Table of Contents
How Drugs Work in the Body: Basic Principles
Drugs act in the body by interacting with specific biological structures and processes. This interaction alters normal physiological functions in a controlled way to produce a desired therapeutic effect (and often, undesired side effects).
Most drugs do not create new functions in the body; they modify existing ones. Typical mechanisms include:
- Enhancing or inhibiting the action of endogenous (body’s own) substances
- Mimicking natural signaling molecules
- Blocking biological pathways that are overactive or harmful (e.g., in infections, cancer, inflammation)
At the molecular level, drugs usually exert their effects by binding to particular target molecules, often called drug targets.
Main Types of Drug Targets
Receptors
Receptors are proteins that receive signaling molecules (ligands) such as hormones or neurotransmitters and translate these signals into a cellular response.
- Drugs that activate receptors are called agonists
- Drugs that block receptors are called antagonists
Binding is usually highly specific and based on complementarity of shape, charge, and other interactions (e.g., hydrogen bonds, hydrophobic interactions).
Examples:
- Beta-agonists in asthma therapy activate receptors that relax bronchial muscles
- Antihistamines are antagonists at histamine receptors, reducing allergic symptoms
Functional Consequences of Receptor Binding
- Change in ion flow across membranes (e.g., opening/closing ion channels)
- Activation or inhibition of intracellular signaling cascades (e.g., via G-proteins, second messengers)
- Regulation of gene expression when receptors are located in the cell nucleus
These changes trigger physiological responses such as altered heart rate, muscle tension, secretion, or perception of pain.
Enzymes
Enzymes catalyze biochemical reactions. Drugs can:
- Inhibit enzymes, slowing or stopping certain reactions
- Less frequently, activate enzymes or provide alternative substrates
Typical mechanisms of inhibition:
- Reversible binding to the active site (competitive inhibition)
- Binding to another site that changes enzyme conformation (allosteric inhibition)
- Irreversible inactivation by covalent modification of the enzyme
Examples:
- Many antibiotics inhibit bacterial enzymes essential for cell wall synthesis
- ACE inhibitors in cardiovascular therapy inhibit an enzyme that produces a vasoconstrictor hormone
Ion Channels
Ion channels are proteins in cell membranes that allow ions such as $ \text{Na}^+ $, $ \text{K}^+ $, $ \text{Ca}^{2+} $, or $ \text{Cl}^- $ to pass through. They are crucial for:
- Nerve impulse conduction
- Muscle contraction
- Regulation of cell volume and membrane potential
Drugs can:
- Block ion channels (channel blockers)
- Stabilize open or closed states
- Alter channel opening probability
Example:
- Local anesthetics block voltage-gated sodium channels in nerves, preventing pain impulses from traveling to the brain
Transport Proteins
Transporters move substances across cell membranes (e.g., neurotransmitter reuptake systems, ion pumps, nutrient transporters).
Drugs may:
- Block reuptake of neurotransmitters, increasing their concentration in the synaptic cleft
- Inhibit pumps that maintain ion gradients
Example:
- Certain antidepressants inhibit serotonin reuptake transporters, increasing serotonin availability in the brain
Nucleic Acids and Other Macromolecular Targets
Some drugs interact directly with DNA or RNA or with other large biomolecules.
Examples:
- Certain anticancer drugs intercalate into DNA, interfering with replication
- Some antivirals influence viral nucleic acid synthesis or processing
Here, the mechanism often aims to selectively interfere with rapidly dividing cells (cancer) or viral replication, though often at the cost of significant side effects.
Key Concepts in Drug–Target Interaction
Affinity and Selectivity
- Affinity: how strongly a drug binds to its target
- Selectivity: how specifically a drug binds to one target versus many others
High affinity and selectivity are generally desired:
- High affinity allows effective action at low doses
- High selectivity reduces binding to unintended targets and thus decreases side effects
Potency and Efficacy
- Potency: how much drug is needed to achieve a certain effect
- A potent drug achieves the effect at low concentration
- Efficacy: the maximum effect a drug can produce, regardless of dose
An agonist with high efficacy can fully activate a receptor’s response, while a partial agonist has lower efficacy and produces only a partial response even when all receptors are occupied.
Agonists, Partial Agonists, Antagonists, Inverse Agonists
- Agonist: activates a receptor and mimics the natural ligand
- Partial agonist: activates the receptor but produces less than the full response
- Antagonist: binds to the receptor without activating it, preventing agonists from binding
- Inverse agonist: reduces the basal activity of receptors that are active even without ligand
The balance between endogenous ligands, agonists, partial agonists, and antagonists determines the final physiological effect.
Dose–Response Relationship
The dose–response curve describes how the magnitude of a drug’s effect depends on its dose or concentration.
Typical features:
- At low doses, small increases in dose lead to noticeably greater effect
- At higher doses, effects approach a plateau (maximal effect), as most targets become occupied or maximally affected
From such curves, important parameters can be derived:
- The concentration required for half-maximal effect (often denoted $ \text{EC}_{50} $ or $ \text{ED}_{50} $)
- The maximal achievable effect
Changes in these parameters help compare different drugs or understand how disease states and other substances (e.g., other drugs) influence drug action.
Regulation and Adaptation: Tolerance and Sensitization
The body adapts to ongoing drug exposure. Cells and tissues can change the number or responsiveness of targets:
- Downregulation of receptors: fewer receptors on the cell surface or lower responsiveness
- Often occurs in response to chronic stimulation by agonists
- Leads to tolerance: reduced effect at the same dose, requiring higher doses for the same effect
- Upregulation of receptors: more receptors or increased sensitivity
- Often occurs after prolonged receptor blockade by antagonists
- Can lead to supersensitivity: exaggerated response when stimulation occurs
These adaptation processes are central to long-term therapy planning and to understanding withdrawal effects.
From Molecular Effect to Clinical Effect
The sequence from drug administration to observable effect can be broken down conceptually:
- Drug reaches target
Absorption and distribution bring the drug to its site of action. - Binding to target
Drug binds to its specific protein or other macromolecule, depending on affinity and concentration. - Molecular response
Changes occur in receptor conformation, enzyme activity, ion fluxes, or gene expression. - Cellular and tissue response
Cell signaling networks integrate the changes and alter cell function. - Organ and system response
The integrated behavior of tissues and organs changes (e.g., blood pressure drops, pain perception decreases, bacterial growth stops). - Clinical effect
The therapeutic goal is reached—or side effects appear, if other systems are also affected.
Understanding the mechanisms of drug action at each level helps in:
- Designing more precise and safer drugs
- Predicting interactions with other medications
- Explaining variability in response between individuals
This mechanistic view connects molecular chemistry, biological function, and therapeutic use.