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MD1 Neuroscience > Drugs of Dependence and Antidepressants 2 > Flashcards

Drugs of Dependence and Antidepressants 2 Flashcards

1
Q

What receptor does LSD act on?

A

Various 5-HT receptors

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2
Q

What mediates LSD’s psychotomimetic effects?

A

5-HT2A receptor agonist actions

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3
Q

What does LSD’s agonist activity at the 5-HT2A receptor cause?

A

Release of glutamate in cortex

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4
Q

What is the effect of LSD in the raphe nuclei?

A

Inhibits firing of 5-HT containing neurons

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5
Q

How does LSD inhibit the firing of 5-HT containing neurons in the raphe nuclei?

A

Acts as agonist on inhibitory autoreceptors of these cells

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6
Q

What are affective disorders?

A

Those that influence mood

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7
Q

What is unipolar/major depression?

A

Extreme melancholia and withdrawal

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8
Q

What is reactive depression?

A

Due to known cause

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9
Q

What is endogenous depression?

A

No known/apparent cause

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10
Q

What is bipolar depression?

A

Mood swings from extreme elation and hyperexcitability to extreme melancholia and withdrawal

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11
Q

What does the monoamine theory of depression state?

A

Drugs that interfere with monaminergic transmission influence mood

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12
Q

What are the monoamine transmitters?

A

Noradrenaline
Serotonin
Dopamine

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13
Q

What does a depletion in monoamine transmitters cause?

A

Depression

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14
Q

What does an acute elevation of monoamine transmitters in the synapse do?

A

Can enhance mood

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15
Q

Why do drugs that elevate mood not necessarily make good antidepressants?

A

Dependence - dopamine related
Toxicity
- Cardiovascular because given systemically
- Psychoses with overuse

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16
Q

How long can antidepressants take to take effect?

A

2-6 wks

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17
Q

What are the first generation drugs used to treat unipolar depression?

A 
Tricyclic antidepressants = "ipramines"
Monoamine oxidase (MAO) inhibitors
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18
Q

What are the second generation drugs used to treat unipolar depression?

A

Selective serotonin uptake inhibitors (SSRIs)

Selective serotonin/noradrenaline uptake inhibitors (SSNRIs)

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19
Q

What are the third generation drugs used to treat unipolar depression?

A

Atypical antidepressants

  • Novel monoaminergic drugs
  • Non-monoaminergic drugs
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20
Q

What drugs are used to treat bipolar depression?

A

Lithium

Some antiepileptics; eg: carbamazepine

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21
Q

What are the pharmacological actions of tricyclic antidepressants?

A

Inhibit neuronal uptake of noradrenaline and serotonin
Antagonise
- Alpha adrenoceptors
- Muscarinic receptors
- Histamine receptors
- Serotonin receptors
Quinidine-like membran stabilising action at very high concentrations > acts as local anaesthetic

22
Q

How long do the clinical effects of tricyclic antidepressants take to develop?

A

Wks despite pharmacological effects taking hrs

23
Q

What is likely to underly the antidepressant activity of tricyclic antidepressants?

A

Adaptive changes in neuronal function

  • Change in receptor sensitivity/density
  • Change in 2nd messenger activity
24
Q

What is the therapeutic window of tricyclic antidepressants?

A

Narrow > limited efficacy

25
Q

What is the consequence of the longish half-life of tricyclic antidepressants?

A

Gradual accumulation possible

Slowly developing side effects

26
Q

What are the side effects of tricyclic antidepressants?

A

Sedation
Anti-cholinergic = SLUD
Postural hypotension
Weight gain

27
Q

What happens in overdose of tricyclic antidepressants?

A 
Confusion
Mania
Cardiac dysrhythmias
Seizures
Impotence
28
Q

What is the pharmacological effect of MAO inhibitors?

A

Increase levels of

  • Noradrenaline
  • Serotonin
  • Dopamine
29
Q

Are MAO inhibitors slow or fast acting?

A

Delayed antidepressant effect

30
Q

Do MAO inhibitors reversible or irreversible?

A

Irreversible

31
Q

What is the cheese reaction?

A

Monoamine oxidase present in gut wall to break down dietary amines (mainly tyramine)
Tyramine can release noradrenaline from storage vesicles in peripheral nerve terminals > indirectly sympathomimetic
MAO inhibitors stop breakdown of tyramine > absorbed > enhanced sympathomimetic effect

32
Q

Where is tyramine commonly found?

A

Cheese
Wines
Chocolate
Bananas

33
Q

What are the sympathomimetic effects of the cheese reaction?

A

Acute hypertension
Throbbing headache
Intracranial haemorrhage

34
Q

What is moclobemide?

A 
MAO inhibitor - most commonly used
Monoamine oxidase A selective > prefers noradrenaline and serotonin
Reversible
Less likely to cause cheese reaction
Interaction with other drugs
35
Q

What are the side effects of moclobemide?

A

Dizziness
Nausea
Insomnia

36
Q

What are some examples of SSRIs?

A

Fluoxtine = prozac
Paroxetine
Sertraline

37
Q

What is the selectivity for SSRIs?

A

Selective for 5-HT uptake

Few adrenergic, histaminergic, and cholinergic actions

38
Q

What is the therapeutic index of SSRIs?

A

High

39
Q

What is the toxicity of SSRIs?

A

Minimal unless combined with other drugs

40
Q

What is the serotonin syndrome?

A 
SSRI +  MAO inhibitor + tricyclic antidepressant
Highly anxious
Hyperthermia
Muscle rigidity
Cardiovascular collapse
41
Q

What effect do SSRIs have in adolescents?

A

Anxiety and suicidal tendencies on commencement

42
Q

What are the side effects of SSRIs?

A 
Nausea
Insomnia
Agitation
Weight change
Loss of libido
43
Q

What is venlaflaxine?

A

SSNRI

44
Q

What is reboxetine?

A

Atypical antidepressant

Monoaminergic mechanism: re-uptake inhibitor

45
Q

What is mianserin?

A

Atypical antidepressant

Monaminergic mechanism: blocks alpha2 adrenoceptors, histamine, and serotonin receptors

46
Q

What is mirtazepine?

A

Atypical antidepressant
Monoaminergic mechanism: blocks alpha2 adrenoceptors and serotonin receptors
Good for people with low mood with basis in anxiety

47
Q

What are some pro-cognitive therapies used in the treatment of depression?

A

Breathing exercise
Physical exercise
Deep brain stimulation

48
Q

What could be the long term changes of depression be caused by, and what should new drug targets focus on?

A

Long term changes because of neuronal death

Targets should include focus on cell survival

49
Q

What is the pharmacological effect of lithium carbonate?

A

Interaction with inositol phosphate 2nd messengers

Tends to reduce Ca in nerves

50
Q

What is the therapeutic index of lithium carbonate?

A

Very low

Plasma levels must be monitored

51
Q

What are the side effects of lithium carbonate?

A

Nausea
Tremor
Impaired renal, thyroid, and neurological function

MD1 Neuroscience (55 decks)

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