Introduction Flashcards
What is pharmacodynamics?
What the drug does to the body
- mechanism of drug action
- cellular and systemic effects
what is pharmacokinetics? what are the components of it?
What the body does to the drug
- absorption
- distribution
- metabolism
- excretion
what is pharmacotherapeutics? what should you consider?
the use of drugs to prevent and treat diseases.
consider the beneficial effects and adverse effects of the drug
what are some general examples of drug targets?
Receptors, enzymes, carriers/transporters, ion channels
Compare and contrast agonists and antagonists
Agonists activate drug targets and mimic or increase physiological responses and effects
antagonists block drug targets and inhibit or decrease physiological responses and effects
what are the two ways drugs can act on drug targets
reversibly (competitively)
irreversibly (non competitively)
What are the four types of receptors?
- ligand gated ion channels (ionotropic) e.g. nicotinic AcH receptor
- G protein coupled receptors (metabotropic) muscarinic AcH receptor
- kinase linked receptors e.g. cytokine receptors
- nucelar receptors e.g. oestrogen receptor
Describe G protein coupled receptors
- most common drug target
- integral membrane protein
- coupled with a G protein
what is the function of the G protein in the coupled receptor?
- acts as a molecular switch inside cells
- involved in transmitting signals from a variety of stimuli outside to its interior
- activation of the receptor activates the G protein OR inhibits a second messenger
What are some targets of the G protein coupled receptors
Adenylate cyclase
Phospholipase C
What is adenylate cyclase?
The enzyme responsible for catalysing the formation of CAMP, which regulates many aspects of cellular function by the activation of protein kinases.
What does cAMP activate?
protein kinases, which in turn regulate the function of many different cellular proteins by controlling phosphorylation (which can activate or inactivate various proteins)
What is the impact of adenylate cyclase on cardiac muscle?
Adenylate cyclase catalyses cAMP which activates protein kinases, which control phosphorylation.
In cardiac muscle the phosphorylation of voltage gated Ca2+ channels increases their permeability to Ca2+, increasing influx during the action potential, thus increasing the force of contraction
What is the impact of adenylate cyclase on smooth muscle?
Adenylate cyclase catalyses cAMP which activates protein kinases, which control phosphorylation.
In smooth muscle, phosphorylation inactivates the enzyme myosin-light chain kinase (MLCK) which is required for contraction, thus causing relaxation
What is the role of phospholipase C?
Catalyses the formation of inositol triphosphate (IP3) and diacylglycerol (DAG) which have important cellular functions
What is the role of IP3?
Catalysed from phospholipase C, it is a mediator in the cytoplasm that acts on the IP3 - a ligand gated Ca2+ channel on the membrane of the ER.
When this is activated, the Ca2+ channel is opened and stores are released in the cytoplasm initiating events including
- contraction
- secretion
- enzyme activation
- membrane hyperpolarisation
What happens when the IP3 receptor is activated?
the Ca2+ channel is opened and stores are released in the cytoplasm initiating events including
- contraction
- secretion
- enzyme activation
- membrane hyperpolarisation
What is the role of DAG?
Activates protein kinase C, which controls many cellular functions by phosphorylating a variety of intracellular proteins
What are the G protein subtypes and their functions?
Gαs - stimulates adenylate cyclase, increasing cAMP formation
Gαi - inhibits adenylate cyclase, decreasing cAMP formation
Gαo - limited effect of alpha subunit
Gq - actiavtes phospholipase C, increasing production of second messengers IP3 and DAG
Gβγ - activates potassium channels, inhibits voltage gated Ca2+ channels, activates GPCR kinases, activates mitogen activated protein kinase cascade, interacts with some forms of adenylate cyclase and phospholipase Cβ
What are the different levels of drug effects?
Drug molecule
- administration
Cell
- cellular effects e.g. depolarisation, contraction
tissue and organ effects
- e.g. decreased cardiac muscle contractility
physiological system
-e.g. decreased BP
individual
- clinical effects e.g. reduced hypertension
population and society
- pharmacoepidemiology and pharmacoeconomics e.g. disease prevalence and health care costs
what is an indication?
a disease or condition that warrants the use of a particular drug
what is a contraindication?
a disease of condition in which a particular drug should not be used
what is an adverse effect?
an unintended effect from normal drug administration
what is a therapeutic index?
quantitative measurement of the relative safety of a drug. a comparison of the amount of an agent that causes the effect to the amount that cause toxicity
