Pharmacodynamics

Scott Kaba Matafwali

 Introduction

• Pharmacodynamics
– Study of the physiological and
biochemical mechanisms of drug
action
– How the drug affects the body
– influence of drug concentrations on
the magnitude of the response

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 Receptors
• Most of the drugs act by interacting with a
cellular component called receptor
• Receptors are protein molecules present
either on the cell surface or with in the cell
– e.g. adrenergic receptors, cholinoceptors,
insulin receptors, etc.
• The endogenous neurotransmitters,
hormones, most of the drugs produce their
effects by binding with their specific
receptors.
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 protein target for drug binding
• Four main kinds of regulatory protein are
commonly involved as primary drug
targets:
– Enzymes : (aspirin + cyclooxygenase)
– Transporters/Carriers : (fluoxetine + serotonin
reuptake transporter)
– Ion Channels : (local anesthetics + Na+
channels)
– Receptor Proteins : (cimetidine + histamine
receptor)
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 Receptor sites
• Where are receptors (drug targets)
found?
– Cell membranes
• usually associated with ion channels, transducer
proteins or enzymes
– Cell nucleus
– Enzymes (many vitamins are co-factors)
– Carrier molecules

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 Receptor super families
1. Ligand gated ion channels
• Receptors for Ach, GABA, serotonin
2. Ligand regulated trans-membrane enzymes
• Polypeptides; linked to tyrosine kinase
• Receptors for PGF, EGF, insulin, etc
3. G protein linked receptors
• Serpentine transmembrane proteins linked to GTP
• Activate or inhibit adenylyl cyclase
• Receptors for most peptide hormones eg GH
4. Intracellular receptors
• Intranuclear or intracytoplasmic; bind to DNA promoters

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Types of receptors

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Ligand gated ion channels

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GPCR

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 How Do Drugs Work (Mechanism of
Action)?

• Fundamental premise of pharmacodynamics is

‘drug-receptor interactions’

• Within the organs of the body are specific

receptors with which specific drugs can
interact

• The analogy often used is ‘lock and key’: only

drugs (chemicals) with the ‘correct’ molecular
shape can interact with a particular receptor.
– this is also known as selectivity
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 Types of drug action
• Intrinsic activity
– Intrinsic activity indicates the ability of receptor-bound
drug to activate the receptor and initiate downstream
events, leading to an effect
• Agonists (sometimes called full agonists)
– produce maximum activation of the receptor and elicit a
maximum response from the tissue.
• Antagonists
– bind but produce no activation of the receptor and
therefore block responses from the tissue
– Competitive and non-competitive antagonism

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 Types of drug action
• Partial agonists
– produce weaker activation of the receptor
than full agonists or the endogenous ligand.
– Partial agonists produce only partial activation
of the receptor and its downstream signaling
events.
• Inverse agonists
– inhibit rather than activate the receptor.
– Cause action opposite of the agonist

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Drug interaction

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 Dose-response
• The exact relationship between the dose and the
response depends on the biological effects and
the concentration
• Potency
– a measure of drug activity expressed in terms of the
amount required to produce an effect of given
intensity
– Strength of binding to receptor and ability to elicit
physiological changes
• Efficacy
– refers to the maximum response achievable from a
drug
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Concentration response curves

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 Therapeutic index
• In animal studies, the therapeutic index is
defined as the ratio of the TD50 to ED50
• TI=LD50 /ED50
• The larger value of the TI is, the wider
margin between effective dose and toxic
dose is. For example, the drug of TI=4 is
more safe than that of TI=2.
 Drug tolerance
• Decrease in the response with repeated
doses
– Desensitisation
• Can be caused by;
– Decreased receptor number (downregulation)
– Decreased receptor affinity
– modulation of downstream responses

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 Individual variation
• Biological characteristics and responses to
drugs vary among individuals
• Pharmacogenetics
– Genetic variation results in different
responses to drugs
• Pharmacogenomics
– Investigation of DNA/RNA characteristics
related to variation
– Mutations eg SNPS

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Thank you