Neuro - Pharmacology of the Nervous System Flashcards
Define pharmacology
A chemical substance interacts with a specific target in a biological system to produce a physiological effect
What 3 questions do we ask when talking about a drug/chemical substance?
- What is the target?
- Where is the effect produced?
- What is the effect produced after target interaction?
What is the target for heroin
Opioid receptors
Where is the effect of heroin produced
Peri-aqueductal grey region
solitary nucleus
tegmental area
What is the effect produced after heroin’s interaction with the target
Cough suppression
Euphoria
Analgesia
What are side effects
Effects produced by a drug that are secondary to the intended effect
Where do side effects arise
On other targets in the same tissue
Other targets in other tissue
Same targets in other tissue
What does location of side effects depend upon?
Dependent on the dosage of the drug administered
What is pramipexole?
Dopamine receptor agonist used to treat Parkinson’s
What must we assume from a drug e.g. pramipexole?
That it may affect all 4 dopaminergic pathways in the brain.
Why may we get constipation from pramipexole?
We have dopamine receptors in the gut, so pramipexole may interact with these and cause constipation (side effects on same target, different tissue)
What characterises the safest drugs?
Largest difference between therapeutic and side (adverse) effect inducing dose
When might we need a hospital setting to administer a drug?
When there’s a narrow margin between the therapeutic and toxic dose
What type of molecule are drug targets mostly?
Proteins
What are the 4 main classes of drug target?
Receptor
Enzyme
Transport protein
Ion channel
What is an example of receptor drug target?
Beta-2 receptors in the lung - salbutamol for asthma (inhaler)
What is an example of enzyme drug target?
HMG-CoA reductase and atorvastatin
What is an example of transport protein drug target?
Selective serotonin reuptake inhibitor (SSRI) antidepressant.
What is an example of ion channel drug target?
Ca2+ channel being blocked by amlodipine for hypertension treatment.
Do all drugs enhance activation?
No, some prevent activation
How do we get a good therapeutic effect with respect to selectivity?
We need a high degree of selectivity for a particular drug target and drug.
What are the 3 main NTs in the CNS?
Dopamine
Noradrenaline
Serotonin
What are the structural similarities between dopamine, noradrenaline and serotonin?
Serotonin loses an OH group and gains a 5C ring to become dopamine
NA loses an Oh group to become DA
What does a close similarity of structure mean?
We might expect drugs to bind to the same target as they will fit into similar binding sites.
Why might drug selectivity be more important than selectivity for endogenous compounds?
Endogenous compounds are synthesised and delivered directly to their target. Drugs are taken into the blood stream so circulate around the body before reaching their target so have more potential to bind to other targets.
What is an adverse effect?
When a side effect has negative effects
Why do we start to see serotonin like effects when increasing the dosage of pramipexole?
Selectivity decreases and eventually pramipexole will being binding to serotonin receptors
What happens when we increase the dose of pramipexole past serotonin induced effects?
We will see noradrenaline like effects
Why do we see serotonin effects before noradrenaline effects with pramipexole?
Serotonin is more structurally similar to dopamine than noradrenaline
What is an example of an on-target side effect?
Heroin’s desired effect in a clinical setting is analgesia however will also induce cough suppression and euphoria
What does a wide margin between the therapeutic dose and toxic dose mean?
We can use the drug comfortably expecting the therapeutic effect with very few if any side effects.
