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
