Pharmacology Lecture 2 Flashcards
Metabolism and Excretion
Define Clearance (Cl)
The volume of plasma completely cleared of drug per unit time.
What does Cp represent?
The concentration of drug plasma
Rate of Elimination equation
Rate of elimination = Cl x Cp
Where can metabolism occur in the body?
- The liver is the main organ for drug metabolism
- Metabolism also occurs in the gut, lungs, skin, blood and kidney
Describe the general process of metabolism?
Metabolism changes one chemical compound into another
What are the 2 phases of metabolism?
Phase 1: catalysed by cytochrome P450 enzymes. Often still chemically active.
Phase 2: Conjugation by adding a glutathione, methyl or acetyl group. More water soluble and easier to excrete. Less active or inactive.
What are hepatocytes?
Hepatocytes are the chief functional cells of the liver that contain enzymes essential for metabolism.
Define Metabolite
A drug metabolite is a byproduct of the body breaking down, or “metabolizing,” a drug into a different substance.
Define first pass metabolism
If a drug is extensively metabolised in the liver we say it undergoes first pass metabolism – Very little (active) drug may end up in the systemic circulation.
Pathway of absorption of oral drugs
GI Tract
Liver
Heart
Systematic Circulation
Name 2 routes that avoid first pass metabolism
Sublingual
Buccal
(Because blood supply from the mouth goes to the heart first - avoids the liver)
What are the 2 classes of tests for hepatic (liver) function in pracice?
Serum tests
Urine tests
What is LFT an abbrev for?
Liver Function Tests
Define excretion
The process by which waste products are removed from body.
Where can excretion occur in the body?
Predominantly by kidney via urine
Also via bile, sweat, faeces, breath, and tears.
Are all drugs metabolised before exrcretion?
No.
e.g. aminoglycoside antibiotics
Name the 3 processes by which the kidney excretes drugs.
- Glomerular filtration
- Tubular secretion
- Tubular reabsorption
Define/describe a nephron
A functional unit of the kidney, the structure that actually produces urine in the process of removing waste and excess substances from the blood. There are about 1,000,000 nephrons in each human kidney.
Describe Glomerular filtration
Small drugs pass easily from blood through glomeruli. Large drugs (e.g. Heparins and protein bound drugs) cannot pass through.
Describe Tubular Secretion
An active process against a chemical gradient. There are
2 Carrier transport systems; basic drugs (amiloride) and acidic drugs (furosemide)
Describe Tubular reabsorption
Transported back into the blood along with water to maintain fluid volume.
(Some of the small molecules will pass back into the blood stream)
Define renal clearance
The renal clearance of any substance is the volume of plasma containing that amount of the substance that is removed by the kidney in unit time
It is the amount of drug removed by kidney over specific time. Varies for different drugs.
Name a (estimated) measure of renal function
Creatinine clearance
or
E-GFR
State the Cockcroft and Gault equation used for calculating creatinine clearance.
CrCl (ml/min) = F x (140-age) (weight kg) / serum creatinine (micromol/L)
Where F = 1.23 (males) and (1.04 females)
NB that CC is an ESTIMATION of renal function.
What does E-GFR stand for and what is it for?
Estimated glomerular filtration rate
Another (better/more accurate) means of estimating renal function, and uses race.
What is the biliary system? What process is it a part of: Metabolism or excretion?
The biliary system consists of the organs and ducts (bile ducts, gallbladder, and associated structures) that are involved in the production and transportation of bile.
Excretion
Examples of some processes that can occur in Phase 1 of metabolism?
Oxidation
Hydrolysis
Reduction
Can drugs undergo Phase 2 only of metabolism (i.e. without phase 1)?
Yes
I don’t think Phase 2 and then Phase 1 can happen though
What is a pro-drug?
a biologically inactive compound which can be metabolized in the body to produce a drug.
What does hepatic function mean?
Liver function
What makes a drug more likely to just be excreted and not metabolised?
If it is highly soluble
What is creatinine?
Creatinine is a chemical waste product of creatine (normal breakdown product), released from muscle breakdown, and undergoes glomerular filtration. Creatinine is removed by the body entirely by the kidneys
What does renal function mean?
Kidney function
