Asthma drugs and antihistamines

Bronchodilators

• Theophylline is metabolised by CYP1A2, so its level depends on that enzyme:

• β-blockers worsen asthma: even timolol eye drops are absorbed through the nasolacrimal mucosa into the circulation (bypassing first-pass) and cause systemic non-selective β-blockade with wheeze. In COPD, cardioselective metoprolol or bisoprolol and calcium channel blockers are acceptable for angina or hypertension.

Anti-inflammatory and preventer drugs

• Methacholine challenge: a patient with episodic symptoms but normal spirometry inhales rising concentrations of methacholine (a muscarinic agonist); a 20% fall in FEV1 at a low concentration shows airway hyperresponsiveness supporting asthma. A negative test makes asthma unlikely.
• Atopic asthma is a Th2, IgE, mast cell and eosinophil disease; specific IgE testing identifies allergens.

Asthma and COPD management in outline

• Asthma steps: as-needed low-dose ICS–formoterol; regular ICS; ICS plus LABA (maintenance and reliever); add LAMA or LTRA; refer for biologics. Check technique and adherence first.
• Acute asthma: oxygen to 94–98%, nebulised salbutamol back-to-back, ipratropium, prednisolone 40–50 mg or IV hydrocortisone, IV magnesium if poor response, aminophylline on senior advice, ICU. Life-threatening signs: PEF below 33%, SpO2 below 92%, normal or rising PaCO2, silent chest, cyanosis, exhaustion.
• COPD: stop smoking, rehabilitation, vaccines; LABA plus LAMA; add ICS if eosinophils are raised (ICS raises pneumonia risk); long-term oxygen if PaO2 below 7.3 kPa; controlled oxygen 88–92% in exacerbations; NIV for hypercapnic acidosis.

Exam trap A normal or rising PaCO2 in acute asthma means exhaustion: life-threatening.

Antihistamines

• H1 antihistamines are inverse agonists. Terfenadine and astemizole were withdrawn for QT prolongation with CYP3A4 inhibitors.
• Cyproheptadine (H1 and 5-HT2A antagonist) is the antidote used in serotonin syndrome that persists after stopping the drugs and giving benzodiazepines; hyperthermia is muscular, so antipyretics alone fail.
• Betahistine (H3 antagonist, weak H1 agonist) for Ménière disease.

Anaphylaxis and allergen immunotherapy

• IM adrenaline first (0.5 mg in adults); antihistamine and steroid are second-line. Mast cell tryptase confirms (peaks at 1–2 hours).
• A child discharged after peanut anaphylaxis needs two adrenaline auto-injectors, training and an allergy referral; poorly controlled asthma raises the risk of fatal anaphylaxis.
• Venom immunotherapy works by inducing IgG4 blocking antibodies (which capture allergen before it reaches mast cell IgE) and regulatory T cells that shift the response away from Th2.

Corticosteroids

• Mechanism: they enter the cell, bind cytoplasmic glucocorticoid receptors and alter gene transcription; effects take hours. They induce annexin-1 (lipocortin), which inhibits phospholipase A2, so arachidonic acid release falls and both prostaglandins and leukotrienes fall. Aspirin blocks only cyclooxygenase.

• So prednisolone 10 mg equals about hydrocortisone 40 mg daily for IV cover when nil by mouth.
• Dexamethasone, with strong glucocorticoid and almost no mineralocorticoid activity, suits cerebral oedema; it cannot replace fludrocortisone.
• In pregnancy, prednisolone is preferred for the mother because placental 11β-HSD2 inactivates most prednisolone; dexamethasone and betamethasone cross intact, which is why they are used for fetal lung maturation.
• Adrenal suppression: more than 3 weeks of therapy suppresses the HPA axis. Stopping prednisolone suddenly after two years causes adrenal crisis (hypotension, hypoglycaemia, hyponatraemia). Taper.
• Sick-day rules: double the oral dose during fever or infection; IV or IM hydrocortisone if vomiting or for surgery.
• Bone protection: anyone likely to take prednisolone 7.5 mg or more for 3 months or longer, especially over 65, starts a bisphosphonate with calcium and vitamin D at the same time.
• Steroid myopathy: painless proximal weakness (stairs, rising from a chair) with normal CK, especially with fluorinated steroids such as dexamethasone; check potassium.
• Ritonavir strongly inhibits CYP3A4, so inhaled or intranasal fluticasone accumulates and causes iatrogenic Cushing syndrome with adrenal suppression. Do not stop the steroid suddenly; switch to beclometasone.
• Acute severe ulcerative colitis (more than 6 bloody stools with fever, tachycardia or raised CRP): admit for IV hydrocortisone; avoid opioids and antidiarrhoeals.

Remember Steroids work upstream at phospholipase A2; NSAIDs work downstream at cyclooxygenase.

Isotretinoin

• Oral isotretinoin for severe nodular acne is highly teratogenic: a pregnancy prevention programme with effective contraception and pregnancy tests before, during and after treatment. Avoid tetracyclines (intracranial hypertension).

How FCPS asks about this

• Theophylline toxicity after ciprofloxacin, or after stopping smoking: CYP1A2 inhibition, or loss of CYP1A2 induction.
• Theophylline mechanism: PDE inhibition raising cAMP, plus adenosine antagonism.
• Chlorphenamine drowsy, loratadine not: only the first crosses the blood–brain barrier.
• Omalizumab target; montelukast target; roflumilast: free IgE; CysLT1 receptor; PDE4.
• Wheeze after timolol drops: systemic non-selective β-blockade.
• Steroid with no mineralocorticoid action for cerebral oedema: dexamethasone; prednisolone 10 mg equals hydrocortisone 40 mg.
• Prednisolone and leukotrienes: annexin-1 inhibits phospholipase A2.