Pharmacology of the Nervous System Flashcards
(20 cards)
What is pharmacology?
Study of how chemical agents (drugs) can influence the function of living systems - bascially looking at a chemical substance that interacts with a specific target within a biological system to produce a physiological effect
What are the 3 factors / questions that contribute to the effect produced by an individual drug?
Apply it to an example e.g. heroine:
Where is the effect produced? (i.e. biological system)
What is the drug’s target site?
What is the response after the drug unteracts with the target site? (i.e. end result, what was the physiological effect caused by the drug)
Heroine acts on different regions of the brain, it targets opiod receptors, the response produced: euphoria, analgesia / pain relief (as heroine is an opiod), cough suppression
What do majority of the drugs target?
What are the 4 main classes / groups of drug targets?
Proteins:
- Receptors
- Enzymes
- Transport proteins
- Ion channels
Fill in the table below:
What are the target sites of these drugs?
[Table contains 4 of the most common drugs prescribed]
- Enzyme - as a statin, it blocks the enzyme HMG-CoA reductase, important in cholestrol synthesis (lowers blood cholestrol)
- Ion channels - Ca2+ channel blocker used to treat hypertension, stops constriction of blood vessels leading to less resistance to blood flow
- Receptor - used in inhalers, gets through the airways and binds to the β₂ adrenergic receptor to dilate the airways
- Transport protein - anti-depressant, selective serotonin reuptake inhibitor, transport protein that removes serotonin from the synapse is blocked so serotonin stays longer in the synapse
When drugs act on a target, what can they do (to the activation of the mechanism)?
- Stimulate an effect - enhance activation (agonise)
- Block an effect from being produced - prevent activation (antagonise)
Another key concept relating to drugs and their drug target sites is selectivity:
Why is a high degree of selectivity in drugs important?
To be an effective therapeutic agent - needs to fit very well into the target to access it
Also, drug cannot be too generic, if it can fit into many targets, effects will be messy / unwanted - so specific to one target produces a selective, wanted effect
What are the similarities and differences between the structures of dopamine, noradrenaline and serotonin?
What implications can this have on a drug target site?
Very similar, majority of the body is the same. Image shows differences
Potentially, all three of these neurotransmitters / hormones, can fit into the target drug sites, hence may have an effect on all of them
Why might a drug need to be more specific in terms of it’s structure and target site than our bodies own endogenous compounds?
Hypothetically, between all three NTs, either of them can fit into each others receptors. However, endogenous compounds in our body are delivered directly to the target site e.g. only dopaminergic nerves produce dopamine, which is exocytosed into the synapse and so dopamine almost only comes in contact with dopamine receptors - localised effect
Whereas drugs, despite administration method, almost always ends up in the bloodstream where it circulates the body, hence can come into contact with multiple target sites - indirectly delivered
So why is it difficult to keep the effects of the drugs selective?
Adminitration method results in indirect delivery to intended drug target site, so the drug can encounter multiple other drug target sites into which it can fit and cause an effect - known as side effects
What is a side effect?
What is an adverse effect?
A secondary effect to the intended effect of the drug
A side effect that has negative health consequences
Though, most side effects have negative consequences, big or small, hence the terms are often used interchangeably
What can cause a side effect?
Drug acting on off-target sites in the same tissue or different tissue
Drug acting on target site but causing secondary effects e.g. if target receptors are present in multiple different tissues in the body but we only intend for the drug to work in one specific tissue / area
Define the terms agonist and antagonist:
Agonist - a chemical that binds to a target and activates it to produce a biological response
Antagonist - a chemical that binds to a target and blocks an action
What is another issue with drugs in relation to how long they stay in the body?
Endogenous chemicals made by the body are released when required and cleared fairly quickly, however, taking a drug that many times a day is unreasonable, so companies aim to design drugs so they live in the body longer
Parkinson’s disease is believed to be caused by lack of dopamine, what type of drug would be ideal to counteract this effect?
A dopamine receptor antagonist (e.g. pramipexole) - a drug shaped like dopamine which can activate dopamine receptors to restore the lost / lacking dopamine to reduce the symptoms of Parkinson’s.
What are the potential issues with a dopamine receptor agonist?
Hypothetically, it could act on other receptors too, such as the noradrenaline or serotonin receptors
What factor of drugs can help control / minimise side effects yet keep the drug acting efficiently for it’s intended purpose?
Drug dosage - higher dosages cause more side effects e.g. acting on other target sites
The optimal drug dosage allows for the intended effect whilst keeping the side effects minimal
How can the right dosage help minimise side effects, using the dopamine receptor agonist as an example?
As the drug is designed to look like dopamine, at a lower dose, the first effect it will have is a dopamine like effect, as it acts on dopamine receptors primarily, and very little on other target sites so not enough to cause an effect
As the dosage is increased, it also begins to effect other receptors, e.g. serotonin receptors
The higher the dose, the greater the accumulative effect so more target sites can be affected
What are the 2 major points to remember when designing a drug?
Specificity / Selectivity
Dosage
(Those two are interlinked - side effects arise from the interaction between those two factors)
Think of dosage
What are the characteristics for the safest drugs to administer?
Where there is a large difference between the dose required to induce the desired / therapeutic effect and the dose require to induce side effects / adverse effects
How severe / extreme are the side effects generally for orally administered drugs VS locally injected drugs?
How do the margins of safety differ for each of these?
Drugs administered orally tend to have wide margins of safety - side effects less severe
Drugs administered locally tend to have narrower margins of safety - side effects may be more serious or extreme
