Pharmacology: Antidepressants Flashcards

Question

What is the MOA of TCAs?

Answer 1

All TCAs **block** the **reuptake of noradrenaline** via NET inhibition. All TCAs are also antagonists at H1, alpha 1, M1 cholinergic receptors and also block voltage sensitive sodium channels Some TCAs are also **potent inhibitors of SERT** (e.g. clomipramine) and some may also act as antagonists at 5HT-2A and 5HT-2C receptors This wide receptor binding explains their extensive side effect profile

Answer 2

Effective agents but limited as many SE Most SEs mediated through: * H1 (sedation, weight gain), * M1 (dry mouth, blurred vision, urinary retention, constipation), * alpha 1 (hypotension, dizziness) and * voltage gated sodium channel blockade (coma, seizures, heart arrhythmias when used in overdose). As well as their unpleasant side effect profile, their risk in overdose means their use is strictly as second line agents

Answer 3

ECG changes include prolongation of the PR, QRS and QT intervals, nonspecific ST segment and T wave changes, atrioventricular block, right axis deviation

Answer 4

MAO exists in two subtypes known as A and B. The A form preferentially metabolises the monoamines most commonly linked to depression (i.e. serotonin and noradrenaline) Inhibiting MAO-B is primarily used in raising dopamine levels in those receiving levodopa treatment for Parkinson’s disease

Answer 5

Phenelzine, Tranylcypromine and Isocarboxazid are all **irreversible enzyme inhibitors.** Normal enzyme activity only returns 2-3 weeks later when new enzyme has been synthesised Moclobemide binds reversibly to MAO-A and therefore it is always competing with native enzyme

Answer 6

Also known as the dietary tyramine interaction Taking a MAOI + consuming tyramine in diet = **risk of developing a hypertensive crisis** Tyramine acts as a **catecholamine releasing agent**. Normally the release of noradrenaline by tyramine is inconsequential as MAO-A destroys it. In the presence of an MAO-A inhibitor noradrenaline can lead to a significant rise in blood pressure *A person normally can metabolise 400mg of tyramine per day and even a high tyramine diet typically contains less than 40mg. When an MAO-A inhibitor is present it may take as little as 10mg to increase blood pressure* Patients advised to have a low tyramine diet. Mostly avoid fermented or aged foods

Answer 7

Potentially life threatening complication = in essence is serotonin toxicity Suspect in those taking high dose antidepressants or multiple antidepressants People taking multiple antidepressants are a risk, especially those taking MAOIs and TCAs **_Tramadol_** also has serotonergic activity and can increase risk

Answer 8

A clinical diagnosis; no tests are available

Answer 9

Mild – Insomnia, anxiety, nausea, diarrhoea, hypertension, hyper-reflexia

Answer 10

Moderate – Agitation, myoclonus, tremor, mydriasis, diaphoresis, low grade fever (38.5 degrees),

Answer 11

Severe – Hyperthermia (\>38.5 degrees),confusion, rigidity, respiratory failure, coma, death N.B – Key take home symptoms. Altered mental status, sweating, fever and hyperreflexia/clonus (they look like a melting snowman!)

Answer 12

Management – Stop antidepressants. Fluids and supportive care. Symptoms typically resolve in 24 hours

Answer 13

All antidepressants have the potential to cause a withdrawal syndrome, especially if taken for \>6 weeks Abrupt cessation should be avoided to avoid symptoms

Answer 14

Venlafaxine and Paroxetine are associated with the great withdrawal symptoms Drugs with **longer half lives** (e.g. Fluoxetine with a half life of 4-6 days) generally are less likely to cause withdrawa

Answer 15

* Restlessness, * sweating, * electric shock sensations in the scalp, * insomnia, * GI upset. * Often described as “flu like symptoms”

Answer 16

Symptoms are **not dangerous**, generally mild and last for 1-2 weeks Aim to **taper over 2-4 weeks** to avoid withdrawal - **Maudsley Prescribing Guidelines** has advice on how to cross taper from one antidepressant to another

Answer 17

A popular name for the plant **Hypericum Perforatum** Can be bought over the counter as a herbal preparation with reported beneficial effects on mood Mechanism **poorly understood** but it may inhibit MAO and inhibit the SERT and NET in addition to affecting serotonin receptor expression

Answer 18

It’s **efficacy in depression** is unclear and it should not be recommended * Is associated with an **increased risk of bleeding like SSRIs** * **Potent hepatic enzyme inducer.** Reduces plasma levels of warfarin, hormonal contraceptives and digoxin * It’s use **may also contribute to the risk of serotonin syndrome** in those taking other antidepressants

Answer 19

Generally 2-6 weeks due to their mechanisms of action often working through altering gene expression

Answer 20

No, they do not change dopamine levels in the mesolimbic reward pathway

Answer 21

Depends on the nature of the illness and risk Rule of thumb: **Continue for 6-9 months following resolution of the episode of illness**

Answer 22

Review regularly (i.e. weekly) when starting antidepressants in the young due to the theoretical increased risk of suicidality

Answer 23

They can precipitate **hypomanic** episodes in those with an underlying bipolar illness The first line treatment for bipolar depression is **mood stabilisers** not antidepressants