Antiidepressants

Question 1

CNS pharmacology?

Answer 1

How drugs alter brain activity and offset pathology

Question 2

Neuropharmacology?

Answer 2

How drugs act on neurons at cellular/molecular level.

Question 3

Psychopharmacology?

Answer 3

How drugs modify behavior, perception, affect and thaught

Question 4

Therapeutic effects of drugs that act on the CNS?

Answer 4

1. Induction of Anesthesia (Anaesthetics)
2. Relief of Pain (Analgetics – Narcotics)
3. Prevention of Epileptic seizures (Antiepileptics)
4. Reduction of Anxiety (hypnotics and anxiolytics/ Antipsychotics))
5. Treatment of Depression (Antidepressants)
6. Treatment of Alzheimer’s disease & Parkinsonism (Antiparkinsonism drugs)

Question 5

Nuerotransmitter imbalances and associated behavioural disorder?

Question 6

Risk factors for depression?

Answer 6

1. genetics
2. changes in hormone levels
3. certain medical conditions
4. stress
5. grief or difficult life circumstances

Question 7

Signs and sypmtoms of depression?

Answer 7

1. Depressed mood
2. Lack of interest in activities normally enjoyed
3. Changes in weight
4. Changes in sleep
5. Fatigue
6. Feelings of worthlessness and guilt
7. Difficulty concentrating
8. Thoughts of death and suicide

Question 8

Neurotransmitters implicated in CNS depression?

Answer 8

1. Dopamine
2. Norepinephrine
3. Serotonin
   - There are other neurotransmitters that can send messages in the brain, including glutamate, GABA, and acetylcholine

Question 9

3 types of depression?

Answer 9

1. reactive or secondary depression
2. endogenous depression
3. The depressive phase of maniac depressive disorders.

Question 10

Describe reactive depression?

Answer 10

usually due to recognisable causes (anxiety, grief, drugs, alcohol) and usually responds to emotional support, psychotherapy and use of sedatives

Question 11

Endogenous depression?

Answer 11

• More serious and more prolonged
• May arise without significant aggravating cause.
• Responds poorly to psychotherapy
• Tends to reoccur
• May be due to genetically determined abnormality
• Usually responds to the tricyclic class of antidepressants

Question 12

The depressive phase of maniac depressive disorders?

Answer 12

• Often indistinguishable from straight endogenous depression, except there is a history of attacks of manic behaviour
• It is also probably due to genetically determined biochemical abnormality
• Lithium is the preferred treatment

Question 13

Classification of antidepressant drugs?

Answer 13

1. Inhibitors of monoamine uptake
2. Monoamine receptor agonists
   e.g., Mitarzepine
3. Monoamine oxidase inhibitors (MAOIs)
   - Irreversible, non competitive inhibitors (Phenelzine)
   - Reversible, MAO selective inhibitors (meclobemide)

Question 14

Inhibitors of monoamine uptake?

Answer 14

1. Classic antidepressants (TCAs)
   e.g., Imipramine, Amitryptilline
2. (Selective serotonin (5H) reuptake inhibitors (SSRIs)
   e.g., Fluoexetin
3. Noradrenalin reuptake inhibitake inhibitors
   e.g., Bupropion

Question 15

Nor-adrenaline reuptake inhibitors?

Answer 15

1. Tricyclics – Tertiary amines (Amitryptalline, doxepin, imipramine)
2. Tricyclics – Secondary amines (Maprotilline, Nortryptilline)

Question 16

Effects of nor-adrenaline reuptake inhibitors?

Answer 16

1. sedation
2. anticholinergic effects
3. postural hypertention
4. impotence seizures
   - In combination with CNS depressants, there is a high risk of ventricular dysrythmias.

Question 17

Effects of antidepressants?

Answer 17

1. Tricyclics prevent presynaptic reuptake of the amines noradrenaline and serotonin
2. SSRIs predominantly block reuptake of serotonin.
3. MAOIs reduce the activity of monoamine oxidase in breaking down presynaptic amines (leaving more available for release into the presynaptic cleft).
4. Some antidepressants (e.g. nefazodone) block postsynaptic receptors directly.

Question 18

The monoamine hypotheses?

Answer 18

in depression, there is deficiency of the neurotransmitter’s noradrenaline and serotonin in the brain which can be altered by antidepressants.
- Drugs that affect depression can modify amine storage, release, or uptake
- Thus, the concentration of amines in nerve endings and/or at postsynaptic receptors is enhanced

Question 19

Findings that support the monoamine hypothesis?

Answer 19

1. Amphetamines, which release presynaptic noradrenalin and dopamine from stores and prevent their reuptake, have a weak antidepressant effect.
2. The antihypertensive agent reserpine, (which prevents normal noradrenaline storage), causes depression, as does experimental depletion of the serotonin precursor tryptophan.
3. The importance of serotonin is further illustrated by the finding that depressed patients may exhibit down-regulation of some postsynaptic serotonin receptors.
4. Specific serotonin reuptake inhibitors, as the class name implies, act predominantly by preventing serotonin reuptake and have more limited effects on noradrenaline reuptake

Question 20

Monoamine oxidase inhibitors?

Answer 20

MAOI’s cause a rapid and sustained increase in 5-HT, noradrenaline, dopamine content in the brain, 5-HT being affected most & dopamine last.
- Similar changes occur in peripheral tissues (Heart, liver & intestines), and an increases in plasma conc. of amines is detectable.

Question 21

Unwanted effects and toxicity of monoamine oxidase inhibitors?

Answer 21

Hypotension is common (displacement of noradrenaline from the storage vesicles and accumulation of amines in sympathetic nerve terminals)
Excessive stimulation may cause tremours, excitement, insomnia and in overdose convulsions

Question 22

Interactions with other drugs and food for monoamine oxidase inhibitors?

Answer 22

1. Cheese reaction- Occurs when normally innocuous amine (Tyramine) produced during fermentation is ingested
2. Tyramine is metabolised MAO in the gut wall and liver and little dietary tyramine reaches systemic circulation)
3. Administration of other indirect sympathomimetic amines (ephedrine, amphetamine) may cause severe hypertension with patients receiving MAOI’s
4. MAOI’s can interact with pethidine to cause severe hyperpyrexia, with restlessness, coma and hypotension

Question 23

Cheese vs monoamine oxidase inhibitors?

Answer 23

Main danger from the cheese effect is mainly ripe cheese and concentrated yeast products like marmite

Question 24

Monoamine oxidase inhibitors vs Tyramine?

Answer 24

MAO inhibition allows tyramine to be absorbed & enhances its sympathomimetic effect and
Cause
1. Acute hypertension
2. Severe throbbing headache
3. May result in intracranial bleeding