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Pharmacology Exam 1 > Factors affecting drug disposition and response > Flashcards

Factors affecting drug disposition and response Flashcards

1
Q

Factors Related to the Animal:

A

Species Differences, Breed, Age, disease, temperament, Idiosyncratic drug reactions, hypersensitivity, tolerance, gender/gestation, body condition, individual factors (genes)

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2
Q

Anatomical Difference Example

A

Ruminants vs. Nonruminants

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3
Q

Physiological Difference Example

A

Urine pH of carnivores is more acidic than herbivores which alters their elimination of some drugs

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4
Q

Biochemical Difference Example

A

Cats are deficient in glucoronyl transferase (glucoronidation) which alters their emtabolism of some drugs

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5
Q

Pharmacodynamic Difference Example

A

Xylaziune doses are far lower for cattle than for equine

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6
Q

Ectotherm vs. Mammals Example

A

Half-life of some drugs may be extremely variable different in fish depending on the ambient temperature, a factor that would not impact half-life in mammals

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7
Q

Boxers are sensitive to?

A

Phenothiazines (acepromazine)

-can exhibit significant adverse cardiovascular effects

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8
Q

Collies are sensitive to?

A

Ivermectin

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9
Q

Australian Terriers are sensitive to?

A

Droperidol/Fentanyl

-exhibit little sedation but may have salvation, tachycardia, muscle tremors, and convulsions

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10
Q

Young Animals have a ___ total body water and generally ___ developed metabolic system.

A

Higher total body water

Less developed metabolic system

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11
Q

What is the gene that is deleted in Collies that causes a sensitivity to Ivermectin?

A

ABCB1 (MDR1)

-normally encodes P-glycoprotein, this gene deletion means less P-gp is produced

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12
Q

Genetic Factors Examples

A

ABCB1 gene deletion in collies

C15-A in canine mu-opiod receptor gene (OPRM1) and dysphoria

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13
Q

Gender and Gestation Examples

A

Spay/Neuter Status

Pregnancy

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14
Q

Body Condition Example

A

Obese vs. Lean vs. Emaciated

Some drug’s effects are terminated by redistribution into fat

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15
Q

When in doubt, consider using ___ dose of lipophlic drugs in very obese patients

A

Lower dose

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16
Q

Drug clearance doesn’t typically reach adult capacity until approximately _____ of age

A

12 weeks

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17
Q

Factors related to young animals:

A
  • Decreased metabolism
  • Increased BBB permeability
  • Decreased plasma protein binding
  • Increased total body water
  • Susceptibility of some adverse effects
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18
Q

Young animals are susceptible to some adverse effects of some drugs. What are some examples of these effects?

A
  • Tetracycline and yellowing of teeth (affects tooth enamel)
  • Fluorquinolones and cartialge damage
  • Glucocorticoids and premature closure of epiphysis
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19
Q

Other factors that a young age can affect in relation to drugs:

A
  • Esophageal groove closure in young ruminants
  • Increased intestinal permeability prior to colostrum absorption
  • Higher gastric pH in very young animals
  • Milk diet can interfere with absorption of some drugs
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20
Q

___ and ___ drugs must be used in caution in geriatric patients.

A

Anesthesia and Sedative drugs

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21
Q

Factors related to geriatric animals:

A
  • Decreased metabolism and excretion
  • Reduced cardiac output and hepatic blood flow
  • Chronic disease
  • Changes in body composition (ex. reduced lean body mass, total body water, and plasma proteins and increased body fat)
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22
Q

Liver disease generally ______ (increase/decrease) liver metabolic function

A

Decrease

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23
Q

Renal disease generally ___ (increase/decrease) renal clearance

A

Decrease

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24
Q

Congestive heart failure general ____ (increase/decrease) drug distribution and clearance

A

Decrease

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25
Q

Temperament of an animal is particularly important in what kind of drugs?

A

Sedative drugs

  • Calm animals generally need a lower dose while aggressive/excited animal may require a higher dose and have reduced efficacy
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26
Q

Idiosyncratic drugs reactions ____ (are/are not) dose dependent and can occur on _____ (first, second, third) exposure.

A

Are not dose dependent and ca occur on first exposure.

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27
Q

If you have an idiosyncratic drug reaction, what should you do?

A

Withdrawal of the drug

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28
Q

Are idiosyncratic drug reactions predictable?

A

No, it is unpredictable

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29
Q

What is an example of a common idiosyncratic drug reaction?

A

Liver damage by griseofulvin in some cats

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30
Q

In what kind of reaction is prior exposure to the drug necessary?

A

Hypersensitivity reaction

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31
Q

In a hypersensitivity reaction, what are two things that a drug can act as?

A

Antigen

Hapten (more common)

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32
Q

What is the most common hypersensitivity reaction in relation to drugs?

A

Type I hypersensitivity (acute allergic, anaphylatic shock)

33
Q

Can cross sensitivity happen with hypersensitivity?

A

Yes

34
Q

What is Tolerance?

A

Gradual decrease in responsiveness to the same administered dose of the drug

35
Q

Does tolerance typically happen with acute or chronic administration?

A

Typically chronic, but can happen acutely

36
Q

What is the acute form of tolerance?

A

Tachyphylaxis

37
Q

What are the Pharmacokinetic mechanisms of tolerance?

A
  • Changes in absorption
  • Enzyme induction (increased metabolism)
  • Increased active excretion of the drug
38
Q

What are the Pharmacodynamic mechanisms of tolerance?

A
  • Desensitization (receptor down-regulation)
  • Loss of receptor
  • Exhaustion of mediator
39
Q

Factors related to the Drug:

A

Route of Administration. Timing of administration, cumulation, Drug-drug interactions,

40
Q

IV route of administration has a ____ onset and ____ duration

A

Rapid onset, Shorter duration

41
Q

PO route of administration has a _____ onset and ____ duration

A

Slower onset, Longer duration

42
Q

Give an example of how a drug can be modified depending on how the drug is given.

A

Local v. Systemic use:

Perineural lidocaine induces local anesthesia but given systemically (IV) it is an antiarrythmic

43
Q

T/F: A drug is NOT affected by the timing of administration

A

F: A drug can be affected by the timing of administration

44
Q

Give an example of how a drug can be affected by the timing of administration in relation to the presence/absence of food.

A

Phenylbutazone ADSORBS to hay which decreses its ABSORPTION in the horse cecum

45
Q

What are some ways that the timing of administration can affect a drug? (3 ways)

A
  • Presence/absence of food
  • Presence/absence of fat
  • Circadian rhythms
46
Q

Give an example of how a drug can be affected by the timing of administration in relation to the presence/absence of fat.

A

Mitotane absorption is greatly increased in the presence of fat or oil

47
Q

Give an example of how a drug can be affected by the timing of administration in relation to circadian rhythms.

A

CNS stimulants and CNS depressants are affected by specific times of the day

48
Q

CNS stimulants are more effective during the ______.

A

Daytime

49
Q

CNS depressants are more effective during the _______.

A

Nighttime

50
Q

What is it called when the rate of elimination is slower than the rate of absorption?

A

Cumulation

51
Q

What happens to the drug concentration in the body with repeated doses of a drug that exhibits cumulation?

A

The drug concentration will increase

52
Q

What are examples of drugs that exhibit cumulation?

A
  • Digitalis
  • Phenylbutazone
  • Thiopental
53
Q

What type of interactions can occur when administering drugs concurrently or sequentially?

A

Drug-Drug interactions

54
Q

Can the effects of drug-drug interactions be beneficial or detrimental?

A

The effects can be BOTH beneficial and detrimental.

55
Q

What are two examples of drug-drug interactions that can be beneficial?

A
  • Trimethoprim and sulfonamide

- ACE inhibitor and thiazide diuretic

56
Q

What are two examples of drug-drug interactions that can be detrimental?

A
  • Aminoglycoside and muscle relaxants

- Chloramphenicol and phenobarbital

57
Q

What are the three types of Drug-Drug interactions?

A
  • Summation
  • Synergism
  • Antagonism
58
Q

What is it called when two drugs have additive effects?

Drug A + Drug B = A + B

A

Summation

59
Q

What is it called when two drugs have a greater efficacy when combined?

(Drug A + Drug B > A + B)

A

Synergism

60
Q

What is it called when there are decreased effects with one or both of the drugs given?

(Drug A + Drug B

A

Antagonism

61
Q

Name the four mechanisms of Antagonistic drug-drug interactions.

A
  • Chemical Antagonism
  • Physiological Antagonism
  • Pharmacokinetic Antagonism
  • Receptor Antagonism
62
Q

Chemical Antagonism

A

The drugs will react to each other causing inactivation of one or the other.

Can occur in-vitro or in-vivo

63
Q

Physiological Antagonism

A

The drugs will work in different ways and have opposing effects that cancel each other out.

64
Q

Receptor Antagonism

A

One drug binds to a receptor and prevents the other drug from having its normal activity at that receptor.

65
Q

Pharmacokinetic Antagonism

A

One drug reduce the concentration of the other drug at its site of action by interfering with its ADME process.

66
Q

How can pharmacokinetic antagonism affect a drug in relation to absorption?

A

One drug can either enhance or inhibit the absorption

Examples:

  • Epinephrine given with lidocaine which causes vasoconstriction and therefore less systemic absorption
  • Topical DMSO which increases the absorption of topical griseofulvin
67
Q

How can pharmacokinetic antagonism affect a drug in relation to distribution?

A

Drugs can compete with each other for binding sites on plasma proteins.

Example:

Phenylbutazone and warfarin

68
Q

How can pharmacokinetic antagonism affect a drug in relation to metabolism?

A

Enzyme inducers and enzyme inhibitors

69
Q

What are some examples of enzyme inducers?

A
  • Phenobarbital
  • Phenylbutazone
  • Rifampin
  • Griseofulvin
  • Kale
70
Q

What are some examples of enzyme inhibitors?

A
  • Chloramphenicol
  • Cimetidine
  • Ketaconazole
  • Grapefruit
71
Q

How can pharmacokinetic antagonism affect a drug in relation to excretion?

A
  • Drugs compete for carrier molecules in the kidney, thereby reducing excretion of other drugs that use the same carrier
  • Changes in urinary pH
72
Q

Acidifying the urine ____ (increases/decreases) excretion of weak bases

A

Increases

73
Q

Alkalinizing the urine increases the excretion of ______ (weak acids/weak bases)

A

Weak Acids

74
Q

Factors related to the Environment:

A
  • Temperature
  • Oxygen
  • Humidity
  • Light
  • Contact with surface
75
Q

Give an example of how temperature can affect a drug.

A

At 122 degrees Fahrenheit the solubility of procaine increases in Penicillin G procaine solutions

76
Q

Give an example of how oxygen can affect a drug.

A

Decreased ambient oxygen can worsen the respiratory depression caused by some drugs

77
Q

Give an example of how humidity can affect a drug.

A

Amoxicillin once reconstituted into solution should be discarded after 14 days

78
Q

Give an example of how light can affect a drug.

A

Some drugs (insulin, diazepam) will be broken down by light and have reduced efficacy

79
Q

Give an example of how contact with surfaces can affect a drug.

A

Some drugs adhere or react to various surfaces such as plastic and therefore cannot be stored in plastic syringes for prolonged periods of time.

Pharmacology Exam 1 (8 decks)

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