pharmacodynamics
TRANSCRIPT
Pharmacodynamics
Dr. Karun Kumar
JR –II
Dept. of Pharmacology
Definition
• Study of the detailed mechanism of action by which drugs produce their pharmacologic effect
• Provides a scientific basis for the selection & use of drugs
Nature of drug receptors
• Receptor [Recipere to receive, accept] 1. a molecular structure within a cell or on the cell surface and characterized by (1) selective binding of a specific substance and (2) a specific physiologic effect that accompanies the binding, e.g., membrane receptors for peptide hormones, neurotransmitters, antigens, complement fragments, and immunoglobulins, and nuclear receptors for steroid hormones. 2. a sensory nerve terminal that responds to stimuli of various kinds; classified in various ways including by the type of stimulus (see chemoreceptor, mechanoreceptor, photoreceptor, and thermoreceptor) and by the location in the body (see exteroceptor, interoceptor, and proprioceptor).
• Ligand (ligare to tie or bind) a molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. 2. a molecule that donates or accepts a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex.
Types of drug receptors
• GPCRs Largest family of receptors
• GPCRs 7 transmembrane domains
• Neurotransmitter transporter proteins 12 transmembrane domain proteins (SSRI/SNRI target them)
• Steroid hormone receptors Intracellular proteins that translocate to the nucleus
Steroid hormones diffuse through cell membrane
↓
Bind to steroid receptors in cytoplasm
↓
Dimerized steroid hormone-receptor complex is translocated to the nucleus
↓
Binds to specific sequences on the DNA of a gene
↓
↑ transcription of gene (↑ mRNA)
↓
↑ translation of proteins
Drug receptor interactions
• Bonds formed between receptor and drug
1. Strong bonds Covalent bonds
a) Anti-neoplastic drugs binding to DNA
b) Irreversible anti-chEs (Ops)
2. Weak bonds
a) Hydrogen bonds
b) Ionic bonds
c) Hydrophobic (van der Waals) bonds
• Binding exhibits stereospecificity (only 1 of the enantiomers will form a 3 point attachment with the receptor)
• Affinity • Tendency/ability of a drug to combine with a receptor
• Measure of the strength of the drug-receptor complex
Drug receptors (HE MAN)
• Hormone receptors
1. Insulin receptors Insulin
2. Opioid receptors Morphine & naltrexone
3. Steroid receptors Cortisol & Tamoxifen
• Enzyme receptors (ABCDE,X)
1. A nA,K+ ATPase Digoxin
2. A Amine oxidase (MAO) Phenlzine, Tranylcypromine, Moclobemide, Clorgyline
1. C Carbonic anhydrase Acetazolamide
2. C chE Donepezil & Physostigmine
3. C COX Aspirin & Celecoxib
4. D DNA polymerase Acyclovir & Zidovudine
5. D DNA topoisomerase Ciprofloxacin
6. H HIV protease Indinavir
7. X Xanthine oxidase Allopurinol
• Membrane transport proteins
1. Ligand GIC Diazepam & Ondansetron
2. Voltage GIC Lidocaine & Verapamil
3. Ion transporter Loop & thiazide diuretics
4. Neurotransmitter transporter Fluoxetine, Cocaine
• Among others
1. Membrane lipids Alcohol & Amphotericin B
2. Nucleic acids Anti-cancer drugs
• Neurotransmitter receptors
1. Adrenoceptors E & Ppnl
2. Histamine recep. Cimetidine, Diphenhydramine
3. 5-HT rec. LSD & Sumatriptan
4. Muscarinic receptors Atropine, Bethanechol