Top 100 Drugs: NSAIDs, Antiplatelets, Statins, Proton Pump Inhibitors

common indication of NSAIDS?

1. ‘As Needed’ treatment of mild to moderate pain and fever

2. regular treatment for pain related to inflammation especially MSK system eg RA.

Mechanism of Action of NSAIDs?

-NSAIDs inhibit prostaglandin synthesis from arachidonic acid by inhibiting COX.

-COX1: stimulates prostaglandin synthesis, COX2: expressed in response to inflammatory stimuli

so the therapeutic benefit of NSAIDs are principally mediated by COX-2 inhibition and adverse effects by COX-1 inhibition

important adverse effects with NSAIDs?

GI Toxicity

Renal impairment

Major adverse cardiovascular events

Warnings with NSAIDs?

-contraindicated in severe renal impairment, heart failure, liver failure, NSAID hypersensitivity

-avoid in peptic ulcer disease, CVD and mild renal impairment

Important interactions with NSAIDs?

-corticosteroids increase risk of peptic ulceration

-anticoagulants and SSRiS increase the risk of GI bleeding

-ACEi, ARB and diuretics increase risk of renal impairment

-NSAIDS generally impair the effectiveness of antihypertensives

common indications for antiplatelet drugs?

1. for treatment of ACS usually in combination with aspirin

2. to prevent coronary artery stent occlusion usually in combination with aspirin

3. for secondary prevention of major adverse cardiovascular events in people with ischaemic heart disease, cerebrovascular disease or peripheral vascular disease, alone or in combination with aspirin.

mechanism of action of anti platelet drugs?

-thrombotic events occur when platelet rich thrombus forms in atheromatous arteries and occludes the circulation.

-antiplatelet drugs prevent platelet aggregation and reduce the risk of arterial occlusion by binding irreversibly to adenosine diphosphate receptors (ADP) on the surface of platelets.

which of the anti-platelet drugs bind reversibly to ADP?

ticagrelor

which of the anti-platelet drugs bind irreversibly to ADP?

clopidogrel and prasugrel

important adverse effects with anti-platelet drugs?

-the most common adverse effect is bleeding, which can be serious, particularly if GI or intracranial

-GI upset, dyspepsia, abdominal pain, diarrhoea

-thrombocytopenia

warnings with anti-platelet drugs?

-should not be prescribed for people with active bleeding

-may need to be stopped 7 days before elective surgery

-use in caution in renal and hepatic impairment

important interactions with antiplatelet drugs?

-clopidogrel is a prodrug - therefore efficacy may be reduced by CYP inhibitors eg omeprazole, ciprofloxacin, erythromycin, some anti fungal and SSRIs, grapfruit juice

-prasgruel is also a prodrug but less suseptible to interactions

-ticagrelor is not a pro-drug but interacts with CYP inhibitors and inducers

warnings with aspirin?

-should not be given to children under 16 due to the risk of Reye’s syndrome

-shouldn’t be taken by people with aspirin hypersensitivity

-should be avoided in the third trimester of pregnancy where prostaglandin inhibition may lead to premature closure of ductus arteriosus

-use in caution in peptic ulceration and gout where is may trigger an attack.

important interactions with aspirin?

aspirin acts synergistically with other antiplatelet agents which is therapeutically beneficial, but can lead to increased risk of bleeding.

So although it can be given with antiplatelet drugs and anticoagulants, caution is required.

common indications of statins?

1. primary prevention of major adverse cardiovascular events in people over 40 years of age with a 10 year cardiovascular risk >10%.

2. secondary prevention of major adverse cardiovascular events in people with ischaemic heart disease, stroke and peripheral vascular disease

3. dyslipidaemia

mechanism of action of statins?

-statins slow the atherosclerotic process and may even reverse it.

-they act by competitive inhibition of HMG-COA reductase.

-this reduces cholesterol production by the liver and stimulates a compensatory increase in LDL uptake from the blood by hepatocytes.

-together these effects reduce LDL cholesterol levels and indirectly reduces triglycerides and slightly increase high-density lipoprotein cholesterol levels.

-statins may also modulate the inflammatory response and improve endothelial function

important adverse effects with statins ?

-statins are generally safe and well tolerated.

-headache, GI upset, muscle aches

-rare: myopathy and rhabdomyolysis

warnings with statins

-use in caution in hepatic impairment

-reduce dose in kidney impairment (except rosuvastatin)

-contraindicated in pregnancy

-avoid in breast feeding

important interactions with statins?

-metabolism of statins is impaired by CYP450 inhibitors eg amiodarone, diltiazem, itraconazole, macrolides, protease inhibitors and grapefruit juice - LEADS TO accumulation of statin and/or its metabolites

-amlodipine has a similar interaction although mechanism is less clear.

if a CYP inhibitor is being used for a short period of time, what to do with statin?

-temporarily withhold the statin.

PPI common indications ?

1. prevention and treatment of peptic ulcer disease

2. treatment of GORD and dyspepsia

3. eradication of H. Pylori infection (in combination with antibiotics

mechanism of action of PPI’s?

-PPi’s reduce gastric acid secretion

-they act irreversibly inhibiting H+/K+ ATPase in gastric parietal cells, this is the proton pump responsible for secreting H+ and generating gastric acid

important adverse effects with PPIs?

-GI upset, headache

warnings with PPIs?

-PPIs may mask symptoms of gastric or oesophageal cancer and significant ulcer disease caused by H-pylori, so prescribers should enquire about ‘alarm symptoms’

-High dose PPIs can increase the risk of fracture in elderly

-people with or at risk of osteoporosis should therefore be identified and treated as appropriate.

important interactions with PPIs?

-PPI’s, in particular omeprazole may reduce the antiplatelet effect of clopidogrel by decreasing its activation by cytochrome P450 enzymes