Elimination Flashcards
What are the routes of drug elimination in the body?
Renal - most common Lung - volatile drugs/alcohol Bile - recirculation of drugs Intestine - excreted in faeces Secretions - sweat, salive and breast milk
What drugs can the kidney excrete?
Only free (Unbound) drug in plasma
Where in the kidneys are drugs filtered?
At the renal glomerulus (GFR 125 ml/min)
How do the kidneys eliminate drugs?
Through urine (Water Soluble)
Describe the process of elimination in the kidneys
1) Free drug enters the glomerular filtrate at Bowman’s capsule
2) Active secretion at proximal tubule
3) Passive reabsorption of lipid soluble drugs distal tubule
4) Excretion of water soluble drugs at the collecting tubule
Describe which drugs can be eliminate via the lungs
Inhaled drugs can be eliminated unchanged
– Gaseous general anaesthetics
– Small quantities of alcohol
Describe the process of biliary excretion of drugs
Enterohepatic recirculation – Hepatocytes transport some drugs into bile (active transport) – Drug circulates back to GIT in bile – Drug can be reabsorbed from GIT – Prolongs effect of drug – Drug can be eliminated in faeces
How are drugs eliminated via the intestines?
• Drugs can be excreted via the faeces
– Unabsorbed orally ingested drugs
– Biliary excreted metabolites that can’t be reabsorbed
• Increased speed of transit through the GIT will lead a greater level of elimination of orally administered drugs
How else can drugs be eliminated?
• Excretion of drugs via other routes is not important for elimination of drugs from the body
– Secretions can lead to a small reduction of highly lipid soluble drugs
– Saliva, Sweat, Tears, Seminal fluid, Breast milk
• Drugs secreted in breast milk can be passed
on to nursing infants
Define clearance of a drug
The clearance of a drug (CL) is the volume of plasma containing the total amount of drug that is removed from the body in unit time
CL = Renal plasma flow x Extraction ratio
a
Elimination Half-Life (t1/2)
• The time it takes the body to eliminate half
the dose of a drug
– Short t1/2 24 hours
• Some drugs do not follow this model as their
elimination can be saturated
What is the half life of a drug?
The half life is the time taken for a drug’s concetration to half
The half life of a drug is the same no matter what the dose.
Describe some of the problems affecting elimination
Impaired renal function (disease & Age)
– Reduced GFR can lead to slow removal
Impaired hepatic function
– Reduced metabolism of drugs
Body composition
– Increase in adipose mass
How and why does age affect drug elimination?
Less efficient on the very young and old
Two main reasons:
– Renal excretion rate
• neonate GFR = 0.2 x adult GFR
• 50y/o GFR = = 0.75 x adult GFR
• 75y/o GFR = = 0.5 x adult GFR
– Expression of metabolising enzymes
• Metabolic enzymes take 8 weeks to achieve adult levels
When do you use a loading dose?
In a situation where you need to rapidly achieve steady state
