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Dr V.N NDIKUM
8-Mar-12
PHARMACOKINETICS
PHARMACODYNAMICS
Resorption
Distribution
Receptor
Excretion
Signal transduction
Cellular reaction
OR
OR
Biochemical and physiological effects of drugs and their mechanisms of action Relationship between drug concentration and effect
Non-protein Targets
Nucleic acid Cell membrane others
or microbes)
Non-protein targets
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therapy DNA / RNA: Antisense oligonucleotides (experimental) Membranes : Inhalation anaesthetics (?) Fluid compartments: Osmotically active solutes
Plasma volume expanders (dextran) Osmotically acting diuretic agents (mannitol) Laxatives (Lactulose)
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Definition of a receptor
(chemically) recognizes a ligand and carries out a function in response to ligand binding.
within the cell, or in the cytoplasm Finite number of receptors in a given cell
Receptor mediated responses plateau upon saturation of all receptors
Types of receptors
Types of receptors
Trans membrane ion channels:
conduct ions across membrane in response to ligand binding, voltage gradient or second messenger; e.g., H+/K+-ATPase
Types of receptors.
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Metabolic receptors
hormone and neurotransmitter receptors that are coupled to biochemical secondary messenger / effector mechanisms
Classes of receptors
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Characteristics of a Receptors
Specificity Receptor interacts with one type of ligand or a structurally related family of ligands Competition between related ligands Example: glucose transporter binds D-glucose specifically Affinity Energetics of ligand receptor interactions Energetics of binding determine specificity Intrinsic activity A measure of the ability of a bound drug to activate the receptor Distinguishes agonist from antagonist Saturability Finite number of binding sites on a receptor, along with specificity of interactions, implies that binding sites can become fully occupied with ligand molecules Additional ligand leads to non-specific binding
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Molecular Level of Drug-receptor interaction Drug must fit receptor (lock and key concept Result: change in cell function
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Second Messenger
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Verapamil, nefidipine
Anti-metabolites
Enter biochemical reactions in place of normal
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