Section 2 - How Drugs and Toxins Act, Molecular Aspects

Click to edit Master title style Click to edit Master text styles Second level Third level Fourth level Fifth level Click to edit Master title style Click to edit Master text styles Second level Third level Fourth level Fifth level Principles of Pharmacology and Toxicology (BIOL3020) Section 2 How Drugs and Toxins Act Molecular Aspects Rang et al 2007 (Chapter 3) Stine and Brown (2006) Principles of Toxicology How Drugs Act The majority of drugs act at protein targets Bind to a specific binding site on the protein How Drugs Act 7  1) Receptors  Receptor in Action (example) Extracellular Intracellular Chemical messenger/drug Activation of downstream protein Receptor-Drug Interaction D Example of a receptor-drug interaction  C  Ligand-gated Ion Channel in Action Na Na Na Na Na Na Na Na Change in Membrane potential Initiates cellular response Chemical messenger/drug Extracellular Intracellular Drugs Affecting Ion Channels g  3) Enzymes  3) Enzymes  4) Transporters (Carrier Molecule) Transporters are membrane proteins that transport ions and small molecules (eg. glucose) across membranes Intracellular Extracellular 4) Transporters (Carrier Molecule) Drugs can act as inhibitors for transporters eg Tricyclic antidepressants and cocaine inhibit noradrenaline uptake at the presynaptic nerve terminal in brain Result is more NA available to bind to receptors  Tricyclic antidepressants Noradrenaline Tricyclic antidepressant Noradrenaline transporter Noradrenaline receptor Nerve Terminal False Substrates for Transporters Drugs can act as false substrates for transporters eg Amphetamines (structurally related to noradrenaline (NA)) competes with noradrenaline for transport back into nerve terminal Result is more NA available to bind to receptors  Amphetamines Noradrenaline Amphetamine Noradrenaline transporter at presynaptic nerve terminal Noradrenaline receptor Effects of Amphetamine-like drugs v  Targets for Toxins and Toxicants Toxicant any harmful substance Toxin a naturally produced toxicant Can interact with the same targets as drugs (proteins, lipids, nucleic acids) Either cause symptoms related to their primary action Or cause symptoms related to a downstream affect Targets for Toxins and Toxicants Enzymes Enzyme inhibition is a common mechanism for poisons Inhibition may be reversible or irreversible Example inhibition of acetlycholinesterase by organophosphate insecticides  Targets for Toxins and Toxicants  Targets for Toxins and Toxicants DNA Toxicants that interact and produce changes in DNA are called mutagens Some (nitrous acid) delete portions of bases Remove an amino group from adenine or cytosine (deamination) Mustard gas (alkylating agents) add alkyl groups to bases