Drug Action Mechanisms

7 methods by which drugs cause their action include: PEFsPdCpRsig (almost PEEPd CpR sig)

1. PHYSICOCHEMICAL ACTIONS
   • Antacids exert their effects by neutralizing gastric acid
   • Chelating agents reduce the concentration of certain metallic ions within the body (eg, desferoxamine and iron, or activated charcoal)
   • CaCl3, KCl, blood, Mg, replase alter or supplement endogenous primary substrates
2. ACTIONS ON ENZYMES
   • Enzymes are biological catalysts, and most drugs that interact with enzymes are inhibitors
   • Increased concentration of the substrate and decreased concentration of the product eg. ACE inhibitors (captopril, enalapril) prevent the conversion of ACEI to ACEII and bradykinin to various fragments
   • Neostigmine inhibits acetylcholinesterase reversibly
3. DRUGS WHICH ACT AS FALSE SUBSTRATES FOR ENZYMES
   • Fluorouracil act as “false substrate”, replaces uracil as an intermediate in purine biosynthesis but cannot be converted into thymidylate 
4. PRODRUGS
   • Require conversion to activated form by metabolic pathway
   • Levodopa → Dopamine
   • Parecoxib → Valdecoxib
5. ALTERATION OF CARRIER PROTEIN PROPERTIES
   • Cardiac glycosides (such as digoxin) inhibits Na-K pump
   • Loop diuretics inhibits Na/K/Cl co-transporter in loop of Henle
   • Cocaine inhibits noradrenaline re-uptake
6. VOLTAGE GATED ION CHANNELS
   • Involved in the conduction of action potentials in excitable tissues
   • Several groups of drugs have specific blocking actions at these ion channels
     • local anaesthetics (eg, lignocaine) block Na channels,
     • calcium channel blockers (eg, diltiazem) acts on vascular smooth muscle ion channels
7. RECEPTORS
   • Definition:
     • A protein, often integral to a membrane, containing a region to which a ligand binds specifically to elicit a response.
     • Binding may be allosteric (at a site distant to the receptor).
     • Grouped into three classes based on mechanism of action:
       1. Altered ion permeability (ion channels / ionotropic)
          • Membrane spanning complexes with the potential to form a channel through the membrane
          • Three families:
            1. Pentameric
               • nicotinic Ach receptor at the NMJ → allows an Na channel to form
               • GABA A receptor which allows a Cl channel to form,
               • 5HT3 receptor
            2. Ionotropic glutamate – NMDA ligand gated ion channels.
               • They form Na, K and (NMDA only) Ca channels when glutamate binds
            3. Purinergic receptors activated by ATP, permeable to Na, K and Ca, and are associated with mechanosensation and pain.
       2. Production of intermediate messengers
          • Membrane bound systems that transduce a ligand gated signal presented on one side of the cell membrane into an intracellular signal transmitted by intermediate messengers. These messengers:
            • G proteins (most common) – eg, Nad and Adr
            • Tyrosine kinase – eg, insulin
            • Guanylyl cyclase – eg, NO, atrial natriuretic peptide
       3. Regulation of gene transcription
          • Steroids and thyroid hormones act through intracellular receptors to alter the expression of DNA and RNA, and indirectly alter the production of intracellular proteins.

Gladwin 2016

Answer by Gladwin