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Vet Prep: Med Math & Intro. to Pharm > Factors Modifying Drug Dose & Response > Flashcards

Factors Modifying Drug Dose & Response Flashcards

- discuss different factors related to animal that modify drug dosage or drug response - differentiate btwn idiosyncratic adverse reactions and pharmacologic adverse reactions - understand different types of drug tolerance - discuss different factors related to drug that modify drug dosage or drug response - understand different types of mechanisms of drug-drug interactions and provide examples - discuss different factors related to the environment that modify drug dosage and drug response

1
Q

factors related to animal

A
  • species, breed, individual
  • body weights age, sex, temperament
  • idiosyncrasy
  • hypersensitivity
  • disease
  • tolerance
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2
Q

Anatomic species differences

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

Physiologic species differences

A
  • salivary enzymes
    • cats lack salivary amylas
  • urine pH
    • cats more acidic
    • dogs more basic
    • horses more basic
    • special species (ie. rabbits, avians)
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4
Q

Biochemical species differences

A
  • metabolic
    • cats deficient in certain drug-metabolizing enzymes
  • plasma protein binding
  • presence of receptors
    • ex: opioid receptors
      • sensitivity to morphine & other opioid drugs
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5
Q

factors related to breed

A
  • 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
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6
Q

factors related to individual

A
  • 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
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7
Q

factors related to body weight & condition and hydration status

A
  • 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
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8
Q

factors related to age

A

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
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9
Q

factors related to sex & temperament

A
  • 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
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10
Q

factors related to idiosyncrasy

A
  • 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
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11
Q

idiosyncratic drug reaction examples

A
  • 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
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12
Q

factors related to hypersensitivity

A

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
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13
Q

factors related to disease

A
  • 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
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14
Q

drug tolerance

A
  • an unusual resistance to ordinary drug dose
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15
Q

Types of drug tolerance

A
  • natural tolerance
  • acquired tolerance
  • cross tolerance
  • tachyphylaxis
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16
Q

natural tolerance

A
  • ruminants tolerant to barbiturates
17
Q

acquired tolerance

A
  • enzyme induction -> faster metabolism
  • increased excretion -> disease state or drug-drug interactions
  • receptor down-regulation -> chronic drug administration
18
Q

cross-tolerance

A
  • drugs in same class
19
Q

tachyphylaxis

A
  • acute acquired tolerance
    • no use in giving more of the same drug
    • different drug needed to achieve desired effect
20
Q

factors related to the drug

A
  • route & timing of administration
  • cumulation
  • drug-drug interaction
21
Q

route of administration

A
  • 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
22
Q

timing of administration

A
  • 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
23
Q

drug accumulation (cumulation)

A
  • 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
24
Q

drug-drug interactions

A
  • 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
25
Q

types of drug-drug interactions

A
  • summation
  • potentiation
  • synergism
  • antagonism
26
Q

summation

A
  • 1+1=2

- sum of the effects of the drugs

27
Q

potentiation

A
  • 1+1>2
  • intensification of effects
  • give another drug with different action
28
Q

synergism

A
  • 1+1>2
  • exaggeration of effects
  • give another drug with same action
29
Q

antagonism

A
  • 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
30
Q

mechanisms of drug-drug interactions

A
  • pharmacokinetic

- pharmacodynamic

31
Q

pharmacokinetic

A
  • 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
32
Q

pharmacodynamic

A
  • 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
33
Q

drug incompatibility

A
  • 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
34
Q

factors related to environment

A
  • 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

Vet Prep: Med Math & Intro. to Pharm (3 decks)

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