Pharmacology II

Question 2

Describe the key symptoms of discontinuation of antidepressants [+]

Answer 2

Discontinuation symptoms
* increased mood change
* restlessness
* difficulty sleeping
* unsteadiness
* sweating
* gastrointestinal symptoms: pain, cramping, diarrhoea, vomiting
* paraesthesia

Answer 3

Cholinergic crisis and spasmy pain in the intestines
- Particularly problematic in pregnant women

Question 4

What is a potentially adverse effect of SSRI in pregnancy on child:
- 1st trimester
- 3rd trimester

Which antidepressant class is the drug of choice? [1]

Answer 4

SSRIs in pregnancy:
- 1st trimester: congenital heart disease
- 3rd trimester: PPH newborn

TCAs are preferable in pregnancy

Question 5

When stopping a SSRI the dose should be gradually reduced over a [] week period (this is not necessary with []).

Answer 5

When stopping a SSRI the dose should be gradually reduced over a 4 week period (this is not necessary with fluoxetine).

Question 6

[SSRI] has a higher incidence of discontinuation symptoms

Answer 6

Paroxetine has a higher incidence of discontinuation symptoms

Question 7

Treatment of bipolar depression:
- what are risks of giving antidepressants? [1]
- Which medications can you use to manage? [1]

Answer 7

May encourage a switch to a manic state & acceleration of the cycle
- antidepressant should not be prescribed (without mood stabilizer or antimanic drug) in people presenting in depressed state if there is a past history of mania/hypomania

Instead: Prescribe Quetiapine

Question 8

Describe the treatment regime for manic / hypomanic state [+]

Answer 8

Lithium salts (priadel, other)
Anticonvulsants (sodium valproate, divalproex (depakote), lamotrigine, carbamazepine)

Antipsychotics/antimanic
- 1st generation antipsychotics – haloperidol
- 2nd generation antipsychotics – quetiapine, olanzapine, risperidone, aripiprazole, lurasidone

Question 9

Which medication should be used to treat bipolar in long term? [1]

Answer 9

Lithium
- works as a mood stabilizers

Question 10

What are key adverse effects of Lithium salts? [+]

Answer 10

• GI tract s-ms (nausea/diarrhoea)
• pretibial oedema
• polyuria/polydipsia
• fine hand tremor
• hypothyroidism
• Teratogenicity potential - to be avoided in pregnancy
• nephrotoxicity: polyuria, secondary to nephrogenic diabetes insipidus

LITHIUM
L - lethargy
I - diabetes insipidus
T - tremor
H - hyper/hypothyroid
I - insides (GI upset)
U - increased urine (due to DI)
M - metallic taste

Question 11

Lithium Toxicity =>[] mmol/L

Answer 11

Toxicity =>1.4mmol/L

Question 12

Describe the features of lithium toxicity [4]

Answer 12

coarse tremor, lethargy, marked polyuria

neurological signs:
* convulsions
* coma

renal failure

Question 13

keep going king

Question 14

Benzodiazepines work on which receptor in the brain? [1]
How? [1]

Answer 14

GABA-A receptor agonists (dampen downs excitibility in the brain)
- CNS depression

Benzodiazepines enhance the effect of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) by increasing the frequency of chloride channels.

Question 15

Which BDZ is preferred in hepatic impairment? [1]

Answer 15

lorazepam

Question 16

Why BDZ avoided in pregnancy? [2]

Answer 16

• baby hypotonia
• withdrawal breastfeeding

Question 17

When are BDZ severly contraindicated? [3]
Why? [1]

Answer 17

Concomitant use of BDZ with pregabalin, alcohol opiates
- Risk of respiratory suppression

Question 18

How do you reverse BDZ overdose? [1]

Answer 18

flumazenil

Question 19

A patient takes pregabalin, x alcohol.

They go into resp suppression.

How do you treat? [2]

Answer 19

Rx flumazenil and naloxone

Question 20

What are key symptoms of withdrawal from BDZ drugs? [5]

Answer 20

• anxiety, nightmares, insomnia
• perceptual problems, psychotic states, pyrexia, seizures

In longer term use - need for tapering off !!

PM:
* Insomnia
* Irritability
* Anxiety
* Tremor
* Loss of appetite
* Tinnitus
* Perspiration
* Perceptual disturbances
* Seizures

Question 21

How long should BDZ be given for anxiety? [1]

Answer 21

Short-term use in anxiety- 2-4 weeks

Question 22

Describe the MoA of Z drugs [1]

Answer 22

act on the same site as BZD – GABA-A receptor agonists
- although short half life

Question 23

What are the AEs of Z drugs like? [2]

Answer 23

similar to benzodiazepines
increase the risk of falls in the elderly !

Question 24

Describe how you would monitor someone who is taking lithium? [5]

Answer 24

when checking lithium levels, the sample should be taken 12 hours post-dose

after starting lithium levels should be performed weekly and after each dose change until concentrations are stable

once established, lithium blood level should ‘normally’ be checked every 3 months

thyroid and renal function should be checked every 6 months

Question 25

How does lithium cause hypothyroidism? [1]

Answer 25

It inhibits the enzyme **thyroid peroxidase**

Question 26

What are key thyroid effects of lithium ? [2]

Answer 26

**hypothyroidism** and **hyperparathyroidism** - lithium affects calcium homeostasis by altering set points for calcium-sensing receptors (CaSR) in parathyroid cells. Lithium acts as a direct agonist at the CaSR. The result is an increased set point for calcium-inhibited parathyroid hormone (PTH) secretion causing inappropriate PTH secretion relative to serum calcium levels

Question 27

You give somone lithium to stabilise their mood. How would you investigate if this has cause nephrogenic DI? [+]

Answer 27

**Water deprivation test** **Stage 1 - Water deprivation** * At the start of the test, the patient should empty their bladder and then have no fluids and only dry foods until the test is complete. * Hourly weights are taken. * 2 hourly urine volume osmolality and volume. * 4 hourly serum osmolality **Stage 2 - Desmopressin** * Only proceed if urine is still dilute at end of the test (< 600mOsmol/kg) * Administer desmopressin 2mcg IM or 20mcg intranasal. * Allow water consumption * Measure hourly urine osmolality for four hours.

Question 28

What are the contraindications to anti-pyschotics? [4]

Answer 28

**Known hypersensitivity**: - Antipsychotics should not be administered to patients with a known hypersensitivity to the drug or any of its components. **Comatose state or CNS depression** - Antipsychotics are contraindicated in patients suffering from a comatose state or severe central nervous system depression . **Blood dyscrasias:** - Certain antipsychotic medications, such as **clozapine**, are contraindicated in individuals with blood dyscrasias due to the risk of agranulocytosis. **Pheochromocytoma and untreated narrow-angle glaucoma:** - These conditions can worsen with the use of certain antipsychotics like **thioridazine**.

Question 29

Which patients should you be cautious with prescribing anti-pyschotics to? [5+]

Answer 29

**Elderly patients with dementia-related psychosis**: - There is an **increased risk of cerebrovascular adverse events and mortality in this population.** Use of antipsychotics should be carefully evaluated against potential risks. - In particular, **atypical antipsychotics** have been associated with an elevated **risk of stroke and transient ischemic attack in elderly patients**. **Parkinson's disease and Lewy body dementia**: - Patients may exhibit **sensitivity to the extrapyramidal side effects of antipsychotics.** **Epilepsy**: - Antipsychotics may **lower seizure threshold;** caution should be exercised with patients with a **history of seizures or EEG abnormalities**. **Cardiovascular disease:** - Antipsychotics, especially atypical ones, may cause **QT prolongation and postural hypotension**. Regular monitoring of **ECG** is recommended in patients with cardiovascular disease. **Liver and renal impairment**: - Dose adjustments may be necessary due to altered drug metabolism and elimination.

Question 30

What are the EPSE of antipyschtoics? [4]

Answer 30

**Parkinsonism** **Acute dystonia:** sustained muscle contraction (e.g. torticollis, oculogyric crisis) **Akathisia** (severe restlessness) **Tardive dyskinesia** (late onset of choreoathetoid movements, abnormal, involuntary, may occur in 40% of patients, may be irreversible, most common is chewing and pouting of jaw)

Question 31

What are the non-EPSE of antipyschtics? [+]

Answer 31

When antipsychotics are used in **elderly patients:** * Increased risk of **stroke** * Increased risk of **venous thromboembolism** **Other side-effects** * **Antimuscarinic**: dry mouth, blurred vision, urinary retention, constipation * **Sedation, weight gain** * **Raised prolactin: galactorrhoea, impaired glucose tolerance** * **Neuroleptic malignant syndrome**: pyrexia, muscle stiffness * **Reduced seizure threshold** (greater with atypicals) * **Prolonged QT interval** (particularly haloperidol)

Question 32

What are the lab. monitoring needed when giving anti-pyschotics? [5]

Answer 32

**Blood tests** - Baseline full blood count (FBC), liver function tests (LFTs), renal function tests (RFTs), lipid profile and glucose levels are recommended before initiating treatment. These should be monitored throughout treatment according to British National Formulary guidelines. - **Clozapine** requires more frequent monitoring including weekly FBCs for the first 18 weeks of treatment. **ECG**: Baseline ECG should be performed in patients with cardiovascular risk factors before initiating antipsychotics, especially those known to prolong the QT interval. Regular monitoring is advised for these patients. **Body Mass Index (BMI):** - Patients on antipsychotics, particularly atypical ones, are at risk of weight gain. Monitor BMI regularly and provide lifestyle advice as necessary. **Prolactin levels:** - Antipsychotics can cause hyperprolactinaemia leading to symptoms such as galactorrhoea, amenorrhoea and sexual dysfunction. Monitor prolactin levels if these symptoms are reported.

Question 33

What class of drugs does mirtazapine belong to? Selective serotonin reuptake inhibitors Serotonin-noradrenaline reuptake inhibitors Monoamine oxidase inhibitors Noradrenergic and specific serotonergic antidepressants Tricyclic antidepressants

Answer 33

Mirtazapine is a noradrenergic and specific serotonergic antidepressant which **increases release of neurotramsitters by blocking alpha2 adrenoreceptors**

Question 34

For moderate/severe OCD, **[]** may be used as an alternative first-line drug treatment to an SSRI if the person prefers [] or has had a previous good response to it, or if an SSRI is contraindicated

Answer 34

For moderate/severe OCD, **clomipramine** may be used as an alternative first-line drug treatment to an SSRI if the person prefers clomipramine or has had a previous good response to it, or if an SSRI is contraindicated

Question 35

You decide together to try venlafaxine as a second-line option. What should be monitored at initiation and dose titration of this medication?

Answer 35

**Blood pressure** - Venlafaxine and other serotonin noradrenaline reuptake inhibitors (SNRIs) are associated with the **development of hypertension.**

Question 36

You review a 47-year-old man with a history of moderate to severe depression. He has a past medical history of type 2 diabetes and also pericarditis following a viral illness. He has a family history of hypertension. He has previously tried fluoxetine without a significant improvement in his mood. His wife finds her citalopram prescription very helpful for her generalised anxiety disorder. He now wishes to try citalopram himself. **What should be monitored prior to starting citalopram in this patient?**

Answer 36

The BNF states that '**QT prolongation, and/or ventricular arrhythmias including torsade de pointes** have been reported in people taking **citalopram or escitalopram**.' The BNF advises taking an ECG and measuring the QT interval in patients with a history of cardiac disease prior to starting citalopram. Given this man's history of pericarditis, ECG is the correct answer.

Question 37

Which specific cardiac issues are associated with citalopram? [3]

Answer 37

The BNF states that '**QT prolongation, and/or ventricular arrhythmias including torsade de pointes** have been reported in people taking citalopram or escitalopram.' The BNF advises taking an ECG and measuring the QT interval in patients with a history of cardiac disease prior to starting citalopram. Given this man's history of pericarditis, ECG is the correct answer.

Question 38

A 75-year-old woman presents to the emergency department with new onset confusion. She has a past medical history of depression, for which she takes sertraline, and oesophagitis for which she takes omeprazole. She also has a diagnosis of type 2 diabetes. Her dose of sertraline was last increased two weeks ago. Her physical observations are within normal parameters. **What would you perform first to identify the cause of this patient's confusion?**

Answer 38

**Urea and electrolytes** - The BNF advises when starting a serotonin specific reuptake inhibitor (SSRI) to 'observe all people taking antidepressants for signs of **hyponatraemia**.

Question 39

How often should you monitor for hyponatraemia in U&Es? [3]

Answer 39

For people at high risk, measure the serum sodium level **before starting treatment,** **2-4 weeks after starting** treatment and **every 3 months thereafter.'**

Question 40

Antidepressants should be continued for at least **[]** after remission of symptoms to decrease risk of relapse

Answer 40

Antidepressants should be continued for at least **6 months** after remission of symptoms to decrease risk of relapse

Question 41

A 45-year-old female complains of lower back pain, constipation, headaches, low mood, and difficulty concentrating. Her presentation is likely due to which of the following medications? Clozapine Quetiapine Olanzapine Imipramine Lithium

Answer 41

**Long-term lithium** use can result in hyperparathyroidism and resultant hypercalcaemia