20 - Introduction to Neuropharmacology Flashcards
(25 cards)
What is a target in neuropharmacology?
A well defined molecular entity
What 3 events at the synapse can be targeted in neuropharmacology?
- Target the transporter (reuptake system) in the presynaptic membrane
- Target the metabolism of the neurotransmitter
- Target the postsynaptic receptor
What is the cause of parkinson’s disease?
Loss of specific cells in the substantia niagra which produce dopamine
Results in a deficit in dopamine
What are the symptoms of parkinson’s disease?
Tremor, rigidity, slurred speech, affected gait
How can you treat parkinson’s disease?
Provide dopamine or L-dopa
What is a problem with the treatment of parkinson’s disease and how can this be overcome?
L-Dopa and dopamine cannot reach the brain
Outside the brain L-dopa is converted to dopamine which can trigger intense vomiting
Overcome this - bind the L-dopa with an enzyme inhibitor of decarboxylase enzyme - L-dopa is not converted to dopamine in the periphery (doesn’t block action in the brain)
Another solution - stimulate dopamine receptors with dopamine receptor agonists
What is the cause of schizophrenia?
Hyperactivity in the central striatum - Increased release of dopamine
What are the symptoms of schizophrenia?
Paranoid behaviour, hallucinations, delusions, withdrawal from friends and family
How do you treat schizophrenia?
Dopamine receptor antagonists
What are some problems with the treatment of schizophrenia?
The antagonists also block other receptors so have adverse side effects
E.g thioridazine also acts on noradrenaline, serotonin, histamine and acetylcholine receptors
Adverse effects - extrapyramidal effects (parkinsonism), rise in prolactin (breast enlargement), weight gain, allergic and toxic reactions, postural hypotension, dry mouth, constipation
What is the cause of depression?
Dysfunction of the activity of the monoamine systems in the brain
Insufficient levels of serotonin and noradrenaline
What are the symptoms of depression?
Low mood, lack of energy, disrupted sleep, loss of interest, tiredness
How can you treat depression?
Increase monoaminergic transmission
E.g inhibitors of transport/reuptake of monoamines such as SSRIs and TCAs
Inhibit the reuptake of monoamines such as serotonin and noradrenaline
What are the issues with the treatment of depression?
Also have affinity for histamine, muscarinic and adrenoceptors
Adverse effects - dry mouth, blurred vision, constipation, urinary retention, fatigue, sedation, weight gain, postural hypotension, dizziness and loss of libido
Also resistance to treatment
How do you solve the problem of adverse effects of drugs?
Reduce dose or change drug
What is the issue with treating addiction?
Often addicted to more than one substance therefore a single drug target doesn’t exist
What is the mechanism of action of cocaine, ecstasy, heroin, nicotine and ketamine?
Cocaine - inhibits uptake of monoamines
Ecstasy - increases release of monoamines
Heroin - Mu opioid receptor agonist
Nicotine - Nicotinic cholinergic receptor agonist
Ketamine - glutamate receptor antagonist
What is the treatment for heroin addiction?
Methadone for heroin substitution
What is a treatment for cocaine addiction?
Antibodies as a vaccine against cocaine
What is a treatment for nicotine addiction?
Nicotine replacement therapy - patches - decreases some of the toxicity associated with addiction
What is a treatment for alcohol addiction?
Aversion therapy - inducing sickness upon alcohol consumption - disulfiram
What quality does a drug need to have to cross the blood brain barrier?
Drug needs to be soluble in lipids
Why might drugs not reach the brain and not pass the blood brain barrier?
Intrinsic or acquired overexpression of multidrug transporters at the BBB restrict brain uptake of drugs
What is an ATP-binding-cascade transporter?
An example of a transporter which restricts brain uptake of drugs
Substrates of these help with epilepsy
