Skip to document
Welcome to StudocuSign in to access the best study resources
Guest user
0followers
HomeMy LibraryAsk AI
  • You don't have any recent items yet.
My Library
  • You don't have any modules yet.
  • You don't have any books yet.
  • You don't have any Studylists yet.

Lecture 4 Notes (Drug Metabolism and Excretion)

Lecture 4 Notes (Drug Metabolism and Excretion)
Module

Pharmacology And Toxicology

81 Documents
Students shared 81 documents in this course
Academic year: 2020/2021
Uploaded by:
Anonymous Student
This document has been uploaded by a student, just like you, who decided to remain anonymous.
Royal Holloway, University of London

Comments

Please sign in or register to post comments.

Students also viewed

Related documents

Preview text

Pharmacology and Toxicology

Lecture 4 Notes: Drug Metabolism and Excretion

Drug Excretion

 Drug excretion is defined as the removal of drugs/drug metabolites externally from the body.  Most drugs are biotransformed (inactivated) in the liver and are then excreted by the kidneys.  Some drugs can also be excreted by other routes including: (a) Sweat (gland) (b) Saliva (gland) (c) Milk (gland) (d) Exhaled air (lungs) (e) Tears (gland) (f) Faeces (intestine) (g) Bile (gland)  The kidney is the main route of drug excretion. The nephrons/renal cells are mostly located within the renal cortex. These receive a small blood supply from the renal artery which it then filters. The filtrate is collected and transformed into urine, collected in the renal pelvis and then transported from the ureter into storage in the bladder.  The kidneys receive relatively high blood flow from the renal artery which is needed for the metabolism and removal of drugs from the body.  The kidney nephron is a tube-shaped cell with a glomerular capsule. The capsule surrounds a small sphere- shaped portion of the renal artery known as the glomerulus. The glomerulus has many pores in the arteriole and acts as a sieve to filter out substances from the blood. These substances are removed and enter the glomerulus before being collected as urine after passing through the tubular structure of the nephron.  Firstly, filtration by the glomerulus sieves out any molecules/ions in the blood below a certain Mw into the glomerular structure. Absorption (specific molecules within the filtrate are reabsorbed back into the blood) and secretion (some molecules are forced out of the blood) is then carried out by the proximal tubule. An osmotic gradient is generated in the loop of Henle which allows for further

reabsorption and secretion in the distal tubule. Finally, water uptake is regulated by the collecting ducts.  Kidney excretion is dependent on three processes: (a) Glomerular filtration (via the glomerulus) (b) Tubular secretion (transporters force drugs out of the blood and through the tubules of the nephron from the proximal tubule) (c) Tubular reabsorption (prevents dehydration, reabsorption of some drugs, occurs via the distal tubule)  Glomerular filtration is a passive process (does not require a large amount of energy). It is a first-pass mechanism which removes about 20% of the drugs from the blood into the glomerular filtrate. Filtration is permeable to molecules with a Mw less than 2000kDa so larger molecules (e. plasma albumin, drugs bound to proteins such as warfarin) are retained in the blood. Drug concentration in the filtrate is similar to that in the blood plasma because it is a passive process.  The glomerular filtration rate (GFR) in a healthy individual is about 110-130 ml/min. Clinically, creatinine clearance in urine is used to measure GFR.  Tubular secretion is a highly efficient (clears most drugs) process which occurs after glomerular filtration when plasma enters the peritubular capillaries. Around 80% of plasma flow enters the peritubular capillaries. Tubular secretion is an active process (i. transfers drugs against their electrochemical gradient) in the proximal tubule of the nephron. Two non-selective carriers (one for acidic compounds, another for organic bases) are involved in this process. This process is able to clear plasma-protein bound drugs into the filtrate.  This process is the most effective drug clearing mechanism in the kidneys due to the non- specific carrier systems which transport molecules into the tubular lumen. For example, penicillin is around 80% protein-bound in the blood, thus is poorly cleared by glomerular filtration, but it is almost completely removed from the blood by proximal tubular secretion.  Competition between drugs for the carriers (e. if two acidic drugs are administered) can occur and influence the duration of drug action. Thus, in the 1940s a high concentration of probenecid was used to competitively compete for the carriers in the kidneys to prolong the action of penicillin (very expensive and limited supply at the time) by retarding its excretion. Competition for carriers may lead to potential drug interactions.  The clearance rate of tubular secretion is much faster than that of glomerular filtration: about 650 ml/min. Clinically, p-aminohippuric acid (PAH) has been used to measure the rate of tubular clearance.

drug concentration to decline by 50%. Clearance depends on how long a drug is handled by filtration, active secretion, and passive diffusion.  The half-life of various drugs varies quite dramatically. For example, phenobarbital has a very long half-life because it is very lipid soluble and therefore can bind to fat, which thus acts as a storage point for this drug from which it is released very slowly. Half-life of a drug will influence the dose that is prescribed.

Was this document helpful?

Lecture 4 Notes (Drug Metabolism and Excretion)

Module: Pharmacology And Toxicology

81 Documents
Students shared 81 documents in this course

University: Royal Holloway, University of London

Was this document helpful?
Pharmacology and Toxicology
Lecture 4 Notes: Drug Metabolism and Excretion
Drug Excretion
Drug excretion is defined as the removal of drugs/drug metabolites externally from the body.
Most drugs are biotransformed (inactivated) in the liver and are then excreted by the
kidneys.
Some drugs can also be excreted by other routes including:
(a) Sweat (gland)
(b) Saliva (gland)
(c) Milk (gland)
(d) Exhaled air (lungs)
(e) Tears (gland)
(f) Faeces (intestine)
(g) Bile (gland)
The kidney is the main route of drug excretion. The
nephrons/renal cells are mostly located within the
renal cortex. These receive a small blood supply
from the renal artery which it then filters. The
filtrate is collected and transformed into urine,
collected in the renal pelvis and then transported
from the ureter into storage in the bladder.
The kidneys receive relatively high blood flow from
the renal artery which is needed for the metabolism
and
removal of drugs from the body.
The kidney nephron is a tube-shaped cell with a
glomerular capsule. The capsule surrounds a small
sphere- shaped portion of the renal artery
known as the glomerulus. The glomerulus has
many pores in the arteriole and acts as a sieve
to filter out substances from the blood. These
substances
are
removed and enter the glomerulus before being
collected as urine after passing through the tubular
structure of the nephron.
Firstly, filtration by the glomerulus sieves out any
molecules/ions in the blood below a certain Mw
into the glomerular structure. Absorption (specific
molecules within the filtrate are reabsorbed back
into the blood) and secretion (some molecules are
forced out of the blood) is then carried out by the
proximal tubule. An osmotic gradient is generated in
the loop of Henle which allows for further

Students also viewed

Related documents