2.4 - Pharmacology of the Nervous System Flashcards
1
Q
What is pharmacology?
A
- pharmacology - the study of how chemical agents (drugs) can influence the function of living systems
- drug - a chemical substance that interacts with a specific target within a biological system to produce a physiologic effect
2
Q
How do individual drugs produce their effects? (Three questions asked)
A
- where is the effect produced?
- what is the target for the drug?
- what is the response produced after interaction with this target?
- e.g. for heroin:
- different areas depending on type of response - peri-aqueductal grey region for analgesia, ventral tegmental area for euphoria, solitary nucleus for cough suppression
- opioid receptors - normally detect endogenous opioids but also exogeneous compounds like heroin and morphine
- different responses - euphoria, analgesia, cough suppression
3
Q
What drug target classes are there?
A
- majority of drug targets are proteins - 4 main classes:
1. receptors (e.g. Salbutamol - beta 2 adrenergic receptor in lung is activated = bronchodilation = helps with asthma)
2. enzymes (e.g. Atorvastatin - HMGCoA reductase)
3. transport proteins (e.g. Citalopram - SSRIs that block serotonin uptake)
4. ion channels (e.g. Amlodipine - blocks Ca2+ channel = vasodilation = reduced BP) - drugs can act on targets to enhance activation (stimulate an effect) or prevent activation (block an effect)
4
Q
Drug selectivity
A
- selectivity is the degree to which a drug acts on a given site relative to other sites
- to be an effective therapeutic agent, a drug must show a high degree of selectivity for a particular drug target –> lock and key hypothesis
- the perfect drug binds to only one drug target
- also important so the drug does not produce unwanted side effects in other parts of the body
5
Q
Why might selectivity be more important for drugs than endogenous compounds like dopamine?
A
- neurotransmitters are very specifically delivered to their target e.g. dopaminergic nerve releases dopamine into synapse where it specifically interacts with dopamine receptor
- drugs however are administered orally / intravenously so they need to be distributed to their relevant tissue
- that drug can be sent to any tissue in the body, which is why they cannot be similar to other compounds or else they may produce unwanted effect in other tissues
6
Q
What are side effects?
A
- a side effect is an effect produced by the drug that is secondary to the intended effect
- if the side effect has negative health consequences, it is also termed an adverse effect (terms used interchangeable since most side effects have some form of negative health effect)
- they can be produced by drug action on other targets in same/other tissue (off-target effects) or on the same target in other tissues
- dependent on the dose of the drug administered
- the safest drugs in terms of side effects are those where there is a large difference between the dose required to induce the desired effect and the dose required to induce side/adverse effects
7
Q
What are off-target side effects?
A
- side effects on areas of the body that aren’t the target area - other targets in same/different tissue
- e.g. Pramipexole selectivity:
- Pramipexole is a dopamine receptor agonist
- as you increase dose from zero, you reach a point where you see dopamine-like effects which are therapeutic and what we want
- if you keep increasing, we start to see serotonin-like effects because dopamine and serotonin are similar and so some of the drug might get into serotonin receptors and make them work
- if you continue increasing, the same can happen with noradrenaline receptors
- these are side effects - as dosage increases, selectivity of drug decreases and side effects increase
8
Q
What are on-target side effects?
A
- drugs that produce side effects on the same target but in a different tissue that is unwanted
- e.g. heroin - if administered for analgesic effect it might also have cough suppression / euphoria effects
