Factors Modifying Drug Dose & Response

Question 1

factors related to animal

Answer 1

• species, breed, individual
• body weights age, sex, temperament
• idiosyncrasy
• hypersensitivity
• disease
• tolerance

Question 2

Anatomic species differences

Answer 2

• digestive tract ruminants vs non ruminants
  
  • rumen pH ~6.0
  • stomach pH (monogastrics) ~2-3
• ability to vomit

Question 3

Physiologic species differences

Answer 3

• salivary enzymes
  
  • cats lack salivary amylas
• urine pH
  
  • cats more acidic
  • dogs more basic
  • horses more basic
  • special species (ie. rabbits, avians)

Question 4

Biochemical species differences

Answer 4

• metabolic
  
  • cats deficient in certain drug-metabolizing enzymes
• plasma protein binding
• presence of receptors
  
  • ex: opioid receptors
    
    • sensitivity to morphine & other opioid drugs

Question 5

factors related to breed

Answer 5

• herding breeds (collies, sheepdogs, etc) sensitive to many drugs
  
  • Multidrug Resistente (MDR-1) Gene
    
    • now called ABCB - delta1gene
  • Ivermectin = classic example
• brachycephalic (boxers, bulldogs, pugs, etc) sensitive to phenothiazines
  
  • increased vagal or parasympathetic tone

Question 6

factors related to individual

Answer 6

• genetic differences
  
  • most are occult
  • not genetically tested routinely unless known breed predisposition
    
    • no test available for most genetic differences…yet…
• learn from individual’s drug response
  
  • record ALL responses to medications
    
    • was drug well tolerated or not?
    • did it help treat the problem for which it was prescribed?
    • were there complications?
• educate client & care staff

Question 7

factors related to body weight & condition and hydration status

Answer 7

• obese
• lean
• hydration status
  
  • severe dehydration causes a decrease in weight
  • dose adjustment may be needed
• most dosages are based on average adult anima:
  
  • cats weigh ~5kg
  • horses weigh ~500kg
  • labradors weigh ~30kg ergo…1 labrador ~6 cats

Question 8

factors related to age

Answer 8

newborn to pediatric

• decreased metabolism
• decreased excretion
• decreased plasma protein binding
• decreased blood-brain barrier (BBB) function
• increased total body water
• growth & susceptibility to adverse drug effects (ie. the growing patient)
  
  • tetracyclines: yellow discoloration of teeth & bones
  • fluoroquinolines: damage to cartilage
  • glucocorticoids: inhibit normal growth

Geriatric

• decreased metabolic enzymes
• decreased hepatic blood flow
• decreased renal function
• decreased cardiac output
• decreased total body water
• decreased plasma protein (albumin)
• decreased lean body mass
• increased body fat
• increased distribution
• presence of chronic disease
  
  • organ function

Question 9

factors related to sex & temperament

Answer 9

• females > fat: lean body mass compared to mature males
• pregnancy
  
  • increased volume of distribution
• lactation
  
  • some drugs get trapped in milk
• aggression
  
  • high sympathetic drive
  • higher dosage may be needed when using sedatives & tranquilizers
• docility
  
  • may not require full dose sedation in some cases

Question 10

factors related to idiosyncrasy

Answer 10

• idiosyncratic drug reaction
• individual drug sensitivity
• idiosyncratic reactions are uncommon genetically determined & unpredictable abnormal drug responses
• not dose-dependent
• can be serious & life threatening
  
  • initial signs can include fever, facial swelling, skin eruptions, or even collapse
  • organ toxicity
  • bone marrow suppression

Question 11

idiosyncratic drug reaction examples

Answer 11

• enrofloxacin -> irreversible retinal damage & blindness in cats
• zonisamide -> reversible neutropenia
• ANY drug ANY patient ANYTIME
• discontinuation of the drug = mainstay of treatment & may be curative
• avoid use of same drug or drug class in same patient in future
  
  • label medical records accordingly
  • educate clients & staff

Question 12

factors related to hypersensitivity

Answer 12

drug hypersensitivity reaction

• allergic drug reaction
• drugs can act as antigens
  
  • human & animal products -> plasma or blood transfusions, human serum albumin, canine serum albumin, hormones (proteins)
  • prior exposure necessary
• drugs can act as haptens
  
  • interact with immune system

Question 13

factors related to disease

Answer 13

• hepatic dysfunction
  
  • can’t metabolize most drugs normally
  • decreased drug metabolism
• renal insufficiency
  
  • can’t excrete most drugs via the kidney & into the urine normally
  • decreased drug excretion
• congestive heart failure
  
  • can’t pump drugs to site of action, metabolism, or excretion normally
  • decreased renal excretion

Question 14

drug tolerance

Answer 14

• an unusual resistance to ordinary drug dose

Question 15

Types of drug tolerance

Answer 15

• natural tolerance
• acquired tolerance
• cross tolerance
• tachyphylaxis

Question 16

natural tolerance

Answer 16

• ruminants tolerant to barbiturates

Question 17

acquired tolerance

Answer 17

• enzyme induction -> faster metabolism
• increased excretion -> disease state or drug-drug interactions
• receptor down-regulation -> chronic drug administration

Question 18

cross-tolerance

Answer 18

• drugs in same class

Question 19

tachyphylaxis

Answer 19

• acute acquired tolerance
  
  • no use in giving more of the same drug
  • different drug needed to achieve desired effect

Question 20

factors related to the drug

Answer 20

• route & timing of administration
• cumulation
• drug-drug interaction

Question 21

route of administration

Answer 21

• onset & duration of action
  
  1. IV route
     
     • rapid onset
     • shorter duration (most drugs)
  2. Oral route
     
     • slower onset
     • longer duration
• action of the drug
  
  • MgSO4 orally: cathartic
  • MgSO4 IV: cardiac depressant/antiarrhythmic & muscle relaxation

Question 22

timing of administration

Answer 22

• oral absorption: usually faster pre-prandial (before meal)
  
  • some require fatty foods for maximal absorption
• endocrine drugs
  
  • ex: insulin, corticosteroids, thyroid supplements
• CNS stimulants & circadian rhythm

Question 23

drug accumulation (cumulation)

Answer 23

• occurs when rate of elimination is slower than rate of absorption
  
  • can also be modified due to factors related to animal
    ex:
• renal insufficiency: can lead to cumulative drug effects
  
  • decreased drug excretion
  • may require dose-reduction
• adipose tissue stores: can lead to accumulation of lipophilic drugs
  
  • increased drug re-distribution
  • slower drug excretion

Question 24

drug-drug interactions

Answer 24

• the administration of drugs concurrently or sequentially

beneficial interactions:

• combined antihypertensive therapy
  
  • ex: ACE-inhibitor + thiazide diuretic
• combined antimicrobial therapy
  
  • ex: trimethoprim-sulfa (TMS) -> potentiated sulfonamide

undesirable interactions:

• aminoglycosides + m. relaxants
  
  • worsen m. weakness
• chloramphenical + phenobarbital
  
  • worse risk of bone marrow suppression

Question 25

types of drug-drug interactions

Answer 25

• summation
• potentiation
• synergism
• antagonism

Question 26

summation

Answer 26

• 1+1=2

- sum of the effects of the drugs

Question 27

potentiation

Answer 27

• 1+1>2
• intensification of effects
• give another drug with different action

Question 28

synergism

Answer 28

• 1+1>2
• exaggeration of effects
• give another drug with same action

Question 29

antagonism

Answer 29

• 1+1=<2
• decreases effect of another drug
• chemical -> heavy metal chelation (ex: EDTA for lead toxicity)
• physiologic -> epinephrine & histamine
• pharmacologic -> competitive, non-competitive, uncompetitive

Question 30

mechanisms of drug-drug interactions

Answer 30

• pharmacokinetic

- pharmacodynamic

Question 31

pharmacokinetic

Answer 31

• absorption -> inhibit vs enhance
• distribution -> plasma protein binding
• biotransformation -> metabolic enzyme induction vs inhibition
• excretion -> urinary alkalinizes vs acidifiers
  
  • ammonium chloride to acidify urine with methylxanthine toxicity

Question 32

pharmacodynamic

Answer 32

• drugs acting on same receptors
  
  • examples of competitive drug antagonism
    
    • acetylcholine & atropine
    • morphine & naloxone
    • diazepam & flumazenil
• drugs acting on different receptors
  
  • to potentiate or produce summative effects
  • to antagonize effects of another drug

Question 33

drug incompatibility

Answer 33

• physical
  
  • tetracyclines + calcium
  • injectable diazepam + hydromorphone
  • drug binding to administration tubing or syringe
  • drug + pH of solution
• chemical
  
  • vit B complex with many antibiotic solutions
  • vit B12 (cobaltine)
  • blood transfusions CANNOT be given with calcium-containing fluids
    
    • antagonize citrate -> blood clots

Question 34

factors related to environment

Answer 34

• ambient temperature
  
  • may alter active drug compounds
• humidity
  
  • denaturing of compounds
• oxygen
  
  • antibiotics used to treat anaerobic infections with not work well in oxygen rich environments
• exposure to light
  
  • some drugs must be protected from direct light sources
    
    • photodegredation -> of altering drug stability
      
      • light-sensitive injectable prescription drugs