What is a drug?

  • Definition:

    • Originally defined as any substance, of animal, vegetable, or mineral origin, used as an ingredient in pharmacy, chemistry, dyeing, or various manufacturing processes.

    • Later usage specifies it as a natural or synthetic substance used in the prevention or treatment of disease, often referred to as a medicine. It may also be defined as a substance that has a physiological effect on a living organism.

    • They are chemical compounds that are able to specifically change the behavious of cells within the body, are effective at treating a disease/modifying a biologic process, are safefor consumption at prescribed dosages, and can vary widely in their effects depending on dosage, method of administration, and individual patient characteristics.

Historical Context

  • Paul Erlich (1854-1915):

    • A European scientist credited with developing key concepts about drug action.

    • Through experiments with dyes that stained specific cell organelles, he introduced the concept of ‘receptor’ as the target of drugs.

    • Coined the term ‘magic bullet’ to describe drug action, indicating a targeted therapeutic effect on specific cells.

    • Developed the first effective drug for the treatment of syphilis, an arsenic-based compound known as Salvarsan.

    • Awarded the Nobel Prize for Physiology or Medicine.

Selective Toxicity

  • Adrien Albert (1907-1989):

    • An Australian medicinal chemist based at Sydney University and the ANU.

    • Coined the term ‘selective toxicity’ to describe drugs that injure one type of cell while sparing neighboring cells. This principle is fundamental in the development of antibiotics and chemotherapeutic agents, as it allows for targeted treatment of diseases while minimizing harm to healthy tissues.

Ideal Properties of Drugs

  • For a drug to be considered useful, it should ideally possess the following properties:

    • Effective: It should actually improve the disease or condition.

    • Potent: High affinity for its target.

    • Low Toxicity: Adverse effects should be significantly lower than the therapeutic benefits.

    • Stable: Able to be stored without losing potency.

    • Absorbable: Must be able to be absorbed or delivered into the bloodstream.

    • Appropriate Residence Time: Should not be prone to excessive excretion or metabolism.

    • Other Properties: For Central Nervous System (CNS) drugs, the ability to cross the blood-brain barrier is crucial.

Patient Considerations in Drug Development

  • Beyond basic pharmacological properties (effectiveness, potency, etc.), patient acceptance and compliance are vital factors in drug development.

    • Issues impacting compliance include:

    • Tablet Quantity: Large numbers of tablets with low potency can lead to poor patient compliance.

    • Dosing Frequency: Frequent dosing due to short durations of action can deter adherence.

    • Administration Method: Injected drugs may not be suitable for all conditions; however, they can be beneficial in clinical settings.

      • Examples include insulin injections, which can be used infrequently (weekly or monthly) even though they require compliance with injection methods.

Oral Drug Delivery

  • Oral delivery is the most preferred route of administration for many drugs, with some exceptions:

    • Direct Deliveries: Drugs that can be delivered directly to the site of action, such as inhaled and topical medications.

    • Long-Range Formulations: Long-acting transdermal formulations and implants.

    • Hospital-based Deliveries: Injected or infused medications are acceptable for use in clinical settings when needed.

    • Bioavailability: Drugs that are not sufficiently orally bioavailable are less likely to be used for non-critical conditions (such as biopharmaceuticals, peptides).

    • Future Perspectives: Small molecules are expected to remain the most widely used drugs, primarily due to their oral delivery capabilities.

    • Advatanges of oral drug delivery includesincreased patient compliance, ease of administration, and the potential for self-administration, thereby allowing for greater convenience and flexibility in treatment.

    • Additionally, manufacturing costs are low and the technologies for formulating oral drugs are well established

Naming of Drugs

  • Drugs can have multiple names, which include:

    • Chemical Name(s): The formal scientific name describing the molecular structure.

    • Company Code(s): Internal designations used by the developing company.

    • Approved Name: Nonproprietary or generic name (e.g., Australian approved name or US adopted name such as AAN, USAN).

    • Example of naming conventions:

      • Generic names in the same class often share common suffixes, such as:

      • -statins: cholesterol-lowering drugs

      • -vir: antiviral drugs

    • Trade Name: The commercial name under which a drug is marketed.

    • Example:

    • Generic name: Remdesivir

    • Trade name: Veklury

    • IUPAC name: 2-Ethylbutyl (2S)-2-{[(S)-{[(2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydro-2-furanyl]methoxy}(phenoxy)phosphoryl]amino}propanoate

    • Company code: GS-5734

    • Indication: Anti-COVID-19 drug

Key Questions

  1. Provide a modern definition of a drug.
    A drug is defined as a natural or synthetic substance used in the prevention or treatment of disease, often referred to as a medicine. It may also be defined as a substance that has a physiological effect on a living organism.

  2. Why is there often a preference for oral drugs?
    Oral delivery is the most preferred route of administration for many drugs due to its convenience. Small molecules, which are predominantly delivered orally, are expected to remain the most widely used drugs.

  3. a) Suggest a condition other than diabetes that would be suitable for treatment with an injected drug.
    A suitable condition for treatment with an injected drug would be cancer, specifically requiring chemotherapy.

    b) Suggest desirable drug properties for treating this condition.
    For an injected drug treating cancer (chemotherapy), desirable properties would include:

    • Effective: It must effectively target and destroy cancer cells.

    • Potent: High affinity for cancer cell targets.

    • Selective Toxicity: Crucially, the drug should injure cancer cells while minimizing harm to healthy neighboring cells. This principle is fundamental to reduce severe side effects.

    • Appropriate Residence Time: Should persist in the body long enough to exert its therapeutic effect without being excessively metabolized or excreted.

    • Low Toxicity: While chemotherapy often has significant side effects, the toxicity should be manageable and significantly lower than the therapeutic benefits, aligning with the goal of preserving healthy tissues as much as possible.