Pharmacology - Biochem S2
What is pharmacology
This is the chemical interference with a cellular system to enhance, modify or block their activity at the levels of whole body, isolated organ or tissue, specific cells or even cellular components
What are the different types of drugs
Endogenous ligands such as hormones
Natural compounds like atropine or opium or penecillin
Synthetic compounds like salbutamol
Semisynthetic compounds like ampicillin
How was aspiring discovered
In history used the white bark of willow trees to make herbal teas and remedies. The issue was though it varied largely in levels of salicylate and also many unwanted contaminants
In 1828 Buchner extracted the active salicylate from the bark
The next step was then the discovery of the chemical structure of the salicylate and that lead the ability to chemically synthesise it calld acetylsalicylic acid but this was toxic and not very effective
Hoffman created asprin that has high purity and no contaminants
There is also much better efficiacy and less toxicity so less side effects
It is repeatable due to consistent amount of ingredients and reproducible effect on patient
What are the stages of drug development
In vitro studies where there is the creation of the lead compound from biological products or chemical synthesis optimisation
Then there is animal testing to see efficiacy, selectivty and the drug mechanims
Then there is clinical testing: Phase 1 to 20-100 subjects to see if drug is safe and find the pharmokinetics, Phase 2 to 100-200 patient to see if drug works, Phase 3 using double blind testing to see if work in larger sample size of 1000-6000
Final stage is the marekting of the drug and get NDA granted to make public - have to restest every 20 yrs for new patent
What are the roles of the pharmalogical agents
Reversiblem blockade of physiological response like muscle relaxents and oral contraceptives
Regulation of the normal physiological response such as neurotransmitters and diseases
Supplmenting normal physiological process
Elimantion of non sefl particles from the body
What are the 2 types of pharmacology
Pharmodynamics - how the drugs act on the body so the drug action and it is specific to the drug or drug class the response
Pharmokinetics - What the body does to the drug and this is non specific
How do drugs act
They act by binding to receptors that are located eother on cell membranes or in the cytoplasm and the binding then will trigger other molecules to activate and start a reaction to then get the desired effect of the drug
What is a drug dose response curve
These are curves that show the concentration of a drug given and then the response of the drug at that concentration, they are good as can find the concentration of the drug to get get a certain level of response for the patient.
There will be a max response so the curve will plateau
What are log dose response curves used for
It wil change the shape of the curve to an S shape and are also useful as they can easily be compared to related compounds that give a parrallel curve
The potencies can also be easily determined as between 20-80-% the curve is linear
It can easily show the entire concentration range due to being in log
The effect of any antagonist can easily be shpnw as the line will shift left or right
How do drugs act
They can be either be reversible if the drug is non covalent when bidnign allows a non covalent change to a receptro or can be irreverisble if cause a covalent change to the receptor
An ideal drug would be selectibe for a particular response for not just a transmitter or enzyme fro the receptor but also the interaction of the transmitter with the target tissue
Most drugs have more than 1 action so morphine is both for pain relief and constipation
What is potency and efficacy
Potency= What concentration is needed to give a response from a drug
Efficacy = How big is the response from a drug at a select concentration
What are agonists and antagonists
Agonist = A drug that will produce a response by bidning and inducing a change to an active configuration that produce a response
Antagonist = A drug that will block a response and has no action itselg by bdinig to the same active site but then wont induce a conformational change in the receptor so no effect and block the agonist from the receptorr
What are the 2 types of antagonists
Pharmacological = Prevent the action of an agonist at its own receptor
Physiological = Agents that have mutually antagonistic responses but they act through different receptors
How do different agonist and antagonists change the log dose response curve
Partial agonist = It will lower the max response level, these can also sometimes be competive antagonist as occupy the receptor
Full agonist = They all have same max response level but there may be a parrallel shift left or right depending on the drug and the different concentrations they may need to achive full response
Compettive antagonists = No change in max response but a parrallel shift to the right
How are different agents able to produce same response by binding to same receptor
Muscarine + Arecoline + Oxotremorine can all be blocked by same antagonist called atropine
Histamine is able to produce same desired response but bind to different receptor thats not blocked by atropine but is blocked by mepyramine but this wont effect acetlycholine
How do drugs bind to receptor
They are able to bid via the lock and key theory where only drugs that are complimentary to receptor can bind and trigger response
There are 2 types of agonist called endogebous that have exactly complimentary shape and also exogenous that have complimenarty bainding site but different non binding site
Antagonists can also bidn if they have similar shape to the receptor and can fit and bind to the receptor
What are irreversible antagonists
These covalently bind to agonist binding site and the effect cannot be overcome by the addition of more agonist
This will then reduce the overall maximum response
What is EC50
This is the drug concentration that gives a 50% of the maximum response of the drug