Clinical pharmacology of older age Flashcards
Define pharmacokinetics
This is pharmacology concerned with the movement of drugs within the body (ADME)
- Absorption
- Disribution
- Metabolism
- Excretion
Define pharmacodynamics
Pharmacology concerned with the effects of drugs and the metabolism of their action (+adverse effects)
What are the 2 key points to know about absorption of drugs ?
- Acidic drugs require an acidic pH (<7.35) environment for absorption (e.g Phenytoin, Aspirin,Penicillins)
- Basic drugs require a basic (pH >7.35) environment for absorption e.g.Diazepam,morphine,pethidine
How can using a PPI affect the absorption of other drugs ?
It can cause decrease in HCl production which will in turn increase the pH of the stomach and ==> potentially affect the absorption of some drugs which require an acidic environment for absorption
How is the environment for absorption in elderly people different from in younger people ?
- Elderly people have a more basic environment so basic drugs will be absorbed more readily and potentially have a greater effect so care must be taken in this class of drugs
- Also there is decreased small bowel surface area for absorption in older people
In the elderly the increased gastric pH and decrease in small bowel surface area is not usually a problem, when can it become a problem?
- Previous GI surgery
- NG tube or PEG feed
- Transdermal patches and oedema
- Proportionally more of basic drugs absorbed
Appreciate these factors when considering the route of administration in elderly people:
- Liquid/syrup for dysphagia
- Can tablets be crushed for PEG or NG tube?
- Confused patients refusing tablets / Acute agitation
- NBM (nil by mouth) patients for surgery or investigations - need to see what the can manage without, what they can take in the morning beforehand as cant just omit all medications
What are the 2 main proteins which bind to drugs and which class of drugs does which protein bind to ?
- Albumin (Basic) binds to acidic drugs
- Alpha-1 Acid Glycoprotein (acidic) binds to basic drugs
How is protein binding of drugs affected in older age ?
Elderly often low albumin but higher A-1 AG ==> acidic drugs can move more freely by diffusion and possibly have a greater effect
Define volume of distribution of a drug
The volume into which a drug appears to be distributed with a concentration equal to that of plasma
Simply put - amount of drug in body divided by plasma concentration
A higher Vd suggests more drug in the tissues and less drug in the plasma (opposite way for lower Vd)
Define half life of a drug
This is the time taken for the plasma concentration of a drug to fall by 50%
What happens to the Vd of lipophylic (like to bind to fat) drugs e.g.diazepam, anaesthetics in older people and why ?
The Vd increases i.e. more in the tissues (in this instance fat) due to the increased fat proportion in older people (think about the sarcopenia and muscle decrease in older people)
This results in a longer half life for these drugs in older people because its harder to remove drug from the tissues than the plasma
What happens to the body water of older people ?
There is a 10-15% decrease of body water - this results in a lower Vd of hydrophilic drugs e.g. lithium, digoxin (as less water for them to go into instead of the plasma)
For hydrophilic drugs as previously stated the Vd decreases so ==> there is a higher conc in the plasma so why does the half life of these drugs not decrease conversely in older people?
Because creatinine clearance (CrCL) decreases in older people
==> both Vd and CrCL decreases which means the half life is usually unchanged significantly in elderly people
How is hepatic metabolism affected in elderly people ?
- Reduced liver function due to decreased liver size, blood flow, and disease (e.g. CHF)
- First pass metabolism reduced (e.g. propranolol) In general
- Bio-transforming enzymes are reduced in the elderly
How do you calculate the theraputic index of a drug ?
Divide the maximum tolerated concentration by the minimum effective concentration (MTC/MEC)
