A brief about the pharmacodynamics of drugs are described here.

1. Pharmacology
By-
Dr. Mrunal R. Akre

2. …………Continue

3. Pharmacodynamics: Mechanism of Drug
Action; Receptor Pharmacology
 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.
However, this alone can have profound medicinal as well as
toxicological impact. 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, omeprazole depresses
gastric acid secretion. 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). 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 on invading parasites or cancer
cells, attenuating them without significantly affecting the host cells is utilized for

4.  MECHANISM OF DRUG ACTION
 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
◦ • Paraamino benzoic acid—absorption of UV rays
◦ • Activated charcoal—adsorptive property
◦ • Mannitol, mag. sulfate—osmotic activity
◦ • 131I and other radioisotopes—radioactivity
◦ • Antacids—neutralization of gastric HCl
◦ • Pot. permanganate—oxidizing property
◦ • Chelating agents (EDTA, dimercaprol)—chelation of heavy metals.
◦ • Cholestyramine—sequestration of bile acids and cholesterol in the
gut
◦ • Mesna—Scavenging of vasicotoxic reactive metabolites of
cyclophosphamide
 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).

5. (A) Enzyme; (B) Transmembrane ion channel; (C) Membrane
bound transporter; (D) Receptor (see text for description)

6.  ENZYMES
◦ Almost all biological reactions are carried out under catalytic influence of enzymes.
 II. ION CHANNELS
◦ Proteins which act as ion selective channels participate in transmembrane signaling and
regulate intracellular ionic composition.
 III. TRANSPORTERS
◦ Several substrates are translocated across membranes by binding to specific
transporters (carriers) which either facilitate diffusion in the direction of the concentration
gradient or pump the metabolite/ion against the concentration gradient using metabolic
energy
 IV. RECEPTORS
◦ The largest number of drugs do not bind directly to the effectors, viz. enzymes,
channels, transporters, structural proteins, template biomolecules, etc.
◦ Receptor: -It is defined as a macromolecule or binding site located on the surface or
inside the effector cell that serves to recognize the signal molecule/drug and initiate the
response to it, but itself has no other function.
◦ Agonist - An agent which activates a receptor to produce an effect similar to that of the
physiological signal molecule.
◦ Inverse agonist- An agent which activates a receptor to produce an effect in the
opposite direction to that of the agonist.
◦ Antagonist - An agent which prevents the action of an agonist on a receptor or the
subsequent response, but does not have any effect of its own.
◦ Partial agonist- An agent which activates a receptor to produce submaximal effect but
antagonizes the action of a full agonist.
◦ Ligand (Latin: ligare—to bind) Any molecule which attaches selectively to particular
receptors or sites.

7. ACTION-EFFECT SEQUENCE
 ‘Drug action’ and ‘drug effect’ are often
loosely used interchangeably, but are not
synonymous.
◦ Drug action- It is the initial combination of the
drug with its receptor resulting in a
conformational change in the latter (in case of
agonists), or prevention of conformational
change through exclusion of the agonist (in case
of antagonists).
◦ Drug effect -It is the ultimate change in
biological function brought about as a
consequence of drug action, through a series of
intermediate steps (transducer).

8. DRUG DOSAGE
 ‘Dose’ is the appropriate amount of a drug needed to
produce a certain degree of response in a given patient.
 The dose of a drug is governed by its inherent potency,
i.e. the concentration at which it should be present at the
target site, and its pharmacokinetic characteristics.
 Standard dose -The same dose is appropriate for most
patients
 Regulated dose -The drug modifies a finely regulated
body function which can be easily measured.
 Target level dose - The response is not easily
measurable but has been demonstrated to be obtained at
a certain range of drug concentration in plasma
 Titrated dose -The dose needed to produce maximal
therapeutic effect cannot be given because of intolerable
adverse effects
 Fixed dose combinations (FDCs) of drugs - A large
number of pharmaceutical preparations contain two or
more drugs in a fixed dose ratio.

9. EXPIRY DATE OF PHARMACEUTICALS
 It is a legal requirement that all
pharmaceutical products must carry the
date of manufacture and date of expiry
on their label.
 The period between the two dates is
called the ‘life period’ or ‘shelf-life’ of the
drug

10. Adverse Drug Effects
 Side effects
◦ These are unwanted but often unavoidable pharmacodynamic effects that occur at therapeutic doses.
 Secondary effects
◦ These are indirect consequences of a primary action of the drug,
 Toxic effects
◦ These are the result of excessive pharmacological action of the drug due to overdosage or prolonged use.
 Intolerance
◦ It is the appearance of characteristic toxic effects of a drug in an individual at therapeutic doses
 Idiosyncrasy
◦ It is genetically determined abnormal reactivity to a chemical.
 Drug allergy
◦ It is an immunologically mediated reaction producing stereotype symptoms which are unrelated to the pharmacodynamic
profile of the drug
 Photosensitivity
◦ It is a cutaneous reaction resulting from drug induced sensitization of the skin to UV radiation.
 Drug dependence
◦ Drugs capable of altering mood and feelings are liable to repetitive use to derive euphoria, recreation, withdrawal from
reality, social adjustment, etc.
 Drug withdrawal reactions
◦ Apart from drugs that are usually recognised as producing dependence, sudden interruption of therapy with certain other
drugs also results in adverse consequences,
 Teratogenicity
◦ It refers to the capacity of a drug to cause foetal abnormalities when administered to the pregnant mother.
 Drug induced diseases
◦ These are also called iatrogenic (physician induced) diseases, and are functional disturbances (disease) caused by drugs
which persist even after the offending drug has been withdrawn and largely eliminated,
 Mutagenicity and Carcinogenicity
◦ It refers to capacity of a drug to cause genetic defects and cancer respectively.

11. To be Continued………..