Factors Modifying Drug Disposition And Response Flashcards
What are some ways species differences can affect drugs.
Anatomical- ruminant or non rum. Physiological -carnivores acidic urine -herbivores alkaline urine Biochemical -drug metabolizing enzymes -- cats are deficient in glucoronyl transferase.
What causes cardiovascular collapse in boxers?
Phenothiazines
Acepromazine
Collies are sensitive to _______, which can cause CNS depression, ataxia, tremor, salvation and coma.
Ivermectin
This drug, when given to Australian terriers caused no sedation/analgesia but does cause salivation, tachycardia, muscle tremors and convulsions.
Droperidol/fentanyl
Genetic factors can cause unwanted drug effects.
ABCB1 (formerly MDR1) gene deletion affects whom and how?
Collies- this gene normal encodes p-glycoprotein.
Mutation or deletion means less p-go produced
35%homozygous in North America
Genetic factors can cause unwanted drug effects.
C-15A SNP, what be that?
Mu-opioid receptor gene
OPRM1)- dysphoria (freaking out
How does gender/gestation affect drug stuff.
Women are complicated, and then they get pregnant and men should run and buy chocolate. But really, know what you can’t give during gestation.
Body condition score
When in doubt lower the dose, large amounts of fat can bind lipophilic drugs.
Young animal drug effects
- decreased ME
- inc. BBB permeability
- dec. Plasma protein binding
- inc. Total body water
- susceptible to adverse effects.
Tetracyclines young animals and go!
Yellowing of teeth
Fluroquinolones young animals!
Cartilage damage
Glucocorticoids young animals
Premature closure of epiphysis
When does drug clearance reach adult capacity?
Not typically until 12 weeks of age.
Factors related to old animals.
Dec. M&E Dec. CO & hepatic blood flow Chronic diseases Changes in body composition -dec. Lean body mass -inc. Body fat -dec. Total body water. -dec plasma proteins
Liver disease drug effects
Decreased drug metabolism
Renal disease causes
Decreased drug excretion
Congestive heart failure causes
Decreases drug distribution and excretion
Calm animals need what kind of dosage on CNS depressants.
Lower doses than aggressive or excited animals
What is idiosyncratic drug reaction?
Unpredictable, abnormal, non dose dependent, requires drug withdrawal, caused by reactive metabolites and they can occur on first exposure!
Liver damage by griseofulvin in some cats
What are the three broad factors that relate to veterinary pharmacology
Factors related to
The animal
The drug
The environment
Hypersensitivity to drugs
Prior exposure is necessary
Cross sensitivity
Type 1 hypersensitivity( allergy and or anaphylaxis)
What drugs are antigens?
Blood, plasma, protein hormones.
What drugs are haptens
Penicillins sulfonamides aspirin
Drugs that are too small to directly bind to the antibody.
What is tolerance
Gradual decrease in responsiveness to chronic drug administration.
What is tachyphylaxis
Acute acquired tolerance
Ephedrine
What are some pharmacokinetic mechanisms
Altered absorption of the drug
Enzyme induction (increased metabolism of the drug)
Increased active excretion of the drug
What are some pharmacodynamic mechanisms?
Desensitization (receptor down-regulation)
Loss of receptor
Exhaustion of mediator
Route of administration affects the drug. How?
IV- fastest onset short duration
PO- slow onset longer duration
Lidocaine- IV- antiarrhythmic
Locally- local anesthetic
Food and drugs
Absorption rate is typically slower with food/fluid
CNS stimulants, when do you give them?
More effective during the day
Circadian effects
CNS depressants when do you give them
More effective at night
Circadian
What is cumulative
Rate of elimination is slower than absorption
Digitalis
Phenylbutazone
Thiopental
Beneficial drug on drug effects
Trimethoprim and sulfonamide
ACE inhibitor and thiazides diuretic
Detrimental DRug on drug reactions
Aminoglycoside and muscle relaxant (and a lot of others as well)
Chloramphenicol and phenobarbital
What is summation
Drug A+ Drug B= A+B
What is synergism
Drug A + Drug B > A+B
What is antagonism
Drug A+ Drug B
What is chemical antagonism
Drugs react chemically to inactivate each other.
Tetracyclines and calcium
Physiological antagonism
Drugs that work in different ways and have opposing effects that cancel each other out.
Pharmacokinetic antagonism
One drug reduces the concentration of the other at its site of action by interfering with its ADME process.
Receptor antagonism
One drug binds to a receptor and prevents the other drug from having its normal activity at that receptor.
What is a pharmacokinetic drug on drug reaction?
Absorption
- one drug can inhibit the absorption of another drug (SQ lidocaine and epi)
- one drug can enhance the absorption of another (topical DMSO & griseofulvin)
Distribution
-binding site competition on plasma protein (warfarin and phenylbutazone)
What are some enzyme inducers?
Phenobarbital, bute, rifampin, griseofulvin, kale
What are some enzyme inhibitors?
Chloramphenicol, cimetidine, ketoconazole, grapefruit
What are the factors modifying excretion?
Competition for carrier molecules (probenecid and penicillin)
Changes in urine pH
Acidic urine= inc excretion of weak bases
Alkaline urine= inc excretion of weak acids
What’s an example of temperature modifying drugs?
At 122oF the solubility of procaine increases in Pen G procaine preparations. Don’t leave in pickup on a hot day.
How does oxygen effect drugs?
Decreased ambient oxygen may worsen respiratory depression induced by pentobarbital.
Why is humidity important?
Reconstituted drugs have varying half lives due to humidity. Amoxicillin
Why is light important
Some drugs react to light
Why is important to know what the drug can bind to?
Some drugs bind to different surfaces.
