Top 100 Drugs: Bisphosphonates, Antimuscarinics – bronchodilators, Antihistamine – H1 receptors antagonists, Leukotriene antagonists, Allopurinol

MOA of antihistamines (H1 receptor antagonists)?

-histamine is released from storage granules in mast cells in response to antigen binding to IgE on the cell surface

-via H1 receptors, histamine induces the features of immediate type 1 hypersensitivity, increased capillary permeability causing oedema formation (wheal), vasodilation causing erythema (flare) and itch as a result of sensory nerve stimulation

-when histamine is released in the nasopharynx, as in hay fever, it causes

-widespread histamine release produces generalised vasodilation and vascular leakage

important adverse effects with antihistamines (H1 receptor antagonists)?

-first gen antihistamines cause sedation - bc histamine has a role in the brain in maintaining wakefulness

-second gens do not cross the BBB so don’t have this effect

warnings with antihistamines (H1 receptor antagonists)?

-sedating antihistamines should be avoided in severe liver disease as it may precipitate hepatic encephalopathy

-

important interactions with antihistamines (H1 receptor antagonists)?

no major interactions

MOA of bisphosphonates?

-reduce bone turnover by inhibiting the action of osteoclasts, the cells responsible for bone resorption

-bisphosphonates have a similar structure to naturally occurring pyrophosphonate and are therefore readily incorporated in to the bone

-as bone is reabsorbed, bisphosphonates accumulate in osteoclasts where they inhibit activity and promote apoptosis

-the net effect is reduction in bone loss and improvement in bone mass

important adverse effects with bisphosphonates?

-oseophagitis and hypophosphataemia

-osteonecrosis of jaw (rare but serious)

-atypical femoral fracture

warnings with bisphosphonates?

-bisphosphonates are renally excreted and should be avoided in severe renal impairment

-contraindicated in hypocalcaemia, so calcium and vitamin D levels should be checked before starting treatment and corrected

-oral administration contraindicated in upper GI disorders

-take care when prescribing for smokers and those with major dental disease due to risk of jaw osteonecrosis

important interactions with bisphosphonates ?

-bisphosphonates bind calcium - their absorption is therefore reduced if taken with calcium salts as well as antacids and iron salts

MOA of antimuscarinics (Bronchodilators)?

-antimuscarinic drugs bind to muscarinic receptors, where they act as competitive inhibitors of acetylcholine

-stimulation of msucarinic receptors brings on parasympathetic effects

-by blocking these receptors - increases heart rate and conduction, reduces smooth muscle tone, including in the respiratory tract, gut and urinary tract

-inhaled anti-muscarinics relieve airway obstruction in COPD and asthma by allowing smooth muscle relaxation, causing bronchodilation and by reducing respiratory secretions

important adverse effects with antimuscarinics (Bronchodilators)?

-dry mouth

-inhalation may irritate the respiratory tract causing cough or hoarse voice

-tachycardia, constipation, urinary retention and blurred vision

warnings with antimuscarinics (Bronchodilators)?

-use in caution in ppl susceptible to angle closure glaucoma and in those with or at risk of arrhythmias or urinary retention

important interactions with antimuscarinics (Bronchodilators)?

interactions are unproblematic due to the small doses used

leukotriene receptor antagonists indication?

-initial add-on therapy for chronic asthma where symptoms are not adequately controlled by a shorting acting B2 agonist and low dose inhaled corticosteroids

-treatment option for allergic rhinitis in those who have asthma where nasal symptoms have not responded to usual treatments such as antihistamines and/or intranasal corticosteroids

MOA of leukotriene receptor antagonists?

-in asthma, leukotrienes produced by mast cells and eosinophils activated the G-protein coupled leukotriene receptor CysLT1

-this activates a cascade of pathways that result in inflammation and broncho-constriction which contributes to the pathophysiology of asthma by blocking the CysLT1 receptor and damping down the inflammatory cascade

important adverse effects of leukotriene receptor antagonists

-generally well tolerated

-headache, abdominal pain, GI upset are the most common adverse effects but usually mild

-increases risk of URTIs

-neuropsychiatric reactions

-churg-strauss syndrome

-warnings with leukotriene receptor antagonists?

-the safety of leukotriene receptor antagonists in pregnancy is uncertain

-but as poorly controlled asthma is a risk during pregnancy it is considered reasonable to continue leukotriene receptor antagonists where they have led to significant improvement in asthma symptoms

important interactions with leukotriene receptor antagonists?

-drugs that induce CYP P450 enzymes can cause a reduction in plasma levels of montelukast, potentially reducing efficacy

indications for allopurinol?

-to prevent recurrent attacks of gout

-to prevent uric acid and calcium oxalate renal stones

-to prevent hyperuricaemia and tumour lysis syndrome due to chemotherapy

MOA of allopurinol?

-allopurinol is a purine analogue that inhibits xanthine oxidase

-xanthine oxidase metabolises xanthine to uric acid

-inhibition of xanthine oxidase lowers plasma uric acid concentrations and reduces precipitation of uric acid in the joints or kidneys

important adverse effects with allopurinol?

-generally well tolerated

-however, starting allopurinol can trigger or worsen an acute attack of gout

-most common side effect is skin rash (ranging from mild to severe (eg Stevens Johnsons syndrome)

how can the risks of triggering an acute attack of gout on starting allopurinol be reduced?

with co-prescription of an NSAID or colchicine in the initiation process

warnings with allopurinol?

allopurinol should not be started during an acute attack of gout but can be continued if already established to avoid sudden fluctuations in serum uric levels

-contraindicated in recurrent skin rash or signs of more recurrent hypersensitivity

-dose should be reduced in hepatic or renal impairment

important interaction with allopurinol?

-the active metabolite of the pro-drug azathioprine is metabolised by xanthine oxidase

-concurrent administration with allopurinol increases the risk of azathioprine toxicity

-co prescription with ACEi or thiazides increases the risk of hypersensitivity reaction and with amoxicillin increases the risk of skin rash

-co-prescribing with amoxicillin increases the risk of skin rash