3. Therapeutic concepts, drug toxicity Flashcards
(12 cards)
Therapeutic concepts:
- Therapeutic index
- Therapeutic window
- Selectivity-Specificity
- Cassification of drug side effects: on- and off-target, toxic metabolites and harmfull immunological effects
- Cellular regulation of drug receptor interactions
therapeutic index
the ratio of the drug that is safe or toxic. Calculated by Lethal dose 50 / Effective dose 50).
If a drug has a high therapeutic index = There is a big difference between the dose that is effective and the dose that is toxic, and the drug is sage.
Therapeutic window
It is the range between the minimum toxic concentration (MIC) and minimum effective concentration (MEC). This is the “safe zone”, where the drug is effective without causing harmful effect. The drug level should stay within these intervals to cause fewer side effects and the best result.
Specificity-selectivity, Specificity
A highly specific drug will bind ONLY to the intended target in the body and have no other effect ⭢ rare.
Example: Lokivetmab, which targets IL-31
Specificity-selectivity, selectivity
A selective drug prefers to bind to its intended target, but might bind to others
Example: B2 agonists, such as salmeterol, which target B2 receptors, but can also affect other receptors to some extent.
Classification of drug side effects, on-target:
Side effects happen when a drug affects the specific receptor it is supposed to target. However, side effects can also arise due to:
- Too high a dose
- Pharmacokinetics
- Individual differences in sensitivity to the drug
- The same receptor can have different effects in different tissues, such as H1
Classification of drug side effects, off-target:
Side effects occur when they affect receptors or other molecules in the body that were NOT the intended target. Example: Beta blockers
Classification of drug side effects, Toxic metabolites:
When the body breaks down a drug, it can produce harmful substances, these toxic substances can cause side effects or damage to the body.
Example: Paracetamol
Classification of drug side effects, harmfull immunolgical effects:
Side effects involving the immune system.
It can be caused by an immune response to the drug or by other mechanisms that do not directly involve the immune system.
Cellular regulation of drug receptor interactions
How the cells control the drug, an important concept is the drug tolerance, which means that the effect of the drug decreases with continued use, and this can happen through several mechanisms:
- Pharmacodynamic tolerance
- Pharmacokinetic tolerance
Cellular regulation of drug receptor interactions, Pharmacodynamic tolerance:
This involves desensitisation, where the receptors respond to the drug decreases. When an agonist continuously binds to the receptor, the receptor can become less responsive. This can happen in a few ways:
- Inactivation The receptor becomes temporarily unable to respond to the drug
- Sequestration The receptor is moved to a different location within the cell, away from the cell surface, so it cannot interact with the drug
- Down-regulation The cell reduces the number of receptors available on the surface. This means fewer targets for the drug to bind to
Example of a drug that can cause this type of tolerance = Opioids
Cellular regulation of drug receptor interactions, Pharmacokinetic tolerance:
This type of tolerance occurs because the body becomes more efficient in breaking down and eliminating the drug.
One common mechanism is the increase of CYP450 enzymes, which are responsible for metabolising many drugs in the liver.
When certain drugs, such as phenobarbital, are used regularly, they can cause an increase in the production of CYP450 enzyme, meaning that the body will metabolise the drug faster, so the effect of the drug is reduced
