Bisphosphonates, Antimuscarinics – bronchodilators, Antihistamine – H1 receptors antagonists, Leukotriene antagonists, Allopurinol

Which bisphosphonates are first-line for osteoporosis?

Alendronic acid and risedronate sodium.

Which bisphosphonates are used for severe hypercalcaemia of malignancy?

Pamidronate and zoledronic acid (after IV rehydration).

Why are bisphosphonates used in myeloma and breast cancer with bone metastases?

To reduce pathological fractures, cord compression, and need for radiotherapy or surgery.

What is the role of bisphosphonates in Paget’s disease?

First-line treatment to reduce bone turnover and pain.

How do bisphosphonates work and what is the overall effect?

They inhibit osteoclasts (cells that crush/breakdown bone).

As bone is resorbed, bisphosphonates acculamate in osteoclasts where they inhibit activity and promote apoptosis.

Overall effect: reduced bone loss and increases bond mass.

Why do bisphosphonates accumulate in bone?

They are structurally similar to pyrophosphate and become incorporated into bone.

What are common adverse effects of bisphosphonates?

Oesophagitis (oral use) and hypophosphataemia.

What rare but serious jaw complication can bisphosphonates cause?

Osteonecrosis of the jaw (especially with high-dose IV therapy).

What rare fracture is associated with long-term bisphosphonate use?

Atypical femoral fracture.

Which patients require caution when using bisphosphonates due to jaw osteonecrosis risk?

Smokers and those with significant dental disease.

When is bisphosphonate use contraindicated?

In severe renal impairment and hypocalcaemia.

Oral therapy can also be contraindicated in active upper GI disorders.

What should be checked before initiating bisphosphonates?

Calcium and vitamin D levels.

What interacts with bisphosphonates?

They bind to milk- so their absorption is reduced if taken with calcium salts (incl. milk) as well as antacids and iron salts.

How should oral bisphosphonates be taken to improve absorption and reduce harm?

Swallowed whole with water ≥30 min before food/meds; remain upright for 30 minutes.

Why should patients see a dentist before and during bisphosphonate therapy?

To reduce the risk of osteonecrosis of the jaw.

How is bisphosphonate efficacy monitored in osteoporosis?

DEXA scans every 3–5 years.

When can bisphosphonates be stopped in low-risk patients?

If BMD T-score is > −2.5.

What safety issues should be monitored during bisphosphonate therapy?

Oesophagitis, jaw osteonecrosis, atypical fractures, and serum calcium.

When would a DEXA scan NOT be necessary to diagnose/treat osteoporosis?

You can assume a diagnosis of osteoporosis in women aged >75 years who have had a fragility fracture and start treatment with a bisphosphonate without further tests for osteoporosis.

What are the common indications for antimuscarinics (as bronchodilators).

1) In COPD- SAMAs are used for relieving acute breathlessness (from exercise/exacerbations), LAMAs as prophylaxis.

2) In acute severe/chronic asthma

What is the MOA of antimuscarinics when used in asthma/COPD?

They are competitive inhibitors of acetylcholine and block muscarinic receptors.

Which muscarinic receptor blockade causes bronchodilation?

M3 receptor blockade → smooth muscle relaxation.

How do inhaled antimuscarinics relieve airway obstruction?

Bronchodilation and reduced respiratory secretions.

What are the common adverse effects of inhaled antimuscarinics?

Dry mouth, cough, hoarse voice.

When should antimuscarinics be used with caution?

In people:

1) Susceptible to angle-closure glaucoma (can precipitate a dangerous rise in intraocular pressure).

2) At risk of arrhythmias or urinary retention.

Why do inhaled antimuscarinics have unproblematic/no interactions?

Due to the small doses used and the low proportion entering the circulation in active form (low bioavailability).

Is ipratropium short or long acting?

It is short-acting and so is taken regularly or as needed for breathlessness.

Is tiotropium short or long acting?

It is long acting and so is taken regularly once- or twice-daily.

How is efficacy of anti-muscarinics monitored?

By enquiring about symptoms such as dry cough (for asthma), reviewing peak flow measurements and checking inhaler technique at every review.

What gas is used to drive nebulisers in asthma? And is it the same for nebulisers in chronic type 2 (hypercapnic) respiratory failure?

Oxygen is used in nebulisers for asthma, and no, medical air is used instead as they are at risk of carbon dioxide retention.

What advice is given to patients if they experience side effects like dry mouth with inhaled anti-muscarinics?

Chew gum, suck sweets (sugar free), or keep a bottle of water with them to relieve these.

Is there any benefit to prescribing SAMAs more often than every 6 hours?

No. More frequent dosing increases adverse effects without increasing benefits.

What are the common indication for

Cetirizine, fexofenadine, loratadine and chlorphenamine are all example of what drug class?

Antihistamines (H1-receptor).

What are antihistamines (H1-receptor antagonists) mainly used for?

1) First-line treatment for allergies, especially seasonal allergic rhinitis (hay fever).

2) To relieve itchiness and hives (due to insect bites, infections and drug allergies.

3) As symptomatic treatment for skin symptoms in anaphylaxis , but AFTER giving adrenaline and other life saving measure.

4) Other drugs can be used as antiemetics.

Why are antihistamines not life-saving in anaphylaxis?

Their onset is too slow; adrenaline and IV fluids are essential initially.

What effects does histamine cause via H1 receptors?

Increased capillary permeability (wheal), vasodilation (flare), and itch.

MOA of antihistamines?

Block H1 (and H2) receptors- stops histamine release from mast cells.

What happens when histamine is released widely?

Anaphylaxis- generalised vasodilation and vascular leakage causing hypotension.

Why do first-generation antihistamines cause sedation?

Histamine helps maintain wakefulness via H1 receptors in the brain.

Give an example of a first-generation antihistamine.

Chlorphenamine.

Why do second-generation antihistamines cause less sedation?

They do not cross the BBB.

Name examples of second-generation antihistamines.

Cetirizine, loratadine, fexofenadine.

In which condition should sedating antihistamines be avoided?

Severe liver disease (risk of hepatic encephalopathy).

Do common H1 antihistamines have major drug interactions?

No major drug interactions.

What advice should be given about chlorphenamine and activities?

Avoid driving or tasks requiring concentration.

How should antihistamine treatment be monitored?

Clinical response, physical signs (e.g. rash), and side effects.

Montelukast and zafirlukast are examples of what class of drug?

Leukotriene receptor antagonists.

What is the main use of leukotriene receptor antagonists in asthma?

Initial add-on therapy for chronic asthma not controlled by a SABA and low-dose ICS.

How are LTRAs used in allergic rhinitis?

As a treatment option when nasal symptoms persist despite antihistamines and/or intranasal corticosteroids, especially in patients with asthma.

MOA of LTRAs?

They block the CysLT1 receptor, which normally activates pathways that result in inflammation and bronchoconstriction → asthma

Which cells produce leukotrienes involved in asthma?

Mast cells and eosinophils.

What are the most common side effects of LTRAs?

Headache, abdominal pain, URTIs and GI upset (usually mild).

What neuropsychiatric reactions can occur with montelukast?

Sleep disturbance, depression, agitation.

Rarely: attention/memory disturbances, hallucinations, and suicidal behaviour.

What rare autoimmune condition has been associated with LTRAs?

Churg-Strauss syndrome.

Are LTRAs safe in pregnancy?

Safety is uncertain, but they may be continued if asthma control benefits outweigh risks.

Which drugs can reduce montelukast plasma levels?

Cytochrome P450 inducers such as phenytoin and rifampicin.

How should montelukast chewable tablets be taken?

1 hour before or 2 hours after food, on an empty stomach.

How is the efficacy of LTRAs monitored?

Symptom diary and peak expiratory flow rate.

When should LTRA treatment be stopped?

If ineffective, causes unacceptable side effects, or if asthma is well controlled for 3 months on stable treatment.

Which asthma patients are most likely to benefit from LTRAs?

Those with aspirin-sensitive, highly atopic, or exercise-induced asthma.

What are the common indications allopurinol?

1) Prevent recurrent attacks of gout.

2) To prevent renal stones formed from uric acid and calcium oxalate

3) To prevent hyperuricemia and tumour lysis syndrome due to chemotherapy.

MOA of allopurinol?

Allopurinol is a purine analogue that inhibits xanthine oxidase, which lowers uric acid in the blood and reduced precipitation in the joints/kidneys.

What effect can starting allopurinol have on an acute gout attack?

Can trigger or worsen an attack.

What common side effect can occur with allopurinol?

Skin rash.

What serious hypersensitivity reactions can allopurinol cause?

1) Stevens–Johnson syndrome (SJS)

2) Toxic epidermal necrolysis

3) Allopurinol hypersensitivity syndrome (fever, eosinophilia, lymphadenopathy, organ involvement).

Should allopurinol be started during an acute gout attack?

No, but it can be continued if already established.

When is allopurinol contraindicated?

Recurrent skin rash or severe hypersensitivity reactions.

How should allopurinol dosing be adjusted in organ impairment?

Reduce dose in severe renal or hepatic impairment.

Which drug's metabolite is affected by allopurinol, increasing toxicity risk?

Azathioprine (active metabolite: mercaptopurine).

Which drugs increase the risk of hypersensitivity or rash when taken with allopurinol?

ACE inhibitors, thiazides, and amoxicillin.

What co-prescription is recommended during initiation of allopurinol?

NSAID or colchicine to prevent acute gout attacks.

How should allopurinol be taken for best results?

After meals, with good hydration (2–3 L/day).

What should patients do if they have an acute gout attack while on allopurinol?

Continue allopurinol and treat the acute symptoms separately.

How is efficacy of allopurinol monitored?

Serum uric acid 4 weeks after starting or changing dose; aim <300 µmol/L.

Which drugs can increase uric acid and trigger gout?

Thiazide/loop diuretics and low-dose aspirin.

What should be considered in new-onset gout if the patient takes diuretics or aspirin?

Drug-induced gout.