PHC5005 Chap.4 Renal Excretion and Dose Adjustment
Renal Excretion and Dose Adjustment
The last step in pharmacokinetics
Excretion is the physical process that removes a drug and its metabolites from the body for good, either unchanged or after metabolism. The kidney is the major route and the one the course examines in depth; bile and faeces, the lungs for gases and volatile liquids, and breast milk are the others.
Because excretory organs other than the lungs remove polar compounds far more efficiently than lipid-soluble ones, excretion depends on metabolism having done its work first. Renal excretion is also the step that sets how long many drugs act and how quickly they are cleared.
Filtration, reabsorption and secretion
The renal balance is filtration minus reabsorption plus secretion.
Glomerular filtration handles only free drug, since protein-bound drug is not filtered, and its efficiency is measured as the glomerular filtration rate, normally about 120 mL per minute. Tubular reabsorption is mainly passive: lipid-soluble and unionised molecules diffuse back into the blood.
Tubular secretion is active, uses carrier systems for organic anions and cations, and is the main excretory mechanism for drugs and their metabolites.
Because those carriers are non-specific, drugs compete for them, which is how probenecid prolongs the action of penicillin.
Ion trapping and urinary pH
A weak acid or base that crosses into tubular fluid can meet a pH at which it becomes ionised and cannot diffuse back.
That principle, ion trapping, is used in poisoning: alkalinising the urine increases excretion of weak acids and is widely used for barbiturate and salicylate overdose, whereas acidifying urine to clear weak bases is not practised clinically because acidosis can worsen outcomes.
What reduces renal excretion
The course names four factors: renal blood flow, urinary pH, age and disease.
Reduced perfusion from heart failure, haemorrhage, cardiogenic shock or NSAID use lowers excretion. Neonates have immature renal function and the elderly have declining function, so both need dose adjustment.
Kidney disease such as glomerulonephritis impairs clearance directly and lengthens half-lives.
From creatinine clearance to a dosing decision
Creatinine clearance estimates glomerular filtration and triggers action for drugs excreted mainly by the kidney: adjust when it falls below 60 mL per minute, modestly between 30 and 60 and substantially below 15, and monitor drug levels.
Two strategies are taught, keeping the dose while lengthening the interval, as with gentamicin, or keeping the interval while lowering the dose, as with digoxin. Drugs cleared mainly through bile, such as ceftriaxone and doxycycline, are the exception that needs no renal adjustment.
What this chapter covers
- 01
Routes of excretion and why polar compounds leave most easily
- 02
Glomerular filtration of free drug and the normal filtration rate
- 03
Passive tubular reabsorption and ion trapping in poisoning
- 04
Active tubular secretion and carrier competition
- 05
Renal blood flow, age and disease as limits on excretion
- 06
Creatinine clearance thresholds for dose adjustment
- 07
Interval extension against dose reduction in renal impairment
Worked example · free
Explaining a deliberate interaction at the kidney
- 2Identify the renal process involved and its mechanism.
- 2Explain how probenecid interferes with it.
- 1State the effect on penicillin.
Key terms
- Excretion
- The physical, irreversible removal of a drug and its metabolites from the body, unchanged or after metabolism.
- Glomerular Filtration Rate
- How much plasma the glomeruli filter each minute, normally about 120 mL, a measure of kidney filtering efficiency.
- Tubular Secretion
- Active, carrier-mediated transfer of drug from peritubular blood into the tubular lumen, the main renal route for drugs.
- Ion Trapping
- Retention of an ionised weak acid or base in a fluid whose pH prevents it diffusing back across the membrane.
- Creatinine Clearance
- The volume of plasma cleared of creatinine per unit time, used to estimate glomerular filtration rate.
- Renal Impairment
- Reduced kidney function that lengthens half-lives of renally cleared drugs and calls for dose adjustment.
Renal Excretion and Dose Adjustment FAQ
Why is protein-bound drug not filtered at the glomerulus?
Filtration passes water and small solutes but holds back plasma proteins, so drug attached to albumin stays in the blood. Only the free fraction enters the tubule, which is why heavy protein binding slows renal elimination and why a change in binding changes excretion.
How does alkalinising the urine help in salicylate poisoning?
Salicylate is a weak acid. In alkaline tubular fluid more of it is ionised, and the ionised form cannot diffuse back into the blood. It is trapped in the lumen and excreted, so raising urinary pH speeds removal of the poison.
Why do NSAIDs reduce the excretion of other drugs?
Drugs such as aspirin and ibuprofen inhibit prostaglandin production, and prostaglandins help maintain renal perfusion. Lower renal blood flow and filtration mean less drug is delivered to the kidney and excreted, which can raise levels of renally cleared companions.
At what creatinine clearance does dose adjustment begin?
For drugs excreted mainly by the kidney the course sets the threshold below 60 mL per minute, with minor adjustment between 30 and 60, major adjustment below 15, and monitoring of blood levels through therapeutic drug monitoring where appropriate.
Why keep the dose and extend the interval for gentamicin but reduce the dose for digoxin?
Both approaches lower the average dose rate to match the reduced clearance. The course pairs gentamicin with interval extension and digoxin with dose reduction at an unchanged interval, and expects each drug to be matched to its strategy when a renal adjustment is described.
Which drugs need no dose reduction in renal failure?
Drugs that leave the body mainly by other routes. The course names ceftriaxone and doxycycline, which are largely excreted into faeces through bile, as examples where renal function does not govern clearance.
Exam move
Draw the nephron once from memory with its three arrows, filtration in, secretion in, reabsorption out, and write beside each arrow what increases it and one drug example. Every excretion question in the course, from poisoning to probenecid to renal dosing, is a question about one of those arrows.
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