Introduction
Pharmacodynamics explains “what the drug does to the body.” It covers the mechanism of drug action, interaction with receptors and the physiological or biochemical changes that occur in the body. This chapter describes different types of drug actions, receptor mechanisms and important concepts like potency, efficacy and dose–response relationships.
Types of Drug Action
1. Stimulation
Some drugs increase the activity of organs or systems. Example: adrenaline stimulates the heart, increasing heart rate and force of contraction.
2. Depression
Certain drugs decrease the activity of organs or the central nervous system. Example: alcohol, barbiturates and general anaesthetics depress CNS activity.
3. Irritation
Some agents cause irritation when applied to skin or mucosa. Counter-irritants like eucalyptus oil and methyl salicylate relieve deeper pain by increasing local blood flow or blocking spinal pain pathways.
4. Replacement
Drugs replace deficient endogenous substances. Example: insulin in diabetes, thyroxine in hypothyroidism.
5. Cytotoxic Action
Certain drugs selectively kill microorganisms or cancer cells. Example: antibiotics and anticancer drugs.
Mechanisms of Drug Action
Drugs act either without involving receptors (non-receptor-mediated) or through specific receptors (receptor-mediated).
Non-Receptor-Mediated Mechanisms
1. Physical Actions
- Osmosis: Mannitol reduces intracranial pressure by osmotic effect.
- Adsorption: Activated charcoal adsorbs toxins in poisoning.
- Demulcent action: Cough syrups soothe irritated mucosa.
- Radioactivity: Radioactive iodine (I-131) destroys thyroid tissue.
2. Chemical Actions
- Neutralisation: Antacids neutralise gastric acid.
- Chelation: Agents like BAL or desferrioxamine bind toxic metals for excretion.
3. Enzyme Inhibition
- ACE inhibitors (e.g., captopril) block angiotensin-converting enzyme.
- Allopurinol inhibits xanthine oxidase to reduce uric acid formation in gout.
4. Ion Channel Blockade
Local anaesthetics block sodium channels, preventing nerve impulse conduction.
5. Antibody Production
Vaccines act by stimulating production of antibodies.
6. Transporter Action
SSRIs block serotonin reuptake transporters, increasing serotonin levels.
7. Other Mechanisms
Some anticancer drugs bind nucleic acids; colchicine binds tubulin and reduces neutrophil migration.
Receptor-Mediated Mechanisms
Receptors are macromolecules located on the cell membrane, cytoplasm or nucleus. Drugs bind to receptors to form a drug–receptor complex, which produces a response.
Key Terms
- Affinity: Ability of a drug to bind to a receptor.
- Intrinsic activity: Ability of a drug–receptor complex to produce an effect.
Types of Ligands
1. Agonists
Have high affinity and high intrinsic activity. Example: adrenaline, morphine.
2. Antagonists
Bind to receptors but do not activate them. They block agonist action. Example: naloxone, atropine.
3. Partial Agonists
Bind to receptors but produce weaker responses than full agonists. Example: buprenorphine, pindolol.
4. Inverse Agonists
Produce effects opposite to agonists. Example: beta-carbolines at benzodiazepine receptors.
Theories of Drug–Receptor Interaction
1. Occupation Theory
Drug effect depends on the number of receptors occupied. Affinity determines binding; efficacy determines response.
2. Rate Theory
Effect depends on the rate of drug–receptor interaction, not on number of occupied receptors.
3. Induced-Fit Theory
The receptor modifies its structure to fit the drug when the drug approaches.
Receptor Families
1. Ligand-Gated Ion Channels
Example: nicotinic receptors, GABAA, glutamate. Response occurs within milliseconds.
2. G-Protein Coupled Receptors (GPCRs)
Example: muscarinic, adrenergic receptors. They activate second messengers like cAMP, IP3, DAG. Response occurs within seconds.
3. Enzyme-Linked Receptors
Example: insulin receptors, growth factor receptors. Response occurs in minutes to hours.
4. Nuclear Receptors
Example: steroid hormone receptors, thyroid hormone receptors. They modify gene expression and act over hours.
Regulation of Receptors
Receptors can become more or less sensitive depending on drug exposure.
Down-Regulation
Occurs due to prolonged stimulation, reducing receptor numbers or sensitivity.
Up-Regulation
Occurs after prolonged blockade, increasing receptor numbers or sensitivity.
Dose–Response Relationship
1. Graded Dose–Response
Shows how response increases with dose. When plotted using log dose, curve becomes sigmoid shaped.
2. Quantal Dose–Response
Shows the percentage of population responding to a particular dose. Responses are all-or-none—for example, induction of ovulation.
Potency and Efficacy
Potency
The amount of drug needed to produce an effect. A more potent drug requires a smaller dose. Example: morphine is more potent than pethidine.
Efficacy
The maximum effect a drug can produce. Example: morphine is more efficacious than aspirin for pain relief.
Therapeutic Window
The safe range of drug concentration between minimum effective concentration and minimum toxic concentration.
Combined Effects of Drugs
1. Additive Effect
Total effect equals the sum of individual effects.
2. Synergistic Effect
Combined effect is greater than additive. Example: alcohol and benzodiazepines.
3. Antagonism
One drug reduces or blocks the action of another. It may be competitive or non-competitive.
Detailed Notes:
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