General Pharmaceutical Council Registration Assessment (GPhC Assessment) Clinical Therapeutics and Disease Management Syllabus

In COPD, how does the presence of 'asthmatic features / steroid responsiveness' change the choice of inhaled maintenance therapy?

With asthmatic/steroid-responsive features, escalate to LABA + ICS (then LAMA + LABA + ICS). Without them, escalate to LABA + LAMA. ICS adds pneumonia risk so is reserved for those features or frequent exacerbations.

What is the typical management of an acute infective COPD exacerbation in terms of drug therapy?

Increase short-acting bronchodilators, a short course of oral prednisolone 30 mg for 5 days, and an antibiotic (e.g. amoxicillin, doxycycline, or clarithromycin) if sputum is purulent or there are signs of pneumonia.

What HbA1c value diagnoses type 2 diabetes, and what range defines 'pre-diabetes' (non-diabetic hyperglycaemia)?

Diabetes is diagnosed at HbA1c $\geq 48$ mmol/mol ($6.5\%$). Non-diabetic hyperglycaemia is HbA1c 42–47 mmol/mol.

What is first-line drug therapy for type 2 diabetes, and what is now recommended in addition for patients with established CVD or heart failure?

First-line is metformin (standard-release, titrated). For those with established/high-risk CVD, chronic HF, or CKD, add an SGLT2 inhibitor with proven cardiovascular benefit.

What are the typical HbA1c targets for a type 2 diabetic managed by lifestyle/single drug versus one on a drug carrying hypoglycaemia risk (e.g. sulfonylurea)?

Target is 48 mmol/mol ($6.5\%$) on lifestyle or a non-hypoglycaemic drug; relax to 53 mmol/mol ($7.0\%$) when on a drug that can cause hypoglycaemia.

What is the biochemical triad defining diabetic ketoacidosis (DKA)?

Hyperglycaemia (blood glucose $>11$ mmol/L or known diabetes), ketonaemia ($\geq 3$ mmol/L) or significant ketonuria, and acidosis (venous pH $<7.3$ or bicarbonate $<15$ mmol/L).

How do you interpret thyroid function tests in primary hypothyroidism versus primary hyperthyroidism?

Primary hypothyroidism: high TSH with low free T4. Primary hyperthyroidism: suppressed (low) TSH with high free T4 and/or T3.

What is the first-line drug for hypothyroidism, how is it monitored, and what counselling point governs absorption?

Levothyroxine, titrated to normalise TSH (rechecked $\geq 4$–8 weeks after dose change). Take on an empty stomach, separated from calcium/iron and food, which impair absorption.

Name the two main antithyroid drugs for hyperthyroidism and the key serious adverse effect patients must be warned about.

Carbimazole (first-line) and propylthiouracil. Warn about agranulocytosis: seek urgent help and a white-cell count if sore throat, fever, or mouth ulcers develop.

For uninvestigated dyspepsia/GORD, what are the two main initial pharmacological strategies after lifestyle advice?

A full-dose proton pump inhibitor for 4–8 weeks, or 'test and treat' for Helicobacter pylori. Review and step down to the lowest effective dose.

What is standard first-line triple therapy for Helicobacter pylori eradication in a penicillin-tolerant patient?

A 7-day course of a PPI (twice daily) plus amoxicillin plus either clarithromycin or metronidazole. In penicillin allergy: PPI + clarithromycin + metronidazole.

Which drug classes most commonly cause or worsen peptic ulcers, and what is the typical gastroprotection strategy?

NSAIDs and aspirin (and corticosteroids/anticoagulants increase bleeding risk). Co-prescribe a PPI for gastroprotection in at-risk patients, and use the lowest effective NSAID dose.

How does the typical distribution and inflammation pattern of ulcerative colitis differ from Crohn's disease?

Ulcerative colitis: continuous mucosal inflammation limited to the colon, starting at the rectum. Crohn's: transmural, patchy ('skip lesions') inflammation anywhere from mouth to anus, often terminal ileum.

What drug classes are used to induce versus maintain remission in mild-to-moderate ulcerative colitis?

Aminosalicylates (mesalazine/sulfasalazine), topical and/or oral, induce and maintain remission. Corticosteroids induce remission in flares but are NOT used for maintenance.

What is the recommended first-line antispasmodic/symptom approach for irritable bowel syndrome (IBS), and which antidepressant class is used second-line?

First-line: antispasmodics (e.g. mebeverine, hyoscine) with dietary/fibre advice; loperamide for diarrhoea, laxatives (avoid lactulose) for constipation. Second-line: a low-dose tricyclic antidepressant, then SSRI.

Classify the four main laxative groups with an example of each.

Bulk-forming (ispaghula husk), osmotic (macrogol, lactulose), stimulant (senna, bisacodyl), and stool softeners/faecal softeners (docusate, glycerin). Bulk-forming is usually first-line for chronic constipation.

In acute infective diarrhoea, when is an antimotility drug such as loperamide contraindicated?

Avoid loperamide if there is bloody diarrhoea, high fever, or suspected/confirmed colitis (e.g. C. difficile, severe Shigella/E. coli O157), as it risks toxic megacolon and prolongs infection.

How is chronic kidney disease classified, and which two parameters define the stage?

CKD is staged by GFR category (G1–G5, by eGFR) and albuminuria category (A1–A3, by albumin:creatinine ratio). Lower eGFR and higher ACR indicate worse disease and risk.

Which drug classes provide reno-protection in CKD with albuminuria, and what monitoring is needed after initiation?

ACE inhibitors/ARBs (titrated to maximum tolerated dose) and SGLT2 inhibitors. Check renal function and potassium 1–2 weeks after starting/uptitrating; a rise in creatinine up to $30\%$ or eGFR fall up to $25\%$ can be acceptable.

Name three common drug classes that require dose reduction or avoidance in significant renal impairment.

Examples: metformin (lactic acidosis risk), DOACs and LMWH (bleeding), gabapentin/pregabalin, opioids (morphine), nitrofurantoin (avoid if eGFR $<45$), and many antibiotics (e.g. aminoglycosides, vancomycin).

What is first-line antibiotic therapy for an uncomplicated lower UTI in a non-pregnant woman per NICE/PHE?

Nitrofurantoin (if eGFR $\geq 45$) for 3 days, or trimethoprim if low resistance risk. Nitrofurantoin is avoided near term in pregnancy; trimethoprim is avoided in the first trimester (folate antagonist).

How do the drug treatments for overactive bladder (urge incontinence) differ from those for stress urinary incontinence?

Urge/OAB: antimuscarinics (oxybutynin, tolterodine, solifenacin) or the beta-3 agonist mirabegron. Stress incontinence: pelvic floor exercises first-line; duloxetine is an option if surgery is declined.

What is the recommended minimum duration of antidepressant treatment after remission of a first episode of depression, and which class is first-line?

Continue for at least 6 months after remission (longer if recurrent/high-risk). A generic SSRI (e.g. sertraline, citalopram) is first-line.

What is serotonin syndrome and what triad of features characterises it?

A potentially life-threatening reaction from excess serotonergic activity (e.g. SSRI + MAOI/tramadol). Triad: neuromuscular excitation (clonus, hyperreflexia, rigidity), autonomic instability (fever, tachycardia), and altered mental state.

Which drug is the gold-standard mood stabiliser for bipolar disorder, and what therapeutic plasma range and toxicity signs must be monitored?

Lithium. Therapeutic range is $0.4$–$1.0$ mmol/L (target often $0.6$–$0.8$), taken 12 hours post-dose. Toxicity ($>1.5$ mmol/L): coarse tremor, ataxia, confusion, seizures; needs regular U&Es and thyroid monitoring.

What is the key metabolic monitoring required for patients on second-generation (atypical) antipsychotics, and why is clozapine special?

Monitor weight, lipids, glucose/HbA1c, and prolactin due to metabolic effects. Clozapine requires mandatory regular full blood count monitoring because of the risk of agranulocytosis/neutropenia.

What is first-line monotherapy for focal (partial) seizures versus generalised tonic-clonic seizures under current MHRA guidance for men/non-childbearing patients?

Focal seizures: lamotrigine or levetiracetam. Generalised tonic-clonic: sodium valproate (but NOT in those able to bear children); lamotrigine or levetiracetam are alternatives.

What are the MHRA pregnancy-prevention requirements around sodium valproate?

Valproate must not be used in anyone able to become pregnant unless conditions of the Pregnancy Prevention Programme are met (high teratogenicity: neural tube defects, neurodevelopmental disorders), with annual specialist review and effective contraception.

Describe the WHO analgesic ladder for pain management.

Step 1: non-opioid (paracetamol $\pm$ NSAID). Step 2: weak opioid (codeine, dihydrocodeine) $\pm$ non-opioid. Step 3: strong opioid (morphine) $\pm$ non-opioid, with adjuvants (e.g. amitriptyline, gabapentin) at any step.

How do you convert oral morphine to subcutaneous morphine and to oral codeine (approximate equivalences)?

Oral to subcutaneous morphine: divide the oral dose by 2. Oral codeine to oral morphine: divide the codeine dose by about 10 (codeine is roughly one-tenth as potent).

What is the first-line drug treatment for idiopathic Parkinson's disease when motor symptoms affect quality of life?

Levodopa (combined with a dopa-decarboxylase inhibitor, e.g. co-careldopa or co-beneldopa). Dopamine agonists or MAO-B inhibitors are alternatives if motor symptoms are not affecting quality of life.

Which class of medication should be avoided in dementia with Lewy bodies and Parkinson's disease dementia, and which drug class is first-line for cognitive symptoms?

Avoid antipsychotics (risk of severe sensitivity reactions). Acetylcholinesterase inhibitors (donepezil, rivastigmine, galantamine) are first-line for cognition; memantine (NMDA antagonist) for moderate-severe or intolerance.

What general principles guide empirical antimicrobial therapy and good antimicrobial stewardship?

Use the narrowest-spectrum effective agent guided by local resistance/sensitivities, prescribe the shortest effective course, review/de-escalate at 48–72 hours, take cultures before starting where possible, and document indication, dose and review/stop date.

Which antibiotics carry an MHRA warning for tendon damage/aortic aneurysm, and which class is associated with C. difficile and QT prolongation?

Fluoroquinolones (e.g. ciprofloxacin) carry warnings for tendon rupture and aortic aneurysm. Broad-spectrum agents (cephalosporins, co-amoxiclav, clindamycin, quinolones) raise C. difficile risk; macrolides and quinolones prolong the QT interval.

What is the standard antibiotic management of community-acquired pneumonia stratified by CURB-65 severity?

CURB-65 0–1 (low): oral amoxicillin (or doxycycline/macrolide). 2 (moderate): amoxicillin + macrolide. $\geq 3$ (severe): IV co-amoxiclav + macrolide, consider hospital/ITU. CURB-65 = Confusion, Urea $>7$, RR $\geq 30$, BP $<90/60$, age $\geq 65$.

What is the empirical treatment approach for suspected bacterial meningitis in the community before hospital transfer?

Give immediate IM/IV benzylpenicillin (unless true penicillin anaphylaxis) and arrange urgent hospital admission; in hospital, IV ceftriaxone/cefotaxime (add amoxicillin for Listeria cover in the very young, elderly, or immunocompromised), plus dexamethasone.

Distinguish a live attenuated vaccine from an inactivated vaccine, and give an example and key contraindication of each.

Live attenuated (e.g. MMR, varicella, nasal flu): weakened organism, generally avoided in significant immunosuppression and pregnancy. Inactivated (e.g. injectable flu, hepatitis B, tetanus): killed/subunit, safe in immunosuppression but may need boosters.

Which vaccines are offered routinely to adults in the UK based on age/risk (give examples), and what is the key counselling point about timing in immunosuppression?

Examples: annual influenza, pneumococcal (PPV23 at 65+/at-risk), shingles (Shingrix), COVID-19, and RSV (75+/late pregnancy). Live vaccines should ideally be given before starting, or after stopping, immunosuppressive therapy.

In cancer chemotherapy, what is neutropenic sepsis and how must it be managed?

A medical emergency: fever (or unwell) with neutrophils $\leq 0.5 \times 10^{9}$/L (or $\leq 1.0$ and falling) within ~6 weeks of chemotherapy. Treat immediately with empirical broad-spectrum IV antibiotics (e.g. piperacillin/tazobactam) without waiting for cultures.

What anti-emetic strategy is used for highly emetogenic chemotherapy, and which receptor is targeted by ondansetron?

Combine a 5-HT3 antagonist (ondansetron), a corticosteroid (dexamethasone), and an NK1 receptor antagonist (aprepitant). Ondansetron blocks 5-HT3 (serotonin) receptors; note its risk of constipation and QT prolongation.

What is tumour lysis syndrome, and which biochemical abnormalities define it?

A metabolic emergency from rapid tumour cell breakdown (often after starting chemo in bulky/haematological cancers): hyperkalaemia, hyperphosphataemia, hyperuricaemia, and secondary hypocalcaemia, risking AKI. Managed with hydration and allopurinol or rasburicase.