Antidepressants [5]

Question 1

Name as many affective disorders as possible

Answer 1

Major depressive disorder (MDD)
Unipolar / bipolar depression
Attention deficit hyperactivity disorder (ADHD)
Obsessive compulsive disorder (OCD)
Panic disorder
Post traumatic stress disorder (PTSD)
Seasonal affective disorder (SAD)

Question 2

Emotional symptoms of depression

Answer 2

Misery
Apathy
Hopelessness
Low self esteem
Guilt
Inadequacy

Question 3

Biological symptoms of depression

Answer 3

Retardation of thought
Loss of libido
Sleep disturbance
Loss of appetite

Question 4

Difference between unipolar and bipolar depression

Answer 4

Unipolar - only negative moods & no evidence for genetic cause
Bipolar - depression + mania & evidence for genetic cause

Question 5

What are the two types of unipolar depression

Answer 5

Reactive and endogenous

Question 6

What is reactive depression

Answer 6

Response to distress
3-10% population
Women > men

Question 7

What is endogenous depression

Answer 7

Biochemical cause
1% population
Women = men

Question 8

What is the monoamine theory of depression and mania

Answer 8

Depression - deficient monoaminergic transmission
Mania - excessive NA & 5-HT transmission

Question 9

What is 5-HT and what does it control

Answer 9

Serotonin
Mood , sleep , sexual behaviour , appetite , sensory perception

Question 10

What are the noradrenaline receptors

Answer 10

Alpha and beta adrenergic receptors

Question 11

What locus does NA bind

Answer 11

Locus coeruleus
Malfunctions cause depression / anxiety

Question 12

How is dopamine made

Answer 12

From the precursor DOPA by DOPA decarboxylase

Question 13

What does dopamine control

Answer 13

Motivation, reward, reinforcement

Question 14

What dopamine receptors increase cAMP

Answer 14

D1 and D5

Question 15

What dopamine receptors decrease cAMP

Answer 15

D2, D3 and D4

Question 16

How are Parkinson’s disease and dopamine linked

Answer 16

Caused by death of dopamine

Question 17

How are schizophrenia and dopamine linked

Answer 17

Caused by overactivity of dopamine levels in certain brain regions

Question 18

How does cocaine affect dopamine

Answer 18

It inhibits uptake
Increased conc of dopamine in synapse
Prolonges it’s action

Question 19

What is the pharmacological evidence for the monoamine theory

Answer 19

Reserpine (inhibits brain storage of NA and 5-HT) causes depression

Question 20

What is the pharmacological evidence against the monoamine theory

Answer 20

Amphetamine (release do NA & blocks reuptake) has no effect in depressed patients
Cocaine (inhibits NA reuptake) has no effect on depressed patients

Question 21

Biochemical evidence for the monoamine theory

Answer 21

Urinary & CSF conc of MOPEG (a NA metabolite) is reduced by 25% in depressed patients
CSF conc of 5-H1AA (5-HT metabolite) is reduced in some depressed patients

Question 22

Biochemical evidence against the monoamine theory

Answer 22

Urinary excretion of 5-H1AA does not change in depression
CSF conc of 5-1AA is not reduced in all patients

Question 23

What are the reuptake inhibitor antidepressant drugs

Answer 23

Serotonin reuptake inhibitors (SRI)
NA reuptake inhibitors (NRI)
Selective SRI (SSRI)
Selective NRI (SNRI)

Question 24

What are tricyclic antidepressants (TCA) structurally closely related to

Answer 24

Neuroleptics
TCA has extra atom in central ring

Question 25

Mechanism of TCAs

Answer 25

Blocks reuptake of amines by nerve terminals Mainly effective on NA and 5-HT with little selectivity

Question 26

Why do TCAs cause side effects

Answer 26

They also bind to Muscarinic receptors Cause dry mouth, blurred vision, constipation and urinary retention

Question 27

How are TCAs metabolised

Answer 27

By N-demethylation and ring hydroxylation (3° -> 2° amines)

Question 28

2 forms of MAO

Answer 28

MAO-A and MAO-B

Question 29

MAO-A has substrate preference for …

Answer 29

5-HT

Question 30

MAO-B has substrate preference for …

Answer 30

Phenylethylamine

Question 31

MAOIs have preference for …

Answer 31

MAO-A

Question 32

Monoamine oxidase regulates what

Answer 32

Concentrations of NA & dopamine

Question 33

Side effects of MAOIs

Answer 33

Hypotension Excessive central stimulation Weight gain Hepatotoxicity

Question 34

Explain the cheese reactions

Answer 34

Caused by MAOIs Tyramine found in mature cheese and marmite Usually metabolised by MAO in gut wall MAOIs cause tyramine to be absorbed and it’s sympathomimetic effect enhances - acute hypertension - severe headache - intracranial bleeding

Question 35

Examples of SSRIs

Answer 35

Fluoxetine, sertraline, citalopram

Question 36

Do SSRIs or TCAs have fewer side effects

Answer 36

SSRI

Question 37

Theory behind the 2-3 weeks therapeutic effect of SSRI

Answer 37

Quick increase in serotonin inhibits serotonin firing Desensitisation of autoreceptors after prolonged SSRI exposure Feedback regulation requires chronic administration to sustain serotonin levels Need to alter delta and beta adrenergic receptor expression

Question 38

4 advantages of SSRIs over TCAs & MAOI

Answer 38

Lack of anticholinergic & cardiovascular side effects No weight gain Low acute toxicity (low risk of overdose) No food reaction

Question 39

Disadvantages of SSRIs

Answer 39

Nausea, anorexia, insomnia Reported increase in aggression

Question 40

What happens when SSRIs is combined with MAOI

Answer 40

Serotonin syndrome

Question 41

Example of NRI

Answer 41

Reboxetine - most effective for social functioning

Question 42

Example of dopamine agonist

Answer 42

Bupropion - blocks reuptake of NA and dopamine