20 - Introduction to Neuropharmacology Flashcards

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1
Q

What is a target in neuropharmacology?

A

A well defined molecular entity

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2
Q

What 3 events at the synapse can be targeted in neuropharmacology?

A
  • Target the transporter (reuptake system) in the presynaptic membrane
  • Target the metabolism of the neurotransmitter
  • Target the postsynaptic receptor
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3
Q

What is the cause of parkinson’s disease?

A

Loss of specific cells in the substantia niagra which produce dopamine
Results in a deficit in dopamine

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4
Q

What are the symptoms of parkinson’s disease?

A

Tremor, rigidity, slurred speech, affected gait

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5
Q

How can you treat parkinson’s disease?

A

Provide dopamine or L-dopa

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6
Q

What is a problem with the treatment of parkinson’s disease and how can this be overcome?

A

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

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7
Q

What is the cause of schizophrenia?

A

Hyperactivity in the central striatum - Increased release of dopamine

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8
Q

What are the symptoms of schizophrenia?

A

Paranoid behaviour, hallucinations, delusions, withdrawal from friends and family

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9
Q

How do you treat schizophrenia?

A

Dopamine receptor antagonists

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10
Q

What are some problems with the treatment of schizophrenia?

A

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

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11
Q

What is the cause of depression?

A

Dysfunction of the activity of the monoamine systems in the brain
Insufficient levels of serotonin and noradrenaline

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12
Q

What are the symptoms of depression?

A

Low mood, lack of energy, disrupted sleep, loss of interest, tiredness

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13
Q

How can you treat depression?

A

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

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14
Q

What are the issues with the treatment of depression?

A

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

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15
Q

How do you solve the problem of adverse effects of drugs?

A

Reduce dose or change drug

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16
Q

What is the issue with treating addiction?

A

Often addicted to more than one substance therefore a single drug target doesn’t exist

17
Q

What is the mechanism of action of cocaine, ecstasy, heroin, nicotine and ketamine?

A

Cocaine - inhibits uptake of monoamines
Ecstasy - increases release of monoamines
Heroin - Mu opioid receptor agonist
Nicotine - Nicotinic cholinergic receptor agonist
Ketamine - glutamate receptor antagonist

18
Q

What is the treatment for heroin addiction?

A

Methadone for heroin substitution

19
Q

What is a treatment for cocaine addiction?

A

Antibodies as a vaccine against cocaine

20
Q

What is a treatment for nicotine addiction?

A

Nicotine replacement therapy - patches - decreases some of the toxicity associated with addiction

21
Q

What is a treatment for alcohol addiction?

A

Aversion therapy - inducing sickness upon alcohol consumption - disulfiram

22
Q

What quality does a drug need to have to cross the blood brain barrier?

A

Drug needs to be soluble in lipids

23
Q

Why might drugs not reach the brain and not pass the blood brain barrier?

A

Intrinsic or acquired overexpression of multidrug transporters at the BBB restrict brain uptake of drugs

24
Q

What is an ATP-binding-cascade transporter?

A

An example of a transporter which restricts brain uptake of drugs
Substrates of these help with epilepsy

25
Q

How do you manage drug resistance?

A

Block the expression/activity of transporters

ABC transporter inhibitors - verapamil, cyclosporine A