Pharmacokinetics 3 Flashcards
Inhibition of Microsomal Enzymes Outline
2 drugs compete for metabolism of the same enzyme. Eg theophylline is admined at same as macrolide antibiotic erythromycin, resulting in cardiac arrythmias and seizures
Impacts of Grapefruit on Metabolism Outline
Inhibits Cytochrome P450 enzyme 3A4, impacting 1st pass metabolism. Increases serum conc of most drugs causing more potent effects.
Examples of increased drug conc in blood result
benzodiazepine = excessive sedation, HGM-CoA result in statins (muscles),
Microsomal Enzymes Induction Outline
Result of changes in nucleic acid transcription and translational and postranslational. Egs ethanol and omeprozol. Decreases serum drug conc = decreasing toxicity
Instances where Enzyme Induction Increases Toxicity
Phase 1 metabolism of certain substances (eg paracetamol) has toxic metabolites. Some drugs increase their own metabolism. Drug conc has positive feedback on it’s enzyme metabolism (kinetics aren’t linear. Double dosage won’t double blood serum con).
Half Life Def
Time taken for a 50% reduction is serum drug conc. Independent of initial drug conc (1st order kinetics)
Extraction Ratio Def
The % drug taken up by the liver in 1st pass metabolism (removed from blood)
Hepatic Blood Flow Outline
The volume (litres) of blood passing through liver per minute
Clearance Def
Volume of drug cleared effectively by liver per unit time
Max Bioavailability Def
% of drug remaining in serum after 1st pass metabolism
Examples of drugs with low max Bioavailability
Doxepin, morphine and Naloxone
Routes of Excretion (in order if importance)
Renal, faeces, expired air, saliva and breast milk
Renal Filtration Outline
Bowman’s Capsule, caused by pressure difference between afferent and efferent arterioles. 20% of plasma is filtered. Most drugs aren’t filtered as they are protein bound (too big)
Renal Active Secretion Outline
Loop of Henlee. Uses energy to form concentration gradients . Contains transport mechanisms for proteins and glucose. Allows for movement of ions aswell. Saturable
Reabsorption Outline
Distill convoluted tubule and collecting duct.
What is the consequence of urne being more acidic then intestine
More acidic substances are secreted the reabsorbed as a larger quantity of it is ionised (impermeable)
Relationship between Glomerular Filtration Rate (GFR) and active secretion
Increased clearance then GFR = active secretion
Relationship between GFR and reabsorption
Clearance is lower then GFR = extensive reabsorption
What is measured to approximate GFR
Creatine clearance. It’s filtered by kidneys and has almost no active secretion or reabsorption . This makes it very close to GFR value
Cockrofft Gault Equation
Male: ((1.23)(140-age)(weight in kg))/ serum creatine. Female: ((1.04)(140-age)(weight in kg))/serum ceratine
Exception to Cockroft Gault
Obese, muscle wasting, ascietes and oedematus patients
Drug administration in anuric(renal impaired people)
Drug dose is adjustable for some drugs
Biliary Excretion Outline
Filter lipid soluble drugs and get reabsorbed with water (not efficent). Acids and bases have excretion mechanism. Only works if molecular weight is high enough
Enterohepatic Circulation
liver, conjugates in bile, conjugates in small intestines, free in colon and free in circulation
Pulmonary Excretion Outline
Volatile (gaseous molecules) via lungs and breath. Especially anesthetics
Salivary and Milk Secretion Outline
Passive diffusion. Conc in milk reflects conc in blood. Conc in sweat depends in sweat plasma coefficent
Why are saliva samples taken
Non-invasive. Reflect free conc in plasma
