Pharmacodynamics1 PDF

Pharmacodynamics Pharmacodynamics Pharmacodynamics describes the actions of a drug on the body. Most drugs exert effects, by interacting with specialized target macromolecules called receptors The drug–receptor complex initiates alterations in biochemical and/or molecular activity of a cel...

Pharmacodynamics Pharmacodynamics Pharmacodynamics describes the actions of a drug on the body. Most drugs exert effects, by interacting with specialized target macromolecules called receptors The drug–receptor complex initiates alterations in biochemical and/or molecular activity of a cell by a process called signal transduction Major receptor families A receptor is defined as any biologic molecule to which a drug binds and produces a measurable response. These receptors may be divided into four families: I. Ligand-gated ion channels II. G protein–coupled receptors III. Enzyme-linked receptors IV. Intracellular receptors I.Transmembrane ligand-gated ion channels The extracellular portion contains the drug- binding site. This site regulates the opening of the pore through which ions can flow across cell membranes The channel is usually closed until the receptor is activated by an agonist, which opens the channel for a few milliseconds. Depending on the ion conducted through these channels, these receptors mediate diverse functions, including neurotransmission and muscle contraction. For example Stimulation of the nicotinic receptor by acetylcholine opens a channel that allows sodium influx and potassium outflux across the cell membranes of neurons or muscle cells leading to depolarization. This generates an action potential in a neuron and contraction in skeletal and cardiac muscle. Agonist stimulation of the A subtype of the γ- aminobutyric acid (GABA) receptor increases chloride influx, resulting in hyperpolarization of neurons and less chance of generating an action potential. II. Enzyme-linked receptors This family of receptors undergoes conformational changes when activated by a ligand, resulting in increased intracellular enzyme activity This response lasts for minutes to hours. The most common enzyme linked receptors possess tyrosine kinase activity. When activated, the receptor phosphorylates tyrosine residues on itself and other specific proteins.  Phosphorylation can substantially modify the structure of the target protein, thereby acting as a molecular switch.  For example, the phosphorylated insulin receptor in turn phosphorylates other proteins that now become