Depression😔 Flashcards

Question

EBL: Mirtazapine Give the chemical structure of the drug clearly identifying the important properties of the molecule which affect its ability to cross the blood brain barrier (BBB). Justification of drug based on pharmacology and pathophysiology of depression Relevant monitoring required and follow up Relevant patient advice A discussion of the advantages and disadvantages of using this treatment with reference to relevant guidelines and patient factors, and your thoughts on whether this is an appropriate choice for this patient

Answer 1

Blood-Brain Barrier (BBB) Penetration (1 slide/minute) Chemical Properties Supporting BBB Penetration Molecular Weight: 265.36 g/mol ✅ (under 400–500 Da) Functional Groups: Tetracyclic ring system Pyridine and pyrazine rings Tertiary amine group Lipophilic nature: Facilitates passive diffusion across BBB P-glycoprotein: Not a strong substrate → less risk of efflux from CNS ✅ Conclusion: Efficient BBB penetration due to lipophilicity, moderate molecular size, and minimal efflux activity. Justification Based on Pharmacology & Pathophysiology of Depression Based on the monoamine hypothesis: depression results from deficiency of serotonin and noradrenaline in the CNS. This imbalance affects mood, motivation, and sleep regulation. Pharmacological Action of Mirtazapine Classified as a NaSSA (Noradrenergic and Specific Serotonergic Antidepressant). Antagonist at central α2-adrenergic autoreceptors → increases release of noradrenaline and serotonin. Also blocks 5HT2 and 5HT3 receptors: Reduces anxiety and nausea. Enhances sedating and appetite-increasing effects via 5HT1A pathway. Clinical Effect Improves mood, motivation, and sleep quality. Faster onset of sedative effect than SSRIs. Relevant Monitoring and Follow-Up Baseline: Weight, BMI, blood pressure, liver function tests Ongoing: Monitor: Mood and sleep Weight changes Blood pressure Liver function Follow-up Schedule: 1–2 weeks: Side effects review 4–6 weeks: Assess therapeutic response 3–6 months: Long-term effectiveness and metabolic effects 4. Patient Advice (1 slide/minute) Administration: Take at night due to sedation. Common side effects: Drowsiness Weight gain Dizziness Driving & alcohol: Avoid driving initially Limit alcohol Missed dose: Skip and take next dose as scheduled – do not double dose. Discontinuation: Taper gradually to avoid withdrawal symptoms. ✅ Advantages Faster sleep improvement than SSRIs. Effective in depression with comorbid anxiety or insomnia. Lower risk of sexual dysfunction compared to SSRIs and SNRIs. ❌ Disadvantages Weight gain, increased appetite Daytime sedation – may impair concentration or work Withdrawal symptoms if stopped abruptly NICE Guidelines Second-line antidepressant if SSRIs are ineffective or not tolerated. Preferred if insomnia or agitation are prominent. Appropriateness for This Patient: ✅ Benefits: Improves sleep and mood; alternative after SSRI failure. ❌ Risks: Daytime sedation may impair performance (e.g., nurse). Weight gain may affect physical health and personal goals. History of DVT: Sedation and weight gain may pose additional risks. Alternative Consideration: A non-sedating SNRI (e.g., venlafaxine) may be more suitable due to better alertness profile.

Answer 2

1. Blood-Brain Barrier (BBB) Penetration Chemical Structure & Physicochemical Properties Molecular formula: C₁₉H₂₃N Structure: Tricyclic compound with: Cycloheptane ring Tertiary amine on the side chain Lipophilic nature: Promotes passive diffusion across BBB Molecular weight: ~277 Da ✅ (within BBB range) Hydrogen bonding: Low number of donors/acceptors ✅ Conclusion: Amitriptyline crosses the BBB efficiently due to small size, lipophilicity, and favourable hydrogen bonding. 2. Pharmacology and Pathophysiology Justification Pathophysiology of Depression Based on the monoamine hypothesis: Depression results from a deficiency of serotonin (5-HT), noradrenaline (NA), and dopamine (DA) in key brain regions. Causes include increased breakdown by monoamine oxidase and reduced neurotransmitter release. Pharmacological Action of Amitriptyline Tricyclic antidepressant (TCA). Inhibits reuptake of serotonin and noradrenaline at the synaptic cleft → increased neurotransmitter availability. Secondary receptor activity: Blocks muscarinic, histaminergic, and α1-adrenergic receptors → contributes to side effects like sedation, anticholinergic symptoms, and hypotension. Clinical Effect Improves mood, energy, and sleep by restoring monoamine levels. Often used at lower doses for neuropathic pain, though higher doses needed for depression. 3. Monitoring and Follow-Up Initial Monitoring: Assess adherence and side effects after 1–2 weeks. Evaluate response at 4 weeks: If no benefit, consider dose increase or switching. If some improvement → continue current dose and reassess at 6–8 weeks. Ongoing Monitoring: Mood, daily functioning, and relationships. Weight/BMI Side effects: Anticholinergic: dry mouth, urinary retention Sedation, dizziness QT interval prolongation (cardiac monitoring may be needed) 4. Patient Advice Duration: Continue for at least 6 months after symptom remission to prevent relapse. Lifestyle: Encourage hobbies, physical activity, social engagement. Psychological support: Recommend CBT or other talking therapies. Caution: Avoid alcohol and recreational drugs. Do not use over-the-counter or herbal meds (especially St John's Wort) without checking with a pharmacist. Urgent/emergency advice: Seek immediate help if suicidal thoughts, hopelessness, or self-harm occur. 5. Advantages, Disadvantages & Patient Suitability ✅ Advantages Proven efficacy similar to SSRIs. May be helpful in sleep disturbances or chronic pain. Effective in severe or melancholic depression. ❌ Disadvantages High side effect burden: sedation, anticholinergic effects, dizziness. Overdose risk: potentially fatal (cardiotoxicity, seizures). QT prolongation risk – ECG monitoring needed in some cases. Interactions with other medications (e.g., increased bleeding with anticoagulants like rivaroxaban). NICE Guidance & Clinical Consideration Not first-line; used if SSRIs/SNRIs fail or are unsuitable. In this patient, SSRIs carry a lower bleeding risk with rivaroxaban than the toxicity risk of TCAs. Conclusion: Not the most appropriate first choice for this patient. Consider SSRI or SNRI or tetracyclic alternatives like mirtazapine first.

Answer 3

1. Blood-Brain Barrier (BBB) Penetration Chemical Properties Supporting BBB Penetration Molecular weight: 324.4 g/mol ✅ (within optimal range) LogP: 3.7–4.2 → indicates moderate lipophilicity Hydrogen bond donors: 0 ✅ Hydrogen bond acceptors: 4 ✅ pKa: 9.5–9.8 → mostly uncharged at physiological pH → facilitates membrane diffusion BBB Penetration: Passively diffuses well due to small size, lipophilicity, and uncharged state Pharmacology and Pathophysiology Justification Pathophysiology of Depression Depression is linked to reduced serotonin (5-HT) neurotransmission in the brain. Low synaptic serotonin levels impair mood regulation and emotional processing. Pharmacological Action of Escitalopram Selective serotonin reuptake inhibitor (SSRI) Mechanism: Inhibits serotonin transporter (SERT) → prevents 5-HT reuptake Increases serotonin concentration in the synaptic cleft Enhances serotonergic neurotransmission → improves mood and reduces depressive symptoms Clinical Note Escitalopram is the S-enantiomer of citalopram and is considered more potent and selective for SERT. Monitoring and Follow-Up Key Monitoring Areas: First few weeks: Monitor for worsening depression or suicidal thoughts Seizures: Discontinue if they occur or worsen Glycaemic control: SSRIs may affect diabetes management Bleeding risk: Caution with NSAIDs or anticoagulants (e.g. rivaroxaban) Hyponatraemia: Especially in the elderly or with diuretics Cardiac: Risk of QT prolongation/arrhythmias Serotonin syndrome: Caution with other serotonergic drugs Renal/hepatic impairment: Adjust if CrCl <30 mL/min Patient Advice Onset: Effects typically take 4–6 weeks Administration: Once daily, with or without food Best taken in the morning if causing insomnia Take at the same time daily Do not stop suddenly → taper under supervision Avoid alcohol Consult pharmacist before using OTC/herbal products (e.g. St John's Wort) Report side effects or worsening symptoms promptly ✅ Advantages Well-tolerated and effective SSRI Once-daily dosing supports adherence Potential improvement in mood and sleep Good option after sertraline failure (as per NICE guidance) ❌ Disadvantages Delayed onset (4–6 weeks) Side effects: Nausea, headaches, insomnia or sedation, sweating, fatigue May affect functioning, especially for ICU nurses Bleeding risk: Increased when combined with rivaroxaban Possible weight gain with long-term use NICE Guidance & Suitability Recommends switching to another SSRI if the first is ineffective. Escitalopram is a logical next step after sertraline non-response. Caution advised due to her clinical role, bleeding risk, and side effect burden — but remains a clinically valid option.

Depression😔 Flashcards

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