Theophylline and Ethylenediamine are combined in a 2:1 ratio to form Aminophylline. Its solubility is improved by the addition of Ethylenediamine. It has a lower potency and a shorter duration of action than Theophylline.
It is used to treat the following conditions:
Heart failure
It is used to treat the following conditions:
COPD
Bradycardias

Aminophylline has the following properties:
Phosphodiesterase inhibitor that increases intracellular cAMP and relaxes smooth muscle in the bronchial airways and pulmonary blood vessels.
Mast cell stabilization is achieved by using a non-selective adenosine receptor antagonist.
It has slight positive inotropic and chronotropic effects, increasing cardiac output and decreasing systemic vascular resistance, lowering arterial blood pressure. It has been used historically in the treatment of refractory heart failure and is indicated by the current ALS guidelines as a substitute treatment for bradycardia.

The daily oral dose for adults is 900 mg, divided into 2-3 doses. For severe asthma or COPD, a loading dosage of 5 mg/kg over 10-20 minutes is given, followed by a continuous infusion of 0.5 mg/kg/hour. The therapeutic range is small (10-20 microgram/ml), hence assessments of aminophylline plasma concentrations are useful during long-term treatment.

Like other non-steroidal anti-inflammatory drugs, Ibuprofen cannot be given with Warfarin as it would increase the bleeding risk of this patient.

Opioids should be avoided in people who have:
A risk of paralytic ileus (opioids reduce gastric motility)
Acute respiratory depressionAn acute exacerbation of asthma (opioids can aggravate bronchoconstriction as a result of histamine release)
Conditions associated with increased intracranial pressure including head injury (opioids can interfere with pupillary response making neurological assessment difficult and may cause retention of carbon dioxide aggravating the increased intracranial pressure)

Juxtapulmonary or ‘J’ receptors are located on alveolar and bronchial walls close to the capillaries. Their afferents are small unmyelinated C-fibres or myelinated nerves in the vagus nerve. Activation causes depression of somatic and visceral activity by producing apnoea or rapid shallow breathing, a fall in heart rate and blood pressure, laryngeal constriction and relaxation of skeletal muscles via spinal neurones. J receptors are stimulated by increased alveolar wall fluid, pulmonary congestion and oedema, microembolism and inflammatory mediators. J receptors are thought to be involved in the sensation of dyspnoea in lung disease.

Flecainide is an antiarrhythmic drug of class Ic that works by blocking the Nav1.5 sodium channel in the heart, prolonging the cardiac action potential and slowing cardiac impulse conduction. It has a significant impact on accessory pathway conduction, particularly retrograde conduction, and significantly reduces ventricular ectopic foci.

Many different arrhythmias can be treated with flecainide, including:
Pre-excitation syndromes (e.g. Wolff-Parkinson-White)
Acute atrial arrhythmias
Ventricular arrhythmias
Chronic neuropathic pain

The use of flecainide is contraindicated in the following situations:
Abnormal left ventricular function
Atrial conduction defects (unless pacing rescue available)
Bundle branch block (unless pacing rescue available)
Distal block (unless pacing rescue available)
Haemodynamically significant valvular heart disease
Heart failure
History of myocardial infarction
Long-standing atrial fibrillation where conversion to sinus rhythm not attempted
Second-degree or greater AV block (unless pacing rescue available)
Sinus node dysfunction (unless pacing rescue available)

Flecainide should only be used in people who don’t have a structural heart problem. The CAST trial found a significant increase in sudden cardiac death and all-cause mortality in patients with an ejection fraction of less than 40% after a myocardial infarction, where it tended to be pro-arrhythmic.

Anti-arrhythmic drugs have a limited and ineffective role in the treatment of atrial flutter. It’s important to keep in mind that flecainide shouldn’t be used by itself to treat atrial flutter. When used alone, there is a risk of inducing 1:1 atrioventricular conduction, which results in an increase in ventricular rate that is paradoxical. As a result, it should be used in conjunction with a beta-blocker or a calcium channel blocker with a rate-limiting effect.

Lymphomas are a group of diseases caused by malignant lymphocytes that accumulate in lymph nodes and other lymphoid tissue and cause the characteristic clinical feature of lymphadenopathy. The major subdivision of lymphomas is into Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) and this is based on the histological presence of Reed-Sternberg cells present in HL. Hodgkin lymphoma can present at any age but is rare in children and has a peak incidence in young adults. There is an almost 2 : 1 male predominance. Most patients present with painless, asymmetrical, firm and discrete enlargement of superficial lymph nodes. Cervical nodes are involved in 60-70% of cases, axillary nodes in 10-15% and inguinal nodes in 6-12%. Modest splenomegaly occurs during the course of the disease in 50% of patients; the liver may also be enlarged. Bone marrow failure involvement is unusual in early disease. The prognosis depends on age, stage and histology, but overall approximately 85% of patients are cured. Alcohol‐induced pain and pruritus are two well‐known but rare symptoms in HL.

Metronidazole and the other 5-nitroimidazole agents inhibit nucleic acid synthesis by forming toxic free radical metabolites in the bacterial cell that damage DNA.

Vancomycin inhibits cell wall peptidoglycan formation by binding the D-Ala-D-Ala portion of cell wall precursors.

Erythromycin inhibits protein synthesis and blocks translocation by binding to the 23S rRNA of the 50S ribosomal subunit.

Chloramphenicol blocks peptidyl transferase at 50S ribosomal subunit.

Gentamicin, an aminoglycoside antibiotic, acts by binding to the 30S subunit of the bacterial ribosome inhibiting the binding of aminoacyl-tRNA and thus preventing initiation of protein synthesis.

An overview of the different mechanisms of action of the various types of antimicrobial agents is shown below:
1. Inhibition of cell wall synthesis
– Penicillins
– Cephalosporins
– Vancomycin
2. Disruption of cell membrane function
– Polymyxins
– Nystatin
– Amphotericin B
3. Inhibition of protein synthesis
– Macrolides
– Aminoglycosides
– Tetracyclines
– Chloramphenicol
4. Inhibition of nucleic acid synthesis
– Quinolones
– Trimethoprim
– 5-nitroimidazoles
– Rifampicin
5. Anti-metabolic activity
– Sulphonamides
– Isoniazid

Atropine 500 mcg IV bolus should be administered if there are any adverse features or risk of asystole. If the reaction is not adequate, repeat the steps every 3 to 5 minutes up to a maximum dose of 3 mg. In the case of acute myocardial ischemia or myocardial infarction, atropine should be taken with caution since the increased heart rate may aggravate the ischemia or increase the size of the infarct.

In adults, the spinal cord typically ends between L1/L2 whereas the subarachnoid space extends to approximately the lower border of vertebra S2. Lumbar puncture is performed in the intervertebral space L4/L5 or L3/L4.

Heparin is a polymer of glycosaminoglycan. It occurs naturally and is found in mast cells. Clinically, it is used in two forms:
1. Unfractionated: widely varying polymer chain lengths
2. Low molecular weight: Smaller polymers only

Heparin works by binding to and activating the enzyme inhibitor antithrombin III. Antithrombin III inactivates thrombin (factor IIa) by forming a 1:1 complex with thrombin. The heparin-antithrombin III complex also inhibits factor Xa and some other proteases involved with clotting. The heparin-ATIII complex can also inactivate IX, XI, XII, and plasmin.

Heparin is not thrombolytic or fibrinolytic. It prevents the progression of existing clots by inhibiting further clotting. The lysis of existing clots relies on endogenous thrombolytics.

Heparin is used for:
1. Prevention and treatment of venous thromboembolism
2. Treatment of disseminated intravascular coagulation
3. Treatment of fat embolism
4. Priming of haemodialysis and cardiopulmonary bypass machines

There is no evidence that heparin is superior to low-molecular-weight heparins in preventing mortality from thrombosis.

Vitamin K is used to reverse the effects of warfarin but not heparin. For heparin, protamine sulphate is used to counteract its effects.

Within the central portion of the tooth lies the dental pulp. The pulp chamber provides mechanical support and functions as a barrier from external stimuli and the oral microbiome. The dental pulp is a unique tissue that is richly innervated and has an extensive microvascular network. Maintaining its vitality increases both the mechanical resistance of the tooth and the long-term survival. The junctional epithelium forms a band around the tooth at the base of the gingival sulcus, sealing off the periodontal tissues from the oral cavity.

Pericarditis is inflammation of the pericardial sac and is the most common pathologic process involving the pericardium. Frequently, pericardial inflammation can be accompanied by increased fluid accumulation within the pericardial sac forming a pericardial effusion, which may be serous, hemorrhagic or purulent depending on aetiology.

The classic presentation is with chest pain that is central, severe, pleuritic (worse on deep inspiration) and positional (improved by sitting up and leaning forward). The pain may also be radiating and may involve the ridges of the trapezius muscle if the phrenic nerve is inflamed as it traverses the pericardium.

Opponens digiti minimi is a triangular-shaped muscle in the hand that forms part of the hypothenar eminence. It originates from the hook of the hamate bone and the flexor retinaculum and inserts into the medial border of the 5thmetacarpal.
Opponens digiti minimi is innervated by the deep branch of the ulnar nerve and receives its blood supply from the ulnar artery.
Opponens digiti minimi draws the fifth metacarpal bone anteriorly and rotates it, bringing the fifth digiti into opposition with the thumb.

The anterior triangle is the triangular area of the neck found anteriorly to the sternocleidomastoid muscle. It is formed by the anterior border of sternocleidomastoid laterally, the median line of the neck medially and by the inferior border of the mandible superiorly. The apex of the anterior triangle extends towards the manubrium sterni. The anterior triangle contains:
Muscles: thyrohyoid, sternothyroid, sternohyoid muscles
Organs: thyroid gland, parathyroid glands, larynx, trachea, esophagus, submandibular gland, caudal part of the parotid gland
Arteries: superior and inferior thyroid, common carotid, external carotid, internal carotid artery (and sinus), facial, submental, lingual arteries
Veins: anterior jugular veins, internal jugular, common facial, lingual, superior thyroid, middle thyroid veins, facial vein, submental vein, lingual veins
Nerves: vagus nerve (CN X), hypoglossal nerve (CN XII), part of sympathetic trunk, mylohyoid nerve

The posterior triangle is a triangular area found posteriorly to the sternocleidomastoid muscle. It has three borders; anterior, posterior and inferior borders. The anterior border is the posterior margin of the sternocleidomastoid muscle. The posterior border is the anterior margin of the trapezius muscle, while the inferior border is the middle one-third of the clavicle. The investing layer of deep cervical fascia and integument forms the roof of the space, while the floor is covered with the prevertebral fascia along with levator scapulae, splenius capitis and the scalene muscles. The inferior belly of omohyoid subdivides the posterior triangle into a small supraclavicular, and a large occipital, triangle.
Contents:
Vessels: the third part of the subclavian artery, suprascapular and transverse cervical branches of the thyrocervical trunk, external jugular vein, lymph nodes
Nerves: accessory nerve (CN XI), the trunks of the brachial plexus, fibers of the cervical plexus

A papule is a solid, well circumscribed, skin elevation measuring less than 0.5 cm in diameter.

A nodule is a solid, well circumscribed, raised area that lies in or under the skin and measures greater than 0.5 cm in diameter. They are usually painless.

A bulla is a visible collection of clear fluid measuring greater than 0.5 cm in diameter.

A furuncle, or boil, is a pyogenic infection of the hair follicle commonly caused by infection with Staphylococcus aureus.

A pustule is a small visible skin elevation containing an accumulation of pus.

Calcium-channel blockers, also known as calcium antagonists, stop calcium from entering cells through the L-type calcium channel. This causes vascular smooth muscle in vessel walls to relax, resulting in a decrease in peripheral vascular resistance.
They can be used for a variety of things, including:
Hypertension
Angina
Atrial fibrillation
Migraine

Calcium-channel blockers can be divided into two categories: dihydropyridines and non-dihydropyridines. The basic chemical structure of these two classes differs, as does their relative selectivity for cardiac versus vascular L-type calcium channels.

Dihydropyridines have a high vascular selectivity and lower systemic vascular resistance and blood pressure. As a result, they’re frequently used to treat hypertension. Modified release formulations are also used to treat angina, but their powerful systemic vasodilator and pressure-lowering effects can cause reflex cardiac stimulation, resulting in increased inotropy and tachycardia, which can counteract the beneficial effects of reduced afterload on myocardial oxygen demand.

The suffix -dpine distinguishes dihydropyridines from other pyridines. Examples of dihydropyridines that are commonly prescribed include:
Amlodipine
Felodipine
Nifedipine
Nimodipine

The phenylalkylamine class and the benzothiazepine class are two subgroups of non-dihydropyridines.

Phenylalkylamines are less effective as systemic vasodilators because they are relatively selective for the myocardium. This group of drugs lowers myocardial oxygen demand and reverses coronary vasospasm, making them useful in the treatment of angina. They are also occasionally used to treat arrhythmias. A phenylalkylamine calcium-channel blocker like verapamil is an example.

In terms of selectivity for vascular calcium channels, benzothiazepines fall somewhere between dihydropyridines and phenylalkylamines. They can lower arterial pressure without producing the same level of reflex cardiac stimulation as dihydropyridines because they have both cardiac depressant and vasodilator effects. Diltiazem is the only benzothiazepine currently in clinical use.

Penicillins and the other ß-lactam antibiotics are bactericidal. They produce their antimicrobial action by preventing cross-linkage between the linear peptidoglycan polymer chains that make up the bacterial cell wall. They, therefore, inhibit cell wall synthesis.
The integrity of the ß-lactam ring is essential for antimicrobial activity. Many bacteria (including most Staphylococci) are resistant to benzylpenicillin and phenoxymethylpenicillin because they produce enzymes (penicillinases, ß-lactamases) that open the ß-lactam ring.

A median nerve injury affecting the extrinsic and intrinsic muscles of the hand will present with:

Loss of sensation to the lateral palm and the lateral three and a half fingers.

Weakness of flexion at the metacarpophalangeal joints of the index and middle finger. This is because of paralysis of the lateral two lumbricals.

Weakness of flexion of the proximal interphalangeal joints of all four fingers due to paralysis of the flexor digitorum superficialis

Weakness of flexion at the distal interphalangeal joints of the index and middle finger following paralysis of the lateral half of the flexor digitorum profundus.
Weakness of thumb flexion, abduction and opposition due to paralysis of the flexor pollicis longus and thenar muscles

Mitochondrial diseases are a group of disorders caused by dysfunctional mitochondria. Most cases are maternally inherited, as we inherit our mitochondrial DNA from our mothers only, although mutations in nuclear DNA cause some cases.

Examples of Mitochondrial Diseases include:
1. Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS)
2. Mitochondrial epilepsy with ragged red fibres (MERRF)
3. Leber’s hereditary optic neuropathy (LHON)
4. Diabetes mellitus and deafness (DAD)
5. Neuropathy, ataxia, retinitis pigmentosa, and ptosis (NARP)
6. Leigh syndrome (subacute sclerosing encephalopathy).

Red-green colour blindness and G6PD deficiency have an X-linked recessive pattern of inheritance.

Tay-Sachs Disease and spinal muscular atrophy have an autosomal recessive pattern of inheritance.

In order for primary active transport to pump ions against their electrochemical gradient, chemical energy is used in the form of ATP. The Na+/K+-ATPase antiporter pump uses metabolic energy to move 3 Na+ions out of the cell for every 2 K+ions in, against their respective electrochemical gradients. As a result, the cell the maintains a high intracellular concentration of K+ions and a low concentration of Na+ions.

Benzodiazepines are used to treat symptoms in patients with acute alcohol withdrawal syndrome.
Benzodiazepines are contraindicated in:
Respiratory depression
Marked neuromuscular respiratory weakness, such as unstable myasthenia gravis
Obstructive sleep apnoea syndrome (symptoms may be aggravated)
Severe hepatic impairment (the elimination half-life of diazepam may be prolonged; increased risk of coma)
Phobic or obsessional states, chronic psychosis or hyperkinesis (paradoxical reactions may occur).

Central cord syndrome is the most common type of incomplete cord injury and almost always occurs due to a traumatic injury. It results in motor deficits that are worse in the upper extremities as compared to the lower extremities. It may also cause bladder dysfunction (retention) and variable sensory deficits below the level of injury.

The majority of these patients will be older and present with symptoms after a fall with hyperextension of their neck. On examination, patients will have more significant strength impairments in the upper extremities (especially the hands) compared to the lower extremities. Patients often complain of sensory deficits below the level of injury, but this is variable. Pain and temperature sensations are typically affected, but the sensation of light touch can also be impaired. The most common sensory deficits are in a cape-like distribution across their upper back and down their posterior upper extremities. They will often have neck pain at the site of spinal cord impingement.

Bladder dysfunction (most commonly urinary retention) and priapism can also be signs of upper motor neuron dysfunction. The sacral sensation is usually preserved, but the clinician should assess the rectal tone to evaluate the severity of the compression.

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

Gastrin is a peptide hormone that aids in gastric motility by stimulating the generation of gastric acid by the parietal cells of the stomach. G-cells in the stomach’s pyloric antrum, the duodenum, and the pancreas release it.

The following stimuli cause the release of gastrin:

Stimulation of the vagus nerve
Hypercalcaemia
stomach bloating
Proteins that have been partially digested, particularly amino acids.
The presence of acid and somatostatin inhibits the release of gastrin.
Gastrin’s main actions are as follows:
Gastric parietal cells are stimulated to release hydrochloric acid.
ECL cells are stimulated to produce histamine.
Gastric parietal cell maturation and fundal growth stimulation
Causes the secretion of pepsinogen by the gastric chief cells.
Improves antral muscle mobility
stimulates gastric contractions
Increases gastric emptying rate and stimulates pancreatic secretion
Gallbladder emptying is induced.

Cushing’s syndrome is a group of symptoms and signs brought on by long-term exposure to high amounts of endogenous or exogenous glucocorticoids.

Iatrogenic corticosteroid injection is the most prevalent cause of Cushing’s syndrome. Cushing’s illness is the second most prevalent cause of Cushing’s syndrome. Cushing’s disease is distinct from Cushing’s syndrome in that it refers to a single cause of the illness, a pituitary adenoma that secretes high quantities of ACTH, which raises cortisol levels.

Because cortisol enhances the vasoconstrictive impact of endogenous adrenaline, patients with Cushing’s syndrome are usually hypertensive.

Hyperglycaemia (due to insulin resistance) rather than hypoglycaemia is a common symptom.
Cortisol levels fluctuate throughout the day, with the greatest levels occurring around 0900 hours and the lowest occurring at 2400 hrs during sleep. The diurnal swing of cortisol levels is lost in Cushing’s syndrome, and levels are greater throughout the 24-hour period. In the morning, levels may be normal, but they may be high at night-time, when they are generally repressed.

A dexamethasone suppression test or a 24-hour urine free cortisol collection can both be used to establish the existence of Cushing’s syndrome.

At three points along their course, the ureters are constricted denoting the most likely areas for renal calculi to lodge:the first point is at the ureteropelvic junction (where the renal pelvis becomes continuous with the ureter)the second point is where the ureter crosses the common iliac vessels at the pelvic brimthe third point is at the vesicoureteric junction (where the ureter enters the wall of the bladder)

The gracilis muscles is innervated by the anterior branch of the obturator nerve (L2-L4).

Passive expiration is produced primarily by relaxation of the inspiratory muscles (diaphragm and external intercostal muscles) and the elastic recoil of the lungs. In expiration, depression of the sternal ends of the ribs (‘pump handle’ movement), depression of the lateral shafts of the ribs (‘bucket handle’ movement) and elevation of the diaphragm result in a reduction of the thorax in an anteroposterior, transverse and vertical direction respectively. This results in a decreased intrathoracic volume and increased intrathoracic pressure and thus air is forced out of the lungs.

An action potential is a self-propagating response, successive depolarisation moving along each segment of an unmyelinated nerve until it reaches the end. It is all-or-nothing and does not decrease in size. Conduction in myelinated fibres is much faster, up to 50 times that of the fastest unmyelinated nerve. Myelinated fibres are insulated except at areas devoid of myelin called nodes of Ranvier. The depolarisation jumps from one node of Ranvier to another by a process called saltatory conduction. Saltatory conduction not only increases the velocity of impulse transmission but also conserves energy for the axon because depolarisation only occurs at the nodes and not along the whole length of the nerve fibre. Larger diameter myelinated nerve fibres conduct nerve impulses faster than small unmyelinated nerve fibres.

The vast majority of systems within the body work by negative feedback mechanisms. This negative feedback refers to the way that effectors act to move the variable in the opposite direction to the change that was originally detected. Because there is an inherent time delay between detecting a change in a variable and effecting a response, the negative feedback mechanisms cause oscillations in the variable they control. There is a narrow range of values within which a normal physiological function occurs and this is called the ‘set point’. The release of oxytocin in childbirth is an example of positive feedback.