Medical Interventions 3.4

• Pharmacogenetics is the study of the role that an individual‘s genetic make-up plays in their response to medication
• The chemotherapy drug azathioprine is prescribed to patients with acute lymphoblastic leukemia (ALL)
• Azathioprine is made of a compound thiopurine.
• Thiopurines work by interfering with DNA replication and stop cancer cells from growing and spreading
• An enzyme called thiopurine methyltransferase (TPMT) is involved in the metabolism and breakdown of thiopurines
• A patient who has low levels of TPMT will have higher concentrations of unmetabolised thiopurines, which can lead to toxicity
• Patients with ALL need thiopurine to keep the cancer cells from replicating but need TPMT to deactivate thiopurine
• Excess thiopurines can cause awful side effects
• A patient‘s SNP correlates with his or her ability to tolerate a particular drug
• Haplotype is a group of genes close together on chromosomes that are inherited together from a parent
• If a patient has 2 defective SNPs (haplotype), the patient has a defective TMPT
• Pharmacogenetics can create personalized medicines that will be more effective for treating diseases
• Nanotechnology in medicine involves using tiny particles to treat diseases
• Nano means 10^-9 (very small)
• Nanoparticles have been created to seek out and bind to certain markers only in cancer cells, thus only killing those cells rather than affecting the entire body
• Other areas being looked at include developing nanoparticles for tumor imaging and molecular profiling of cancer bio markers
• Clinical trial is a testing phase for a potential therapeutic agent
• A nanometer is a billionth of a metere
• Nanotechnology is the creation of useful materials, devices and systems through the manipulation of matter in this minuscule scale
• Nanomaterials have large surface areas relative to their volumes; therefore friction and sticking are more important
• Challenges for use of nanomaterials

  1. can be so small that the body clears them too fast to be effective for detection of cancer
  2. larger nanoparticles may accumulate in organs and become toxic
• Two approaches to design of nanodevices

  1. top down approach: molding/etching materials into Smaller components (used in computers and electronics)
  2. bottom up approach: assembling structures atom by atom (useful in medicine)
• Nanodevices are small enough to enter a cell and detect changes in molecules in cells before diagnostic image detection
• Nanodevices can preserve cells in active state; no alteration to cells (can be tested again later)
• Types of Nanodevices are the cantilever, nanopores, nanotube, quatum dots, nanoshells and dendrimer
• Cantilever are nanodevices that can improve cancer detection and diagnosis
• Cantilevers can bind to altered DNA sequences or proteins present in cancer
• Surface tension changes, causing cantilevers to bend; can allow for early detection
• Nanopores are tiny holes that allow DNA to pass through one strand at a time
• Scientists can monitor the shape and electrical properties of each base of nanopores; can look at error in the code associated with cancer
• Nanotubes detect the presence of altered genes, but they may help researchers pinpoint the exact location of those changes
• Quantum dots are tiny crystals that blow when they are stimulated by ultraviolet light
• Nanoshells are minuscule beads coated with gold; these beads absorb specific wavelengths of light
• Dendrimer are man-made molecules about the size of an average protein and have a branching shape
• The purpose of clinical trials is to assess the safety and efficacy of

  1. experimental treatments
  2. new combinations of drugs
  3. new approaches to surgery or radiation therapies
  4. better disease prevention
  5. better diagnostic approaches
• Phase 1 trial consists of evaluating safety of drug, determining safe dosage range, identifying side effects.
• Phase 1 trials tests small group of people (<100)
• Phase 2 trial consists of learning about safety and side effects, sharpening estimates of proper dosage, and determining effectiveness
• Phase 2 trails test a larger group of people (>=200)
• Phase 3 trails determine effectiveness, and side effects