Aspirin inhibits cyclo-oxygenase irreversibly by covalently acetylating the cyclo-oxygenase active site in both COX-1 and COX-2. The production of prostaglandin and thromboxane is reduced as a result. As a result, platelet activation and aggregation are reduced. A single dose of aspirin has a half-life of 7-10 days, which is the time it takes for the bone marrow to produce new platelets.

Aspirin only inhibits COX-1, the enzyme that produces thromboxane A2, at low doses (75 mg per day), and thus has a primarily anti-thrombotic effect.

Aspirin inhibits both COX-1 and COX-2 at medium to high doses (500-5000 mg per day). COX-2 is involved in the production of prostaglandins, so it has an anti-inflammatory effect at these concentrations.

Aspirin, when used as an antipyretic for a viral illness in children, can cause Reye’s syndrome. Reye’s syndrome is a potentially fatal liver disease that causes encephalopathy and liver failure.

The inability of aspirin to reduce platelet production of thromboxane A2, and thus platelet activation and aggregation, is known as aspirin resistance. Although the exact frequency and mechanism of aspirin resistance are unknown, it is thought to affect about 1% of users. Women are more likely than men to experience this phenomenon.

According to new research, taking aspirin on a regular basis lowers the risk of colorectal cancer. It may also protect against cancers of the breast, bladder, prostate, and lungs.

Etomidate causes the least cardiovascular depression of the intravenous induction agents, with only a small reduction in the cardiac output and blood pressure. In the past, etomidate was widely used to induce anaesthesia in the shocked, elderly or cardiovascularly unstable patient. However, more recently it has become less popular as a single induction dose blocks the normal stress-induced increase in adrenal cortisol production for 4 – 8 hours, and up to 24 hours in elderly and debilitated patients. Although no increase in mortality has been identified following a single dose during induction of anaesthesia, the use of etomidate has declined due to a perceived potential morbidity.

Amiodarone is a class III potassium channel blocker used to treat multiple types of arrhythmias.

Side effects include:
1. pulmonary fibrosis
2. blue discolouration of the skin
3. phototoxicity
4. corneal deposits
5. hepatic necrosis
6. thyroid dysfunction
7. sleep disturbances
8. peripheral neuropathy.

Xanthopsia is a condition where the patient complains of seeing yellow lines and is seen in digoxin overdose.

The current recommendations by NICE suggest that gastro-protection should be considered if patients have ≥1 of the following:

Aged 65 or older
– Using maximum recommended dose of an NSAID
– History of peptic ulcer or GI bleeding
– Concomitant use of: antidepressants like SSRIs and SNRIs, Corticosteroids, anticoagulants and low dose aspirin
– Long-term NSAID usage for: long-term back pain if older than 45 and patients with OA or RA at any age

The maximum recommended dose of ibuprofen is 2.4 g daily and this patient is on 400 mg of ibuprofen TDS.

The primary hip extensors are the gluteus maximus and the hamstrings such as the long head of the biceps femoris, the semitendinosus, and the semimembranosus. The extensor head of the adductor magnus is also considered a primary hip extensor.

The hip abductor muscle group is located on the lateral thigh. The primary hip abductor muscles include the gluteus medius, gluteus minimus, and tensor fasciae latae.
The secondary hip abductors include the piriformis, sartorius, and superior fibres of the gluteus maximus.

Overdosing on calcium-channel blockers should always be taken seriously and regarded as potentially fatal. Verapamil and diltiazem are the two most lethal calcium-channel blockers in overdose. These work by binding the alpha-1 subunit of L-type calcium channels, preventing calcium from entering the cell. In cardiac myocytes, vascular smooth muscle cells, and islet beta-cells, these channels play an important role.

The following summarises the toxicity of calcium-channel blockers:
Cardiac effects
Vascular smooth muscle tone affects
Metabolic effects
Excessive negative inotropy: myocardial depression
Negative chronotropy: sinus bradycardia
Negative dromotropy: atrioventricular node blockade
Decreased afterload
Systemic hypotension
Coronary vasodilation
Hypoinsulinaemia
Calcium channel blocker-induced insulin resistance

The ventilation/perfusion ratio (V/Q ratio) is a ratio used to assess the efficiency and adequacy of the matching ventilation and perfusion.

A pulmonary artery carries deoxygenated blood from the right side of the heart to the lungs. When a large pulmonary embolus completed blocked a pulmonary artery the alveoli were ventilated but not perfused at all, then the V/Q ratio would be infinity.

Polycythaemia vera (PCV), which is also referred to as polycythaemia rubra vera, is a clonal haematological malignancy in which the bone marrow produces too many red blood cells. It may also result in the overproduction of white blood cells and platelets. It is most commonly seen in the elderly and the mean age at diagnosis is 65-74 years.
Patients can be completely asymptomatic and it is often discovered as an incidental finding on a routine blood count. Approximately 1/3 of patients present with symptoms due to thrombosis, of these 3/4 have arterial thrombosis and 1/4 venous thrombosis. Features include stroke, myocardial infarction, deep vein thrombosis and pulmonary embolism.
The other clinical features of PCV include:
Plethoric appearance
Lethargy and tiredness
Splenomegaly (common)
Pruritis (in 40% – particularly after exposure to hot water)
Headaches, dizziness and sweating (in 30%)
Gouty arthritis (in 20%)
Budd-Chiari syndrome (in 5-10%)
Erythromyalgia (in <5% – burning pain and red/blue discolouration of hands and feet)
Increased incidence of peptic ulcer disease (possibly related to increased histamine release from mast cells)
The diagnosis of PCV requires two major criteria and one minor criterion, or the first major criterion and two minor criteria:
Major criteria:
HB > 18.5 g/dl in men, 16.5 g/dl in women
Elevated red cell mass > 25% above mean normal predicted value
Presence of JAK2 mutation

Minor criteria:
Bone marrow biopsy showing hypercellularity with prominent erythroid, granulocytic and megakaryocytic proliferation
Serum erythropoietin level below normal range
Endogenous erythroid colony formation in vitro
The main aim of treatment is to normalize the full blood count and prevent complications such as thrombosis. Venesection is the treatment of choice but hydroxyurea can also be used to help control thrombocytosis.

Excretion of lithium may be reduced by thiazide diuretics, NSAIDs, and ACE inhibitors thus predisposing to lithium toxicity. Loop diuretics also cause lithium retention but are less likely to result in lithium toxicity.

Sickling of red blood cells can lead to several different clinical syndromes. If the sickling occurs in the corpora cavernosa, it can lead to a sustained, painful erection of the penis, referred to as priapism. One of the complications is long-term impotence. It is important to seek a urological opinion immediately in this case, but in the interim, treat with perineal ice packs and walk up and down the stairs.