Factors Modifying Drug Dosage & Response Flashcards
Species
Anatomical, Physiological, Biochemical
Ex. GI Tracts In Ruminants & Monogastrics, Vomiting, Urine pH, Drug-Metabolizing Enzymes, Plasma Protein Binding
Breed
Collies - Sensitive To Ivermectin
Boxers - Sensitive To Phenothiazines
Australian Terriers - Tolerant To Droperidol-fentanyl Combo But Sensitive To Its Toxic Effects
Body Weight
Obese, Lean, or Severely Dehydrated Animals Require Dosage Modification
Newborns
Decreased Drug Metabolism, Excretion, Blood-Brain Barrier, & Plasma Protein Binding
Increased Body Water
Susceptible To Yellowing Of Teeth By Tetracyclines, Cartilage Damage By Fluoroquinolones, & Growth Inhibition By Glucocorticoids
Geriatric
Decreased Metabolism, Cardiac Output, Renal Function, Lean Body Mass, Total Body Water, Plasma Albumin, & Hepatic Blood Flow
Sex
Mature Females Generally Have More Fat Than Males
Reproductive Cycle In Females May Modify Drug Response
Differences In Drug Biotransformation
Temperament
Calmer Animals May Need Lower Doses Of CNS Depressants Than Aggressive Animals
Idiosyncrasy (Individual Sensitivity)
Genetically Determined Unpredictable Abnormal Reactions
Not Dose-Dependent & Require Drug Withdrawal
Most Are Caused By Reactive Drug Metabolites (RDMs)
Hypersensitivity
Some Drugs Act As Antigens
Prior Exposure Is Necessary
Antigen-Antibody Rxns Can Cause Allergy Or Anaphylaxis
Some Drugs Acts As Haptens & Cause Hypersensitivity Rxns By Interaction With Immune System
Disease
Liver Disease Decreases Drug Metabolism
Kidney Disease & Congestive Heart Failure Decrease Renal Excretion
Ex. Of Idiosyncratic Reactions
Enrofloxacin MAY Cause Retinal Damage In SOME Cats
Griseofulvin MAY Cause Liver Damage In SOME Cats
Captopril MAY Cause Renal Damage In SOME Dogs
Tolerance (3 Types)
Unusual Resistance To Ordinary Dose Of The Drug
- Natural Tolerance (Ex. Ruminants To Barbituates)
- Acquired Tolerance
- Cross Tolerance (Thiopental In Animal Under Phenobarb Treatment)
Tachyphylaxis
Acute Acquired Tolerance
Route Of Administration
Can Modify Onset & Duration Of Action
Can Modify Action Of Drug
-Mg Sulfate Orally: Cathartic Effect. Intravenously: Cardiac Depression & Muscle Relaxation
-Lidocaine Locally: Anesthetic. Intravenously: Antiarrhythmic
Timing Of Administration (Ex. Oral & CNS)
Oral: Absorption Is Faster Before Meals Than After Meals
CNS: Stimulants May Be More Effective During Daytime & Depressants May Be More Effective At Nighttime
Cumulation
Occurs When Rate Of Elimination Is Slower Than Rate Of Absorption
Ex. Of Beneficial Drug-Drug Interactions
- Combined Antihypertensive Therapy (1)
- Combined Antimicrobial Therapy (2)
ACE Inhibitor - Thiazide Diuretic
Trimethoprim - Sulfonamide
Penicillin G - Streptomycin
3 Ex. Of Undesirable Drug Interactions
Aminoglycoside Antibiotic - Aminoglycoside Antibiotic
Aminoglycoside Antibiotic - Muscle Relaxant
Chloramphenicol - Phenobarbital
Types Of Drug-Drug Interactions
Summation
Potentiation
Synergism
Antagonism
Summation (Addition)
1+1=2
Ex. 2 Anticholinergics
Potentiation (Intensification)
Combined Effect > Sum Of 2 Drugs Acting Independently (1+1>2)
Ex. Probenicid - Penicillin G
Epinephrine - Procaine
Synergism
Exaggeration Of Effect Of A Drug By Giving Another Drug That Has Same Action (1+1>2)
Ex. Neuroleptic - Inhalation Anesthetic
Trimethoprim - Sulfonamide
Antagonism
Administration Of Drug Results In Decrease In Pharmacological Response Of Another Drug
Types Of Antagonism
Chemical (Ex. EDTA & Lead)
Physiological (Ex. Epinephrine & Histamine)
Pharmacological: Competitive (Ex. Atropine & Acetylcholine)
Noncompetitive (Ex. Phenoxybenzamine & Epinephrine)
Mechanisms Of Drug-Drug Interactions
Pharmacodynamic
Pharmacokinetic
Pharmacodynamic Interactions
2 Drugs Acting On Same Receptors
Ex. Acetylcholine & Atropine On Muscarinic Receptors
Pharmacokinetic Interactions
Alteration Of Absorption, Distribution, Biotransformation, Excretion
Alt. Of Absorption
Drugs May Inhibit Or Enhance Absorption Of Other Drugs
Ex. Calcium Orally Inhibits Tetracycline Absorption
Ex. epinephrine SQ Inhibits Systemic Absorption Of Local Anesthetics
Alt. Of Distribution
Drugs That Bond Strongly To Plasma Proteins Displace Weakly Bound Drugs Increasing The Effects Of The Weak Ones
Alt. Of Biotransformation
Enzyme Inducers (Ex. Phenobarbital) May Decrease Effects Of Other Drugs Enzyme Inhibitors (Ex. Chloramphenicol) May Increase Effects Of Other Drugs
Alt. Of Excretion
Urinary Alkalinizers (Ex. NaHCO3) Enhance Renal Excretion Of Weak Acidic Drugs (Ex. Phenobarbital, Phenylbutazone, Aspirin) Urinary Acidifiers (Ex. Ammonium Chloride) Enhance Renal Excretion Of Weak Basic Drugs (Ex. Strychnine, Procaine, Amphetamine) Ex. Probenicid Inhibits Tubular Secretion Of Penicillin G By Competing On The Carrier Molecule
Drug Incompatibility
Physical & Chemical Interactions Ex. Vitamin B Complex With Many Antibiotic Solutions Xylazine With Thiopental Tetracyclines With Calcium NaHCO3 With Epinephrine
