Pharmaceuticals for Infectious Disease (HSC SSCE Biology): Revision Notes

Pharmaceuticals for Infectious Disease

Introduction to chemotherapy and antimicrobial agents

When people hear the word chemotherapy, they often think of cancer treatment. However, in medical terminology, chemotherapy has a broader meaning: it refers to the use of any medication to treat any disease. This approach is particularly important in managing infectious diseases.

The chemotherapeutic method for controlling infectious diseases involves using medications to treat infections in humans, animals, and plants. Antimicrobial agents are specially designed drugs that target and control diseases caused by microorganisms (microbes). These agents work by reducing the number of pathogens in infected hosts, which helps limit disease transmission.

Classes of antimicrobial medications

There are four main categories of antimicrobial drugs, each targeting different types of pathogens:

Class of medication	Pathogens targeted	Examples
Antibiotics (antibacterials)	Bacteria	Penicillins, tetracyclines, polymixins, sulfonamides, cephalosporins
Antivirals/antiretrovirals	Viruses	Tamiflu® (oseltamivir) for influenza (antiviral); Abacavir for HIV/AIDS treatment (antiretroviral)
Antifungals	Fungi	Fluconazole, amphotericin B, caspofungin
Antiprotozoals	Protozoa	Doxycycline, metronidazole, mefloquine

Antiviral medications

How antiviral medications work

Antiviral drugs are used to manage viral infections, but it's important to understand that they don't actually kill viruses. Instead, they work by preventing viruses from developing and reproducing inside infected cells. These medications don't cure viral diseases; rather, they slow down the disease progression, giving your body's immune system time to fight the infection effectively.

When taken early in the disease course, antiviral medications can reduce symptom severity and shorten illness duration. They also help prevent viral diseases from spreading to other people, making them valuable tools for controlling epidemics and pandemics.

Managing viral infections in developing countries

In many developing countries, people may carry multiple viruses simultaneously, including hepatitis B, hepatitis C, and HIV. Managing these viral infections presents challenges beyond simply prescribing antiviral drugs.

Development of antiviral drugs

Compared to antibiotics, antiviral medications are relatively recent developments in medical science. The viruses most commonly targeted by antiviral drugs include:

• HIV (Human Immunodeficiency Virus - note that HIV is the virus, while AIDS is the disease it causes)
• Seasonal influenza A
• Herpes viruses
• Hepatitis B and C viruses

The HIV epidemic in the 1980s sparked a coordinated global research effort that significantly advanced our understanding of viral biology. This research led to breakthroughs in antiviral drug development.

Viral genetics

Understanding viral genetics is essential for developing effective antiviral medications. Viruses vary genetically in the following ways:

• Their genetic material can be either DNA or RNA
• The genetic material can be single-stranded (ss) or double-stranded (ds)

Viral replication in host cells

Once scientists better understood the life cycle and genetics of viruses, they identified several stages where antiviral drugs could potentially intervene. The diagram below shows the five main stages of viral replication in a host cell:

The viral replication cycle consists of:

1. Attachment to host cell: The virus binds to specific receptors on the host cell membrane
2. Release of viral genome: The virus injects its genetic material and enzymes into the host cell
3. Viral replication: The virus uses the host cell's machinery to make multiple copies of its genome
4. Assembly: Viral particles are assembled into complete viruses inside the cell
5. Release: New viruses burst out of the host cell and go on to infect additional cells

Influenza antivirals available in Australia

Three antiviral medications are registered in Australia for treating influenza:

• Oseltamivir (Tamiflu®)
• Zanamivir (Relenza®)
• Amantadine (Symmetrel®)

These drugs are effective against seasonal influenza A strains. However, scientists remain cautious about their effectiveness against pandemic influenza strains, such as the H1N1 subtype. Research has shown beneficial effects in patients with lower respiratory complications like pneumonia. Studies from the 2009-2011 pandemics showed that Tamiflu® and Relenza® were associated with reduced death rates.

Drug efficacy and timing

The efficacy of a medication refers to its ability to produce the desired outcome. For influenza antivirals, efficacy is greatest when the drugs are taken early in the illness.

Antibiotics

How antibiotics work

Antibiotics are medications designed to control bacterial infections. They work through two main mechanisms:

• Killing bacteria directly (bactericidal action)
• Slowing down bacterial growth (bacteriostatic action)

When antibiotics are most effective

Antibiotics work best under the following conditions:

• Appropriate use: They are used only for bacterial infections, not viral infections
• Bactericidal action: Bactericidal antibiotics (such as penicillins and cephalosporins) that kill bacteria are chosen rather than bacteriostatic ones that only inhibit growth
• Narrow-spectrum selection: Narrow-spectrum antibiotics that specifically target the pathogenic bacterium are used
• Drug delivery: The antibiotic can reach the infection site and kill the bacteria (barriers like the blood-brain barrier or damaged tissue may prevent this)
• Therapeutic levels: Appropriate blood concentrations are maintained throughout treatment
• Complete course: The entire course of antibiotics is taken to reduce bacterial resistance risk (though recent research has begun questioning this long-held principle, and further studies are needed before practice changes)
• Proper identification: A Gram stain, culture, and sensitivity tests are performed to ensure the correct antibiotic has been chosen and the bacterium has been correctly identified as the disease-causing agent

Impact of antibiotics on death rates

The discovery of penicillin by Alexander Fleming in 1928 and the subsequent commercial development of antibiotics dramatically changed infectious disease outcomes. Antibiotics have had their most notable effect in reducing infant mortality and maternal deaths during childbirth.

The graph above shows death rates from infectious diseases in the USA from 1900 to 1996. Key milestones marked on the graph include:

• Establishment of state health departments
• Introduction of water chlorination
• The 1918 influenza pandemic (visible as a spike)
• First use of penicillin
• Introduction of the Salk polio vaccine
• Passage of the Vaccination Assistance Act

The overall trend shows a dramatic decline in death rates throughout the 20th century, with the introduction of penicillin in the early 1940s contributing significantly to this reduction.

Antibiotic resistance

The problem of resistance

Bacterial resistance to antibiotics significantly limits their effectiveness in controlling infectious disease outbreaks. This problem occurs when an antibiotic becomes less effective over time at treating a particular bacterial disease.

How resistance develops

You should be familiar with the concept of selection pressure on populations. When a mutation or gene (genotype) gives bacteria resistance to an antimicrobial substance, those bacteria can survive or grow in higher antimicrobial concentrations than most other strains of the same species. This results in a resistant phenotype.

The graph above shows mortality rates from infectious diseases in England and Wales before and after vaccination introduction. Notice the general decline in deaths from diseases like measles, scarlet fever, whooping cough (pertussis), and diphtheria. The graph illustrates how multiple interventions (including both vaccines and antibiotics) have contributed to reducing infectious disease deaths.