effects
• GI upset if given w/o food
Bismuth/Charcoal; MOA, Use, Adverse Effects
MOA
• Adsorbant
Use
• may absorb toxins during Ds (poor efficacy)
Adverse Effects
• Black stool
• GI upset if given w/o food
Metronidazole; MOA, Use, Adverse Effects
MOA
• Disrupts bacterial DNA synthesis
• Effective against certain protozoal species and anaerobic bacteria
Use
• antibiotic responsive diarrhea or GI dysbiosis
• chronic enteropathy, exocrine pancreatic insufficiency, hepatic encephalopathy
• Giardia or Clostridium
• anaerobic infections (Ex: hepatitis)
Adverse Effects
• Hepatotoxicity
• GI upset
• Neurotoxicosis
• Reduced olfactory function in dogs
• Can cause multi-drug resistance
Tylosin; MOA, Use, Adverse Effects
MOA
• Macrolide antibiotic
• Inhibits 50s subunit of bacterial ribosomes to inhibit protein synthesis, mainly bacteriostatic
Use
• antibiotic responsive diarrhea or GI dysbiosis
• chronic enteropathy, exocrine pancreatic insufficiency
Adverse Effects
• Few and mild
3 Types of Laxatives & MOA
Fiber
• Absorb water, soften stool, add bulk
• Preferred treatment due to safety, tolerance, and efficacy
• Psyllium, wheat dextrin, pumpkin
Osmotic
• Attract fluid into lumen to soften stool
• Lactulose
Lubricants
• Mineral oil, petroleum, paraffins
• Not generally advised due to risk of aspiration
Treatment for Megacolon
• Laxatives – Lactulose or Fiber
• Cisapride
• High fiber, low residue diet
• Enemas
• Surgery – subtotal colectomy
Treatment for Megaesophagus
• Upright feedings
• Change diet consistency - meatballs, slurry, etc.
• Sildenafil
• Treat secondary esophagitis w/ Omeprazole & Sucralfate
• metoclopramide, cisapride, bethanacol (in cats)
Sildenafil; MOA, Use, Adverse Effects
MOA
• Phosphodiesterase-5 inhibitor -> relaxes smooth muscle -> vasodilation.
• short time ~20-60 mins
• dogs & cats
Use
• Megaesophagus
• LES dysfunction
• Pulmonary hypertension
Adverse Effects
• Maybe hypotension
EPI Treatment
Viokase, Pancreazyme, etc
• Dried extracts of bovine or porcine pancreas
• Powdered form is preferred
Vit B12 (Cyanocobalamin)
Vit B12; MOA, Use
MOA
• Absorbed in Ileum
Use
• EPI
• Chronic enteropathy
• Pancreatitis (especially cats)
Chronic Enteropathy Treatment
Immunosuppressants such as:
• Steroids (dogs or cats)
• Cyclosporine (dogs or cats)
• Mycophenolate (mostly dogs)
• Chlorambucil (dogs and especially cats)
• Azathioprine (dogs only)
• Leflunomide (mostly dogs)
Ursodeoxycholic acid or ursodiol; MOA, Use, Adverse Effects
MOA
• Deceases hepatic synthesis/secretion of cholesterol and intestinal absorption of cholesterol.
• Increases bile flow
• May protect hepatic cells from toxic bile
• In patients with chronic hepatitis, may reduce hepatocellular inflammatory changes and fibrosis.
Use
• Cholestasis
• Gallbladder sludge
Adverse Effects
• None
Hepatoprotectants
Denamarin + Denosyl
S-adenosyl methionine (SAMe)
o Normally produced in the liver and needed for several metabolic pathways in the liver
Silymarin (milk thistle)
o Free radical scavenger/antioxidant
o Inhibits TNF
o Prevents toxin penetration into hepatocytes
Hepatic Encephalopathy Treatment; Drugs & MOAs
Lactulose
o Increases osmotic pressure drawing water into the bowel ->
o Metabolized by bacteria into acid metabolites ->
o The acidification causes ammonia NH3 (ammonia) to migrate from the blood into the colon where it is trapped as [NH4]+ ->
o expelled w/ the feces
Neomycin (Amoxicillin, metronidazole)
o Aminoglycoside
o Reduce ammonia producing bacteria in GI
Furosemide; MOA & Use
MOA
• Inhibit Na+-K+-2Cl- symporter
• Inhibits Ca reabsorption in the thick ascending limb of the loop of Henle
Use
• Hypercalcemia
• Fast acting
Bisphosphonates; MOA, Drugs & Adverse Effects
MOA
• Inhibits osteoclast activity and bone resorption
• Promotes apoptosis and inhibits osteoclastogenesis, angiogenesis, and cancer cell proliferation
• slow acting
Alendronate PO
• GI
• esophagitis
Pamidronate – injectable
• Renal tox
• Electrolyte abnormalities
Zoledronate – injectable
• Maybe renal tox
Cinacalcet; MOA
• Calcimimetic agent,
• increases sensitivity of Ca-sensing receptors to activation by extracellular Ca.
• negative feedback and suppression of PTH release
Calcium Gluconate; MOA, Use, Adverse Effects
MOA
• Direct replacement of Ca
Use
• Emergency hypoclacemia
Adverse Effects
• Arrhythmias or arrest if given too fast IV
Calcium Carbonate; MOA, Use
MOA
• Direct replacement of Ca
• Binds dietary phosphate
Use
• chronic hypoclacemia
Calcitriol; MOA, Use, Adverse Effects
MOA
• Activated Vit D
• Replaces Vit D
Use
• Hypoparathyroidism
• Renal secondary hyperparathyroidism
Adverse Effects
• Hypercalcemia
• Tissue mineralization
• Ca oxalate uroliths
DDAVP; MOA, Use, Adverse Effects
MOA
• Synthetic anolog of vasopressin (ADH)
• Replaces ADH
Use
• Central diabetes insipidus
• Differentiate Central diabetes insipidus from nephrogenic
Adverse Effects
• Uncommon ocular irritation
Thiazide Diuretics; MOA, Use
MOA
• inhibit Na-Cl cotransporter in early distal tubule
• enhanced excretion of Na and water
Use
• reduce clinical PU/PD in diabetes insipidus
Synthetic Levothyroxine; Drugs, MOA, Use, Adverse Effects
Drugs
• Thyro-tabs
• Sythroid
MOA
• Direct T4 replacement
Use
• Treatment of choice for hypothyroidism
Adverse Effects
• Increases myocardial O2 demand
• Start with ½ dose in dogs w/ cardiac disease
• Development of hyperthyroidism with overdose
• Food decreases bioavailability
Synthetic Liothyronine; MOA, Use, Adverse Effects
MOA
• Directly replaces T3
Use
• Use when levothyroxine has poor GI absorption
Adverse Effects
• Not recommended
• Does not increase T4
• T3 produced by T4 so may overdose T3 in some tissues
Thyroid Extracts or Dessicated Thyroid
o Not recommended
o Potential for allergies/sensitivities
o Too much variability
Methimazole; MOA, Use, Adverse Effects
MOA
• Inhibits thyroid peroxidase
• Inhibits iodide binding tyrosine
Use
• Drug of choice for hyperthyroidism
Adverse Effects
• GI
• Neutropenia
• Thrombocytopenia
• Facial excoriation
• Hepatotoxicity
• May unmask underlying renal dz
I-131; MOA
MOA
• I-131 concentrated in hyperfunctional thyroid cells ->
• β-particles destroy hyperfunctional tissue ->
• normal thyroid tissue is suppressed and not producing hormone so it is preserved
Synthetic Adrenocorticotropic Hormone (ACTH) Use
• ACTH Stimulation Test
• Evaluates the maximal response of the adrenal glands to ACTH
• diagnosis of hyperadrenocorticism, hypoadrenocorticism, and iatrogenic Cushing’s
Dexamethasone; Use in Testing, Adverse Effects
Use
• Dexamethasone suppression test
• diagnosing and differentiating between pituitary and adrenal dependent Cushing’s
Adverse Effects:
• Single low dose no significant side effects
• GI ulcer if given w/ NSAIDs
Trilostane; MOA, Use, Adverse Effects
MOA
• Competitive enzyme inhibitor that blocks formation of cortisol
• Inhibits 3β-hydroxysteroid dehydrogenase
• Also some effect on aldosterone and androgen synthesis
Use
• Hyperadrenocorticism
Adverse Effects
o Idiosyncratic adrenal necrosis
o hyperkalemia, hyponatremia
o GI signs, lethargy, hypovolemia
o Ketoconazole may potentiate its effects
Mitostane; MOA, Use, Adverse Effects
MOA
• Adrenolytic/adrenal cytotoxic
Use
• Less useful for hyperadrenocorticism
Adverse Effects
• Addisonian state (GI signs, lethargy)
• Liver changes – congestion, centrolobular atrophy, fatty degeneration
• Phenobarbital & spironolactone decrease efficacy
Ketoconazole; MOA, Use, Adverse Effects
MOA
• Inhibits steroid biosynthesis
• Interferes with the imidazole ring and cytochrome p-450 enzyme systems
Use
• Hyperadrenocorticism
• Not Recommended
Adverse Effects
• GI signs
• Hepatotoxicity
• Thrombocytopenia
• Suppression of sex hormone
Selegiline; MOA, Use
MOA
• Enhances dopamine mediated inhibition of ACTH release from the pars intermedia of the pituitary
Use
• Hyperadrenocorticism
• Not Recommended
Metyrapone; MOA, Use
MOA
• Enzyme inhibitor that blocks formation of cortisol
Use
• Short-term feline hyperadrenocortcism (Cushing’s)
Prednisone; MOA, Use, Adverse Effects
MOA
• Direct glucocorticoid replacement
Use
• Hypoadrenocorticism
Adverse Effects:
• Should be minimal to non-existent at proper dose
• If steroid side effects are seen the dose may need to be decreased
Desopxycorticosterone pivalate (DOCP); MOA, Use, Adverse Effects
MOA
• Direct mineralcorticoid replacement
Use
• Hypoadrenocorticism
Adverse Effects:
• Irritation at the injection site
• GI signs
• PU/PD, fluid retention, edema
Fludrocortisone; MOA, Use, Adverse Effects
MOA
• Direct gluco and mineralcorticoid replacement
Use
• Hypoadrenocorticism
Adverse Effects:
• PU/PD,
• hypertension,
• edema,
• hypokalemia
Glucocorticoids as Immunosuppressants; MOA, Drugs, Indications, Adverse Effects
MOA
• Lipocortin -> PLA2
• Rapid onset
• Affect innate & acquired immunity
Drugs
• Pednisone/prednisolone
• Dexmethasone (better bioavailability)
Indications
• First-line in inflammatory & immune dz
• Immune-mediated anemia & polyarthritis
• IBD
Adverse Effects
• GI ulceration, especially in dogs treated with high doses or for long durations.
• Iatrogenic hyperadrenocorticism
• Adrenal gland suppression
• Insulin resistance and secondary diabetes mellitus (esp cats)
• Muscle catabolism
• Delayed wound healing
• Opportunistic infections
• behavior changes
Glucocorticoids as Immunosuppressants; Hemopoietic Effects, Anti-inflammatory Effects
Effects on Hemopoietic system
• Decrease proliferation, differentiation, and survival of inflammatory cells (T lymphocytes and macrophages)
• High doses kill lymphocytes
• Reduced size of thymus, spleen, and lymph nodes
• Neutrophils, platelets, & RBCs increased
• eosinophils decreased
Anti-inflammatory Effects
• inhibit release of cell adhesion molecules reducing recruitment of inflammatory cells
• Prevent release and actions of IL-1, IL-2, TNF-
• Prevent release of histamine, serotonin, and lyzosomal enzymes from mast cells
Calcineurin Inhibitors; Drugs, MOA, Indications, Adverse Effects, Drug Interactions
Drugs
• Cyclosporine
• Tacrolimus
MOA
• bind to a cytoplasmic receptor protein ->
• complex then binds and inhibits calcineurin ->
• decreased expression of IL-2 and other cytokines necessary for T-cell activation
Indications
• First line for perianal fistulas & Keratoconjunctivitis (ophthalmic drops)
• 2nd line or add-on drug for other immune-mediated diseases such as IMHA, IBD
Adverse Effects
• Variable patient-patient reactions & poor bioavailability
• Immunosuppression
• Gingival hyperplasia (Less likely)
• Hepatotoxicity
• Thromboembolism
• Self-limiting GI upset
Drug Interactions
• Efficacy diminished when administered w/ azoles & phenobarbital(cats)
Janus Kinase Inhibitor; Drug, MOA, Indications, Adverse Effects
Drug
• Oclactinib
MOA
• Inhibit proinflammatory cytokines (IL-31)
Indications
• hypersensitivity induced cutaneous pruritis in dogs > 12 months of age
• 1st choice fast relief
Adverse effects
• vomiting, diarrhea, lethargy, anorexia, and bloodwork changes
• can’t use in pregnant/lactating dogs
Caninized monoclonal antibody against interleukin-31; Drug, Indications
Drugs
• Cytopoint
Indications
• Management of allergic puritis flares
• Injection w/ long lasting effect
Antimetabolites; Drug, MOA, Indications, Pharmacokinetics, Adverse Effects
Drugs
• Azathioprine
MOA
• Interfere with incorporation of purines or pyrimidines into DNA
• Prodrug metabolized to a purine analog (6-mercapto purine)
Indications
• Immune-mediated diseases such as IBD, hemolytic anemia, etc.
• decrease dose of Glucocorticoids while maintaining remission.
Pharmacokinetics
• delayed several days to weeks so monotherapy with azathioprine should not be the initial treatment for immune-mediated diseases
• PO
• Metabolized in liver by TPMT
Adverse Effects
• Contraindicated in cats & horses due to lack of TPMT
• Bone marrow suppression
• Hepatotoxicity
• GI
Alkylating Agents; Drug, MOA, Indications, Adverse Effects
Drugs
• Cyclophosphamide
• Chlorambucil
MOA
• Alkylate DNA ->
• chemical cross-links in DNA ->
• interfere w/ DNA replication
Indications
• Chlorambucil - Second-line immunosuppressive in cats
Adverse Effects
• Cyclophosphamide – BAG & neutropenia
Mycophenolate mofetil; MOA, Indications, Adverse Effects
MOA
• inhibits type II isoform of inosine-5’-monophosphate dehydrogenase ->
• no synthesis of guanosine nucleotides
Inidications
• 2nd or 3rd line immunosuppressive agents in dogs
• immune-mediated anemia, thrombocytopenia, polyarthritis, glomerulonephritis, skin dz
• myasthenia gravis
• meningoencephalomyelitis
• may be usable w/ prednisolone in cats
Adverse Effects
• GI
• Don’t use in pregnant patients
Antihistaminic Drugs for Immunosuppression; Drugs, MOA, Efficacy
Drugs
• Dipenhydramine
MOA
• inverse agonist (H1) ->
• reverses effects of histamine on capillaries ->
• reduces allergic reaction symptoms
Efficacy
• Limited research to show efficacy
