Factors Modifying Drug Dosage & Response

Question 1

Species

Answer 1

Anatomical, Physiological, Biochemical

Ex. GI Tracts In Ruminants & Monogastrics, Vomiting, Urine pH, Drug-Metabolizing Enzymes, Plasma Protein Binding

Question 2

Breed

Answer 2

Collies - Sensitive To Ivermectin
Boxers - Sensitive To Phenothiazines
Australian Terriers - Tolerant To Droperidol-fentanyl Combo But Sensitive To Its Toxic Effects

Question 3

Body Weight

Answer 3

Obese, Lean, or Severely Dehydrated Animals Require Dosage Modification

Question 4

Newborns

Answer 4

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

Question 5

Geriatric

Answer 5

Decreased Metabolism, Cardiac Output, Renal Function, Lean Body Mass, Total Body Water, Plasma Albumin, & Hepatic Blood Flow

Question 6

Sex

Answer 6

Mature Females Generally Have More Fat Than Males
Reproductive Cycle In Females May Modify Drug Response
Differences In Drug Biotransformation

Question 7

Temperament

Answer 7

Calmer Animals May Need Lower Doses Of CNS Depressants Than Aggressive Animals

Question 8

Idiosyncrasy (Individual Sensitivity)

Answer 8

Genetically Determined Unpredictable Abnormal Reactions
Not Dose-Dependent & Require Drug Withdrawal
Most Are Caused By Reactive Drug Metabolites (RDMs)

Question 9

Hypersensitivity

Answer 9

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

Question 10

Disease

Answer 10

Liver Disease Decreases Drug Metabolism

Kidney Disease & Congestive Heart Failure Decrease Renal Excretion

Question 11

Ex. Of Idiosyncratic Reactions

Answer 11

Enrofloxacin MAY Cause Retinal Damage In SOME Cats
Griseofulvin MAY Cause Liver Damage In SOME Cats
Captopril MAY Cause Renal Damage In SOME Dogs

Question 12

Tolerance (3 Types)

Answer 12

Unusual Resistance To Ordinary Dose Of The Drug

1. Natural Tolerance (Ex. Ruminants To Barbituates)
2. Acquired Tolerance
3. Cross Tolerance (Thiopental In Animal Under Phenobarb Treatment)

Question 13

Tachyphylaxis

Answer 13

Acute Acquired Tolerance

Question 14

Route Of Administration

Answer 14

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

Question 15

Timing Of Administration (Ex. Oral & CNS)

Answer 15

Oral: Absorption Is Faster Before Meals Than After Meals
CNS: Stimulants May Be More Effective During Daytime & Depressants May Be More Effective At Nighttime

Question 16

Cumulation

Answer 16

Occurs When Rate Of Elimination Is Slower Than Rate Of Absorption

Question 17

Ex. Of Beneficial Drug-Drug Interactions

• Combined Antihypertensive Therapy (1)
• Combined Antimicrobial Therapy (2)

Answer 17

ACE Inhibitor - Thiazide Diuretic

Trimethoprim - Sulfonamide
Penicillin G - Streptomycin

Question 18

3 Ex. Of Undesirable Drug Interactions

Answer 18

Aminoglycoside Antibiotic - Aminoglycoside Antibiotic
Aminoglycoside Antibiotic - Muscle Relaxant
Chloramphenicol - Phenobarbital

Question 19

Types Of Drug-Drug Interactions

Answer 19

Summation
Potentiation
Synergism
Antagonism

Question 20

Summation (Addition)

Answer 20

1+1=2

Ex. 2 Anticholinergics

Question 21

Potentiation (Intensification)

Answer 21

Combined Effect > Sum Of 2 Drugs Acting Independently (1+1>2)
Ex. Probenicid - Penicillin G
Epinephrine - Procaine

Question 22

Synergism

Answer 22

Exaggeration Of Effect Of A Drug By Giving Another Drug That Has Same Action (1+1>2)
Ex. Neuroleptic - Inhalation Anesthetic
Trimethoprim - Sulfonamide

Question 23

Antagonism

Answer 23

Administration Of Drug Results In Decrease In Pharmacological Response Of Another Drug

Question 24

Types Of Antagonism

Answer 24

Chemical (Ex. EDTA & Lead)
Physiological (Ex. Epinephrine & Histamine)
Pharmacological: Competitive (Ex. Atropine & Acetylcholine)
Noncompetitive (Ex. Phenoxybenzamine & Epinephrine)

Question 25

Mechanisms Of Drug-Drug Interactions

Answer 25

Pharmacodynamic

Pharmacokinetic

Question 26

Pharmacodynamic Interactions

Answer 26

2 Drugs Acting On Same Receptors

Ex. Acetylcholine & Atropine On Muscarinic Receptors

Question 27

Pharmacokinetic Interactions

Answer 27

Alteration Of Absorption, Distribution, Biotransformation, Excretion

Question 28

Alt. Of Absorption

Answer 28

Drugs May Inhibit Or Enhance Absorption Of Other Drugs
Ex. Calcium Orally Inhibits Tetracycline Absorption
Ex. epinephrine SQ Inhibits Systemic Absorption Of Local Anesthetics

Question 29

Alt. Of Distribution

Answer 29

Drugs That Bond Strongly To Plasma Proteins Displace Weakly Bound Drugs Increasing The Effects Of The Weak Ones

Question 30

Alt. Of Biotransformation

Answer 30

Enzyme Inducers (Ex. Phenobarbital) May Decrease Effects Of Other Drugs
Enzyme Inhibitors (Ex. Chloramphenicol) May Increase Effects Of Other Drugs

Question 31

Alt. Of Excretion

Answer 31

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

Question 32

Drug Incompatibility

Answer 32

Physical & Chemical Interactions
Ex. Vitamin B Complex With Many Antibiotic Solutions
Xylazine With Thiopental
Tetracyclines With Calcium
NaHCO3 With Epinephrine