Week 1 - D - Pharmacology- Neuropathic pain, Depression (SSRI, SNRI, TCA, MAOI, Atypicals)&Bipolar disorder (acute&mood stabilisation)

Question 1

Antidepressant drugs have lots of different clinical use Moderate/severe depresion Dysthymia - how long does dysthymia last? Generalised anxiety Panic disorder, OCD, PTDS Premenstrual dysphoria Bulima nervosaa Neruropathic pain

1st line for neuropathic pain & trigeminal neuralgia?

Answer 1

Dysthymia is persistent mild depression lasting longer than 2 years - in some patients this progresses to major depression - (major encompasses moderate to severe usually)

1st line treatment for trigeminal neuralgia - carbamazepine

If this fails - lamotrigine, gabapentin or phenytoin (basically stick with the anti-epileptics for trigeminal neuralgia)

1st line treatment for neuropathic pain - 1st line is amitryptlyine or gabapentin or pregablin or duloxetine

Question 2

How does carbamezapine (1st line for trigeminal neuralgia), lamotrogine, gabapentin and phenytoin (all three are 2nd line options) work? How does amitryptiline work, and gabapentin and pregablin and duloxetine? (all 1st line options for neuropathic pain that isnt trigeminal neuralgia)

Answer 2

* Carbamezapine - Na+ channel blocker - stabalises inactivated Na+ channels - anti-convulsant

* Lamotrigine - Na+ channel blocker- anti-convulsant

* Phenyotin - believed to be a Na+ channel blocker

Amitryptiline - tricyclic antidepressant, selectively blocks reuptake of monoamines into the presynaptic terminal (mainly serotonin (5HT) and noradrenaline)

Gabapentin/pregablin - GABA analogue - blocks voltage gated Ca 2+ channels decreasing release of glutamate & substance P

Duloxetine-SNRI -blocks reuptake of serotonin&noradrenaline

Question 3

What are the three main classes of antidepressants?

Answer 3

Monoamine reuptake inhibitors (SSRIs, tricylics, SNRIs, other non-selective reuptake inhibtiors) Monoamine oxidase inhibitors Atypical drugs - they exhibit post-synaptic effects

Question 4

Name 3 types of monamine? Monoamine neurotransmitters are neurotransmitters and neuromodulators that contain one amino group that is connected to an aromatic ring by a two-carbon chain (such as -CH2-CH2-).

Answer 4

Monoamine refer to specific neurotransmitters eg Noradrenaline Serotonin Dopamine

Question 5

What do monoamine reuptake inhibitors do?

Answer 5

These stop the reuptake of the monoamines (noradrenaline, serotonin and dopamine) resulting in an increase in concentrations of neurotransmitters in the synapse

Question 6

What is the monoamine hypothesis?

Answer 6

This hypothesis stipulates that depression results from a functional deficit of monoamine transmitters particularly serotonin and noradrenaline Drugs that deplete the stores of monoamines can therefore induce low mood And therefore drugs that treat depression will work by increasing the concentrations of monoamines

Question 7

What are the different types of anti-depressants mainly?

Answer 7

Monoamine reuptake inhibitors (SSRIs, Tricyclics, SNRIs, Other-non selective uptake inhibtors) Monoamine oxidase inhibitors Atypicals - exhibit post-synaptic effects

Question 8

How do monoamine oxidase inhibitors work? (MAOI)

Answer 8

Monoamine oxidase inhibitors can either be reversible or irreversible of monoamine oxidase A or B Monoamine oxidase inhibitors prevent the action of monoamine oxidase which catalyses the activation and inactivation of monoamine neurotransmitters

Question 9

MAOI - Inhibit monoamine oxidase -> decreased breakdown of the monoamine neurotransmitters (norepinephrine, serotonin, dopamine) leading to increased levels in the synapse Why are they not used first line?

Answer 9

They are highly effective in patients with treatment resistant depression but patients need to be able to follow the dietary restrictions which is difficult

Question 10

What are examples of irreversible and reversible MAOIs?

Answer 10

Irreversible - phenelzine Reversible - moclobemide

Question 11

MAOIs are Highly effective in some patients with treatment resistant depression but patients need to be able to follow the diet and medication restrictions What are side effects of MAOI?

Answer 11

Postural hypotension Reduces metabolism of other drugs potentiating their effects Insomnia Peripheral oedema Cheese crisis aka hypertensive crisis

Question 12

What needs to be avoided in diet when taking MAOIs due to the risk of hypertensive crisis? What causes the hypertensive crisis?

Answer 12

Foods containing the ingredient tyramine need to be avoided Tyramine is a very potent release of noradrenaline and is usually broken down by MAO-A. If taking a MAOI and a high tyramine meal is taken, then this noradrenaline accumualtion can cause a hypertensive crisis Foods high in tyamine - CHEESE (hence the cheese crisis), alcohol and many others Symptoms of crisis - headache, SOB, nosebleed

Question 13

How do tricylic anti-depressants work? What are examples of tricyclic agents?

Answer 13

Tricyclics work by blocking the reuptake of monoamine neurotransmitters in the presynaptic terminals - increasing their time in the synaptic cleft (mainly noradrenaline and serotonin) * Amitriptyline * Imipramine * Clomipramine * Lofeparmine

Question 14

What are common side effects of tricylic anti-depressants? What happens in amitryptiline toxicity?

Answer 14

Anti-cholinergic so dry mouth , blurred vision, constipation, urinary retention - they block your parasympathetics Sedation Weight gain Also cardiovascular - eg postural hypotension, tachycardia, arrhythmia Amitryptiline is cardiotoxic in overdose

Question 15

How do selective serotonin reuptake inhibitors (SSRIs) work? Name 3 examples

Answer 15

Selective serotonin reuptake inhibitors - SSRIs These work by selectively inhibiting the serotonin reuptake in the presynaptic terminals increasing serotonin (5HT) in the synaptic cleft 4 examples * Fluoxetine * Citalopram * Paroxetine * Sertraline

Question 16

Common side effects of SSRIs? What can SSRIS cause transiently in patients of what age group?

Answer 16

GI side effects Anxiety Sexual dysfunction Headache Hyponatraemia Can cause a transient increase in self-harm / suicidal ideation in patients aged under 25 years of age

Question 17

Why can SSRIs cause cause hyponatraemia? What other anti-depressant class can cause this?

Answer 17

Many drugs including tricyclic antidepressants, and all SSRIs can cause SIADH. This increased water retention causes increased sodium loss leading to a hyponatraemia. Antidepressant-induced SIADH has been reported mostly in patients above 65 years of age, mostly due to the use of fluoxetine.

Question 18

What is the other main monoamine reuptake inhibitor? What is its mode of action? (dual reuptake inhibitor) Name 2 examples?

Answer 18

This would be serotonin and noradrenaline reuptake inhibitors (SNRIs) - they block the reuptake of serotonin and noradrenaline in the presynaptic terminals Duloextine and venlafaxine

Question 19

What are the side effects of SNRIs?

Answer 19

They are similar to SSRIs but lack the major blocking side effects so have fewer side effects than tricyclics Side effects GI effects Anxiety Sexual dysfunction

Question 20

Give two examples of atyical drugs? Atyical drugs worked via mixed receptor effects

Answer 20

Mirtazapine and bupropion

Question 21

What type of atypical is mirtazpine? (how does it work) What are its side effects and what can it block if given with SSRIs?

Answer 21

Mirtazapine as a noradrenergic and specific serotonergic antidepressant (NaSSA) Blocks alpha2, 5-HT2 and 5-HT3 receptors Side effects include weight gain and sedation Can block the serotenergic side effects f given with SSRIs

Question 22

What is the combination of mirtazapine and venflafaxine known as?

Answer 22

Basically if monotherapy with SSRIs and/or mirtazapine hasnt worked then give SNRIs SNRIs- not usually first line due to higher risk of side effects than SSRIs. Commonly used when SSRI and/or mirtazapine haven’t worked. Venlafaxine is excellent in combination with mirtazapine when monotherapy hasn’t worked (“California Rocket Fuel”)

Question 23

How does the atypical bupropion work?

Answer 23

Bupropion is a dopamine uptake inhibitor

Question 24

What is important to note about all anti-depressants?

Answer 24

They all take several weeks to have onset

Question 25

Which drugs are most commonly given as the first line treatment for depression? Name examples? When should they be taken and why?

Answer 25

This would be the SSRIs - selective serotonin reuptake inhibitors * Citaloram * Fluoxetine * Paraoxetine * Sertaline Should take in the morning to avoid insomnia - a known side effect

Question 26

What are the options for the second line treatment of depression?

Answer 26

* SNRI - serotonin and noradrenaline reuptake inhibitors * * Tricylcics - blocks reuptake of monoamines in the synaptic cleft (mainly serotnonin and noradrenaline) * * Atypicals - mirtazapine (noradrenergic and specific serotonergic antidepressant NaSSA) or bupropion (dopamine uptake antagonist)

Question 27

Which drug is commonly out of the three options mentioned used as second line in the treatment of depression? When may this drug be used 1st line?

Answer 27

Mirtazapine - may be used first line in patients with insomnia and/or poor appetite Often used though when SSRIs dont work

Question 28

SNRIs are not usually first line due to higher risk of side effects than SSRIs When are they usually used? When are tricyclics used?

Answer 28

SNRIs are usualy used if treatment has not responded to SSRIs or mirtazapine Tricylcics are used after SNRI, avoid in those with cardiac problems

Question 29

If the patients hasnt responded to the different Monoamine reuptake inhibitors or the atypical drugs What is the treatment that can be given? Give two examples

Answer 29

Monoamine oxidase inhibitors - prevent the oxidation and inactivation of monamines by the enzyme monoamine oxidase Can be irreversible - phenelzine Can be reversible - Moclobemide

Question 30

What are the side effects associated with MAOIs?

Answer 30

Postural hypotension Peripheral oedema Insomnia Hypertensive crisis - due to foods containing cheese which require MAO to break it down - tyramine increases noradenaline production which leads to increased BP Also potentiates effects of other drugs by blocking their metabolism

Question 31

What is non-response to an antidepressant defined as? How long should the treatment be continued after resolution of depressive symptoms at first appearance?

Answer 31

Non-responsive treatment to an antidepressant can be defined as no or inadequate response after six weeks at maximum or best tolerated dose - swap the antidepressant Continue treatment fora after at least 6 months after a full resolution of symptoms after a first episode

Question 32

How long should treatment be continued after a recurrence of depression? How long should anti-depressant treatment be continued after a third episode?

Answer 32

After a recurrence, continue treatment for at least 12, up to 24 months after full resolution of symptoms After third episode, continue indefinitely if willing

Question 33

Electroconvulsive therapy is a very effective treatment for depression What are the indications for the use of ECT in the treatment of depression?

Answer 33

It is recommended that electroconvulsive therapy (ECT) is used only to achieve rapid and short-term improvement of severe depressive symptoms after an adequate trial of other treatment options has proven ineffective and/or when the condition is considered to be potentially life-threatening, in individuals with: * catatonia * a prolonged or severe manic episode.

Question 34

What is catatonia? What condition is it typically seen in?

Answer 34

Cataonia is the abnormality of movement and behaviour arising from a disturbed mental state (typically schizophrenia)

Question 35

What are the common catatonic behaviours?

Answer 35

Patients can present as Rigid or in a stupor Staying in uncomfortable positions without moving Performing erratic movements Echolalia - repetition of words or behaviours

Question 36

How long are the typical course lengths of ECT? What should happen to the medication when ECT is about to be started?

Answer 36

Typical course lentghs are 6-12 sessions (usually 2 per week) Current medication should be reduced and continued when starting ECT

Question 37

What are the side effects of ECT?

Answer 37

Short-term side-effects headache nausea memory loss of events prior to ECT short term retrograde amnesia Long-term side-effects some patients report impaired memory

Question 38

What are the principles of treating bipolar disorder?

Answer 38

The acute treatment is to raise the mood in depressive and to decrease the mood in manic bouts However for long term - give a mood stabilizer

Question 39

Which drug is usually used 1st line to treat the depressive episodes in bipolar disorder if this is what they present with?

Answer 39

For the treatment of depression options include: Fluoxetine combined with olanzapine, or Olanzapine alone, or Quetiapine alone, or If these do not work can try lamotrigine. And after successful treatment move to a long term mood stabilizer

Question 40

If a person develops mania or hypomania and is not taking an antipsychotic or mood stabiliser, offer what drugs?

Answer 40

Usually offer an atypical or typical antipsychotic to treat the acute mania episode (haloperidol (typical), quetiapine, olanzapine, risperidone (atypicals) - generally the atypicals are used) or Try valproate semisodium

Question 41

What is the most effective treatment for stabilizing bipolar disorder and how is it thought to work?

Answer 41

This would be lithium carbonate Thought to work by blocking phsophatidylinositol pathway or inhibiting glycogen synthase kinase 3B

Question 42

What is the hypothesis by which lithium is thought to work?

Answer 42

Thought to work via the inositol depletion hypothesis

Question 43

What are the side effects of lithium? Why is the drug dangerous?

Answer 43

The side effects - GI upset, sedation, feeling of weakness, fine tremor, polyuria - causes diabetes insipidus, ankle swelling, renal impairment, hypoparathyroidism and hypothyroidism

Question 44

What are the toxic effects of lithium?

Answer 44

Vomiting, diarrhoea, ataxia, coarse tremor, drowsiness, convulsions, coma

Question 45

If patient compliance is good, what needs to be seen as normal before commencing a patient on lithium? What must be checked when making sure lithium is in the therapeutic range?

Answer 45

* If the patient compliance is good, then check to make sure U&Es, TFTs and ECG is normal and then start the patient on lithium Get patient to therapeutic range by checking U&Es every 7 days and checking lithium levels 12 hours after each dose until within stable range Stable range is when 12 hours after last dose the lithium levels are in therapeutic range in the blood

Question 46

After the patient then continues on lithium when concentrations are stable, how often are lithium level, U&Es and TFTs checked?

Answer 46

After starting lithium levels should be performed weekly and 12 hours after each dose change until concentrations are stable * Once established, lithium blood level should ‘normally’ be checked every 3 months * Check TFTs and U&Es every 6 months

Question 47

If hypothryoidism does happen, what do you do to the lithium? What type of diabetes insipdus does the lithium cause? How do you monitor the lithium after you change its dose?

Answer 47

If patient becomes hypothyroid, then do not stop the lithium but instead prescribe levothyroxine Lithium causes nephrogenic diabetes insipidus where the kidneys do not respond to ADH After a change in dose, lithium levels should be taken a week later and 12 hours after the last dose

Question 48

What are causes of lithium toxicity? What is the treatment?

Answer 48

Causes - increased dose, dehydration (pshyical illness, exercise, alcohol, decreased fluid intake), drug interaction and reduced salt intake Treatment - stop lithium, IV fluids and may need dialysis if severe

Question 49

What other drugs can be used in the long term treatment of bipolar disorder? Usually options when lithium is not giving good control Give drug examples of both options

Answer 49

Anticonvulsatns can be used as mood stabiliser - valproic acid, lamotrigine and carbamezapine Antipsychotic drugs can be used - usually atypicals - olanzapine, quetiapine, aripiprazole

Question 50

What is the mode of action anti-psychotics? What are the side effects?

Answer 50

Anti-psychotics - dopamine antagonism and 5HT antagonism Side effects - Sedation and weight gain, metabolic syndrome (insulin resistance, fatness) (also get galactorrhea and gynaecomastia due to blocking of dopamine and increased prolactin) Extrapydramidal side effects

Question 51

What are side effects of the different anticonvulsant options?

Answer 51

Anti-convulsants Side effects Carbamezapine - can cause SIADH and pancytpenia Valproic acid - teratogenic, weight gain, thrombocytopenia Lamotrigine - Steven-johnson syndrome

Question 52

Which drug mentioned in this card set is dangerous for suicidal people as it can be used to easily overdose?

Answer 52

This would be tricyclic antidepressants - side effects is in overdose they are cardiotoxic