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Types of Drug Action

For medical students3 min readUpdated 2026-10-10

The types of drug action represent a foundational pharmacological classification describing exactly how a drug interacts with the organism. Effects may develop directly at the site of tissue contact or after absorption into the bloodstream, serve as the primary therapeutic goal or an undesirable accompaniment, and influence cells either directly or via complex reflex mechanisms.

Main targetsVoltage-gated ion channels of cell membranes (sodium, potassium, calcium)

Resorptive effectDevelops only after the substance enters the systemic circulation

Central actionRequires the drug to cross the blood-brain barrier (BBB)

Side effectOccurs even when using the drug in strict therapeutic doses

Site of Effect: Local and Resorptive Action

Depending on where the drug begins to work and contact tissues, actions are divided into local and resorptive.

Local action develops directly at the site of application. The drug interacts with sensory nerve endings on the skin or mucous membranes. Typical examples include ointments, lotions, patches, gargles, eye and ear drops, or surface anesthesia. It is important to remember that even with local administration, a fraction of the substance can be absorbed into the blood, leading to unexpected systemic effects, or the drug may trigger reflex reactions.

Resorptive action (from the Latin resorbeo — to absorb) occurs only after the drug enters the systemic circulation and is distributed throughout the body. This is achieved via absorption into the vascular bed or through direct intravenous administration.

Direct, Indirect, and Reflex Influence

Drugs can alter the function of organs and systems through three different pathways depending on the distance to the target:

Direct (primary) action involves the immediate contact of the drug with the target organ tissue. For example, cardiac glycosides bind directly to cardiomyocytes, exerting a positive inotropic effect (increasing the force of myocardial contraction).
Indirect (secondary) action is a cascade of physiological changes resulting from the primary effect on another organ. For example, improved diuresis under the influence of cardiac glycosides occurs not from a direct effect on the kidneys, but due to increased cardiac output and resolution of circulatory failure.
Reflex action is mediated through the nervous system. The drug excites receptors, a signal is transmitted via a reflex arc to the central nervous system, and a stimulating or inhibitory command is sent to distant organs. One can target skin exteroceptors (mustard plasters cause irritation and a subsequent trophic effect in internal organs) or vascular interoceptors (intravenous lobeline stimulates carotid sinus chemoreceptors, which stimulates the respiratory and vasomotor centers).

Therapeutic Goal and Selectivity

In clinical practice, the effects of the same drug are strictly divided into desirable and undesirable, and their focus of action is evaluated.

Main (principal) action is the intended therapeutic result for a specific condition. It depends on the pathological context. For example, phenytoin is used in an epileptic patient for its primary anticonvulsant action, whereas for arrhythmias caused by glycoside intoxication, its main effect is antiarrhythmic.
Side effect includes any additional alterations occurring with drug administration in therapeutic doses. Most commonly, these are undesirable and may necessitate discontinuation of therapy. Classic examples include the ulcerogenic action of acetylsalicylic acid (gastric mucosal ulceration) or ototoxicity (hearing impairment) from aminoglycosides such as gentamicin.
Selective action means that a substance predominantly affects a specific organ. Oxytocin acts on the uterine myometrium, cardiac glycosides on the myocardium, and hypnotics on central nervous system structures.

Nervous System Localization and Bond Strength

Based on localization within the nervous system, actions are classified as central action (direct effects on the brain and spinal cord, as with general anesthetics or antidepressants) and peripheral action (effects on peripheral nerves, synapses, or tissues). For example, curare-like muscle relaxants relax skeletal muscle by blocking neuromuscular synapses, while vasodilators relax vascular smooth muscle. Drugs with central action may produce peripheral side effects (the neuroleptic chlorpromazine blocks peripheral $\alpha$-adrenergic receptors, lowering blood pressure).

At the cellular level, frequent targets include voltage-gated ion channels (opening upon membrane depolarization, unlike ligand-gated receptors). Drugs can block ion influx or activate currents.

Based on the nature of the chemical bond with the target molecule, actions are divided into two types:

Reversible: the drug binds via weak bonds (hydrogen, ionic, van der Waals). The complex dissociates through competition for the binding site or natural dissociation.
Irreversible: strong covalent bonds are formed. For example, acetylsalicylic acid irreversibly acetylates the active site of the cyclooxygenase (COX) enzyme. The effect ceases only after the body synthesizes new enzyme molecules.

Mnemonic

The pair of "Direct and Indirect Action" is easily remembered using the falling domino analogy: direct action is the strike against the first tile, while indirect action is the falling of all subsequent figures resulting from that initial push.

Frequently asked questions

What factors determine the rate of onset of a drug's resorptive action?

The rate of onset of resorptive action (absorption rate) is primarily determined by the route of administration. This process is also influenced by:

Physicochemical properties — lipophilic nonpolar compounds are absorbed best, whereas for solid forms, water-soluble salts accelerate absorption.
Particle size and surface area — micronization increases contact area and accelerates absorption.
Blood flow intensity — tissue vascularization (e.g., subcutaneous adipose tissue), which can be altered by massage, compresses, or vasoconstrictors (epinephrine).
Tissue permeability — can be enhanced by administering the enzyme hyaluronidase.
Diffusion rate — acts as a limiting factor in the aqueous environment of the intestine.

What major cellular targets exist for drugs besides ion channels?

Aside from ion channels, major cellular targets for drugs include receptors, enzymes, and transport systems.

Receptors — specific structures that drugs bind to (e.g., P2Y12 purinergic receptors for thienopyridines).
Enzymes — substances can act as their inhibitors (e.g., cyclooxygenase, MAO-A, proton pump).
Transport proteins — carrier proteins whose blockade disrupts substance transport across membranes (e.g., neurotransmitter reuptake blockade).
Ion pumps — active ion transport systems (e.g., $Na^+$-$K^+$-ATPase, blocked by cardiac glycosides).

Which drugs exert irreversible action through covalent bond formation?

Irreversible action via covalent bond formation with target molecules is established for:

Acetylsalicylic acid — irreversibly acetylates the active site of cyclooxygenase.
Thienopyridines (ticlopidine, clopidogrel) — active metabolites covalently bind to cysteine residues of platelet P2Y12 receptors.
Phenoxybenzamine — forms a stable covalent bond with $\alpha_1$- and $\alpha_2$-adrenergic receptors.

What types of adverse drug reactions exist outside of classical side effects?

In addition to classical side effects occurring at therapeutic doses, adverse reactions include:

Toxic reactions — can occur when exceeding maximal therapeutic doses or related to direct chemotherapeutic action.
Allergic reactions — mediated by the immune system and typically require a sensitization period.
Idiosyncrasy — a genetically determined aberrant drug reaction that can occur upon first exposure.
Drug intolerance — an unpredictable reaction unrelated to dose.
Organotoxic reactions — damage to specific organs.

Which receptor groups are excited during the reflex action of drugs?

During the reflex action of drugs, the following receptors are excited:

Exteroceptors — receptors of the skin and mucous membranes. For example, mustard plasters irritate the skin, eliciting a trophic effect in internal organs.
Interoceptors — specifically, carotid sinus vascular chemoreceptors. Intravenous lobeline excites them, leading to stimulation of the respiratory and vasomotor centers.
Gastric receptors — targeted by reflex-acting emetics and expectorants.

How does local drug action differ from resorptive action?

Local action develops directly at the site of drug contact with tissue (on skin or mucous membranes), whereas resorptive action manifests only after the substance is absorbed into the systemic circulation and distributed throughout the body.

Can the exact same drug action be both principal and a side effect?

Yes, this depends on the therapeutic goal. For example, CNS depression is the main action for hypnotics, but acts as a side effect (somnolence) when taking certain antihistamines.

How does the body recover after irreversible drug action?

During irreversible action, the substance binds to the target (enzyme or receptor) via strong covalent bonds that cannot be broken. Function recovers solely through physiological protein turnover—when the body synthesizes new target molecules.

Go deeper

Mechanisms of voltage-gated ion channels
Role of the blood-brain barrier in central drug action
Interaction of drugs with interoceptors and exteroceptors
Ulcerogenic action and ototoxicity: mechanisms of typical side effects
Physiological protein turnover processes in irreversible binding