Factors affecting drug disposition and response Flashcards by Brittany Parsons

Factors Related to the Animal:

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

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Anatomical Difference Example

Ruminants vs. Nonruminants

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Physiological Difference Example

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

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Biochemical Difference Example

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

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Pharmacodynamic Difference Example

Xylaziune doses are far lower for cattle than for equine

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Ectotherm vs. Mammals Example

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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Boxers are sensitive to?

Phenothiazines (acepromazine)

-can exhibit significant adverse cardiovascular effects

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Collies are sensitive to?

Ivermectin

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Australian Terriers are sensitive to?

Droperidol/Fentanyl

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

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

Higher total body water

Less developed metabolic system

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

ABCB1 (MDR1)

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

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Genetic Factors Examples

ABCB1 gene deletion in collies

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

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Gender and Gestation Examples

Spay/Neuter Status

Pregnancy

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Body Condition Example

Obese vs. Lean vs. Emaciated

Some drug’s effects are terminated by redistribution into fat

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

Lower dose

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

12 weeks

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Factors related to young animals:

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

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

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

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

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

Anesthesia and Sedative drugs

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Factors related to geriatric animals:

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

Decrease

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Renal disease generally ___ (increase/decrease) renal clearance

Decrease

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

Decrease

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

Sedative drugs - Calm animals generally need a lower dose while aggressive/excited animal may require a higher dose and have reduced efficacy

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

Are not dose dependent and ca occur on first exposure.

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

Withdrawal of the drug

Are idiosyncratic drug reactions predictable?

No, it is unpredictable

What is an example of a common idiosyncratic drug reaction?

Liver damage by griseofulvin in some cats

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

Hypersensitivity reaction

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

Antigen | Hapten (more common)

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

Type I hypersensitivity (acute allergic, anaphylatic shock)

Can cross sensitivity happen with hypersensitivity?

Yes

What is Tolerance?

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

Does tolerance typically happen with acute or chronic administration?

Typically chronic, but can happen acutely

What is the acute form of tolerance?

Tachyphylaxis

What are the Pharmacokinetic mechanisms of tolerance?

- Changes in absorption - Enzyme induction (increased metabolism) - Increased active excretion of the drug

What are the Pharmacodynamic mechanisms of tolerance?

- Desensitization (receptor down-regulation) - Loss of receptor - Exhaustion of mediator

Factors related to the Drug:

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

IV route of administration has a ____ onset and ____ duration

Rapid onset, Shorter duration

PO route of administration has a _____ onset and ____ duration

Slower onset, Longer duration

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

Local v. Systemic use: Perineural lidocaine induces local anesthesia but given systemically (IV) it is an antiarrythmic

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

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

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

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

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

- Presence/absence of food - Presence/absence of fat - Circadian rhythms

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

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

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

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

CNS stimulants are more effective during the ______.

Daytime

CNS depressants are more effective during the _______.

Nighttime

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

Cumulation

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

The drug concentration will increase

What are examples of drugs that exhibit cumulation?

- Digitalis - Phenylbutazone - Thiopental

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

Drug-Drug interactions

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

The effects can be BOTH beneficial and detrimental.

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

- Trimethoprim and sulfonamide | - ACE inhibitor and thiazide diuretic

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

- Aminoglycoside and muscle relaxants | - Chloramphenicol and phenobarbital

What are the three types of Drug-Drug interactions?

- Summation - Synergism - Antagonism

What is it called when two drugs have additive effects? | Drug A + Drug B = A + B

Summation

What is it called when two drugs have a greater efficacy when combined? (Drug A + Drug B > A + B)

Synergism

What is it called when there are decreased effects with one or both of the drugs given? (Drug A + Drug B

Antagonism

Name the four mechanisms of Antagonistic drug-drug interactions.

- Chemical Antagonism - Physiological Antagonism - Pharmacokinetic Antagonism - Receptor Antagonism

Chemical Antagonism

The drugs will react to each other causing inactivation of one or the other. Can occur in-vitro or in-vivo

Physiological Antagonism

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

Receptor Antagonism

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

Pharmacokinetic Antagonism

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

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

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

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

Drugs can compete with each other for binding sites on plasma proteins. Example: Phenylbutazone and warfarin

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

Enzyme inducers and enzyme inhibitors

What are some examples of enzyme inducers?

- Phenobarbital - Phenylbutazone - Rifampin - Griseofulvin - Kale

What are some examples of enzyme inhibitors?

- Chloramphenicol - Cimetidine - Ketaconazole - Grapefruit

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

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

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

Increases

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

Weak Acids

Factors related to the Environment:

- Temperature - Oxygen - Humidity - Light - Contact with surface

Give an example of how temperature can affect a drug.

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

Give an example of how oxygen can affect a drug.

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

Give an example of how humidity can affect a drug.

Amoxicillin once reconstituted into solution should be discarded after 14 days

Give an example of how light can affect a drug.

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

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

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