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NLM2 > Neuropharmacology > Flashcards

Neuropharmacology Flashcards

0
Q

What is substance dependance?

A

When an individual persists in use of alcohol/drugs despite problems related to the substance

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1
Q

What is substance abuse?

A

A maladaptive pattern of use of a substance that is not considered dependant

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2
Q

What is substance use disorder?

A

Substance abuse along with substance dependance

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3
Q

What is tolerance?

A

A person no longer responds to a drug. A higher drug doses are required to achieve the same effect

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4
Q

What is dependence?

A

A state in which a person functions normally only in the presence of a drug. There is physical or psychological disturbance when the drug is withdrawn

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5
Q

List some consequences of dependence

A
  1. Compulsive behaviour
  2. Loss of control in limiting intake
  3. Intense cravings even years after sobriety
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6
Q

What factors could pre-dispose you to having drug dependence?

A
  1. Genetics
  2. Personality
  3. Environment
  4. Pharmacokinetic properties of the drug
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7
Q

How is drug dependence associated with rationality?

A

Rationality is used to obtain goals but choosing our goals is often based on biological and social factors - not rationality. Drugs that cause dependence break down rationality. They chemically change our behaviour, values and feeling of “self”.

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8
Q

How do drugs cause addiction

A

Stimulation of the mesolimbic pathways. Dopamine release from VTA to the nucleus accumbens, pre frontal cortex, hippocampus and amygdala.
This results in euphoria, pleasure, motivation, compulsion.

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9
Q

Name some dependence inducing drugs and where they act.

A 
Nucleus Accumbens (NAcc) - Cocaine, Amphetamine, Opiods, THC
VTA - Ethanol, Nicotine, Opioids, THC
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10
Q

What biological changes occur during dependence?

A
  1. Upregulation of inhibitory autoreceptors in VTA
  2. Reduced dopamine release in NAcc
  3. Loss of inhibitory effect of D2 receptors with increased AC
  4. Supersensitivity of D1 receptors
    - All leads to drug tolerence (drug is essential to maintain normal levels of pleasure)
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11
Q

What is (Delta)FosB?

A

A transcription factor that alters neural dendritic branches within the NAcc and the Prefrontal cortex. This leads to sensitised responses after repeat exposure to drug.

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12
Q

What are the two hypothesises of relapse in dependance?

A
  1. Structural change hypothesis

2. Behavioural change hypothesis

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13
Q

What types of drugs are used to treat Parkinson’s?

A
  1. Levodopa (Dopamine precursor) with peripheral decarboxylase inhibitor, Carbidopa / Benserazide
  2. Dopamine agonists - Ergot derivatives/Non-ergot derivatives/Non selective D agonist
  3. MAOb inhibitors
  4. COMT inhibitors
  5. Antimuscarinics
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14
Q

What are the Dopamine agonists that can be used in Parkinson’s?

A
  1. Ergot derivatives: Bromocriptine, lysuride, pergolide. Risk of pulmonary fibrosis in a small amount of patients
  2. Non-ergot derivatives: Ropinirole, rotigotine.
  3. Non-selective D agonist: (SC) Apomorphine.
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15
Q

What are the side effects of Dopamine agonists?

A 
Vomiting (use Domperidone - peripheral D2 antagonist)
Hallucinations
Postural hypotension
Sudden sleep onset
Manic behaviour - gambling
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16
Q

What is the mechanism of amantidine?

A
  1. Enhances release of stored Dopamine
  2. Blocks reuptake of Dopamine
    Helps bradykinesia, tremor and rigidity. However, rapid tolerance (<1 year)
17
Q

What are the MAOb inhibitors that can be used in Parkinson’s?

A

Selegiline and rasagiline.

These increase CNS [Dopamine] and have 8-12 month window of efficacy.

18
Q

What are side effects of selegiline and rasagiline (MAOb inhibitors)?

A
  1. Nausea
  2. Hallucinations
  3. Confusion
  4. Dizziness
19
Q

What are the COMT inhibitors that can be used in Parkinson’s?

A
  1. Entacapone
  2. Tolcapone
  3. Alcapone
    These act to increase peripheral [Dopamine].
20
Q

What are the side effects of entacapone, tolcapone and alcapone (COMT inhibitors)?

A
  1. Diskinesias
  2. Hallucinations
  3. Hepatotoxicity
21
Q

What antimuscarinics can be used in Parkinson’s disease?

A

Benzhexol, orphenadrine, procyclidine

22
Q

What are some side effects of Antimuscarinics?

A
  1. Constipation
  2. Urinary retention
  3. Confusion
  4. Hallucinations
23
Q

Outline the pathway of Dopamine production.

A

L-tyrosine (tyrosine hydrooxylase)
L-DOPA (DOPA decarboxylase) —– MAO and COMT
Dopamine —– MAO and COMT

24
Q

What groups of drugs can be used to treat schizophrenia?

A
  1. D2 antagonists - Phenothiazides and non-phenothiazides (improve positive features)
  2. Atypical drugs - Also block 5HT2A receptors (improve negative features)
25
Q

What are the positive and negative features of schizophrenia?

A 
Positive: 
1. Hallucinations
2. Delusions
3. Behavioural disorders
Negative:
1. Social withdrawal
2. Apathy
3. Blunted emotions
26
Q

What phenothiazide drugs can be used to treat Schizophrenia? Also, what patients would you use these drugs on?

A
  1. Chloropromazine - Agitated/Violent. Sed +++ Dry mouth ++ Mov ++
  2. Pipotiazine - Elderly. Sed + Dry mouth +++ Mov ++
  3. Fluphenazine - Young/fit. Sed + Dry mouth + Mov ++++
27
Q

What non-phenothiazide drugs could be used to treat Schizophrenia?

A

Haloperidol, flupenthixol, pimozide.

All have similar side effects to older phenothiazides - chlorpromazine.

28
Q

What are the atypical drugs that can be used to treat Schizophrenia?

A
  1. Clozapine - 2% agranulocytosis
  2. Risperidone
  3. Remoxipride - rarely causes aplastic anaemia
  4. Sulphride - high dose improves positive features, low dose improves negative features
  5. Quetiapine - sedative
  6. Olanzapine - weight gain and increase stroke risk in elderley
29
Q

Where else do D2 receptor antagonists bind and what side effects does doing so cause?

A
  1. Nigrostriatal pathways - Parkinson’s symptoms. Tremor, hypokinesia, tardive diskinesia, akathisia.
  2. Hypothalamus - Interferes with hormone release to pituitary. Prolactin increase thus dysmenorrhoea. ACTH increase, Cortisol increase thus Cushing’s.
  3. Histamine receptors - Sedation
  4. Muscarinic receptors - Dry mouth, constipation, urinary retention, blurred vision, confusion, impotence
  5. Alpha adrenoreceptors - postural hypotension, hypothermia
30
Q

List the anti-depressant drugs

A
  1. Selective serotonic reuptake inhibitors - Fluoxetine, atalopram
  2. Serotonin-noradrenaline reuptake inhibitors - Venlafaxine, duloxetine
  3. Bupropion (SNRI and increases release of both)
  4. Tricyclic antidepressants - Clomipramine, amitriptylline, imipramine
  5. MAO inhibitors - Phenelzine, lithium
  6. Mirtazapine - NA alpha 2 antagonist, 5HT1 antagonists (NA and 5HT autoreceptors), 5HT2 and 5HT3 antagonists
  7. Agomelatine - 5HT2c antagonist, MT1 and MT2 agonist. Also, enhances release of NA and Dopamine in the prefrontal cortex.
31
Q

What are some side effects associated with antidepressant drugs

A

Increased nervousness in the first week of treatment
Self harm risk in children and adolesents
SSRIs - 40% worse sexual function
TCAs and mirtazapine - weight gain and drowsiness
Venlafaxine - elevated blood pressure

32
Q

What groups of drugs can be used to treat nausia and vomitting?

A
  1. Dopamine antagonists - acting on D2 receptors at the CTZ in the area of postrema
  2. 5HT3 antagonists - acting on 5HT3 receptors at CTZ and on vagal sensory fibres
  3. Antimuscarinics - on the vomitting centre of MO
  4. Antihistamines - on vomitting centre of MO
  5. Substance P antagonist - on CTZ
  6. Cannabinoids - on CTZ
33
Q

What are the afferent fibres of the Vomitting centre?

A
  1. Limbic cortex
  2. CTZ
  3. Nucleus solitarius
  4. Spinal cord
  5. Vestibular system
34
Q

What dopamine antagonists can be used to treat nausia and vomitting?
Side effects?

A
  1. procholorperazine
  2. metoclopramide
  3. domperidone
    S/Es - extrapyramidal. Movement disorders
35
Q

What 5HT3 antagonist is used in nausia and vomitting?

A

Ondansetron

36
Q

What antimuscarinic is used to treat nausea and vomitting?

A

Hyoscine

37
Q

What cannabinoid is used to treat nausea and vomitting?

A

Nabilone

38
Q

What substance P antagonist is used to treat nausea and vomitting?

A

Aprepitant

39
Q

What antihistamines are used to treat nausea and vomitting?

A

cyclizine, cinnarizine, promethazine

NLM2 (7 decks)

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