Dosage Adjustment - Pre Lecture Flashcards
What is the effects of cardiac failure on absorption?
Mucosal edema and reduced GI blood flow will alter absorption of some drugs
What is the effects of cardiac failure on distribution?
- Decreased tissue perfusion and altered fraction of drug distributed the between plasma and tissue compartment
- Usual dose can elevate plasma concentration to toxic
Quinidine or lidocaine
What is the effects of cardiac failure on elimination?
- Decreased hepatic perfusion accompanies reduced cardiac output
- Reduces renal elimination of drug from reduced filtration, increasing toxicity (ahminoglycosides and digoxin)
- High ER drugs (lidocaine) show limited perfusion limited clearance therefore increase concentrations at low cardiac output
- Decreased hepatic metabolic capacity by tissue hypoxia and cellular damage
What is the major route of elimination for parent drugs and metabolites?
Renal excretion
How does renal disease affect absorption?
- Urea is cleaved therefore gastric pH increases
- Ammonia and buffers are yielded
- Nephrotic syndrome
- Reduction of ferrous iron absorption and other drugs
What is nephrotic syndrome?
Resistance to oral diuretics and malabsorption of loo[ diuretics through the edematous intestine
How does renal disease affect distribution?
- Accumulation of acidic substances that compete with drug binding sites (albumin)
- PK of drugs are altered
What is the exception of drug PK changes due to renal disease?
Phenytoin, therapy is guided by plasma concnetration
Describe phenytoin properties during renal impairment?
Drug protein binding reduction by competition of accumulated molecules normally cleared by kidney (albumin)
How does renal disease affect metabolism?
CYP3A4 of phase 2 are reduced, phase 2 is less affected
How does renal disease affect excretion?
- Filtration and secretion fall into step
- Excretion is related to GFR
What is the main site of metabolism?
Liver
What is the solution to liver disease’s unpredictable effects on drug handling?
- Unsuccessful in determining the correlation between PK of drugs and liver function
- Close clinical monitoring is better
How does liver disease affect absorption?
- Portal hypertension and hypoalbuminia from mucosal edema
- anastomoses allow bypassing of first-metabolism increasing bioavailability
How does liver disease affect distribution?
Reduced albumin binding -> increased apparent Vd
