Drug Excretion Total Session Time: 120 minutes
Session 4: Drug Excretion
Total Session Time: 120 minutes
Prerequisites
None
Learning Tasks
By the end of this session students are expected to be able to:
Describe routes of drug elimination
Describe factors affecting renal drug excretion
Calculate clearance
Describe clinical importance of elimination half life
Resources Needed:
Flip charts, marker pens, and masking tape
Black/white board and chalk/whiteboard markers
Computer and LCD Projector
SESSION OVERVIEW
Step
Time
Activity/
Content
Step
Time
Activity/
Content
Step
Time
Method
Content
Method
Method
1
1
05 minutes
05 minutes
Presentation
Introduction, Learning Tasks
Introduction, Learning Tasks
2
2
25 minutes
25 minutes
Presentation/
Routes of Drug Excretion
Routes of Drug Excretion
2
2
25 minutes
25 minutes
Buzzing
Routes of Drug Excretion
Routes of Drug Excretion
Buzzing
3
3
40 minutes
40 minutes
Presentation/
Factors Affecting Renal Drug Excretion
Factors Affecting Renal Drug Excretion
3
3
40 minutes
40 minutes
brainstorming
Factors Affecting Renal Drug Excretion
Factors Affecting Renal Drug Excretion
brainstorming
4
4
20 minutes
20 minutes
Presentation
Calculation of Clearance
Calculation of Clearance
5
5
20 minutes
20 minutes
Presentation/
Description of Clinical Importance of
Description of Clinical Importance of
5
5
20 minutes
20 minutes
Brainstorming
Elimination Half Life
Elimination Half Life
Brainstorming
Elimination Half Life
Elimination Half Life
6
6
05 minutes
05 minutes
Presentation
Key Points
Key Points
7
7
05 minutes
05 minutes
Presentation
Evaluation
Evaluation
PST 05104 Pharmacology & Therapeutics 26 NTA Level 5 Semester 1 Facilitator Guide
SESSION CONTENTS
STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)
READ or ASK students to read the learning tasks and clarify
ASK students if they have any questions before continuing.
STEP 2: Routes of Drug Elimination (25 minutes)
Activity: Buzzing (5 minutes)
ASK students to pair up and buzz on the following question for 2 minutes
What routes are involved in the excretion of drugs?
ALLOW few pairs to respond and let other pairs add on points not mentioned
WRITE their response on the flip chart/board
CLARIFY and SUMMARIZE by using the content below
Removal of a drug from the body may occur via a number of routes, the most important being through the kidney into the urine.
Other routes include o the bile,
o intestine, o sweat
o lung,
o Milk in breastfeeding mothers.
Renal excretion:
Most drugs are renally cleared and differ greatly in the rate at which they are excreted by the kidney
Some drugs are almost completely cleared renally such as penicillin and others are slowly cleared, eg diazepam
Three fundamental processes account for renal drug excretion: o glomerular filtration
o active tubular secretion
o passive diffusion across tubular epithelium
Excretion via Breast Milk
Breast milk is a quantitatively relatively minor route of drug excretion.
PST 05104 Pharmacology & Therapeutics 27 NTA Level 5 Semester 1 Facilitator Guide
Nevertheless, it is clinically important for breastfeeding mothers and their infants.
The baby will ingest drugs excreted in the breast milk.
Moreover, breast milk has a lower pH than plasma.
Accordingly, basic drugs will be concentrated in the breast milk through the phenomenon of ion (pH) trapping.
A number of drugs can reach clinically significant concentrations in the breast milk and thereby affect nursing babies.
Pulmonary excretion
Is important for gaseous lipophilic substances.
The gaseous general anaesthetics are the most common example.
Drug diffuses from the plasma into the alveolar space and is excreted during expiration.
Biliary Excretion:
Biliary excretion involves active secretion of drug molecules or their metabolites from hepatocytes into the bile.
The bile then transports the drugs to the gut, where the drugs are excreted.
The transport process is similar to those described for renal tubular secretion.
The efficiency of biliary excretion is quite variable.
Enterohepatic cycling.
Although many drugs may reach the gut through Biliary Excretion, deconjugating enzymes in the gut and the gut pH causes many drugs to assume nonpolar lipophilic forms that then are promptly reabsorbed by diffusion into the plasma.
Drugs that undergo extensive enterohepatic cycling generally have long durations of action e.g Rifampicin
STEP 3: Factors Affecting Renal Drug Excretion (40 Minutes)
Activity: Brainstorming (5 minutes)
Ask students to brainstorm on the following question:
What are the factors affecting renal drug clearance?
ALLOW few students to respond
WRITE their responses on the flip chart/ board
CLARIFY and SUMMARISE by using the content below
PST 05104 Pharmacology & Therapeutics 28 NTA Level 5 Semester 1 Facilitator Guide
Renal excretion of a drug is affected by the following factors depending on the mechanism:
Glomerular filtration:
Molecular weight of a drug
Glomerular capillaries allow drug molecules of molecular weight below about 20 000 to pass into the glomerular filtrate.
Plasma albumin (molecular weight approximately 68 000) is almost completely impermeant, but most drugs-with the exception of macromolecules such as heparin or biological products can cross the barrier freely.
Protein binding
If a drug binds to plasma albumin, only free drug is filtered.
If, like warfarin, a drug is approximately 98% bound to albumin, the concentration in the filtrate is only 2% of that in plasma, and clearance by filtration is correspondingly reduced.
Disease or age
Glomerular filtration rate decreases approximately 1% per year and may be significantly compromised in elderly patients.
The decline in glomerular filtration rate is accelerated by disease states such as diabetes.
For drugs that are eliminated by glomerular filtration, dosages are often adjusted based on the patient‘s glomerular filtration rate.
Tubular secretion
Secretory mechanisms in the renal tubules actively transport endogenous substances and drug molecules from the plasma in peritubular capillaries to the tubular lumen.
Although quite diverse in some characteristics, the tubular transporters can be classified into two major groups: the organic anion transporter (OAT) and the organic cation transporter (OCT) families.
Tubular transporters exhibit saturability.
o Transporters reach a maximum rate of excretion, after which further increases in drug concentration do not cause further increases in secretion.
Tubular secretion is especially important for drugs that are highly plasma protein bound, because these drugs are not excreted effectively by glomerular filtration.
Important in delivering some drugs, such as diuretics, to their site of action in the renal tubule.
Is not affected by the degree to which a drug binds to plasma proteins.
Tubular secretion can be manipulated clinically via the use of inhibitors to extend the duration of action and increase the plasma concentration of drugs that are rapidly excreted by tubular secretion.
PST 05104 Pharmacology & Therapeutics 29 NTA Level 5 Semester 1 Facilitator Guide
For example, the drug probenecid blocks the OAT transporter responsible for secretion of some penicillin and cephalosporin antibiotics into the renal tubule.
Probenecid can be prescribed along with antibiotics in the penicillin and cephalosporin families to prolong their duration of action.
Reduced in neonates, infants, and the elderly.
Affected by genetic polymorphisms in the OAT and OCT family of transporters.
Tubular reabsorption
Once in the renal tubule, the nonionized form of the drug is able to diffuse across the tubular membrane and re-enter the plasma.
Water is reabsorbed along the renal tubule the tubular drug concentration increases, providing a concentration gradient favouring drug reabsorption.
Manipulation of the pH of the tubular fluid can be used to enhance or inhibit tubular reabsorption according to the Henderson-Hasselbalch relationship.
Acidification of urine can be used to decrease reabsorption of weak bases by increasing the proportion of drug in the ionized form.
Conversely, alkalinization of urine can be used to increase the renal excretion of acidic drugs because a greater proportion of the drug is in the ionized form.
STEP 4: Calculation of Clearance (20 Minute)
Activity: Brainstorming (5 minutes)
Ask students to brainstorm on the following question:
ALLOW few students to respond?
WRITE their responses on the flip chart/ board
CLARIFY and SUMMARISE by using the content below
Clearance (CL) is the volume of plasma containing the total amount of drug that is removed from the body in unit time
Clearance: volume of plasma cleared of drug per unit time.
Total Clearance is obtained by adding individual clearences depending on the route of elimination of that drug
PST 05104 Pharmacology & Therapeutics 30 NTA Level 5 Semester 1 Facilitator Guide
Therefore, for a drug that is cleared through kidneys, liver and lungs the total clearance is obtained as follows;
STEP 5: Clinical Importance of Elimination Half life (20minutes)
Half-life refers to the time required for the body to eliminate 50% of the drug.
Elimination Half-life of refer to time for plasma concentration to decrease by half.
Elimination half-life (t ½) can be used to predict how long it will take from the start of dosing to reach steady-state levels during multiple dosing or continuous intravenous (i.v.) infusion.
Also elimination half life help in determination of dosing frequency
The time to reach steady state is dependent only on t½ of a drug, i.e. 4-5 t½
o For example, drugs with a short half-life (2–4 hours) need to be administered frequently, whereas a drug with a long half-life (21–24 hours) requires less frequent dosing.
o For example, digoxin has a long half-life (36 hours) and requires once-daily dosing. o However, aspirin has a short half-life and requires frequent dosing.
o
Difficulty in excreting a drug increases the half-life and increases the risk of toxicity.
STEP 6: Key Points (5 minutes)
The kidney cannot excrete non-polar substances efficiently, since these diffuse back into blood, as the urine is concentrated.
Renal impairment reduces the elimination of drugs that depend on glomerular filtration
Passive reabsorption limits the efficiency with which the kidney eliminates drugs.
STEP7: Evaluation (5 minutes)
What are the factors affecting renal elimination?
What is the clinical application of elimination half-life?
What is the importance of acidifying or alkanizing urine?
PST 05104 Pharmacology & Therapeutics 31 NTA Level 5 Semester 1 Facilitator Guide
References
Katzung, B. G. (2018). Basic and clinical pharmacology. New York: Mcgraw Hill Education.
Santos, R. R., Rang, H. P., Dale, M. M., Ritter, J. M., & Flower, R. J. (2007). Rang & Dale Farmacologia. Rio de Janeiro: Elsevier.
Tripathi, K. (2018). Essentials of Medical Pharmacology. Place of publication not identified:
Jaypee Brothers Medical P.
Ministry of Health and Social Welfare. (2013). Standard Treatment Guidelines & National Essential Medicines List Tanzania Mainland (4th ed.). Dar es salaam, Tanzania government printers.
Sally S.R, Jeanne C.S. (2000). Introductory Clinical Pharmacology (6th ed) New York, Lippincott Williams and Wilkins.
School of Pharmaceutical sciences. (2011).Tanzania Pharmaceutical Handbook (2nd ed.).
Dar es Salaam, ARDHI University press.
PST 05104 Pharmacology & Therapeutics 32 NTA Level 5 Semester 1 Facilitator Guide
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