A Pharmacological Revolution by the Year 20001 Predictions suggest that there will be In the next 20 years new drugs will replace present acceptable treatments and provide solutions to current therapeutic prOblems. Further, new drug delivery systems will be designed. A large group of Japanese scientists have predicted that the next 2 significant scientific developments will be the manufacture of artificial vaccines and the effective use of antiviral drugs, including interferon. However, then there will be no further therapeutic gains until we understand the immune response and the biology of cancer. Thus, 'a strong basic research effort is essential' but predictions are that these processes will be clarified within the next 20 years and the control of autoimmune diseases and the development of anticancer agents will subsequently follow. Of course future predictions cannot be made easily. 40 years ago antibiotics were the 'wonder drugs' and future advances were expected to include viral diseases. Now bacterial resistance to antibiotics provides a major problem and, still, there are no broad spectrum antiviral agents. However, so long as proven approaches, such as immunisation, are not ignored and work with viruses (thought to possibly initiate several major illnesses) continues progress will be made.
New drug classes will evolve . .. To achieve these therapeutic advances, new drugs will differ from agents that are currently available in 3 ways : • they will have greater specificity • they will act closer to the abnormality- in structure or function • a group of natural therapeutic agents based on body substances will develop because of genetic engineering e.g. peptides and proteins. . To achieve greater specificity, more information needs to be obtained regarding the interaction of natural body chemicals with their receptors. Monoclonal antibodies and computers are being used in this search. Innovations in the next 20 years may find widespread therapeutic applications for the following drug classes or techniques. tmmunomodulators, for example interferon, are 'natural substances that maintain proper functioning of the immune system in the body'. The development of this class of drugs, following clarification of the mechanism of the immune system, would see it used in enhancing the immune system firstly in immunodeficiency diseases such as AIDS, but also in preventing the rejection of transplanted organs and possibly in cancer. The elucidation of neurotransmitters may see advances in Parkinson's disease, senile dementias, amyotrophic lateral sclerosis and schizophrenia. A search is also going on to identify neurotrophic hormones. A deficiency of these compounds may be responsible for the death of the nerve cells prodUCing neuro" transmitters . The development of antidepressants specific for brain regions involved in depression, the finding of a natural tranquilliser to act on benz:odiazepine receptors or the use of endorphins may see new mood-altering drugs. The endorphins are proteins discovered to produce analgeSia by acting on the same .receptors as morphine but they may also be involved in mood alteration. Genetic engineering can be used to produce large amounts of medically useful materials through the work of recombinant bacteria, to correct genetic disease by the insertion of the correct functional gene where applicable, and to prevent cancer. To prevent cancer, genetic engineering would provide antioncogenes to control oncogenes. Oncogenes 'may well be necessary functional genes in their normal state' but are associated with maligancy when they are not regulated. Monoclonal antibodies, prostaglandins and vaccines are further ideas for new drug classes. In cancer chemotherapy, monoclonal antibodies would be toxic to cancer cells by combining with antigens only present on the surface of these cells. In bone-marrow transplantations, monoclonal antibodies would kill donor cells (again by combining with surface antigens) to prevent a reaction with the recipient's cells. This reaction would normally result in the rejection of the graft. In infections due to Pseudomonas. the antibodies would act against the protein coat of the organism. . Although prostaglandins are involved in promoting the aggregation of platelets, prostacyclin [epoprostenol] is a natural clot inhibitor which may find wide use not only as an anti-clotting agent but also in preventing myocardial infarction. Thus, the synthesis of orally stable prostaglandins will be a major therapeutic advance. They could also be useful in preventing ulcers while prostaglandin inhibitors may be equally important in asthma and inflammation .
. . . and the reVolution will include drug delivery systems Controlled release systems are 'the most visible sign of the revolution in drug delivery.' Various techniques are used to deliver the drug at a constant rate in these systems, some of which are already in use. Drugs can be mixed with a polymer to form either a matrix which is broken down inside the body to release the drug or a maze from which molecules such as proteins travel out of. Transmucosal delivery systems already involve glyceryl trinitrate [nitroglycerin] patches for angina, hyoscine [scopolamine] patches for motion sick-
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ness and a transdermal product containing clonidine for hypertension. However, not all drug molecules are of a suitable size to pass through the skin. Future transdermal systems may involve iontophoresis in which the drug is 'propeUed across the skin by a positive electric charge.' In controlled release suspensions ionised drugs are displaced from a polymer by ions in the stomach while in osmotic devices drugs are forced from a core through a laser hole in the surrounding membrane when water enters the membrane. Not all drugs are suitable for inclusion in a controlled release system so pulse delivery may be a future possibility. The drug would have to be loaded in different concentrations in various layers of a cylinder to be released at the correct time. Magnetic systems involving implants and microspheres are being developed for targeting at localised sites. Implants can be positioned at a specific site and the drug then released by an externally controlled magnetic field. The microspheres (containing the drug and magnetite molecules) would travel through the body to a specific site, which is for example malignant or inflammed, attracted by the magnetic field being focused on that site. The drug would then leach out of the biodegradable polymer. Implanted pumps , the use of sprays for respiratory delivery, liposomes , and a system such as intracerebral injection to deliver neurotransmitters to specific brain areas are all delivery systems being developed further. The difficulty with liposomes is that the body treats them as foreign matter and eliminates then via the liver and lungs. However, there is hope that the drug included in these lipid-water emulsions could treat liver and lung cancer or the additional inclusion of monoclonal antibodies would make the liposomes specific for a particular body organ. So what does the future hold? The use of computers to control time release preparations and to plan individualised drug dosing is not unforeseeable. In the 21st century, the pills and intravenous solutions that are so familiar at present may be replaced on the pharmacists' Shelves with 'pumps, patches, time-relaxed pills, liposomes, implants and vials of tailored monoclonal antibodies.' The pharmaCist's future role will certainly be different and will likely involve a greater requirement to be a provider of information. We have yet to see whether the drug market will expand with the addition of the new drug classes to the existing market or whether existing drugs will be entirely replaced with the new agents. 'Sut it seems safe to say that many current agents will be diminished in attractiveness, while many upcoming drugs will fill currently empty niches.' Further, the low-technology approach involving public awareness of factors such as the benefits of a healthy diet and exercise, self-treatment with vitamins or home monitoring of blood pressure will not be lost as the race to develop high-tech delivery systems continues. 'Soth approaches will be developed to the fullest. ' Checks. w.A.: American Journal of Hospital Pharmacy 41: 1536 (Aug 1984)
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