L5 Flashcards
What are the 4 ways that small molecules cross cell membranes?
- Diffusion through lipid membranes
- Diffusion through aqueous pores
- Transmembrane carrier proteins
- Pinocytosis
What 2 mechanisms are important for drug movement?
- Lipid-mediated transport
- Carrier-mediated transport
Lipid solubility is crucial for what 3 factors?
- drug absorption
- Penetration into the brain and other tissues
- elimination
Weak acids and bases exist in what two forms depending on pH? (2)
- Ionized (charged)
- Unionized (uncharged)
What happens in pH partitioning with weak acids and weak bases? (2)
- Weak acids accumulate in regions of high pH (alkaline).
- Weak bases accumulate in regions of low pH (acidic).
What does pH partitioning affect?
Drug distribution across different body regions.
What is carrier-mediated transport and where is it important? (2)
- Involves binding to a transmembrane protein that changes conformation to transport molecules.
-Important in the renal tubule, biliary tract, blood-brain barrier, and gastrointestinal tract.
What is the role of plasma proteins in drug activity?
Drugs bound to plasma proteins are pharmacologically inactive
What plasma protein primarily binds drugs, especially acidic ones?
Albumin.
What does extensive plasma protein binding affect?
It slows drug elimination (metabolism and/or excretion).
How is drug distribution measured?
Volume of Distribution (Vd) = Dose/[Drug]plasma.
If a drug has a high Volume of Distribution (Vd), where does it tend to accumulate?
In tissues such as muscle and fat.
How do most drugs leave the body?
Via urine, either unchanged or as polar metabolites.
What organ plays a key role in drug metabolism?
The liver.
Which enzyme family is primarily responsible for drug metabolism?
Cytochrome P450.
What happens in Phase I and Phase II of drug metabolism?
Phase I: P450 introduces reactive groups (e.g., hydroxyl).
Phase II: Glucuronide is attached, forming an inactive, excretable product.
What is the role of the P450 enzyme family?
- They metabolize drugs, making them more polar and aiding in their elimination.
What are some common substrates for CYP1A2 and CYP3A4/5 enzymes? (2)
- CYP1A2: Caffeine, paracetamol.
- CYP3A4/5: Ciclosporin, nifedipine.
What can influence variations in P450 activity?
- Genetic polymorphisms
- Environmental factors (e.g., grapefruit juice, cigarette smoke)
What is the effect of metabolism on prodrugs?
Metabolism can convert inactive prodrugs into active drugs or toxins.
What percentage of drugs are passively reabsorbed by diffusion in the kidney?
Lipid-soluble drugs are passively reabsorbed unless converted to polar metabolites.
How does urine pH affect drug elimination?
- Alkaline urine enhances elimination of acidic drugs.
- Acidic urine enhances elimination of basic drugs.
What does the half-life of a drug refer to?
The time it takes for 50% of the drug to be eliminated from the body.
What is toxicokinetics?
The study of how poisons are absorbed, distributed, metabolized, and eliminated in the body.
What are two common tissues where toxicants accumulate?
- Fat (e.g., DDT)
- Liver and kidney (for heavy metals)
