Pharmacodynamics,Tolerance, Ideosynchracy, ADRs,Hypersensitivity. By Dr. Baqir Naqvi.pptx

1. Pharmacodynamics
Tolerance & Dependence, Adverse Drug Reactions, Idiosyncrasy, Hypersensitivity
By
Dr. M. Baqir Raza Naqvi
(Lecturer Pharmacology)
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Nazar College of Pharmacy
DAKSON Institute of Health Sciences, Islamabad

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22. Receptors mediated Actions
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• Agonists: molecules that activate receptors.
• Antagonists: molecules that prevent receptor activation.
- Competitive: bind reversibly to receptors (They compete with
agonists for receptor binding. The receptor will be occupied with agent
present at high conc.)
- Noncompetitive: bind irreversibly to receptors.
• Partial agonists: produce maximal effect that is lower than that of a
full agonist. In addition, they can act as antagonist.
• For Example: Anti-histamine suppress allergy symptoms by binding to
receptor of histamine thus preventing activation of these receptors by
histamine.

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33. • These are sometimes called inotropic receptors.
• They are involved mainly in fast synaptic transmission.
• There are several structural families, the commonest
being heteromeric assemblies of four or five subunits,
with trans membrane helices arranged around a central
aqueous channel.
• Ligand binding and channel opening occur on a milli-
seconds timescale.
• Examples include the nicotinic acetylcholine, GABA
type-A (GABA-A) and 5-hydroxytryptamine type 3 (5-HT3)
receptors. 33
1. Ligand Gated Ion Channels

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36. •Mechanism: These cell surface receptors, also
called ligand gated ion channels, enclose ion selective channels
(for Na+, K+, Ca2+ or Cl¯ ) within their molecules.
• Agonist binding opens the channel and
causes depolarization/hyper polarization/ changes in cytosolic
ionic composition, depending on the ion that flows through.
• Most useful drugs in clinical medicine act by mimicking or blocking
the actions of endogenous ligands that regulate the flow of ions
through plasma membrane channels.
• The natural ligands include acetylcholine, serotonin, aminobutyric
acid (GABA), and the excitatory amino acids (e.g, glycine,
aspartate, and glutamate).
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37. 2. G-protein Coupled Receptors (GPCRs)
• G protein-coupled receptors (GPCRs) are a class of trans membrane receptors
that span the cell membrane.
• They are activated by ligands such as hormones, neurotransmitters, and light.
When a ligand binds to the receptor, it causes a conformational change in the
receptor that ultimately leads to the activation of a G protein.
• Importance: The Activated G-protein, in turn, activates downstream signaling
molecules, ultimately leading to cellular responses such as the regulation of
gene expression, the contraction of smooth muscle, or the release of
intracellular second messengers.
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The molecule has 7 α-helical membrane
spanning hydrophobic amino acid segments –
3 extracellular and 3 intracellular loops.

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40. Role of G-proteins;
• G-proteins function is to recognize activated GPCRs and pass on
the message to the effector systems that generate a cellular
response. They represent the level of middle management in the
organizational hierarchy.
• They are called G-proteins because of their interaction with the
guanine nucleotides, GTP and GDP.
• G-proteins consist of three subunits: α, β and γ .
• Guanine nucleotides bind to the α subunit, which has
enzymes' activity, catalyzing the conversion of GTP to GDP.
• The β and γ subunits remain together as a β-γ complex.
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4. Enzymes Receptors

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•These are intracellular (cytoplasmic or nuclear) soluble proteins which
respond to lipid soluble chemical messengers that penetrate the cell.
•The ligand receptor dimer moves to the nucleus and binds other co-
activator/co-repressor proteins which have a modulatory influence on its
capacity to alter gene function.
•These includes Receptors for corticosteroids, mineralocorticoids,
thyroid hormones, sex hormones and Vit. D etc.
4. Nuclear Receptors

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Important
for
Viva,
SQs
&
MCQs

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Important
for
Viva,
SQs
&
MCQs

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Important
for
Viva,
SQs
&
MCQs

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ADR most common
• Women
• Elderly (>60 y old)
• Very young (1-4y)
• Patients taking
more than one
drug (Multiple
drugs)

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Side Effects v/s Adverse Effects
Important
for
Viva,
SQs
&
MCQs

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iii)

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The term 'idiosyncratic drug reaction' has been used for unpredictable
reactions that occur in only a small percentage of patients receiving the drug
and which do not involve known pharmacological properties of the drug.
Important
for
Viva,
SQs
&
MCQs

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Important
for
Viva,
SQs
&
MCQs

98. Thank you !
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