Pharmacodynamics Flashcards
what are the protein targets for drugs?
enzymes, receptors, ion channels and carrier channels
why are proteins good targets for drugs?
due to having a narrow specificity as they are very intricately folded
how can an inhibitor cause an increase of biological availability of a drug?
if the inhibitor binds to an enzyme that catalyses the breakdown of the drug then less of the drug will be broken down so more present in the body
what are examples of monamine oxidase transmitters?
dopamine, noradrenaline and serotonin
what is MAO designed to do?
prevent constant release of neurotransmitter
how is MAO able to reduce the level of neurotransmitter in the synaptic cleft?
a transport protein will pump the neurotransmitter back into the pre-synaptic cleft and MAO will then convert this to inactive products
what can MAO inhibitors be used to treat?
depression as if MAO is inhibited then it will not be able to breakdown the neurotransmitter so more will be present in order to bind to receptors and cause effect
what does Ach do?
it is a neurotransmitter that binds to nicotinic receptors
what is the effect of inhibiting AchE?
this prevents as much Ach from being broken down so that more is able to bind to nicotonic receptors
what can AchE inhibitors be used to treat?
donepezil is used to treat Alzheimers as preventing the breakdown of acetylcholine results in better communication between nerve cells
how does AchE inhibitors help myasthenia gravis?
drugs such as neostigmine prevents breakdown of Ach so greater stimulation of nicotinic receptors
what does ACE do? what effect does this have?
converts angiotensin I to angiotensin II which then leads to an increased blood pressure
what can ACE inhibitors be used to treat?
hypertension and heart failure due to blocking the production of angiotensin II so blood pressure levels do not increase
what is HMG CoAR?
HMG-CoA reductase, which converts HMG-CoA to mevalonic acid which is then converted to cholestrol
what kind of drugs inhibit HMG-CoAR and why?
statins as they inhibit the enzyme and therefore result in reduced cholesterol production for diseases such as atherosclerosis
what are COX inhibitors?
cyclooxyrgenase inhibitors
how is COX produced and what does this cause?
cell membrane damage liberates arachidonic acid to be converted to prostaglandins via COX
why might the production of prostaglandins want to be reduced?
because they are associated with inflammation and pain
what kind of drugs inhibit COX?
NSAIDS (non-steroidal anti-inflammatory drugs) such as aspirin
how might enzyme inhibition lead to bacterial cell death?
transpeptidase inhibitors prevent the formation of transpeptidase that holds the peptides in the cell wall together, so when inhibited, this causes inability to synthesise a cell wall so leads to cell death
what is an example of a drug that is a transpeptidase inhibitor?
penicillin
what is a receptor agonist?
binds to a receptor due to affinity and also has high efficacy so has the ability to activate the key group and therefore generate a cellular response
what is a receptor antagonist?
binds to the receptor due to affinity yet does not have efficacy so only able to block the receptor rather then cause a response
what is an example of a receptor antagonist?
beta blockers
what is the dose-response relationship?
the response to an agonist is proportional to the number of receptors used
what is the shape of the curve for a dose-response relationship?
hyperbolic curve
what is the EC50 of a drug?
the concentration that produces 50% of the maximum response
how can the EC50 be calculated?
the log of the concentration of the drug is plotted against the response from which the EC50 can be determined
why is an EC50 graph useful?
allows comparison of drug potencies
what are the receptor families?
G-protein receptors, ion-channel linked receptors, enzyme linked receptors, intracellular receptors, voltage ion channels and carrier proteins
why is a G-protein coupled receptor metabotrobic?
because it works through a second messenger model
how does a G-protein coupled receptor work?
an agonist occupies the receptor which allows it to interact with a G-protein, which then activates an enzyme which produces a 2nd messenger chemical
what receptors work via G-protein coupling?
Ach receptor and beta 2 adrenoreceptor
what is an example of a second messenger?
cyclic AMP
what are examples of drugs that work via G-proteins?
adrenaline or salbutamol
how does an ion channel-linked receptor work?
the receptor is directly linked to an ion channel so when an ion binds, this causes the opening of the channel, allowing the ion to enter
what is an example of an ion channel-linked receptor?
ligand binding to its receptor or Act binding to a nicotinic receptor and causing the opening of sodium ion channels
how does a GABA receptor work?
in the CNS, GABA binds to the GABA receptor which causes the opening of chloride ion channels which reduces neurone excitability
what are enzyme linked receptors?
mainly peptides or protein receptors that are usually linked to kinases
how does the insulin enzyme linked receptor work?
when insulin binds, the tyrosine kinases becomes activated which then causes a change to metabolic activity
what are intracellular receptors?
receptors that control gene expression, a lipid soluble drug enters the nucleus and binds to a receptor that controls gene expression
how does the binding to an intracellular receptor cause a change in cellular effects?
stimulation of protein synthesis which causes a production of a protein that causes the cellular effects
what is an example of a drug that binds to intracellular receptor?
anti-inflammatory steroids such as hydrocortisone which causes the production of a protein that inhibits synthesis of prostaglandins
what kind of drugs use voltage operated ion channels?
local anaesthetics
what do vinca alkaloids do?
inhibit cell division by preventing formation of the mitotic spindle by binding to tubules molecules and preventing them from forming the spindle
what do taxanes do?
bind to tubules molecules and prevent disassembly
