Pharmacology Part 2 delves into the mechanisms of drug actions, focusing on pharmacodynamics and the effects of various drug classes. It explores how drugs interact with biological systems, detailing stimulation, depression, irritation, replacement, and cytotoxic actions. Key topics include enzyme interactions, ion channels, transporters, and receptors, providing insights for medical students and healthcare professionals. This resource is essential for understanding drug efficacy, safety, and therapeutic applications in clinical settings.

Key Points

  • Explains pharmacodynamics and the mechanisms of drug action.
  • Covers interactions between drugs and biological targets like enzymes and receptors.
  • Discusses the effects of drugs including stimulation, depression, and cytotoxicity.
  • Includes detailed examples of drug classes and their clinical applications.
Chinaza Okoli
43 pages
Language:English
Type:Study Guide
Biology
Chinaza Okoli
43 pages
Language:English
Type:Study Guide
Biology
321
/ 43
Nwogueze BC Part 2
1
Week 5
MECHANISMS OF DRUG ACTIONS
Pharmacodynamics is the study of drug effects. It attempts to elucidate the complete action-
effect sequence and the dose-effect relationship. Modification of the action of one drug by
another drug is also an aspect of pharmacodynamics.
Principles of Drug Action
Drugs (except those gene based) do not impart new functions to any system, organ or cell;
they only alter the pace of ongoing activity. The basic types of drug action can be broadly
classed as:
1. Stimulation: It refers to selective enhancement of the level of activity of specialized cells,
e.g. adrenaline stimulates heart, pilocarpine stimulates salivary glands. However, excessive
stimulation is often followed by depression of that function, e.g. high dose of picrotoxin, a
central nervous system (CNS) stimulant, produces convulsions followed by coma and
respiratory depression.
2. Depression: It means selective diminution of activity of specialized cells, e.g. barbiturates
depress CNS, quinidine depresses heart. Certain drugs stimulate one type of cells but depress
the other, e.g. acetylcholine stimulates intestinal smooth muscle but depresses SA node in
heart. Thus, most drugs cannot be simply classed as stimulants or depressants.
3. Irritation: This connotes a nonselective, often noxious effect and is particularly applied to
less specialized cells (epithelium, connective tissue). Mild irritation may stimulate associated
function, e.g. bitters increase salivary and gastric secretion, counterirritants increase blood
flow to the site. But strong irritation results in inflammation, corrosion, necrosis and
morphological damage. This may result in diminution or loss of function.
4. Replacement: This refers to the use of natural metabolites, hormones or their congeners in
deficiency states, e.g. levodopa in parkinsonism, insulin in diabetes mellitus, iron in anaemia.
5. Cytotoxic action: Selective cytotoxic action for invading parasites or cancer cells,
attenuating them without significantly affecting the host cells is utilized for cure/palliation of
infections and neoplasms, e.g. penicillin, chloroquine, zidovudine, cyclophosphamide, etc.
Mechanism of Drug Action
Majority of drugs produce their effects by interacting with a discrete target
biomolecule, which usually is a protein. Such mechanism confers selectivity of action to the
drug. Functional proteins that are targets of drug action can be grouped into four major
categories, viz. enzymes, ion channels, transporters and receptors. However, a few drugs do
act on other proteins (e.g. colchicine, vinca alkaloids, taxanes bind to the structural protein
tubulin) or on nucleic acids (alkylating agents). Only a handful of drugs act by virtue of their
simple physical or chemical property; examples are:
• Bulk laxatives (ispaghula)—physical mass
• Dimethicone, petroleum jelly—physical form, opacity
Nwogueze BC Part 2
2
• Paraamino benzoic acid—absorption of UV rays
• Activated charcoal—adsorptive property
• Mannitol, mag. sulfate—osmotic activity
• Antacids—neutralization of gastric HCl
• Pot. permanganate—oxidizing property
• Chelating agents (EDTA, dimercaprol)—chelation of heavy metals.
• Cholestyramine—sequestration of cholesterol in the gut
• Mesna—Scavenging of vasicotoxic reactive metabolites of cyclophosphamide
Types of Drug Action
Four major types of biomacromolecular targets of drug action, namely, (A) Enzyme; (B)
Transmembrane ion channel; (C) Membrane bound transporter; (D) Receptor
1. Enzymes
Almost all biological reactions are carried out under catalytic influence of enzymes; hence,
enzymes are a very important target of drug action. Drugs can either increase or decrease the
rate of enzymatically mediated reactions. However, in physiological systems enzyme
activities are often optimally set. Thus, stimulation of enzymes by drugs, that are truly
foreign substances, is unusual. Enzyme stimulation is relevant to some natural metabolites
only, e.g. pyridoxine acts as a cofactor and increases decarboxylase activity. Several enzymes
are stimulated through receptors and second messengers, e.g. adrenaline stimulates hepatic
glycogen phosphorylase through β receptors and cyclic AMP. Stimulation of an enzyme
increases its affinity for the substrate so that rate constant (kM) of the reaction is lowered
Apparent increase in enzyme activity can also occur by enzyme induction, i.e. synthesis of
more enzyme protein. Inhibition of enzymes is a common mode of drug action.
a. Nonspecific inhibition: Many chemicals and drugs are capable of denaturing
proteins. They alter the tertiary structure of any enzyme with which they come in
contact and thus inhibit it. Heavy metal salts, strong acids and alkalies, alcohol,
formaldehyde, phenol inhibit enzymes non-specifically. Such inhibitors are too
damaging to be used systemically.
Nwogueze BC Part 2
3
b. Specific inhibition: Many drugs inhibit a particular enzyme without affecting others.
Such inhibition is either competitive or non-competitive.
Competitive (equilibrium type): The drug being structurally similar
competes with the normal substrate for the catalytic binding site of the enzyme
so that the product is not formed or a nonfunctional product is formed, and a
new equilibrium is achieved in the presence of the drug. Examples:
o Physostigmine and neostigmine compete with acetylcholine for
cholinesterase.
o Sulfonamides compete with PABA for bacterial folate
synthetase.
o Moclobemide competes with catecholamines for monoamine
oxidase-A (MAO-A).
o Captopril competes with angiotensin 1 for angiotensin
converting enzyme (ACE).
o Letrozole competes with androstenedione and testosterone for
the aromatase enzyme.
o Allopurinol competes with hypoxanthine for xanthine oxidase;
is itself oxidized to alloxanthine (a non competitive inhibitor).
o Carbidopa and methyldopa compete with levodopa for dopa
decarboxylase.
Non-competitive: The inhibitor reacts with an adjacent site and not with the
catalytic site, but alters the enzyme in such a way that it loses its catalytic
property. Examples include;
o Acetazolamide — Carbonic anhydrase
o Aspirin, indomethacin — Cyclooxygenase
o Disulfiram — Aldehyde dehydrogenase
o Omeprazole — H+ K+ ATPase
o Digoxin — Na+ K+ ATPase
o Theophylline — Phosphodiesterase
o Propylthiouracil — Peroxidase in thyroid
o Lovastatin — HMG-CoA reductase
o Sildenafil — Phosphodiesterase-5
2. Ion Channels:
Proteins which act as ion selective channels participate in transmembrane signaling and
regulate intracellular ionic composition. This makes them a common target of drug action.
Drugs can affect ion channels either through specific receptors (ligand gated ion channels, G-
protein operated ion channels), or by directly binding to the channel and affecting ion
movement through it, e.g. local anaesthetics which physically obstruct voltage sensitive Na+
channels. In addition, certain drugs modulate opening and closing of the channels.
/ 43
End of Document
321

You May Also Like

FAQs

What are the main types of drug actions discussed in this document?
The document outlines several main types of drug actions, including stimulation, where drugs enhance the activity of specific cells; depression, which reduces cell activity; irritation, which can cause harmful effects; replacement, where drugs substitute for natural substances; and cytotoxic action, targeting harmful cells without affecting healthy ones. Each type of action is illustrated with examples, providing a comprehensive understanding of how drugs can influence biological systems.
How do drugs interact with enzymes according to the document?
Drugs interact with enzymes primarily through inhibition or stimulation. Inhibition can be competitive, where a drug competes with the substrate for the active site, or non-competitive, where the inhibitor binds elsewhere on the enzyme, altering its function. Stimulation often involves enhancing the enzyme's activity or increasing its production. The document provides specific examples of drugs that illustrate these interactions, highlighting their clinical significance.
What role do receptors play in drug action?
Receptors are crucial in drug action as they are the binding sites for drugs that initiate physiological responses. The document explains that receptors can be classified into various types, such as those that are ligand-gated or G-protein coupled. Agonists activate receptors to produce effects similar to natural signals, while antagonists block these effects. Understanding receptor dynamics is essential for developing effective therapeutic agents.
What are some examples of drug classes mentioned in the document?
The document discusses various drug classes, including alkylating agents, which interfere with DNA; antimetabolites that disrupt metabolic processes; and drugs that target ion channels and receptors. Each class is described with its mechanism of action and clinical applications, providing a broad overview of pharmacological treatments available for different conditions.
How does pharmacodynamics relate to drug efficacy?
Pharmacodynamics is the study of how drugs affect the body and is directly related to drug efficacy. The document explains that understanding the dose-effect relationship and the mechanisms of action helps in predicting the therapeutic outcomes of drugs. It emphasizes the importance of pharmacodynamics in optimizing treatment regimens and ensuring patient safety.

Related