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Topic last updated: 24 Nov 2021
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How medicines work

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Treating non-bacterial infections

As you have just seen many of the communicable diseases affecting people all over the world are not caused by bacteria, and so cannot be treated by antibiotics. So what do we do when we are attacked by non-bacterial pathogens?

 

Antiretroviral drugs have revolutionised the lives of people affected by HIV/AIDS in countries such as the UK (Photo credit: National Institute of Health)

Viral diseases cause millions of deaths every year around the world, from simple gastrointestinal infections causing sickness and diarrhoea to diseases such as HIV/AIDS. There is no equivalent of antibiotics for viral infections. Viruses infect and take over human cells when they act as pathogens. For more about viruses as pathogens see Pathogens and the immune system.

This makes it very difficult to develop drugs that will eradicate the viruses without damaging the cells of their host. Drugs developed against the ‘flu virus have been shown to have very limited effect in most people, reducing the period of infection by hours rather than days.

The biggest success story so far has been the antiretroviral medicines developed against HIV/AIDS. If these are given in the minutes or first hour or two after exposure to the virus, they may prevent infection. If they are given within the first days, they may greatly reduce the risk of full-blown AIDS developing. If an individual is diagnosed as HIV positive, once the virus starts to affect the functioning of their immune system they will be given antiretroviral drugs for the rest of their life. An individual infected by HIV in a country such as the UK or US may have an almost normal life expectancy thanks to the range of drugs that have been developed.

Antifungal medicines

There are three main types of fungal infections in people – skin infections such as athletes foot and ringworm, infections of the mucosa of the mouth or vagina (thrush), and systemic fungal infections that usually affect immunocompromised patients and can be life threatening.

For more about fungi as pathogens see Pathogens and the immune system

Fungal diseases in people are not as common and often not as serious as bacterial and viral diseases, so there has been less development of anti-fungal drugs. Ideally anti-fungals are specific to fungal cells (so they have no effect on human cells), broad spectrum (affect many different types of fungal pathogen), kill the fungus and are affordable.

Glucans in the cell walls of fungi are a good drug target because they are specific to fungi – but the glucans are often hidden by other compounds such as chitin. One area of research is looking at ways of revealing the glucan layer in the cell walls – making it an easier target both for other anti-fungal drugs and for the body’s own immune system.

Medicines against protozoa

Protozoan diseases include amoebic dysentery, sleeping sickness and malaria. You can learn more about protozoans as pathogens in Pathogens and the immune system. Protozoans – and the protista as a whole - are a very diverse collection of organisms. As a result it is impossible to develop broad spectrum treatments that affect many different protozoans, as is possible with some antibiotics. Protozoan diseases are often very difficult to treat. The protozoa often have complex lifecycles that frequently involve at least two different hosts. They often mutate rapidly, changing their surface antigens and making them a difficult target for drugs and vaccines. The fact that they often spend part of their life cycle inside human cells makes it difficult to develop drugs that attack them without also damaging the human cells.

 

Sleeping sickness

The trypanosomes that cause sleeping sickness spend part of their life cycle in the subcutaneous tissues, blood and lymph. At this stage they can be treated relatively easily with drugs that destroy them. Then they cross the blood-brain barrier, a selectively permeable membrane that separates the brain from the blood and prevents the entry of many substances from the blood into the brain. Once the protozoa enter the brain the disease symptoms get worse and the risk to life is high. It also makes it much harder to reach the parasites as the medicines also have to cross the blood-brain barrier.

Tsetse fly
(Photo credit: CC BY-SA, International Atomic Energy Agency)

Trypanosome
(Photo credit: Blaine Mathison, CDC)

The trypanosomes that cause sleeping sickness go through many different lifestyle stages, some in the tsetse fly and some in mammals such as people or cattle.

 

Five different drugs have been developed against sleeping sickness. Two act against the early stages of the infection, and three can cross the blood-brain barrier to attack the trypanosomes in the brain itself. These drugs are provided free in all the countries affected by the disease, and the number of reported cases has fallen dramatically. As a result of these medicines, along with people taking measures to prevent the spread of the disease, we may yet eliminate sleeping sickness from Africa and so from the world.

 

Malaria

Malaria is probably the best known protozoan disease. The Plasmodium parasite spends part of its lifecycle in the female Anopheles mosquito. This is when it reproduces sexually. It spends the other part in the human body, where it reproduces asexually. There are a number of antimalarial drugs that target the malaria parasite at different stages of its life cycle. The malaria parasites have developed resistance to antimalarial drugs in much the same way as bacteria have developed resistance to antibiotics. The most effective way of dealing with malaria remains the control of mosquitoes and the prevention of infection in the first place. This can be done by the use of insecticide- impregnated mosquito nets, suitable clothing and controlling access to water.

 

Targets for anti-malarial drugs:

  • The food vacuoles of the parasites when in the human red blood cells where drugs can then affect the breakdown of the haemoglobin (eg quinine and chloroquine)
  • Enzymes involved in DNA replication, preventing reproduction of the parasite, eg. pyrimethamine
  • Enzymes in specific biochemical pathways such as dihydropteroate synthetase, eg. sulphonamides
  • Killing the pathogen by unknown means, eg. artemisinin
  • Protein synthesis in the protozoan, eg. doxycycline