Patient Case
Patient X, a 60-year-old male presented with an intermittent dull burning pain in his left hypochondriac region, which had been radiating to his neck and left arm. This had been ongoing for 4-5 months and was initially very painful but had improved over time. The patient had been experiencing no other systemic symptoms apart from pins and needles in his hands. Patient X does not drink alcohol and has a healthy diet and active occupation. However, has smoked 10-20 cigarettes per day for 30 years but had tried stopping twice. He had undergone an exercise tolerance test which showed ST depression in V4, V5 and V6. The man had no known allergies and was on three medication which are listed below:
Drug name
Bisoprolol
90mg
Oral
Ticagrelor
75mg
Oral
Aspirin
2.5mg
Oral
Bisoprolol – Beta-adrenergic receptor antagonist
Bisoprolol is classed as a selective beta adrenergic receptor antagonist (“beta blocker”) and used to treat patients who have high blood pressure, stable heart failure, atrial fibrillation and other arrhythmic heart conditions. It has also been found to be useful in the prevention of myocardial infarctions, strokes and chest pain caused by angina.1 Bisoprolol has a half-life of roughly 9-12 hours and patients are normally advised to take bisoprolol once a day usually in the morning. It is recommended to take the first initial dose in the evening due to an initial dizziness that is sometimes felt when starting this medication.
The mechanism of action (pharmacodynamics) of bisoprolol is reducing cardiac output by decreasing cardiac muscle contractility and heart rate. It does this by selective and competitive inhibition of the 1 adrenergic receptors which can be found in cardiac muscle cells and juxtaglomerular kidney cells.2
The 1 cardiac receptors are stimulated by a catecholamine and activate a signalling cascade, which involves increased adenylyl cyclase activity and a Gs (stimulatory G-protein) signal transduction pathway. This increase in adenylyl cyclase triggers an increase in cAMP (cyclic adenosine monophosphate) activating PKA (Protein Kinase A), that then leads to the phosphorylation of proteins, which stimulates cellular activity to increase heart rate and the force of contraction.2
However, 1 adrenergic receptor antagonists competitively inhibit the activation of this cascade and therefore decreases the stroke volume and heart rate, and by doing so reduces the work and oxygen demand on the cardiac muscle allowing for better perfusion. Due to the presence of 1 receptors in the kidneys, it also inhibits and suppresses the renin system (RAAS), which is found to lower blood pressure.1, 2
Figure 1: 1 signalling cascade.2
There are several side effects to be aware of when taking Bisoprolol, the most common being headaches, dizziness and weakness, nausea and vomiting, cold peripheries, constipation and diarrhoea, as well as impotence in men. More serious side effects include an allergic reaction, dyspnoea and cough, signs of worsening heart failure and jaundice indicating liver problems.3
Bisoprolol is contra-indicated if you have had a previous allergic reaction to the medication, if you have hepatic failure, hypotension, bradycardia, suffered a recent MI or worsening heart failure, Raynaud’s disease, metabolic acidosis, asthma or lung disease or if you are pregnant or breast feeding.4
Drug interactions occur between bisoprolol and other medications, including: calcium channel blockers, hypertension medications, antidepressants, steroids, diabetes medications, asthma medications, allergy medication and specific antibiotics.4
Ticagrelor – P2Y12 receptor antagonist
Ticagrelor is classed as a P2Y12 receptor antagonist that is used as an antiplatelet medicine to avoid potentially dangerous blood clots for those with an increased risk, such as those with unstable angina or who have a previous myocardial infarction. Patients normally take ticagrelor twice daily, often in combination with low dose aspirin. It has been found to be more beneficial than the commonly used alternative clopidogrel, another antiplatelet and P2Y12 receptor antagonist.5
Ticagrelor and other P2Y12 antagonists function by inhibiting a key platelet signalling pathway by what appears to be antagonism of the ADP (adenosine diphosphate) activation of the P2Y12 receptor. This then blocks the intra-platelet signalling which would lead to inhibition of cAMP production, thromboxane A2 production and glycoprotein IIb/IIIa receptor activation, as well as granulation, therefore preventing aggregation of platelets that would form a blood clot.6
Although this antagonism is non-competitive meaning that there are separate binding sites for ADP and ticagrelor, unlike other P2Y12 antagonists, which allows for consistent inhibition and faster onset.7
Figure 2: Ticagrelor binding to P2Y12 and allosteric site.7
Common side effects of Ticagrelor include: bleeding more easily than normal; unexpected shortness of breath while at rest; pain and swelling in your joints – which may be signs of gout; headaches; mild rash; dizziness; nausea; indigestion; diarrhoea; and constipation. However, more serious side effects are haemoptysis, haematuria, hematemesis, melena, and weakness on one side of your body, indicating a stroke or an allergic reaction.4,8
Ticagrelor is contraindicated for patients who are allergic, susceptible to bleeding, have a stomach ulcer, asthma or COPD, have an arrhythmia, previous stroke caused by bleeding in the brain, gout or high uric acid levels, liver problems and are pregnant or breastfeeding.4,8
Different drugs that you need to be careful prescribing Ticagrelor alongside are rivaroxaban or apixaban, NSAIDs, antidepressants (SSRIs), antibiotics, epilepsy medications such as phenytoin and carbamapezine, statins and digoxin.4,8
Aspirin – Non-steroidal anti-inflammatory drug, Anti-platelet
Aspirin (acetylsalicylic acid) is a non-steroidal anti-inflammatory drug as well as being an anti-platelet drug and is used for analgesia of acute pain and fever, inflammation, headaches, ischaemic heart conditions, atrial fibrillation and to prevent thrombotic events in patients with arterial disease.9
Aspirin irreversibly inhibits the cyclooxygenase (COX-1) enzyme to halt the production of thromboxane A2 from arachidonic acid, which is essential for platelet aggregation. By preventing platelets from producing thromboxane A2 the process of platelet aggregation is inhibited and thrombotic events are averted. Aspirin also modifies the activity of the COX-2 enzyme which normally produces prostaglandins, a class of prostanoid that mediate inflammatory and anaphylactic reactions, and changes it to an enzyme which metabolizes fatty acids, producing anti-inflammatory effects.9,10,11
Figure 3: Aspirin and the platelet aggregation pathway.11
Common side effects of aspirin include mild indigestion and bleeding more easily than normal. Whereas more serious side effects include red blistered and peeling skin, haemoptysis, haematuria, hematemesis, melena, jaundice, painful joints indicative of gout and swollen hands or feet which can be a sign of water retention.4,12
Taking aspirin is contraindicated if you have an allergy, stomach ulcer, stroke, hypertension,
indigestion, asthma or a lung disease, blood clotting problems, liver or kidney problems, gout, heavy periods, and if you are pregnant or breastfeeding.4,12
Care must be taken when prescribing Aspirin alongside medicines to thin blood or prevent blood clots such as clopidogrel and warfarin, anti-inflammatory medications such as ibuprofen and prednisolone, immunosuppressive medications, anti-hypertensive medications such as furosemide and Ramipril, medication for heart problems such as digoxin, medication for mental health problems and methotrexate, a medicine used to stop the immune system overreacting and sometimes to treat some types of cancer, diabetes medication.4,12,13
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