drug development

Question 1

Q: What are the main steps in the drug development process?

Answer 1

1. Discovery and Preclinical Development

Discovery Phase:
Identification of a biological target (e.g., receptor, enzyme).
Screening of compounds for therapeutic potential.
Optimization of lead compounds.
Preclinical Testing:
In vitro (cell-based) and in vivo (animal model) studies.
Assess safety, efficacy, pharmacokinetics (absorption, distribution, metabolism, excretion), and pharmacodynamics (drug effects).
2. Clinical Development

Phase I:
Purpose: Evaluate safety and dosage in a small group of healthy volunteers or patients.
Focus: Side effects, tolerability, pharmacokinetics.
Phase II:
Purpose: Assess efficacy and further safety in a larger group of patients with the target condition.
Focus: Optimal dosage, proof of concept.
Phase III:
Purpose: Confirm efficacy, monitor side effects, and compare with existing treatments in a large patient population.
Focus: Data for regulatory approval.
3. Regulatory Approval

Submission to Regulatory Authorities:
Agencies like the FDA (U.S.), EMA (EU), or MHRA (UK) review data.
Approval based on safety, efficacy, and manufacturing quality.
Example: New Drug Application (NDA) or Biologics License Application (BLA).
4. Post-Marketing Surveillance (Phase IV)

Purpose: Monitor long-term safety and effectiveness after the drug is on the market.
Focus: Detect rare side effects, real-world efficacy, and additional applications.
Example: Reporting of adverse drug reactions through systems like the Yellow Card scheme.

Question 2

there are many ways that drugs work, explain how monoclonal antibodies work and give examples of tnf-alpha drugs.

Answer 2

• knowing how antibodies target damaging antigens, finding ways to create these and inserting them into humans - transplant from rats - Monoclonal antibodies (mAbs) are laboratory-made proteins engineered to bind specifically to a target molecule, usually an antigen on cells. They mimic natural antibodies but are designed for therapeutic purposes
• there are lots of drugs that are monoclonal antibodies that are used to block TNF-a
• TNF-a can cause endotoxin posioning, septic shock and chronic inflammation
  the 3 approaches to neutralise this are:
• chimeric antibody - infliximab
• fusion protein (etanerecept)
• human antibody (adalimumab)

infliximab:
- monoclonal mouse antibody against TNF alpha
- used for arthiritis

entranercept:
- dimeric fusion of TNF type II receptor - no mouse protein
- receptor antagonist
- binds to TNF-alpha, preventing it from binding to receptors

adalimumab
- TNF-alpha antibody
Inhibits lymphocyte proliferation, down regulates inflammatory reactions associated with autoimmune disease
Subcutaneous (self-inject), fortnightly
adalimumab - HUman

Question 3

where do we get drugs from, knowing about molecular medicine, how does this help.

Answer 3

• monoclonal antibodies - mice and rats or artificially made in lab
• from animals eg insulin and steroids produces from animals, altered to prevent rejection
• drugs that target the dna - used for cancer a lot - gene therapy
• mrna interference
• immunotherapy
• Targeting Disease Pathways - Drugs designed to block specific molecular pathways involved in disease progression.
  Example: Tyrosine kinase inhibitors (e.g., imatinib for chronic myeloid leukemia).

Question 4

what is gene therapy and why is it a good upcoming approach?

Answer 4

an experimental technique that uses genes to treat or prevent disease, in the future this technique may be used by doctors to treat a disorder by inserting a gene into patients cells instead of using drugs or surgery, reserchers are taking several approaches to this therapy including:
- replacing a mutated gene that causes disease with a healthy copy of the gene
- inactivating or knocking out a mutated gene that is functioning improperly
- introducing a new gene into the body to help fight a disease
-

Question 5

outline what is rational drug design.

Answer 5

The process of finding new medications based on the knowledge of a biological target.

Involves the design of molecules that are complementary in shape and charge to the bio-molecular target with which they interact and therefore will bind to it.

Relies on computer modeling techniques (computer-aided drug design).

Relies on the knowledge of the three-dimensional structure of the bio-molecular target is known as structure-based drug design.

Used to target specific disease causing mutations