Mechanisms of Drug Action Flashcards
Learning Outcomes •Describe the different types of drug receptors (e.g. ion channel receptors, G-protein coupled receptors, membrane-bound enzymes)review •Explain the necessity for second messengers •Describe the basic processes of drug-receptor interactions •Describe the concepts of agonist, antagonist and receptor •Explain the dose-response relationship
What is pharmacodynamics?
‘What the drug does to the body’
Modes of action
Interaction with receptors and signaling pathways
Dose response relationships Biochemical and physiological effects of drugs
What are the 4 molecular mechanisms of Action?
- (Direct physicochemical effect)
- Transport systems
- Enzymes
- Interaction with the 4 major types of receptors (Cell signalling Part II)
Others: adhesion molecules, organelles and structural proteins
What are the three main transport systems?
- Ion Channels
- Cell membrane ion pumps
- Transporter (carrier proteins)
Give two examples of Ion Channels (see also Cell Signalling lecture)
Voltage (and Ligand-gated) ion channels Second-messenger-regulated – a second messenger regulated by a G-coupled protein receptor
Give three examples of Cell membrane ion pumps (see also Fundamentals of Physiology lecture)
Active transport of ions against their concentration gradients
Proton pump inhibitors (e.g., omeprazole) - K+/H+-ATPase in gastric parietal cells
Digoxin - Na+/K+-ATPase (cardiac tissue)
Give two examples of Transporter (carriers) proteins (see also Fundamentals of Physiology lecture)
Symport, Antiport
Thiazide diuretics - Block Na+ /Cl− co-transport in the renal tubule (symport)
Enzymes are involved in intracellular and extracellular synthesis and degradation of substrates, how?
A drug can inhibit the enzyme by:
- Binding to the active site – enzyme not able to bind to substrate
- Binding to another site in the enzyme, changing its conformation – enzyme not able to bind to substrate
(Drugs might be able to activate enzyme / increase its genetic transcription)
What are the 4 major types of receptors?
- Ligand gated ion channels (iontropic receptors)
- GPCR
- Kinase Linked receptors
4 Nuclear receptors
What 3 major types of receptors are transmembrane surface receptors, order by speed
- Ligand gated ion channels (iontropic receptors)
- GPCR
- Kinase Linked receptors
Which major type of receptor is cytoplasmic/ Nuclear receptor?
- Nuclear receptor
Brief outline of Ligand gated ion channels (iontropic receptors)
- Hyperpolarisation or depolarisation
- milliseconds
- Nicotinic/ACh receptor
Brief outline of GPCR (metabotropic)
- G-proteins
- Second messenger
- ions change in excitability
- protein phosphorylation
- Ca2+ release
- seconds
- Muscarinic/ACh receptors
Brief outline of Kinase Linked receptors
- Receptor/enzyme
- protein phosphorylation
- gene transcription
- hours
- cytokine receptors
Brief outline of Nuclear receptors
- nuclear receptor
- gene transcription
- protein synthesis
- hours
- oestrogen receptor
Gas, Gai, Gaq
Ga proteins coupled with intracellular signalling pathways. Can be stimulatory or inhibitory depending on the second messenger systems activated.