Due to their increased risk of cardiovascular adverse events, coxibs and diclofenac are contraindicated in people with ischaemic heart disease, cerebrovascular disease, peripheral arterial disease and mild, moderate, or severe heart failure. Other NSAIDs are only contraindicated in people with severe heart failure. Selective inhibition of COX-2 is associated with less gastrointestinal intolerance. In single doses NSAIDs have analgesic activity comparable to that of paracetamol, therefore given their side effect profile, paracetamol is preferred, particularly in the elderly. Pain relief starts soon after taking the first dose and a full analgesic effect should normally be obtained within a week, whereas an anti-inflammatory effect may not be achieved (or may not be clinically assessable) for up to 3 weeks. Mefenamic acid has only very mild anti-inflammatory properties.

Pectoralis major is a thick, fan-shaped muscle situated in the chest. It makes up the bulk of the chest musculature in the male and lies underneath the breast in the female. It overlies the thinner pectoralis minor muscle.
Superficial muscles of the chest and arm showing pectoralis major (from Gray’s Anatomy)
Pectoralis major has two heads; the clavicular head and the sternocostal head. The clavicular head originates from the anterior border and medial half of the clavicle. The sternocostal head originates from the anterior surface of the sternum, the superior six costal cartilages and the aponeurosis of the external oblique muscle. It inserts into the lateral lip of the bicipital groove of the humerus.
Pectoralis major receives dual innervation from the medial pectoral nerve and the lateral pectoral nerve.
Its main actions are as follows:
Flexes humerus (clavicular head)
Extends humerus (sternocostal head)
Adducts and medially rotates the humerus
Draws scapula anteriorly and inferiorly

Blood group O has no antigens, but both anti-A and anti-B antibodies and thus is the universal donor.

In the United Kingdom, antibiotic resistance is becoming a significant factor in the treatment of urinary tract infections and pyelonephritis. E. coli (the main causative organism of both urinary tract infections and acute pyelonephritis) resistance to the following antibiotics in laboratory-processed urine specimens is:
30.3 percent trimethoprim (varies by area from 27.1 to 33.4 percent )
19.8 percent co-amoxiclav (varies by area from 10.8 to 30.7 percent )
Ciprofloxacin (Cipro): 10.6% (varies by area from 7.8 to 13.7 percent )
Cefalexin has a concentration of 9.9%. (varies by area from 8.1 to 11.4 percent )

Pathogenicity is the ability to cause disease.

The pain associated with external haemorrhoids is carried by a branch of the pudendal nerve, specifically the somatic fibres (S2-S4).

It innervates the external anal sphincter and most of the skin over the perineum.

The Focused Assessment with Sonography in Trauma (FAST) is an ultrasound protocol developed to assess for hemoperitoneum and hemopericardium. Numerous studies have demonstrated sensitivities between 85% to 96% and specificities exceeding 98%.

The FAST exam evaluates four regions for pathologic fluid: (1) the right upper quadrant, (2) the subxiphoid (or subcostal) view, (3) the left upper quadrant, and (4) the suprapubic region.

The right upper quadrant (RUQ) visualizes the hepatorenal recess, also known as Morrison’s pouch, the right paracolic gutter, the hepato-diaphragmatic area, and the caudal edge of the left liver lobe. The probe is positioned in the sagittal orientation along the patient’s flank at the level of the 8 to 11 rib spaces. The hand is placed against the bed to ensure visualization of the retroperitoneal kidney. The RUQ view is the most likely to detect free fluid with an overall sensitivity of 66%. Recent retrospective evidence suggests the area along the caudal edge of the left lobe of the liver has the highest sensitivity, exceeding 93%.

Ciprofloxacin is recommended for use as meningococcal chemoprophylaxis in all age groups and in pregnancy, and is the most appropriate for this patient.

However, rifampicin is the drug of choice for meningococcal chemoprophylaxis because it is licensed for chemoprophylaxis, but multiple doses are necessary and it is not readily available in community pharmacies. It also interacts with oral contraceptives.

The Likelihood Ratio (LR) is the likelihood that a given test result would be expected in a patient with the target disorder compared to the likelihood that that same result would be expected in a patient without the target disorder.

The LR is used to assess how good a diagnostic test is and to help in selecting an appropriate diagnostic tests or sequence of tests. They have advantages over sensitivity and specificity because they are less likely to change with the prevalence of the disorder, they can be calculated for several levels of the symptom/sign or test, they can be used to combine the results of multiple diagnostic test and they can be used to calculate post-test probability for a target disorder.

A LR greater than 1 produces a post-test probability which is higher than the pre-test probability. An LR less than 1 produces a post-test probability which is lower than the pre-test probability. When the pre-test probability lies between 30 and 70 per cent, test results with a very high LR (say, above 10) rule in disease. An LR below 1 produces a post-test probability les than the pre-test probability. A very low LR (say, below 0.1) virtually rules out the chance that the patient has the disease.

Molecular weight is the main factor in determining whether a substance is filtered or not – molecules < 7 kDa in molecular weight are filtered freely e.g. glucose, amino acids, urea, ions but larger molecules are increasingly restricted up to 70 kDa, above which filtration is insignificant. Negatively charged molecules are further restricted, as they are repelled by negative charges, particularly in the basement membrane. Albumin has a molecular weight of 69 kDa and is negatively charged, thus only very small amounts are filtered (and all of the filtered albumin is reabsorbed in the proximal tubule), whereas small molecules such as ions, glucose, amino acids and urea pass the filter without hindrance. This means that ultrafiltrate is virtually protein free, but otherwise has an identical composition of that of plasma. The epithelial lining of the Bowman's capsule consists of a single layer of cells called podocytes. The glomerular capillary endothelium is perforated by pores (fenestrations) which allow plasma components with a molecular weight of < 70 kDa to pass freely.

Endocarditis is infective or non infective inflammation (marantic endocarditis) of the inner layer of the heart and it often involves the heart valves.

Risk factors include:
Prosthetic heart valves
Congenital heart defects
Prior history of endocarditis
Rheumatic fever
Illicit intravenous drug use

In the presentation of endocarditis, the following triad is often quoted:
Persistent fever
Embolic phenomena
New or changing murmur

A combination of vancomycin, rifampicin and gentamicin is advised if the patient has a cardiac prostheses, is penicillin allergic, or if methicillin-resistant Staphylococcus aureus (MRSA) is suspected. In this case the patient has a prosthetic valve making this the most appropriate initial treatment regimen.

Flucloxacillin and gentamicin are current recommended by NICE and the BNF for the initial ‘blind’ therapy in endocarditis. This patient has prostheses and this is not the most appropriate initial treatment regimen.

Other features that may be present include heart failure, splenomegaly, finger clubbing, renal features (haematuria, proteinuria, nephritis), and vasculitic features (splinter haemorrhages, Osler’s nodes, Janeway lesions, Roth’s spots).

In facial nerve palsy, LMN damage will involve the forehead and there will be an inability to close the eyes due to paralysis of the orbicularis oculi or raise the eyebrows due to paralysis of the occipitofrontalis muscle.
UMN damage causes sparing of the forehead as the occipitofrontalis and orbicularis oculi muscles have bilateral cortical representation.

Heart Sound – Phase of Cardiac Cycle – Mechanical Event:
First heart sound – Start of systole – Caused by closure of the atrioventricular (mitral & tricuspid) valves
Second heart sound – End of systole – Caused by closure of the semilunar (aortic and pulmonary) valves
Third heart sound – Early diastole – Caused by rapid flow of blood from the atria into the ventricles during the ventricular filling phase
Fourth heart sound – Late diastole – Caused by filling of an abnormally stiff ventricle in atrial systole

Noradrenaline (the sympathetic neurotransmitter) is a positive inotrope; it binds to β1-adrenoceptors on the membrane and causes increased Ca2+entry via L-type channels during the AP and thus increases Ca2+release from the SR. Noradrenaline also increases Ca2+sequestration into the SR and thus more Ca2+is available for the next contraction. Cardiac glycosides (e.g. digoxin) slow the removal of Ca2+from the cell by inhibiting the membrane Na+pump which generates the Na+gradient required for driving the export of Ca2+; consequently the removal of Ca2+from the myocyte is slowed and more Ca2+is available for the next contraction. Acidosis is negatively inotropic, largely because H+competes for Ca2+binding sites.

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.

>10 tablets of verapamil (160 mg or 240 mg immediate or sustained-release capsules) or diltiazem can cause serious toxicity (180 mg, 240 mg or 360 mg immediate or sustained-release capsules)

In children, 1-2 tablets of verapamil or diltiazem (immediate or sustained-release)

Symptoms usually appear within 1-2 hours of ingestion with standard preparations. However, with slow-release preparations, significant toxicity may take 12-16 hours to manifest, with peak effects occurring after 24 hours.

The following are the main clinical features of calcium-channel blocker overdose:
Nausea and vomiting
Hypotension
Bradycardia and first-degree heart block
Myocardial ischaemia and stroke
Renal failure
Pulmonary oedema
Hyperglycaemia

The following are some of the most important bedside investigations to conduct:
Blood glucose
ECG
Arterial blood gas
Other investigations that can be helpful include
Urea & electrolytes
Chest X-ray (pulmonary oedema)
Echocardiography

The oculomotor nerve is the third cranial nerve. It is the main source of innervation to the extraocular muscles and also contains parasympathetic fibres which relay in the ciliary ganglion. Damage to the third cranial nerve may cause diplopia, pupil mydriasis, and/or upper eyelid ptosis. The clinical manifestations of third cranial nerve dysfunction reflect its constituent parts.

End-organ damage (e.g. encephalopathy, intracranial haemorrhage, acute myocardial infarction or ischaemia, dissection, pulmonary oedema, nephropathy, eclampsia, papilledema, and/or angiopathic haemolytic anaemia) characterises a hypertensive emergency (also known as ‘accelerated hypertension’ or malignant hypertension’ It’s a life-threatening condition that necessitates rapid blood pressure reduction to avoid end-organ damage and a negative outcome.

Hypertensive encephalopathy is a syndrome that includes headaches, seizures, visual changes, and other neurologic symptoms in people who have high blood pressure. It is reversible if treated quickly, but it can progress to coma and death if not treated properly.

Any patient with suspected hypertensive encephalopathy should have an urgent CT scan to rule out an intracranial haemorrhage, as rapid blood pressure reduction could be dangerous in these circumstances.

The drug of choice is labetalol, which reduces blood pressure steadily and consistently without compromising cerebral blood flow.
An initial reduction of approximately 25% in mean arterial pressure (MAP) over an hour should be aimed for, followed by a further controlled MAP reduction over the next 24 hours. In patients who are unable to take beta-blockers, nicardipine can be used as a substitute.

Damage to the long thoracic nerve results in weakness/paralysis of the serratus anterior muscle causing difficulty abducting the upper limb above 90 degrees and giving a ‘winged ‘ scapula appearance where the medial border, particularly the inferior angle, of the scapula moves laterally and posteriorly away from the thoracic wall (this becomes more pronounced if the patient presses the upper limb against a wall).

The liver produces bile on a constant basis, which is then stored and concentrated in the gallbladder. In a 24-hour period, around 400 to 800 mL of bile is generated.

Bile is involved in the following processes:
Fats are broken down into fatty acids.
Waste products are eliminated.
Cholesterol homeostasis is the balance of cholesterol in the body.

The enteric hormones cholecystokinin and secretin are primarily responsible for bile secretion. When chyme from an unprocessed meal enters the small intestine, they are released, and they play the following function in bile secretion and flow:

Cholecystokinin promotes gallbladder and common bile duct contractions, allowing bile to reach the intestine.
Secretin enhances the secretion of bicarbonate and water by biliary duct cells, increasing the amount of bile and its flow into the gut.

Bile acids have a hydrophobic and hydrophilic area, making them amphipathic. Bile acids’ amphipathic nature allows them to perform the following crucial functions:

Emulsification of lipid aggregates increases the surface area of fat and makes it easier for lipases to digest it.
Lipid solubilization and transport: solubilizes lipids by creating micelles, which are lipid clumps that float in water.

There usually isn’t any additional bronchodilation with intravenous (IV) aminophylline compared to standard care with inhaled bronchodilators and steroids. IV aminophylline may cause side effects such as arrhythmias and vomiting. However, some additional benefit may be gained in patients with near-fatal asthma or life-threatening asthma with a poor response to initial therapy (5 mg/kg loading dose over 20 minutes unless on maintenance oral therapy, then continuous infusion of 0.5 – 0.7 mg/kg/hr).