Exam 1 Flashcards
What are prodrugs?
• inactive
• need to be biotransformed into active form
Half lives to reach steady state?
5
Goal of fixed dosing
o Designed to generate plasma drug conc. w/in therapeutic range
Factors that vary individually & how they affect drug’s therapeutic effect
o Physiology
o Pathoglogy
o Pharmacologic effects (drug interactions etc)
Above effects on PK are unpredictable
Drug & Disease Criteria for using Trial and error approach to dosing
Drugs
• Gas inhalants
• Ultrashort thiobarbituate anesthetics
• Rapid anticonvulsants
• Lidocaine in treatment of arrhythmias
• Drugs w/ large therapeutic window
Diseases
• Illnesses that are not serious
Types of Drugs to Use TDM
o Drugs that cause serious toxicity
o Steep dose response curve
o Poorly defined clinical end point
o Narrow therapeutic range
o Nonlinear pharmacokinetics
o combo drugs that may interact
o Very specific target therapeutic range
Criteria for Using TDM
o Response to drug must match plasma conc.
o Must measure compound or metabolite or both depending on which produces therapeutic effect
o Drug must be measurable
o Assay available to detect drug rapidly & accurately
When to Measure the Peak Vs the Trough
Peak
• short half-life drug
• If toxicity is concern
Trough
• short half-life drug
• If efficacy is concern
Either
• If drug has a long half life
Factors that may influence the incidence and significance of DDIs
o Relative doses of the interacting drugs
o Type of drug and condition being treated
o Dosage forms and routes of administration
o Duration of treatment
o Order of drug administration
o Multiple drug therapy
o Individual patient factors (liver/kidney dz)
Drugs w/ Low Therapeutic Index
o Beta-blockers
o Anesthetics
o Phenytoin
o Theophylline
o Digoxin
o Cyclosporine
o Phenobarbital
o Warfarin
Drug Drug Interactions Interfering w/ Absorption
Change in GI pH
• drug that makes pH basic when other drug needs acidic environment
Drug binding in GI tract
• Two drugs bind in GI tract and can’t be absorbed
Change in GI motility
• One drug changes motility -> decreases absorption of drug 2
Malabsorption
Drug Drug Interactions Interfering w/ Distribution
o Drug 1 displaces drug 2 from binding site
o Drug 1 can induce transporter of drug
Drug Drug Interactions Interfering w/ Elimination-Metabolism
Induction of Metabolism
• Drug 1 induces hepatic microsomal enzymes (cytochrome P450 enzymes, CYPs) ->
• Drug 2 metabolized by the induced CYP isoform may have reduced efficacy/duration
OR
• Induction of metabolism could increase drug effect
• Occurs after 2-3wks
• After removal of drug 1, returns to normal after 2-3wks
Inhibition of Metabolism
• Can increase drug effect OR decrease
• Can happen directly after 1st dose
Reporting Adverse Drug Reactions to FDA
o Adverse or non-efficacious
o Should be reported even if drug was used off-label
Drugs Prohibited in Food Animals
o Chloramphenicol
o Clenbuterol
o Diethylstilbestrol (DES)
o Dimetridazole, ipronidazole and other nitroimidazoles
o Furazolidone and nitrofurazone (except for approved topical use)
o Extralabel use of fluoroquinolones
o Glycopeptides
Drugs Prohibited Specifically In Dairy Cows
Sulfonamide drugs EXCEPT
• Sulfadimethoxine
• Sulfabromomethazine
• Sulfaethoxypyridazine
Phenylbutazone in 20mo or older
Special Considerations for Using Cephalosporins in Food Animals
Prohibited in cattle, swine, chickens, turkeys for:
• disease prevention (ok for treating dz)
• At unapproved doses, frequencies, durations, or routes of administration
• If the drug is not approved for that species and production class
Special Considerations for Using Adamantane and Neuraminidase inhibitors in Food Animals
o approved for treating or preventing influenza A.
o prohibited from extra‐label uses in chickens, turkeys, and ducks
Extra label use in food animals
o allowed if vet can establish extended withdrawal time to insure that the edible tissues are safe for human consumption
o Use FARAD for withdrawal time info
o Must: diagnose condition, maintain animals ID, establish extended withdrawal, ensure no illegal drug residues
Prescribing Human Drugs to food animals
can’t prescribe an approved human drug if there’s a drug approved for food‐producing animals
o Ex: if a drug approved for chickens is available, you must first use that drug to treat a sick cow before reaching for a drug approved for people
o Exceptions: animal drug does not contain active ingredient needed, required dosage, required conc., or is clinically ineffective
Extralabel Drug Use in companion animals
o In companion animals, you can prescribe an approved human drug for an extra‐label use even if an approved animal drug is available
o must keep records for 2 years or time required by federal or state law, whichever is longer
Scheduled Drugs
Schedule I
o No accepted medical use in US
Schedule II/IIN
o High potential for abuse
o Sever psychological or physiological dependency
Schedule III/IIIN
o Abuse less likely
o Moderate physical dependency
o High psychological dependency
Schedule IV
o Low potential for abuse
Most Important Functions of Kidney
o Regulation of water & electrolytes
o Excretion of metabolic waste
o Regulation of arterial pressure
o Acid-base balance
o Regulation of 1,25 cholecalciferol
o EPO production
o Glucose synthesis
Function of Glomerulus, Proximal Tubule, Loop of Henle, Distal Tubule
Glomerular Function
o GFR affects drug clearance
o Prevents protein loss into urine
Proximal Tubule Function
o Resorption of water
o Loss of solutes
Loop of Henle Function
o Dilutes urine
o Develops medullary conc. gradient
Distal Tubule
o Dilutes urine
o Resorps Na
o ALD
o Bicarb formation
Carbonic Anhydrase Inhibitor, Drug, area, MOA
o Acetazolamide
o Works on proximal tubules
Mechanism
• Decreases H+
• Decreased Na absorption via the Na+/H+ antiporter
• K+ wasting and increased HCO3‐ secretion -> alkaline diuresis
Carbonic Anhydrase Inhibitor, Indications & Toxicity
Indications
• Metabolic alkalosis
• Glaucoma
• Hyperkalemic periodic paralysis (equine)
Toxicity
• Allergen to those allergic to sulfonamide
• Causes metabolic acidosis
• Cause electrolyte disturbance
Osmotic Diuretics; Drug, area, MOA
o Mannitol
o Mainly proximal tubule
Mechanism
• Expands extracellular fluid volume
• Inhibit water & Na+ reabsorption in medullary collecting ducts
• Increase inner medullary blood flow
Osmotic Diuretics; Indications & Toxicity
Indications
• Relieve intratubular obstruction
• Increase GFR, renal blood flow, urine production
• Glaucoma
Toxicity
_ Acute
• Rapid volume expansion ->
• increased blood pressure and hyponatremia ->
• may precipitate cardiac failure and pulmonary edema
_ Chronic
• Dehydration
• Electrolyte disturbance
Loop Diuretics; Drug, area, MOA
• Furosemide
• Loop of Henle
Mechanism
• Inhibit Na/K/Cl symporter
• Increase prostaglandin release -> increase renal blood flow
• Inhibits Ca & Mg reabsorption
• Increases K & H+ excretion
• Increases renin release
• Increases venous compliance
• Decrease R atrial P
• Decrease pulmonary artery P
Loop Diuretics; Indications & Toxicity
Indications
• Most commonly used diuretic
• Treatment of edema due to cardiac, hepatic, or renal
• Increased urine output in renal failure
• Hypercalcemia
• Hyperkalemia
• Udder edema (cows)
• Exercise induced pulmonary hemorrhage (horses)
Toxicity
• Additive risk for nephrotoxicity w/ other nephrotoxic drugs
• Additive risk of ototoxicity
• Hypokalemia
• Dehydration
Loop Diuretics; Transport, Drug Interactions, Contraindications
Transport
• Potent, rapid, short-lived
• Action limited by amount of Na
• Must be transported to loop by organic anion transporter
Drug Interactions
• Efficacy inhibited by NSAIDs
Contraindications
• Patients w/ anuria
• Preexisting electrolyte or H2O abnormalities
• Conditions that lead to electrolyte or H2O abnormalities
• Hypotension
• Hepatic encephalopathy
Thiazide Diuretics; Drug, area, MOA
Drugs
o Chlorothiazide
o Hydrochlorothiazide
Sit of Action
o Early distal tubule
MOA
o WEAK diuretic
o Inhibits Na-Cl transporter
o Enhances excretion of Na, Cl, H2O, K. Mg, P, Iodide, Bromide
o Decreases Ca excretion (opposite of furosemide)
Thiazide Diuretics; Indications, Toxicity
Indications
o Prevent calcium oxalate uroliths in dogs
o Decrease PU/PD in diabetes insipidus
o Used to enhance effects of diazoxide in treatment of insulinomas in dogs
o Hyperkalemic periodic paralysis in horses
Toxicity
o Dehydration
o Hypokalemia
o GI effects
o Alkalosis
o Sulfonamide hypersensitivity
o Exacerbate hyperglycemia
Aldosterone Antagonists; Drug, area, MOA
Drugs
o Spironolactone
Site
o Distal tubules
MOA
o Inhibits ALD binding
o Increase excretion of Na, Cl, H2O
o Decrease excretion of K, ammonium, phosphate
Aldosterone Antagonists; Indications, Toxicity
Indications
o w/ furosemide or ACE for CHF
o w/ loop or thiazide diuretics to decrease K waisting
o ascites
Toxicity
o Hyperkalemia
o Dehydration
o Metabolic acidosis
o Lead to digoxin tox
K-Sparing Diuretics; Drug, area, MOA
Drugs
o Amiloride
Site
o Distal Tubules
MOA
o Block Na channels
o Less K excreted into lumen
K-Sparing Diuretics; Indications, Toxicity
Indications
o Uncommon in vet med
o Combine w/ loop or thiazide to decrease K wasting
o Edema in hepatic encephalopathy
Toxicity
o hyperkalemia
Renal Secondary Hyperparathyroidism Basics
• Less functional kidney (decreased GFR)
• Phosphorus is not excreted
• High phos causes low iCa
• PTH release stimulated
• Phos still high so keeps stimulating PTH release
• Increased PTH causes increased Ca
• Parathyroid hyperplasia develops
• treated w/ calcitrol
Calcitrol; MOA, Toxicity, Form, Monitoring
MOA
• Replaces activated vit D
• Improves GI Ca absorption
• Inhibits PTH production
Toxicity
• Hypercalcemia
• Tissue mineralization
• Do not use if serum P >6
Form
• Large capsule
Monitoring
• Ca, P, & PTH
Erythrocyte Stimulating Agents; Drugs, MOA, Indications, Toxicity, Form, Monitoring
Drugs
o Epoetin alfa
o Darbepoetin alfa
MOA
o Directly replace EPO to stimulate RBC production
Inidcations
o Clinical anemia
Toxicity
o Polycythemia
o Hypertension
o Autoantibody formation
Delivery Form & monitoring
o Injectable
o Should give w/ Fe supplement
o Monitor PCV
Opiates Used for Anti-tussives
Morphine
• Poor bioavailability in dogs
Codeine
• less addictive
• Poor bioavailability in dogs
Hydrocodone
• similar to codeine
Butorphanol
• FDA approved
• most used
• poor oral bioavailability but oral dosing achieves therapeutic levels
Opiates as Anti-tussives; MOA, Indications, Toxicity
MOA
• Directly depress cough center in the medulla via either mu or kappa opiate receptors
Indications
• Moderate to severe coughing that interferes with patient’s quality of life
Toxcicity
• Potential for abuse
• Sedation
• Constipation
• Respiratory depression (less of a problem with butorphanol)
• Excitation/dysphoria in cats and horses (except butorphanol)
Dextromethorphan; Basics, MOA, Indications, Toxicity
o Anti-tussive
o Many OTC formulations should not be used in animals
o Poor oral bioavailability & short half-life in dogs
MOA
• Unknown
• dextromethorphan is an opiate derivative but does not stimulate opiate receptors
Indications
• Moderate to severe coughing that interferes with patient’s quality of life
Toxicity
• Vomiting and CNS toxicity at high doses (dogs and cats)
Tramadol; Basics, MOA, Indications, Toxicity
o Non-opiate anti-tussive
o NOT a controlled substance
o Has greater oral bioavailability than true opiates
MOA
• Non-opiate that is a partial mu agonist, serotonin and alpha‐2 activity
Indications
• Moderate to severe coughing that interferes with patient’s quality of life.
Toxicity
• Sedation, nausea, vomiting
• Efficacy reduced w/ drugs that inhibit CYP 2D
Uses & MOA for Bronchodilators
o reactive airway disease in cats (feline asthma)
o recurrent airway obstruction (heaves in horses)
o chronic obstructive airway disease and inflammatory airways disease (horses)
o allergic bronchitis in dogs
MOA
o inhibition of phosphodiesterase (PDE)
o Adenosine receptor antagonists
Methylxanthines; Class, Indications, Toxicity, interactions
o Bronchodilators
Indications
• Feline asthma
• Canine allergic bronchitis
• Recurrent airway obstruction horses (heaves/COPD)
• Does not work in cattle
Toxicity
• CNS stimulation (limits use in horses)
• Tachycardia
• Nausea/vomiting
• mild diuresis
Drug-drug Interactions
• Fluroquinolones & cimetidine inhibit CYP 450 & cause methylxanthine toxicity
• Phenobarbital & rifampicin induce CYP and reduce methylxanthine conc.
Drugs
• Theophylline
Beta 2 Adrenergic Agonists; MOA, Drugs, Toxicity
MOA
• increases intracellular cAMP and causes relaxation of smooth muscle
• increase mucociliary clearance
• short-acting used in emergencies
• long-acting used for chronic conditions
Drugs
• Terbutaline
• Metaproterenol
• Albuterol (short acting)
• Salmeterol (long acting; 12hrs)
• Clenbuterol (long acting 6-8hrs)
Toxicity
• Short-acting agents stimulate alpha & beta 1 & 2 -> tachycardia
• Beta-2 at high doses also stimulate Beta 1 -> cardiac toxicity
• Tolerance to beat agonists occurs
• Clenbuterol -> muscle tremors, sweating in horses
• Tocolytic effects (anti-contraction of uterus)
• Hypokalemia
Anticholinergics; MOA, Indications, Toxicity, Drugs
MOA
• Inhibit muscarinic receptor type 3
Indications
• Short-term bronchodilation
Toxicity
• Tachycardia
• ileus, constipation, dry mouth
• decreased mucocilliary clearance
• CNS excitation leading to coma
Drugs
• Atropine - Crosses BBB
• Glycopyrrolate - IV does not cross BBB
• Ipratropium bromide - Aerosol not absorbed from drugs -> no systemic effects
Cromolyn; Route, MOA, Indications
Route
• Inhalation/nebulization
MOA
• Inhibits mast cell degranulation by interfering with Ca transport across cell membrane.
• Has no bronchodilator effects
Indications
• Must be administered prior to exposure to allergen
Corticosteroids; MOA, Indications, Toxicity, Drugs
MOA
• Produces lipocortin -> blocks PLA2
• Decrease inflammation
• Augment beta-2 bronchial smooth muscle relaxation
• Prevent downregulation of beta-2 adrenergic receptors
Indications
• Inhalation for feline asthma
• Allergic bronchitis
• Non-septic pulmonary dz
• Horses in resp distress
Toxicity
• Dogs – weight gain, Gi ulcers, secondary infections
• Cats – weight gain, hyperglycemia, secondary infections
• Horses – maybe laminitis
Drugs
• Prednisone(dogs) / prednisolone(cats/horses) – PO
• Methylprednisolone acetate – IM
• Dexmethasone – PO horses ONLY
Expectorants; Indications, Drugs
Indications
• Increase output of bronchial secretions / decrease viscosity
Drugs
• Saline – vagally mediated reflex on gastric mucosa
• Guaifenesin – vagal stimulation on bronchial secretion
Doxapram; MOA, Indications
MOA
• Stim resp center of brain
• Also might stim carotid & aortic chemoreceptors
Indications
• Use Stimulate respiratory center in emergency situations
• Anesthetic emergencies
• Overdoses‐opiates, benzodiazepines, macrocyclic lactones
• Neonates
• Laryngeal exam
Acetylcysteine MOA
• Mucolytic effects
• Breaks disulfide bonds on mucoproteins
Sildenafil & Tadalafil MOA
• Type V phosphodiesterase inhibitor ->
• nitric oxide production ->
• dilate vessels in lungs
Use for Pseudoephedrine
decongestant
