Top 100 Drugs: Laxatives, Beta-2-agonists, Corticosteroids (inhaled)

common indications for laxatives?

-constipation

-bowel preparation prior to surgery or endoscopy

-hepatic encephalopathy

mechanism of action of laxatives?

-can be either stimulant or osmotic

-stimulant: increase water and electrolyte secretion from the colonic mucosa, thereby increasing the volume of colonic content and stimulating peristalsis. They also have a direct pro-peristaltic action.

-osmotic laxatives are based on osmotically active substances that are not digested or absorbed.

important adverse effects with laxatives?

-flatulence, abdominal cramps, diarrhoea, nausea

-prolonged use of stimulant laxatives: melanosis coli

warnings with laxatives?

-contraindicated in intestinal obstruction due to risk of perforation

important interactions with laxatives?

-laxatives have no significant adverse interactions with other drugs

but there is an important interaction between macrogols and starch based thickeners which are used in dysphagia

common indications of B2-agonists?

-asthma: short-acting b2-agonists are used to relieve bronchospasm during acute asthma attacks, and for intermittent breathlessness

-COPD

MOA of B2-agonists

-b2 receptors are found in smooth muscle of the bronchi, gut, uterus and blood vessels

-stimulation of these GPCRs activates a signalling cascade that leads to smooth muscle relaxation and bronchodilation

-this improves airflow, reducing breathlessness

-they also stimulate NA+/K+ATP pumps on cell membranes, which shifts K+ from the extracellular to intracellular compartment

important adverse effects of B2-agonists?

-tachycardia, palpitations, anxiety, tremor and headache

-hypokalemia

-elevated serum lactate

-promotes gylcogenolysis so may cause hyperglycaemia

warnings with b2 agonists?

-care should be taken when prescribed in CVD as tachycardia may provoke angina or arrhythmia

important interactions wit b2-agonists?

-b-blockers may reduce the effectiveness of b2-agonists

-concomitant use of high-dose nebulised b2-agonists with theophylline and corticosteroids increases the risk of hypokalaemia, so serum potassium concentrations should be monitored.

MOA of inhaled corticosteroids?

-corticosteroids pass through the plasma membrane and interact with receptors in the cytoplasm

-the activated receptor then passes into the nucleus to modify transcription of a large number of genes

-pro-inflammatory interleukins, cytokines and chemokine are down regulated, while anti-inflammatory proteins are upregulated

-in the airways, this reduces mucosal inflammation, widens the airways, and reduces mucus secretion

-this improves symptoms and reduces asthma and COPD exacerbations.

important adverse effects with inhaled corticosteroids?

-changes in taste sensation and voice

-oral candidiasis

-increased risk of Pneumonia in those with COPD

-adrenal suppression, osteoporosis, growth retardation

-paradoxical bronchospasm

warnings with inhaled corticosteroids?

-high dose inhaled corticosteroids, particularly fluticasone should be used with caution in those with COPD with a history of pneumonia.

-and in children due to the risk of growth retardation.

important interactions with inhaled corticosteroids?

-CYP 450 inhibitors, in particular protease inhibitors, increase systemic exposure to inhaled corticosteroids by inhibiting their metabolism.