Excretion of drugs in the urine, bile, expired air and milk
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- Created on: 18-04-19 19:45
What kind of drugs are excreted by expired air?
Drugs with high vapour pressure (e.g. halothane).
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What kind of drugs are excreted in urine?
Water-soluble drugs/metabolites with low molecular weight (<350).
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What kind of drugs are excreted in bile?
Water-soluble drugs with high molecular weight (>350).
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What kind of drugs are excreted in sebum/sweat?
Very minor - e.g. tetracycline in sebum (acne).
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What are most drugs present in maternal blood detectable in?
Breast milk - usually no problem.
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What classes of drugs are there problems with when detected in breast milk + why?
Antithyroid drugs - cause thyroid suppression in infant. Sulphonamides - haemolytic anaemia. Anticoagulants - coagulation problems. ACEi - profound hypotension.
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What is the purpose of the hepatic metabolism of drugs?
Make them more water soluble.
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What are the characteristics of drugs excreted in bile?
Active transport process for highly-polar compounds of molecular weight >350.
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Generally, excretion in bile is a minor route for...
unmetabolised drugs.
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What may excretion in bile be a major route for?
Drug metabolites (e.g. glucuronides).
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What may excretion in bile serve as an alternative route for in patients with renal impairment?
Excretion of polar drugs.
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What is there the possibility of occurring in drugs that are excreted in bile?
Enterohepatic recirculation.
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What is enterohepatic recirculation?
Liver actively metabolising drug, excreted in bile, enters GI tract and then some is reabsorbed back to the liver - cyclic.
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What are the possible consequences of enterohepatic recirculation?
Prolongation of drug action - e.g. ezetimibe. Localisation of drug action - e.g. loperamide, budesonide.
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Where is loperamide localised to due to enterohepatic recirculation? + what is a benefit of this?
GI tract. Limits systemic effects when localised.
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In terms of excretion in urine, what type of drugs are renally excreted and what type follows the hepatic route?
Smaller, water soluble drugs are renally excreted. Larger and lipophilic drugs follow the hepatic route.
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Give some examples of some drugs that are excreted in urine and are renally excreted as a major route of their termination of action.
Aminoglycosides, some cephalosporins, some pencillins, methotrexate, digoxin and lithium.
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Why does the regimen of aminoglycosides have to be altered in renal dysfunction?
Have much longer half life in renal dysfunction.
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What are the pharmacokinetics of lithium governed by?
Electrolyte balance in body and renal function.
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What are the 3 stages in the renal handling of drugs?
Glomerular filtration, active secretion, passive reabsorption.
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All ......... drug and ......... are freely filtered in glomerular filtration.
unbound, metabolites
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Why does protein-bound drugs not being filtered not impede excretion?
Because binding is weak and readily reversible.
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What does extensive protein binding limit?
Amount of drug that can be filtered.
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What are there separate mechanisms for in active secretion?
Acids and bases.
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What is a key drug interaction here at the level of the WA transporter?
Methotrexate and aspirin. Aspirin competes with methotrexate for excretion so plasma levels of methotrexate rise (toxicity).
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What does the tubule behave like?
A typical lipid barrier.
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What is reabsorption dependent on in the renal handling of drugs?
pH, pKa and lipid solubility.
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At what pHs are acidic and basic drugs in the ionised form respectively?
Acid in ionised form at alkaline pH. Basic in ionised form at acid pH.
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What does a high urine flow rate increase the conc. gradient for?
Reabsorption.
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What may you need to do for drugs whose action is terminated by urinary excretion in patients with renal impairment?
Reduce dose. (Inherent toxicity and therapeutic index also important).
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What is sometimes used in place of eGFR when determining drug dosage in renal failure?
Creatinine clearance or serum creatinine.
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Give an example of a drug that may cause nephrotoxicity and one which may cause cardio toxicity.
Aminoglycosides - nephrotoxicity. Digoxin - cardiotoxicity.
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What else does this problem of dosage in renal failure arise with?
Drugs metabolised to active metabolites normally excreted in urine.
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How much digoxin is renally cleared?
2/3.
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What does digoxin enter if renally impaired?
Toxic levels.
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How is digoxin brought back within the safe therapeutic window in renal impairment?
Reduced dosage.
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What happens to creatinine levels in renal impairment?
They rise.
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What age group is renal function inefficient in? + coupled with what?
Newborn infants. Coupled with inefficient drug metabolism.
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By what age does renal function mature by?
Age 2 years.
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Between what ages does renal function plateau at?
20 - 30 years.
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After this plateau, at what rate does renal function decline?
1-2% per year.
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By 80 years old, renal function is only ......% of that of a young adult.
50%.
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What does this mean you need to consider at the extremes of age?
Dose reduction.
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What are some alternative approaches to use in renal impairment?
Choose short acting agents (e.g. tolbutamide as a choice of sulphonylurea). Increase the dosage interval (e.g. gentamicin). Choose non-really excreted alternatives (e.g. amlodipine in hypertension, gliclazide in type II diabetes).
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Why are short acting agents an alternative approach in renal impairment?
Shorter half life so less likely to accumulate.
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Why is increasing the dosage interval an alternative approach in renal impairment?
Spreading out doses ensures get sub therapeutic level for period of time.
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Why is amlodipine used for hypertension in patients who are renally impaired?
Because its more dependent on hepatic clearance.
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Give an example of a drug that MUST be AVOIDED in renal impairment.
Metformin.
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What is metformin usually first line for?
Type II diabetes.
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Why must metformin be avoided in renal impairment? + what can be used instead?
Potentially toxic. Choose drug like gliclazide or tolbutamide instead.
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Why may some drugs become ineffective in renal impairment? + example.
Some drugs require renal excretion to act so may become ineffective in renal impairment - e.g. thiazide diuretics.
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What, in terms of pharmacokinetics, is not usually affected in renal impairment?
Loading doses. (Give normal loading dose to get right conc. then spread out dose interval for subsequent doses).
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What may drug excretion/accumulation be altered in by drug permeability?
Periotneal dialysis or haemodialysis - consult specialist advice.
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Why may dialysis affect drug excretion/accumulation?
Membranes are different from kidneys in terms of whether drugs are excreted or reabsorbed.
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What is a poor guide for prescribing in hepatic impairment? + why?
LFTs because they can't predict hepatic clearance.
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What are some of the considerations when prescribing in hepatic impairment?
Hepatic clearance, protein binding, sodium and fluid retention, effects on coagulation (INR may be increased), gastric effects, CNS effects, sedation.
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What will drugs which are sodium retaining worsen in hepatic impairment?
Ascites.
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What may NSAIDs pose a greater risk of in hepatic impairment?
Gastric bleeding.
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What drugs should be avoided in breast feeding women?
Anticancer drugs, amiodarone, lithium, iodine containing radiocontrast media, tetracyclines (also avoid tetracyclines in pregnancy and up to age 14).
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Many drugs, especially what, are eliminated by renal excretion?
Antibiotics.
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Other cards in this set
Card 2
Front
What kind of drugs are excreted in urine?
Back
Water-soluble drugs/metabolites with low molecular weight (<350).
Card 3
Front
What kind of drugs are excreted in bile?
Back
Card 4
Front
What kind of drugs are excreted in sebum/sweat?
Back
Card 5
Front
What are most drugs present in maternal blood detectable in?
Back
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