Pharmacodynamics: Principles of Drug Action

Study Notes

Pharmacodynamics studies the biochemical and physiological effects of drugs and their mechanisms of action.
It encompasses the action-effect sequence and the dose-effect relationship.
Clinically, pharmacodynamics focuses on:
- Dosage of drugs
- Receptors
- Drug effects
- Side effects/adverse effects
- Therapeutic efficacy and safety
- Drug interactions
- Therapeutic basis of drugs
- Mechanisms of action
A drug is a chemical substance that, when taken from outside the body, causes physical or biochemical changes in the cellular environment.
Drugs are also known as xenobiotics, as they are foreign substances that influence the body's internal environment.

Drugs generally do not introduce new functions or systems, but rather modify or alter existing processes.
Drugs modulate intrinsic physiological functions in the body.
Four main ways drugs work:
- Replacement or substitution for missing chemicals
- Increase or stimulation of cellular activities
- Depression or slowing down of cellular activities
- Interference with the functioning of foreign cells, like microorganisms or tumors (chemotherapeutic agents)

Stimulation: e.g., adrenaline's effect on the heart (excessive stimulation can be problematic).
Depression: e.g., barbiturates depress the CNS, quinidine depresses the heart. Some drugs can stimulate one organ and depress another (e.g., acetylcholine).
Irritation: Nonselective, often noxious effect, particularly on less specialized cells, leading to increased secretions or blood flow. Strong irritation can cause inflammation, corrosion, necrosis, and damage (e.g., alcohol, smoking, substance abuse).
Replacement: e.g., levodopa in Parkinsonism, insulin in diabetes, iron in anemia.
Cytotoxic action: Penicillin, chloroquine, zidovudine, cyclophosphamide, etc. This is commonly referred to as chemotherapy.

Drug Receptor Interaction:
- Drugs typically interact with specific molecular components of an organism (usually proteins) causing biochemical and physiological changes.
- Most drugs target biomolecules (mainly proteins) within cells. There are four main types:
  - Receptors
  - Enzymes
  - Ion Channels
  - Carrier Molecules
- Non-receptor mediated mechanisms: The drug's action is based on its physical, chemical, or biochemical properties. Examples include:
  - Bulk laxatives (ispaghula) for physical mass
  - Dimethicone, petroleum jelly for physical form, opacity
  - Paraamino benzoic acid (PABA) for absorption of UV rays
  - Activated charcoal for adsorption properties
  - Mannitol, magnesium sulfate for osmotic activity
  - I-131 and other radioisotopes for radioactivity
  - Antacids for neutralization of HCl
  - Potassium permanganate for oxidizing properties
  - Chelating agents (EDTA, dimercaprol) for chelation of heavy metals
  - Cholestyramine for sequestration of cholesterol in the gut
  - Mesna for scavenging reactive metabolites of cyclophosphamide
  - Simethicone for adsorbing gases (antiflatulent)
  - Magnesium sulfate for osmosis (purgative)
  - Alkylating agents for covalent reaction with biomolecules.