adverse drug reactions 2 Flashcards
(45 cards)
most clinically significant ADRs are due to what?
Most clinically significant ADRs are due to altered drug disposition in the target species !!
what species considerations should we take into account when administering a drug
Species differences….
o Makes extrapolating dosage regimens across species challenging
- GI tract
- Body composition
- Blood volume
> Cat (~70 mL/kg), Dog (~90 mL/kg)
Drug metabolism……
o Phase I reactions (oxidation, reduction, hydrolysis)
o Phase II reactions (conjugation)
- Glucuronide
- Glutathione
- Sulfate
- Acetyl group
- Amino acids
o Metabolism of some drugs produces toxic metabolites
- Acetaminophen in cats
what age factors should we take into account regarding dose-dependent ADRs? geriatrics vs neonates
In geriatrics:
- diminished organ function
-altered body composition (more fat, less water)
In neonates:
-overall increased bioavailability
-larger Vd
-slower elimination
Drugs capable of organ toxicity more likely to do so if what exists?
organ disease or significantly reduced organ function exists
Elderly patients with significant reduction in organ function and/or suffering from organ disease are more likely to have a problem with what?
drug disposition changes (PKs)
In relation to drug therapy, most profound changes in drug disposition are found with what?
decline in renal function
what kidney issues are related to age?
-Functioning nephron mass declines with age
-Chronic renal failure is common amongst aging individuals
why are the kidneys highly vulnerable to ADRs?
- Kidneys receive ~20-25% of the cardiac output
- Kidneys concentrate drugs and toxicants
- Kidneys have high metabolic activity
what part of the kidney is more commonly damaged and why?
Proximal tubule damage is more common due to high renal cortex blood flow
chronic renal failure is associated with what issues related to drugs?
-Reduced clearance of drugs by the kidney
- Uremia can reduce protein binding and hepatic metabolism some drugs
- Renal protein loss and dehydration affecting drug distribution
what should we do when choosing drugs if CRF is present?
Avoid the kidney if possible, when CRF is present
- Choose drugs not eliminated by the kidney
- Choose drugs that at not toxic to the kidney
- Use TDM and dosage adjustments when possible
Drugs capable of renal ADRs
Aminoglycosides (gentamicin, amikacin)
- NSAIDs
Primary or compensatory cardiovascular disturbances lead to…..
- Renal and sodium retention
-increased sympathetic nervous system output and blood redistribution
what effects on drug deposition does cardiovascular disease have?
Effects on drug disposition are difficult to predict
what drug administration changes should we make if a patient has cardiovascular disease?
-Critical drugs should be given IV
-Potentially toxic drugs given IV slowly
-TDM and dosage adjustments when possible
why is the liver highly vulnerable to ADRs?
q Liver also receives a high cardiac output %
q Liver is the “portal of entry” of most drugs
q Liver is the major site of metabolite formation
q Liver has very high metabolic activity
possible consequences of liver disease:
q Reduced enzyme function
q Increased fraction of plasma unbound drug
> Hypoalbumemia, bilirubinemia
q Reduced hepatic blood flow
reactive metabolites can cause liver related ADRs in this way:
hepatocellular injury
what changes in drug disposition can we see in patients with hepatic disease? how much liver disease do we need to see an ADR?
-it is more difficult to predict changes in drug disposition in patients with hepatic disease.
-Drugs metabolized and inactivated by the liver may achieve higher plasma levels with reduced hepatic function.
-Prodrugs requiring hepatic activation may see reduced plasma drug levels and therapeutic failure. –Generally significant liver disease or decline in function needs to be present before clinically relevant changes in drug disposition and risks of ADRs occur.
how can we avoid ADRs in patients with liver disease?
o Avoid the liver if possible, when significant liver disease is present
o Choose drugs eliminated primarily by extra-hepatic mechanisms if possible
o Use TDM and dosage adjustments when possible
drugs capable of hepatic ADRs:
*Corticosteroids (prednisolone, dexamethasone)
*Anticonvulsants (phenobarbital, primidone)
-Diazepam
-Carprofen
-Acetaminophen
what is a drug interaction?
change in the magnitude or duration of a pharmacologic effect of a drug due to the presence of another drug, food or environment factor
when can a drug interaction occur?
before or after the drug is absorbed by the host
the incidence of drug interactions increases with
number of drugs; polypharmacy
duration of drug use
