Pharmacodynamics

Lecture 2

OCTS3704 Pharmacology
Ms R van Wyk
 Lecture Outline

• Pharmacodynamics
• Definitions
 Pharmacodynamics Definition

• The effects of drugs and their action

• The study of the detailed description of mechanisms of action of drugs
and how they exert their effects
• The study of the biochemical & physiologic effects of drugs on biological
processes
• What the drug does to the body
• The effects of the drug on the body
• The mechanism of action of the drug

(Compare with pharmacokinetics: how the body handles a drug (absorption,

distribution, metabolism, excretion)
 Medication; Dosage form

Drug Solution Pharmaceutics

E.g. You drink the paracetamol tablet for headache. The
tablet then dissolves to release the paracetamol

Absorption E.g. The paracetamol is absorbed from the

gastro-intestinal tract to the blood
Distribution E.g. The paracetamol is distributed through
the body via the blood to get to the place it needs to work
Metabolism E.g. The paracetamol has worked, e.g. Pharmacokinetics
relieved the pain, but it can’t stay in the body – it is then
metabolised by the liver to be excreted
Excretion E.g. The metabolites of paracetamol is excreted
by the kidney

Drug: Receptor interaction;

Mechanism of action

Effect Pharmacodynamics
E.g. The mechanism of action of paracetamol in order to
relief the headache
The mechanism of action description consists at a minimum
of a drug target & what the drug does on the target
How drugs work: Mechanisms of drugs to exert effects

• Receptor mechanisms
• Non-receptor mechanisms
 Receptor mechanisms

• Drugs stimulate or inhibit/block receptors

• Most drugs bind to cellular receptors & Initiate a series of biochemical reactions
and physiological changes with cellular responses (e.g. the normal cellular function
is inhibited or switched on), leading to the effects of the drug
 Non-receptor mechanisms

– Drugs block ion channels: e.g. local anaesthetics, calcium channel blockers –
treatment for hypertension
– Drugs enhance ion movement (neurotransmission): e.g. antidepressants
– Drugs inhibit enzymes: e.g. MAO - treatment for depression; COX - treatment
for inflammation; ACE – treatment for hypertension; Carbonic anhydrase –
treatment for glaucoma
– Drugs cause cytotoxic actions: anti-cancer drugs
– Drugs act by physical properties: e.g. fiber laxatives
– Drugs act by chemical reactions: e.g. antacids neutralise gastric acid
– Metal chelating agents: e.g. desferrioxamine binds to iron
– Drugs inhibit DNA/RNA synthesis: e.g. antibiotics, anticancer drugs, antivirals
– Drugs kill bacteria, fungi: antibiotics, anti-fungal drugs
– Drugs inhibit pumps in cell membrane: e.g. Na/K ATPase - treatment for heart
failure; Proton pump – treatment for peptic ulcer
 Receptors
• A receptor is a macromolecular component, usually protein, which is a specific
site on which a group of drugs or naturally occurring substances (ligands), e.g.
neurotransmitters/hormones bind (definition)
• Usually situated on cell membranes
• Also situated on organelles within cell / in cytoplasm
• Different types of receptors, and in different organs
• Drugs and receptors are selective for an organ: only the organ with a specific
receptor can react to a specific drug (e.g. beta-1 in heart, beta-2 in lung)
• Drugs are specific for receptors in an organ: there are various receptors in an
organ, each with a different function (e.g. alpha-1 stimulation = vasoconstriction,
beta-2 stimulation = vasodilatation)
• Endogenous mediators / ligands normally activate a specific receptor and the
activation leads to intracellular changes
• A drug and its receptor is like a lock and its key: Only a specific key opens a
specific lock
• Receptors provide an important site for drug action
• Many drugs exert their effects by combining/binding with a receptor and:
– either mimic the effect of the natural mediator (stimulate the receptor)
= an agonist or
– blocking it = an antagonist
Terminology referring to events that occur at cellular level
(Definitions)

AFFINITY
• The strength of binding between a drug and its receptor

INTRINSIC ACTIVITY
• The ability of a drug to elicit a response from the receptor (after binding)
or
• The ability to initiate a cellular response
Terminology referring to events that occur at cellular level
(Definitions)
AGONIST
• A substance/drug that stimulates / activates the receptor to produce effects
• A drug that alters the physiology of a cell by binding to a receptor & causes a
certain response

• Agonists must have affinity & intrinsic activity

ANTAGONIST
• A drug that inhibits / blocks the responses caused by agonists

• Antagonists have affinity, but no intrinsic activity

• Different types of antagonists: Competitive, Non-competitive, Irreversible,
Functional, Chemical
Terminology referring to events that occur at cellular level
(Definitions)
COMPETITIVE ANTAGONIST
• The antagonist binds to the same receptor as an agonist but fails to activate it
(the antagonist blocks the receptor)
– E.g. Histamine is the natural occurring agonist that binds to & stimulates
the Histamine-1 receptors to cause an allergic reaction; The competitive
antagonist, an antihistamine binds to the Histamine-1 receptors and blocks
them = Histamine cannot bind to its receptors = Allergy is treated
– E.g. Adrenaline/noradrenaline are the natural occurring agonists that bind
to and stimulate beta-receptors to increase blood pressure; The
competitive antagonists, Beta-antagonists/blockers block the beta-
receptors so that adrenaline/noradrenaline cannot bind to the receptors =
decreased blood pressure

NON-COMPETITIVE ANTAGONIST
• The antagonist binds to a different receptor to that to which the agonist binds,
& induces a conformational change in the receptor so that the agonist no
longer “recognizes” the receptor (agonist-binding domain)
Terminology referring to events that occur at cellular level
(Definitions)
IRREVERSIBLE ANTAGONIST
• The antagonist combines/binds permanently to the receptor

PHYSIOLOGICAL / FUNCTIONAL ANTAGONIST

• Two agonists, in unrelated reactions, cause opposite effects
– Physiological Antagonism: 2 Agonists act on different receptors in different
systems, causing opposing effects
• E.g. Acetylcholine stimulates the muscarinic receptor on the sphincter
pupillae (circular muscle in iris) to cause miosis; Adrenaline stimulates
the α1 receptor on the radial muscle of the iris to cause mydriasis
– Functional Antagonism: 2 Agonists act on different receptors in the same
organ
• E.g. Histamine stimulates H1 receptors to cause vasodilatation;
Adrenaline stimulates α1 receptors to cause vasoconstriction
Terminology referring to events that occur at cellular level
(Definitions)

CHEMICAL ANTAGONIST / ANTAGONISM BY NEUTRALIZATION

• A drug binds chemically to an agonist drug & thereby prevents the agonist
from binding to its receptor
– E.g. protamine sulphate binds to heparin = heparin is inactivated
 Terminology relating to drugs (Definitions)

POTENCY
• The dose / concentration of a drug that is necessary / required to produce 50%
of the maximum response / effect that the drug is capable to produce
• The dose at which a drug exerts 50% of its maximal effect
– E.g. a smaller amount/dose of morphine is required postoperative than
codeine for pain relief = morphine is more potent (morphine and codeine
have the same mechanism of action)

EFFECTIVITY
• The degree to which a drug is capable to cause maximum effects (not dose
related). The degree of which the drug is capable to stimulate receptors after
binding to a receptor have occurred
– E.g. Drug A needs to occupy 100 receptors to obtain maximum effect &
Drug B needs to occupy 1000 receptors for a similar effect than Drug A =
Drug A is more effective than Drug B
 What is important to know for the test

• All the definitions

• Mechanisms by which drugs exert their effects
• Examples of non-receptor mechanisms