50 Questions
What is the focus of PHAM1126?
Drug-receptor interactions
Which area does Chapter 14 of 'An introduction to medicinal chemistry' focus on?
Optimizing access to the target
What does MSOP1016 primarily cover?
Pharmacokinetics
What is the main topic of Lecture 3: Prodrugs and optimising access to the target?
Optimizing access to the target
Which of the following approaches is NOT used to improve drug efficacy?
Reducing molecular flexibility
What is the purpose of self-destruct drugs?
To reduce the risk of toxicity and side effects
Which drug is used to increase the absorption of another drug, particularly analgesics for migraine?
Metaclopromide
What is the function of alliance drugs?
To localize the activity of another drug
Which approach is used to make drugs more resistant to hydrolysis and metabolism?
Using steric shields, electronic effects, and group shifts
What can be changed to optimize the hydrophilic/hydrophobic properties of drugs?
Varying hydrophobic substituents
What is an example of a prodrug used to increase the absorption of dopamine?
Levodopa
Which drug constricts the blood vessels near the injection site to keep another drug in the vicinity for longer?
Adrenaline
What type of drugs can be made highly polar or ionized to prevent absorption for gastrointestinal infections?
Molecular transport system drugs
What is the purpose of using steric shields, electronic effects, and group shifts in drug design?
To resist hydrolysis and metabolism
What approach can be used to make specific use of molecular transport systems in tumour cells?
Alliance drugs
What is an example of a drug that is chemically stable under one set of conditions but unstable and degradable under another?
Pilocarpine
Which type of prodrug involves combining an active drug with a carrier to produce a compound with desired chemical and biological properties?
Carrier prodrugs
What is the main example of a bioprecursor prodrug mentioned in the text?
Prontosil
Which property is considered ideal for prodrugs to help improve patient acceptance?
Improved oral bioavailability
What is the primary purpose of prodrug design?
To improve site-specificity of the drug
What can carrier prodrugs help address?
Brain delivery of hydrophilic drugs
What is a characteristic of polymer prodrugs?
Absorption in the colon
How can prodrugs be helpful in addressing side-effects associated with NSAIDs?
By reducing stomach pain, headaches, and high blood pressure
What do ideal prodrug properties include?
Non-toxic carrier
What characteristic can help ensure a prodrug reaches the target site?
Site-specificity
What is an example of a side-effect that prodrugs can help address related to opiates?
Nausea and vomiting
How can bioprecursor prodrugs be classified?
As inactive compounds
What do carrier prodrugs involve?
Ampicillin esters and their combination with a carrier to produce a compound with desired properties
Which enzyme metabolises most of the Levodopa before it reaches the Central Nervous System?
Dopa decarboxylase
Which compound has been used to inhibit dopa decarboxylase and reduce the necessary dose of Levodopa?
Carbidopa
What is the primary reason for using carbidopa alongside Levodopa in Parkinson's treatment?
To prevent the conversion of Levodopa to dopamine
Why is carbidopa unable to cross the Blood-Brain Barrier (BBB)?
It is highly polar and not an amino acid
Which strategy involves modifying the drug itself to optimize hydrophilic/hydrophobic properties and resistance to chemical and enzymatic degradation?
Optimizing drug design
What is the main issue with oligonucleotides as drugs?
They are susceptible to metabolic degradation
What approach involves linking a drug to polymers or antibodies to improve its delivery to specific targets?
Drug targeting
Why are peptides and proteins used as peptidomimetics in drug design?
To mimic the function of endogenous peptides and proteins
Which compound is used as a mimic of a peptide lead in drug development?
Peptidomimetics
What is the primary use of antibodies as drugs?
To carry drugs to specific targets in the body
Which type of prodrug is Valdecoxib?
COX-2 selective prodrug
What is the function of Lisdexamphetamine as a prodrug?
Decarboxylated in the brain to methyldopamine
What strategy is NOT a part of prodrug design?
Lower water solubility, improve taste
What is the main focus of drug optimisation with regards to target access?
Modification of drug
What happens if a drug is too polar or hydrophilic?
It can't cross cell membranes
How is hydrophobic character measured in drugs?
By the partition coefficient (P)
What is the primary purpose of using prodrugs?
To modify drug characteristics
What role do COX-2 inhibitors play in prodrug design?
Enhance water solubility for parenteral use or improve bioavailability
What distinguishes Lisdexamphetamine from other prodrugs mentioned in the text?
It is decarboxylated in the brain to methyldopamine
What characteristic should hydrophobic drugs possess for distribution?
High P (partition coefficient)
What strategy aims to prolong drug activity?
Esters, N-methylation, Trojan horse approach
Which commercially available prodrug enhances water solubility for parenteral use?
Valdecoxib
Study Notes
- NSAIDs and prodrugs: Many have been made, only a few reached clinical use
- Non-selective COX-2 inhibitors: Avoid GI irritation by using prodrugs
- COX-2 inhibitors: Enhance water solubility for parenteral use or improve bioavailability
- Commercially available NSAID prodrugs:
- Parecoxib: Water-soluble injectable
- Valdecoxib: COX-2 selective prodrug
- Nalbumetone: Bioprecursor prodrug metabolized in the liver
- Flurbiprofen: Carrier prodrug
- Flurbiprofen axetil
- Lisdexamphetamine: Prodrug of dextroamphetamine used in ADHD treatment
- Methyldopa: Prodrug of methyldopamine, decarboxylated in the brain to methyldopamine
- Prodrug design:
- Improve membrane permeability
- Esters, N-methylation, Trojan horse approach
- Prolong drug activity
- Mask drug side effects and toxicity
- Lower water solubility, improve taste
- Increase chemical stability, activated by external agents
- Drug optimisation:
- Aim for drugs that are absorbed, reach target effectively, stable, eliminated in a reasonable time
- Strategies to optimize access to targets: modification of drug, hydrophilic/hydrophobic properties, resistance to degradation, targeting
- Hydrophilic/hydrophobic properties:
- Balance crucial for solubility and ADME
- Too polar/hydrophilic: can't cross cell membranes
- Too non-polar/hydrophobic: go into fats/fatty tissue
- Hydrophobic drugs (high P) distributed to hydrophobic compartments
- Hydrophilic drugs (low P) found in aqueous compartments
- Absorption and distribution:
- For a drug to cross a membrane barrier, it must be soluble in both lipid and aqueous phases.
- Hydrophobic character measured by the partition coefficient (P).
Test your knowledge about NSAIDs and prodrugs, including their clinical use, COX-2 inhibitors, water solubility, bioavailability, and commercially available options. Explore the concepts of prodrugs and their application in pharmaceuticals.
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