Exam 2: Prodrugs Flashcards
What is a prodrug?
A pharmacologically inactive compound that is converted into an active drug by a metabolic biotransformation
What is the difference between a pro and soft drug?
Pro: inactive compounds metabolized to active form
Soft: pharmacologically active metabolized to promote excretion
What is drug latentiation?
A prodrug after administration is expected to be appropriately metabolized to the active form
What are the 2 classes of drug latentiation?
- Carrier-linked prodrug
- Bioprecursor prodrug
What are carrier-linked prodrugs?
Contains an active drug linked to a carrier group that can be removed enzymatically such as an ester
What are subclasses of carrier-linked prodrugs?
- Bipartate prodrug
- Tripartate prodrug
- Mutual prodrug
What is a bipartate prodrug?
Comprised of one carrier attached to one drug
What is a tripartate prodrug?
Comprised of a carrier attached to a linker that is attached to the drug
What is a mutual prodrug?
Consists of two, usually synergistic, drug attached to each other
What is an example of a tripartate-mutual prodrug?
Etofibrate
What are bioprecursor prodrugs?
Consists of a compound that is metabolized by molecular modification into a new compound which is the active principle drug or is metabolized further to the active drug
What is a hard drug?
Nonmetabolizable drug charactered by either high lipid solubility and accumulation in adipose tissues and organelles or high water solubility
Why are hard drug poor substrates for metabolism?
Can be sterically hindered or the hydrogen atoms are substituted with halogens that block oxidation
What are soft drugs?
Biologically active drugs designed to have predictable and controllable metabolism to nontoxic and inactive products after they have achieved their desired pharmacological effect
What are the advantages of soft drugs?
- Elimination of toxic metabolites, increases the therapeutic index
- Avoidance of pharmacologically active metabolites
- Elimination of drug-drug interactions
- Simplification of pharmacokinetics problems
What are prodrug utilized for?
- Aqueous solubility
- Absorption and distribution
- Site specificity (toxicity)
- Instability
- Prolonged release
- Toxicity
- Poor patient acceptibility
- Formulation problems
Why is the purpose of aqueous solubility of a drug?
Least water soluble is poor bioavailability
Why is bioavailability important?
For drug’s absorption and distribution
In what ways are prodrugs desired depending on the desired site of action?
- Plasma proteins effect drug binding
- Drugs are designed to enhance or reduce plasma protein binding which will determine tissue site and penetration
Why is site specificity important for prodrug manufacturing?
- High concentrations of an enzyme can cleave the prodrug moieties to unmask the active drug
- Prodrug functionality can direct the drug to particular target tissue
What causes instability of a drug?
Rapid metabolism that doesn’t give a the drug enough time to have a pharmacological effect
How do prodrugs prevent rapid metabolism?
By blocking initial sites of metabolism
Why are prodrugs used for prolonged release?
Has the ability to convert an active molecule with a short half-life or duration of activity into an extended release prodrug
Why is it important for a pro drug to be slowly converted to active form?
Enables the desired drug to be released at a steady low concentration over a longer period of time
