Responsive Drugs Flashcards
How do responsive drugs work?
Dosage done in inactive form, then drug must be activated at the site of disease.
What are the benefits of responsive drugs?
Avoidance of side effects as drug is only activated at the site of disease
How do Pt(IV) responsive drugs work?
Inert and inactive towards DNA binding in this form. Reduction in hypoxic conditions (tumour) forms Pt(II) which will DNA bind.
What is the general structure of a tumour?
Tumour attached to blood vessel. Near the blood vessel, fine like a usual cell. Further away, more hypoxic and acidic environment due to rapid growth and consumption of available material.
What are some of the challenges involved in making pH-responsive drugs?
Change in pH window is very small. Cellular pH ~ 7.2-7.6, whereas tumour pH ~ 6.7. Challenges arise from different cell compartments having different pHs and attempting to match the pKa with this small window!
What are the advantages and disadvantages of light-activated drugs?
Advantages: selective activation by only irradiating some congregations at site of disease (no worries if drug ends up somewhere else too!), reduced side effects, high levels of precision in light administration
Disadvantages: Need to get light to target area, how long does the photosensitivity last, wavelength of light restricted
How does PDT work?
Photosensitiser given to patient, localises at site of action, irradiated with light which leads to generation of ROSs –> cell apoptosis.
What is a key limitation of PDT?
PDT mode of action works by reaction of O2 with drug in excited triplet state to generate ROS. O2 is required for mechanism. Need for O2 limits the use of this technique for tumours due to the hypoxic environment.
How does ICP-MS work?
Cells given metals and left, then mix is digested and sample is injected and aerosolised. Detection of metal ion via mass spec type techniques, quantitative so can calculate concentration of metal complex uptake.
How can Pt(IV) drugs be stabilised or destabilised?
Rate of reduction varied by changing axial ligand. This can be made into another drug itself.
What is the phototherapeutic window?
This is the window of light where a drug could be activated - between 620 and 850 nm. Below 620, haemoglobin absorbs light and above 850, water absorbs light.
