MEDICOSPOOL - Top Doctors in Nepal: May 2021

A case of ACL tear-A 25-year-old man has been hurt during football match by his opponent player

CLINICAL CASE SCENARIO KNEE INJURY-ANTERIOR CRUCIATE LIGAMENT TEAR

A 25-year-old man has been hurt during football match by his opponent player.He falls and twists his right leg.On examination, the right knee is swollen and tender. With the patient sitting on the stretcher with his knee flexed, the lower leg seems to have several centimeters of excess anterior mobility.

Most likely diagnosis: Anterior cruciate ligament (ACL) tear

Mechanism of injury: Excessive rotational force strains or ruptures the ligament

CLINICAL CORRELATION

Injuries to the knee are very common because it bears weight, combines mobility in flexion and extension, and allows some rotation. The stability of the knee depends entirely on its ligaments and muscles. Sports injuries to the knee are most commonly caused by high-speed and rotational forces applied to the leg through the knee joint. In addition, certain ligaments are anatomically related to the menisci, on which the distal femur articulates. This 25-year-old man was involved in a football match, a common setting for ACL injury. The ACL passes from the posterior aspect of the distal femur to the intercondylar region of the anterior aspect of the proximal tibia; it limits anterior movement of the tibia in relation to the femur. Thus, on examination, this patient exhibits the “anterior drawer sign,” or excessive anterior mobility of the tibia with the knee flexed. This injury will usually require surgical repair.

Case of Wrist fracture-Clinical Anatomy

A 23-year-old male reports that during a game of basketball, he tripped while driving the ball to the basket, and fell on his outstretched right hand with the palm down. Two days later, he phoned his anatomist father and related that his right wrist was painful. Later that day, he visited his father, who noted that the wrist was slightly swollen and tender but without deformity. He instructed his son to extend the right thumb, thereby accentuating the anatomical “snuffbox,” which is extremely tender to deep palpation. His father advised him to get his hand and wrist x-rayed.

Discussion:

Most likely diagnosis: Wrist fracture

Most likely anatomical defect: Fracture of the narrow middle portion of the scaphoid carpal bone

CLINICAL CORRELATION

This young man tripped while playing basketball and stretched out his right hand to protect himself. His hand, with the palm down and probably deviated to the side of the radius, took the brunt of the fall, resulting in significant impact force to the wrist. This resulted in pain and swelling of the wrist, especially on the radial side, with point tenderness deep in the anatomical snuffbox. This is the common mechanism for a fracture of the scaphoid carpal bone, the most commonly fractured carpal bone. Point tenderness over a bone or bony process is a hallmark of a fracture at that site. Radiologic confirmation of a fracture is important. The scaphoid bone has a unique blood supply, and proper reduction and alignment of the segments is necessary to decrease the risk of avascular necrosis. A fall on an outstretched hand such that it produces hyperextension of the wrist may result in dislocation of the lunate bone. The lunate is usually displaced anteriorly into the carpal tunnel and may impinge on the median nerve. The lunate is the most commonly dislocated carpal bone. A fall on an outstretched palm may also result in a transverse fracture of the distal radius or a Colles fracture, which produces a dorsal displacement of the distal fragment, resulting in the characteristic “dinner fork” (also termed “bayonet”) deformity. A Smith fracture of the radius in the same region of younger individuals is less common. In a Smith fracture, there is trauma to the dorsal aspect of a flexed wrist, and the wrist is deformed with the distal radial fragment displaced ventrally in a “spade” deformity.

Everything about brachial plexus-Anatomy,Clinical Importance.

The brachial plexus arises from the inferior portion of the cervical spinal cord enlargement. It is formed by the ventral primary rami of spinal nerves C5 through C8 and most of T1. The network of nerves that form the brachial plexus is divided anatomically from proximal (medial) to distal (lateral) into roots, trunks, divisions, cords, and terminal branches (mnemonic: “R. Travis drinks cold Texas beer”). The roots unite to form superior, middle, and inferior trunks. The suprascapular nerve and the nerve to the subclavius muscle arise from the superior trunk. Each trunk is divided into anterior and posterior divisions, which will innervate musculature of the anterior and posterior compartments, respectively. The anterior divisions of the superior and middle trunks unite to form the lateral cord, which branches off to the lateral pectoral nerve. The anterior division of the inferior trunk continues distally as the medial cord, whose branches are the medial pectoral, medial brachial cutaneous, and medial antebrachial cutaneous nerves. The posterior divisions of all three trunks unite to form the posterior cord, and its branches are the upper and lower subscapular and thoracodorsal nerves. The three cords are named according to their relation to the axillary artery, which passes through the plexus at this level. The terminal branches of the brachial plexus are the axillary, musculocutaneous, median, ulnar, and radial nerves. The axillary nerve (C5 and C6) arises from the posterior cord and courses posteriorly around the surgical neck of the humerus, where it is at risk for injury. The posterior circumflex humeral artery accompanies the nerve in this course. The axillary nerve supplies the deltoid and teres minor muscles, is sensory to the skin over the lower portion of the deltoid, and is optimally tested on the “shoulder patch” portion of the upper arm. Axillary nerve injury, such as that due to fracture at the surgical neck of the humerus, results in an inability to abduct the arm at the shoulder to a horizontal position and in sensory loss in the shoulder patch area . The musculocutaneous nerve (C5–C7) is the continuation of the lateral cord. It courses distally through the coracobrachialis muscle to innervate it in addition to the biceps brachii and brachialis muscles. The lateral antebrachial cutaneous nerve to the skin of the lateral forearm represents the terminal continuation of this nerve. Damage to the musculocutaneous nerve causes weakness in supination and flexion of the shoulder and elbow. The upper portion of the brachial plexus arises from spinal cord segments C5 and C6; forms the superior trunk; and makes major contributions to the axillary, musculocutaneous, lateral pectoral, and suprascapular nerves and the nerve to the subclavius muscle. Injury to the upper plexus typically occurs with an increase in the angle between the shoulder and the neck. This can occur in a newborn during an obstetrical delivery or in adults as the result of a fall on the shoulder and side of the head and neck, which produces a widened angle. The resultant muscle paralysis due to such an injury may be understood more easily in an adult with such an injury. The upper extremity hangs limp by the side because the deltoid and supraspinatus (abductors of the arm) are paralyzed as a result of injury of the axillary and suprascapular nerves, respectively. In addition, the anterior deltoid, biceps brachii, and coracobrachialis (flexors of the arm) are paralyzed due to injury of the axillary and musculocutaneous nerves. The elbow is extended and the hand is pronated because of paralysis of the biceps brachii and brachialis muscles, both of which are innervated by the musculocutaneous nerve. The extremity is medially rotated because of paralysis of the teres minor and infraspinatus muscles (lateral rotators of the arm) and injury to the axillary and suprascapular nerves. The palm of the hand is turned posteriorly in the “waiter’s tip” sign. There is loss of sensation along the lateral aspect of the upper extremity, which corresponds to the dermatome at C5 and C6.

The upper brachial plexus injury is known as Erb’s or Duchenne-Erb palsy. The ulnar nerve (C8 and T1) is a continuation of the medial cord, which enters the posterior compartment through the medial intermuscular septum and passes distally to enter the forearm by curving posteriorly to the medial epicondyle. Here it is superficial and at risk for injury. It enters the anterior compartment of the forearm, where it innervates the flexor carpi ulnaris and the bellies of the flexor digitorum profundus to the ring and little fingers. The ulnar nerve enters the hand through a canal (Guyon canal) superficial to the flexor retinaculum. The nerve supplies all the intrinsic muscles of the hand except for the three thenar muscles and the lumbricals of the index and middle fingers. It is sensory to the medial border of the hand, the little finger, and the medial aspect of the ring finger. Damage to the ulnar nerve in the upper forearm causes lateral (radial) deviation of the hand, with weakness in flexion and adduction of the hand at the wrist and loss of flexion at the distal interphalangeal joint of the ring and little fingers. Damage to the ulnar nerve in the upper forearm or at the wrist also results in loss of abduction and adduction of the index, middle, ring, and little fingers due to paralysis of the interossei muscles.

A “claw hand” deformity results, and with longstanding damage, atrophy of the interosseous muscles occurs. Injury to the lower brachial plexus, known as Klumpke palsy, occurs by a similar mechanism, that is, an abnormal widening of the angle between the upper extremity and the thorax. This may occur at obstetrical delivery by traction on the fetal head or when an individual reaches out to interrupt a fall. The roots from C8 and T1 and/or the inferior trunk are stretched or torn. Spinal cord segments C8 and T1 form the ulnar nerve and a significant portion of the median nerve. Most of the muscles of the anterior forearm are innervated by the median nerve and will display weakness. Most of the muscles of the hand are innervated by the ulnar nerve. There will be loss of sensation along the median aspect of the arm, forearm, hypothenar eminence, and little finger (C8 and T1 dermatome).

Clinical case scenario-Schizophrenia

S is a 32-year-old moderately obese man brought into the ED by the police after attempting to cut himself with a piece of glass from his bathroom mirror. He said he had to cut himself in order to "let the evil out!"· In the examination room, S looked suspiciously at the interviewer and was muttering to himself.

His Past Medical History is significant for chronic schizophrenia. HTN, hyperlipidemia, and major depressive disorder. Medications include thioridazine, benztropine. paroxetine, atorvastatin, and metoprolol, although he states he discontinued all his medications 3 weeks ago for fear he was being poisoned.

PE: On physical examination, he has noticeable cuts on his hands. During the interview, he demonstrated noticeable facial grimacing and lip smacking, a stooped posture, and sluggish gait.

Case Conclusion S's symptoms are consistent with the diagnosis of uncontrolled chronic schizophrenia (paranoid type). Because S is experiencing positive and negative symptoms and has evidence of(EPS) Extra Pyramidal Symptoms. he should be switched to an atypical antipsychotic agent Olanzapine is traditionally reserved for treatment-resistant patients and is not a first line agent due to the risk of agranulocytosis. Olanzapine and quetiapine can be problematic due to weight gain and potential insulin resistance (if the patient has family history of diabetes mellitus type 2). Risperidone is also associated with a higher incidence of EPS symptoms compared with other atypical agents. In addition, He is also taking paroxetine that can significantly elevate levels of risperidone. Therefore, ziprasidone would be the best choice for this patient

DISCUSSION

Atypical antipsychotic agents or "newer" agents alleviate both positive and negative symptoms. The atypical antipsychotics also improve cognitive deficits associated with schizophrenia. Although these agents are much safer, they have added cost and have been associated with their own class of adverse effects.

Extrapyramidal symptoms are common adverse effects of traditional neuroleptics, although they may still occur with atypical agents. Pseudoparkinsonism, akathisia, and acute dystonic reactions are the three early-onset types of EPS. Atypical agents have a low risk for inducing EPS.The management of early-onset EPS symptoms includes drug discontinuation, dosage reduction of the antipsychotic agent, or switching to an agent with less risk for inducing EPS. Anticholinergic agents (diphenhydramine, benztropine) can be used to treat acute dystonic reactions, parkinsonism, and akathisia.

Management of Myocardial infarction

In any acute myocardial infarction the first priority is to assess the patient’s clinical stability and assess the requirement for, and urgency associated with, coronary revascularisation.

Remember: patients presenting with an infarction could present with acute pulmonary oedema, cardiogenic shock, malignant ventricular tachyarrhythmias or severe bradycardia. Once the patient’s haemodynamic stability and cardiac rhythm stability are established, perform an urgent ECG to confirm the diagnosis and identify the nature of the infarction—whether it is an ST segment elevation infarction (STEMI) or a non-ST segment elevation infarction (non-STEMI).

STEMI

If the infarction is a STEMI, urgent reperfusion therapy is needed. Acute reperfusion therapy could be primary percutaneous transluminal coronary angioplasty (primary PTCA) with insertion of a stent or thrombolysis. If the centre offers a primary angioplasty service and the patient fulfils the criteria (see below), urgent transfer to the cardiac catheterisation laboratory should take place. Patients presenting in the first 4–6 hours of onset of chest pain are considered suitable for primary PTCA. Previous coronary artery bypass grafts, peripheral vascular disease, untreatable terminal illness and dementia are exclusion criteria for this procedure. If primary PTCA is not an option, the patient should be thrombolysed with the relevant thrombolytic agent. If the patient presents within the first hour after the onset of chest pain, thrombolysis would be a preferred option (the ‘golden hour’ phenomenon). Usually a recombinant tissue plasminogen activator (rTPA) or an analogue is given to the patient immediately. Streptokinase is an alternative for patients over the age of 65 or those with evidence of an inferior myocardial infarction presenting after 4 hours of the onset of chest pain. Those who have been treated with streptokinase previously should not be given streptokinase again, due to the heightened risk of an allergic reaction. The ECG criteria for primary PTCA and thrombolysis are similar (see below), but thrombolysis may be useful up to 12 hours or even 24 hours after the onset of chest pain.

Criteria for primary PTCA or thrombolysis

• ST segment elevation of more than 1 mm in more than two contiguous limb leads

• ST segment elevation of more than 2 mm in more than two contiguous precordial leads

• new left bundle branch block.

If the decision is made to administer thrombolytics, the patient should not have any contraindications (e.g. risk of haemorrhage or allergy) to such therapy. If thrombolytic therapy has not been effective and the patient is a strong candidate for reperfusion therapy, attempts should be made to organise urgent rescue angioplasty.

Non-STEMI

If a non-STEMI, the patient should be managed initially with anticoagulation and antiplatelet therapy. The patient should subsequently be referred for early coronary catheterisation. All patients presenting with myocardial infarction (STEMI or non-STEMI) or acute coronary syndrome (unstable angina or non-STEMI) should be considered for antiischaemia therapy. The routinely used agents include oral or IV beta-blockers, as guided by the pulse rate and blood pressure, and aspirin. Patients treated with primary PTCA and stenting are given clopidogrel in addition to aspirin. If the patient complains of angina, oral, topical or IV nitrates and/or morphine should be administered. An ACE inhibitor should be commenced within the first 24 hours of the infarction if the blood pressure permits. Angiotensin II receptor blockers are also useful in this setting. Patients with post-infarction heart failure benefit from aldosterone antagonist eplerenone. Unless the patient has been treated with primary PTCA or streptokinase, they should be anticoagulated with unfractionated or fractionated heparin. According to current evidence, all patients presenting with coronary ischaemia benefit from statin therapy regardless of the baseline fasting cholesterol level. Patients with acute coronary syndrome benefit from IV antiplatelet therapy in the way of platelet glycoprotein IIb/IIIa inhibitor agents such as tirofiban or eptifibatide in addition to heparin. The patient should be admitted to the CCU for continuous ECG monitoring. Serial cardiac enzymes or troponin levels should monitored. Patients who sustain right ventricular damage may become profoundly hypotensive. They need IV volume infusion as the first line of therapy. Those in cardiogenic shock require inotropic therapy in the form of IV dobutamine or dopamine to support cardiac function and haemodynamic stability.

Post-infarct ventricular fibrillation

Ventricular fibrillation within the first 24 hours of an infarction indicates a more favourable prognosis than those occurring afterwards. Episodes of ventricular fibrillation after the first 24 hours signify a guarded prognosis, and consideration should be given to the implantation of a cardiac defibrillator. Inferior or posterior myocardial infarctions can damage the AV node or the cardiac conduction system, leading to heart block. These patients need urgent insertion of a temporary pacemaker. Some may recover their nodal and conduction function as the oedema and inflammation associated with the acute event settles, but others who sustain permanent damage need insertion of a permanent pacemaker (PPM). Complete heart block in a patient who suffers an anterior myocardial infarction signifies a bad prognosis due to the extensive area of myocardial damage.

Follow-up

Follow-up management includes a transthoracic echocardiogram to assess the ejection fraction and to look for segmental left ventricular wall motion abnormalities, valvular defects, ventricular septal defect, ventricular thrombus and ventricular aneurysms. Ejection fraction can also be assessed by performing a nuclear gated heart pool scan. Patients who have an ejection fraction of less than 40% after an infarction are at high risk (30%) of sudden cardiac death over the next 5 years. These patients qualify to be treated with a prophylactic implanted cardiac defibrillator (ICD) usually 40 days after the infarction, according to current evidence. Patients suffering from post-infarct angina need early coronary angiography to define the coronary anatomy before deciding on definitive therapy. Stable patients should have an exercise stress study, looking for reversible ischaemia. This may take the form of a stress echocardiography, stress ECG or nuclear medicine perfusion study. The presence of reversible ischaemia or ischaemia associated with stress are indications for coronary angiography. Definitive treatment with angioplasty, with or without stenting of the involved artery, or coronary artery bypass grafting, should be decided upon as guided by the coronary anatomy. Prior to discharge, patients should be recruited to a post-myocardial infarction rehabilitation program and modification of cardiovascular risk factors should be encouraged. Some patients may need counselling and significant reassurance to help them recover from the acute event. Others may need advice on lifestyle and occupational issues, relevant information and education, counselling on sexual matters, dietary advice, help with giving up smoking and partner counselling.

Clinical case of Myasthenia Gravis for MBBS

#Mr X is a 25-year-old businessman . Over the last 6 months, he experienced "strange" symptoms. He had severe eyestrain when he read for longer than 15 minutes. He became tired when he chewed food, brushed teeth, he had extreme fatigue on the work. He does not like people not doing work on time but he himself is unable to do works at time due to fatigue. Serum was sent for Anti-AChR ab(antibody).

DISCUSSION:

Neuromuscular transmission is the process whereby an action potential in a motor neuron produces an action potential in the muscle fibers that it innervates. The steps in neuromuscular transmission, are as follows:

(1) An action potential is propagated down the motor neuron until the presynaptic terminal is depolarized.

(2) Depolarization of the presynaptic terminal causes voltage-gated Ca2+ channels to open, and Ca 2+ flows into the nerve terminal.

(3) Uptake of Ca2+ into the nerve terminal causes exocytosis of stored acetylcholine (ACh) into the synaptic cleft.

(4) ACh diffuses across the synaptic cleft to the muscle end plate, where it binds to nicotinic ACh receptors (AChR).

(5) The nicotinic AChR is also an ion channel for Na+ and K+, WhenACh binds to the receptor, the channel opens.

(6) Opening of the channel causes both Na+ and K+ to flow down their respective electrochemical gradients, As a result, depolarization occurs.

(7) This depolarization, called the end plate potential, spreads to neighboring regions of the muscle fiber.

(8) Finally, the muscle fibers are depolarized to threshold and fire action potentials, Through this elaborate sequence of events, an action potential in the motor neuron causes an action potential in the muscle fibers that it innervates.

In myasthenia gravis, abnormal antibodies to AChR (AChR-ab) are produced, circulate in the blood, and bind to nicotinic receptors on the muscle end plates. When antibodies are bound to AChR, the receptors are not available to be activated by ACh that is released physiologically from motor neurons. Thus, while normal action potentials occur in the motor neurons and ACh is released normally, the ACh cannot cause depolarization of muscle end plates. Without depolarization of muscle end plates, there can be no action potentials or contraction in the muscle.

After ACh binds to and activates AChR on the muscle end plate, it is degraded by acetylcholinesterase, an enzyme that is also present on the muscle end plate. This degradative step, whose byproducts are choline and acetate, terminates the action of ACh on muscle.

Pyridostigmine is an acetylcholinesterase inhibitor that binds to acetylcholinesterase and thereby prevents binding and degradation of ACh at the muscle end plate. In the treatment of myasthenia gravis, pyridostigmine prevents degradation ofACh, increases its synaptic concentration, and prolongs its action. The longer the muscle end plate is exposed to high concentrations of ACh, the greater the likelihood that action potentials and contraction in the muscle will occur.

He was given pyridostigmine.Mr X immediately felt better while taking the drug; his strength returned to almost normal.

USE OF CALCIUM CHANNEL BLOCKERS IN HYPERTENSION

#A 60 year old woman presents to the clinic for a 6-month follow-up examination newly diagnosed HTN,which has not been adequately controlled by dietary and lifestyle changes.

Past Medical History: Angina and asthma.

On examination- Vital signs: BP 160/99 mm Hg, HR 55 beats/min. Allergies: Sulfa-based drugs. Medications: Albuterol inhaler, fluticasone inhaler, and nitroglycerin sublingual tablets.

Management: Diuretics and beta-blockers are first-line agents for treating HTN. Because this patient has asthma, beta-blockers should be avoided. Calcium channel blockers are favorable therapeutic options in patients with both angina and HTN. Because her heart rate is low, diltiazem and verapamil are not optimal choices because they can slow down AV nodal conduction. A long-acting dihydropyridine, amlodipine, was started.

CASE DISCUSSION-

Calcium channel blockers inhibit l-type calcium channels in cardiac and smooth muscle. As a result, inhibition of calcium influx into cells occurs, causing a decrease in myocardial contractility and rate, resulting in reduced oxygen demand. Cardiac rate is slowed by the ability of calcium channel blockers to block electrical conduction through the atrioventricular{AV) node. In addition, calcium channel blockers can reduce systemic arterial pressure by relaxing arterial smooth muscle and decreasing systemic vascular resistance.

Both diphenylalkylamines (verapamil) and benzothiazepines (diltiazem) exhibit effects on both cardiac and vascular tissue. With specificity for the heart tissue, these two types of calcium channel blockers can slow conduction through the AV node and are useful in treating arrhythmias. The dihydropyridines (nifedipine is the prototypical agent) are more potent peripheral and coronary artery vasodilators. They do not affect cardiac conduction, but can dilate coronary arteries. They are particularly useful as antianginal agents. Bepridil is unique in that it blocks both fast sodium channels and calcium channels in the heart. All calcium channel blockers, except nimodipine and bepridil, are effective in treating HTN.

Verapamil and diltiazem can both cause sinus bradycardia and may worsen CHF. Constipation has been associated with verapamil use. The dihydropyridines often cause symptoms associated with vasodilatation, such as facial flushing, peripheral edema, hypotension, and headache. Because dihydropyridines are potent vasodilators, they can cause reflex tachycardia, which may precipitate palpitations, worsening angina, or MI.

HYPERSENSITIVITY REACTIONS -TYPE I TO TYPE IV

Type I reactions

Type I hypersensitivity reactions are rapid and short-lived anaphylactic reactions that do not cause chronic tissue injury. Prior antigenic exposure to certain antigens leads to IgE synthesis, which serves as antigen receptor on the surface of mast cells. Binding of antigen to IgE triggers mast cell degranulation, releasing histamine and other acute inﬂammatory mediators. For example, hydatid cyst rupture can cause anaphylaxis.

Type II reactions

Tissue damage associated with type II hypersensitivity reactions are mediated by antibodies to microbial antigens that cross react with host cell antigens.For example,certain M serotypes of the Lanceﬁeld group A Streptococcus pyogenes stimulate high titres of immunoglobulin G (IgG) that cross-react with host cell antigens in the heart,joints and neural tissue, leading to the carditis, arthritis and Sydenham’schorea,whch characterize rheumatic fever.

Type III reactions

Type III hypersensitivity reactions to infectious diseases are also mediated by antibodies.Immune complex formation between antigens and antibodies results in activation of complement and chemotaxis of neutrophils that release tissue-damaging enzymes. Aggregation of platelets also causes formation of micro-thrombi and release of vasoactive amines. Many different tissues may be affected and polymorphonuclear inﬁltration, oedema and vasculitis characterize lesions. The natural history of such reactions is commonly persistent and chronic. Examples include glomerulonephritis associated with bacterial endocarditis, erythema nodosum leprosum (a hypersensitivity reaction to persistent M. leprae antigens in the skin) and allergic bronchopulmonary aspergillosis (which causes pulmonary inﬁltration and airﬂow obstruction in response to Aspergillus fumigatus.

Type IV reactions

Type IV reactions cause cell-mediated tissue pathology in which there is delayed-type hypersensitivity (DTH).The accumulation of large numbers of highly activated macrophages and formation of granulomas characterize tissue lesions. This is the classical mechanism by which the host response may cause very extensive and chronic tissue damage. Examples include TB, tuberculoid leprosy and periportal hepatic ﬁbrosis in Schistosoma mansoni infection.

She also has a productive cough and pleuritic chest pains-Clinical Vignette-Asthma

A 28-year-old female patient has been admitted with fever, chills and rigors. She also has a productive cough and pleuritic chest pains. She has been recently diagnosed with asthma. She smokes 5–10 cigarettes a day. She works in a bakery and describes symptoms of rhinorrhoea and wheezing while at work and after work. She has been prescribed an inhaler by her GP, but has not been compliant. On examination her temperature is 38°C and respiratory rate 20. Her oxygen saturation is 88% on room air. There are diffuse polyphonic wheezes in the lung fields, with bronchial breath sounds in the left mid to lower zone. Her sputum mug shows rusty purulent sputum.

Approach to the patient

Symptoms of chronic cough, especially nocturnal cough, wheezing and complaints of chest tightness, can be clues to consider asthma in the list of differential diagnoses in the dyspnoeic patient. In the known asthmatic, there are some questions that should invariably be asked.

Ask about:

• the current asthma management regimen, and frequency of bronchodilator use. Check whether the patient is using a bronchodilator at an unusually high frequency.

• what the known precipitants of asthma attacks are and how often the patient experiences exacerbations

• whether the patient has ever been hospitalised or treated in the intensive care unit for exacerbation of asthma

• whether the patient has a nocturnal cough

• whether the patient monitors their airway function with a peak flow meter at home. If they do monitor the peak flow, ask how often it is performed and the usual and most recent readings.

• the variability of the peak flow meter readings before and after bronchodilator therapy. Persistent variability is indicative of poor disease control.

• seasonal variation of symptoms and association with exercise

• whether an allergist has been consulted or special tests for allergy (skin prick test and radioallergosorbent (RAST) test) have been performed

• corticosteroid use—how often the patient is prescribed oral steroids, the maximum dose and the minimum dose ever, and the side-effect profile the patient has experienced

• how this chronic condition has affected the patient’s day-to-day life and occupational activities.

Drugs used in asthma

Asthma medications are broadly classified into two categories based on their clinical effects. The first category is the group of medications that improve symptoms (relievers) and the second category prevent exacerbations (preventers).
• Relievers—are short-acting beta2 agonists such as salbutamol, terbutaline, and long-acting beta2 agonists such as efemetorol. Tiotropium and ipratropium bromide are inhaled anticholinergic bronchodilator agents with a slower onset of action. Theophylline, which is capable of relaxing bronchial smooth muscle, is also used to treat severe and acute exacerbations of asthma. However, due to its wide adverse effects profile (nausea, diarrhoea, arrhythmias) it is rarely used these days.

• Preventers—include inhaled corticosteroids such as beclomethasone, budesonide, fluticasone and ciclesonide. Other preventers are leukotriene receptor blockers (montelukast) and cromoglycates (mast cell stabilisers).

– Inhaled corticosteroids have proven benefits in reducing exacerbations, reducing mortality and recurrent hospital admissions. These agents are known to improve overall quality of life in chronic asthmatics. However, long-term high-dose therapy with topical corticosteroids can bring about systemic adverse effects such as cataracts, osteoporosis, glaucoma and cutaneous fragility.

– Leukotriene inhibitors such as montelukast have particular use in the treatment of aspirin-induced asthma and in preventing exercise-induced asthma. They can be combined with inhaled steroids when adequate control is not achieved with single-agent therapy.

– Cromones such as nedocromil sodium and sodium cromoglycate are capable of preventing early and late bronchoconstrictor reactions to allergen exposure and therefore have particular use in seasonal allergic asthma. They have shown benefit in the prevention of exercise-induced asthma. Nedocromil is useful in the treatment of asthma-associated cough.

CLINICAL CASE SCENARIO-ACUTE CORONARY SYNDROME

Pain mimicking GERD

A 48-year-old man with a history of hypertension was referred as an emergency to the local casualty department by his GP .He had developed central chest pain earlier in the day, which was gradually increasing in severity. Although he had initially thought that it might have been indigestion, he had called his GP when it d id not ease with antacids. On arrival to casualty, he was breathless and in pain. He was noted to be clammy and pale.His blood pressure was 190/110 and his heart rate was 105 and regular. The remainder of the clinical examination was normal.A12-lead ECG showed ST-segment elevation across the anterior chest leads, with left axis deviation and voltage criteria for left ventricular hypertrophy.

The diagnosis is acute anterior myocardial infarction.

The ﬁrst consideration in the treatment of this patient is resuscitation: he should receive oxygen, and intravenous access will be established. He should initially be treated in the resuscitation area of casualty before transfer to the coronary care unit.Soluble aspirin(300mg) should be given with intravenous opiates for pain relief. At this point a decision needs to be taken with regard to his treatment: he can be treated with thrombolysis, in which case his blood pressure needs to be reduced to a safe level, or, if the facilities are available, he can undergo primary percutaneous coronary intervention.

Presents to OPD with recent onset chest pain on exertion

Mr Z is a 48-year-old man who presents to the general medicine clinic complaining of recent onset of chest pain (CP) on exertion. He says that he was feeling fine until about a week ago when he started experiencing intermittent CP while mowing the lawn. He also states that the CP subsides after sitting down in the shade and resting for about 5 minutes.

FamilyHistory: Father who died at age 46 secondary to coronary artery disease (CAD).

Smoking History: One pack of cigarettes per week for 20 years.

Conclusion

After the cardiac work-up for Mr Z, it was concluded that he had a diagnosis of unstable angina. He was prescribed nitroglycerin sublingual tablets for chest pain and a beta-blocker to help decrease the workload of the heart and decrease myocardial oxygen demand. His lipid panel revealed elevated cholesterol (250 mg/dL with lowdensity lipoprotein [LDL] 140 mg/dL and high--density lipoprotein [HDL] 40 mg/dL) and triglycerides (296 mg/dL). He was started on atorvastatin to help lower his cholesterol because it is a component of atherosclerotic plaques. Smoking cessation counseling was given, and the patient was advised to start on nicotine patches.

Angina pectoris is a symptom of ischemic heart disease that is frequently characterized by chest pain. There are three basic categories of angina: stable (exertional) angina, unstable angina. and vasospastic angina. Both stable and unstable angina reflect underlying atherosclerotic narrowing of coronary arteries. Vasospastic angina, or Prinzmetal's variant angina, is usually not associated with CAD and is due to coronary spasms that result in decreased myocardial blood flow.

Nitrates are the drugs of choice for relieving angina because they decrease preload and myocardial oxygen demand by venous dilatation. In addition, nitrates dilate coronary arteries even in the setting of atherosclerosis. The two proposed mechanisms by which nitrates promote venodilatation are stimulation of cyclic guanosine monophosphate (GMP) production and inhibition of thromboxane synthetase.

Adverse effects

Headache

Postural hypotension

Syncope

After several days of therapy, tolerance develops and headache and hypotension should resolve.Patients with nitrate induced syncope should have their dose reduced.

Drug interactions

Sildenafil is contraindicated because of potentiation of hypotensive effects of Nitrates.

HYPERTENSION MANAGEMENT PROTOCOLS

MANAGEMENT

It is not wise to commence treatment at the first diagnosis itself unless there is malignant hypertension, end-organ damage (see below) or significant other vascular risk factors, or comorbidity. (Treat with antihypertensive agents if the diastolic pressure is > 100 mmHg, or systolic > 200 mmHg, or systolic pressure > 160 mmHg together with end-organ damage. The presence of other cardiovascular risk factors would be another indication for treatment.) Observation for 3–6 months with recommendation of non-pharmacological methods such as progressive muscle relaxation, weight reduction (if relevant), reduction of alcohol consumption, salt restriction and regular physical exercise would suffice initially. It is important to advise the patient against smoking. If present, hyperlipidaemia and diabetes should be treated. If the blood pressure remains elevated (>140/90 mmHg) despite adequate lifestyle modification (or due to failure of lifestyle modification), pharmacotherapy should be initiated.

End-organ damage due to hypertension

• Myocardial infarction

• Left ventricular hypertrophy

• Cardiac failure

• Stroke

• Hypertensive nephropathy

• Hypertensive retinopathy

• Arteriosclerosis

Selection of the appropriate antihypertensive agent should be guided by several factors, including: the patient’s comorbidities, age, sex, ethnic background and drug allergies. Initially an attempt should be directed at monotherapy, and the commonly used agents are thiazide diuretics, beta-blockers, calcium channel blockers, angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blocker (ARB). If monotherapy is inadequate, combination therapy can be considered. An ACE inhibitor with a diuretic, or a beta-blocker with a diuretic, are two such combinations. There are combination pills containing an ACE inhibitor or an ARB together with a thiazide diuretic that can be prescribed. Hypertension that is not well controlled with conventional agents even with up titration and combination warrants further investigation and the addition of potent, less commonly used agents such alpha receptor blockers, centrally acting agents or arterial vasodilators.

Comorbidities that can influence the choice of therapy

• Diabetes mellitus —ACE inhibitors are the most suitable agents. Where ACE inhibitors are not tolerated, the other options to consider include ARBs and calcium channel blockers. Beta-adrenergic receptor blockers and thiazide diuretics can interfere with glycaemic control. ACE inhibitors and ARBs have significant and useful synergy in severe high blood pressure and diabetic nephropathy.

• Gout —beta-blockers, ACE inhibitors, calcium channel blockers and alphablockers are suitable. Thiazide diuretics can exacerbate gout.

• Dyslipidaemia —ACE inhibitors, calcium channel blockers and alpha-blockers are recommended. Beta-blockers may be less desirable due to their adverse effects on the lipid profile.

• Ischaemic heart disease —diuretics, beta-blockers, calcium channel blockers, ACE inhibitors and ARBs are suitable because of their protective properties in coronary vascular disease.

• Congestive cardiac failure —ideal agents include beta-blockers, ACE inhibitors, ARBs and diuretics, which also have proven value in the management of cardiac failure.

• Peripheral vascular disease —calcium channel blockers, alpha-adrenergic receptor blockers and diuretics are desirable agents. Beta-blockers are contraindicated.

• Pregnancy —for mild hypertension in pregnant patients, methyldopa and the alpha- and beta-adrenergic receptor blocking agent labetolol are good choices. In preeclampsia, nifedipine is a suitable agent; however, urgent delivery of the baby is an absolute requirement. Severe hypertension in the pregnant patient can be managed with intravenous (IV) hydralazine.

Adverse effects of some antihypertensive agents

It is important to have a commanding knowledge of the properties and adverse effects of the commonly used antihypertensive agents. Below is a list of adverse effects seen with different classes of antihypertensive agents, together with some important properties of selected agents.

• Thiazide diuretics —hypercholesterolaemia, hyperglycaemia, thrombocytopenia and gout • Beta-blockers —bradycardia, postural hypotension, depression and cold peripheries.

• ACE inhibitors —angio-oedema, cough, postural hypotension, hyperkalaemia, progression of renal failure and first-dose hypotension. First-dose hypotension is a rarity but is seen particularly in patients on low-sodium diets and high-dose diuretics.

• Angiotensin II receptor blockers —similar to ACE inhibitors but cough is less common

• Calcium channel blockers —headaches, sweating, palpitations and ankle oedema

• Alpha-blockers —first-dose hypotension. Long-acting alpha-blockers such as doxazocin have less first-dose hypotension effect.

• Vasodilators —minoxidil is an agent used in resistant hypertension. It is one of the most potent antihypertensive drugs available. Minoxidil can cause sodium and water retention, leading to ankle oedema and, in the rare case, pericardial effusion. Another undesirable side effect of minoxidil is hypertrichosis.

Hydralazine has its use in pregnancy and sometimes in cardiac failure. Hydralazine can cause drug-induced lupus. Nitroprusside is another vasodilator agent that is used in hypertensive crises and dissection of the aorta.

CLINICAL CASE SCENARIO OF DIGOXIN TOXICITY FOR MEDICAL STUDENTS

Mrs X is a 67-year-old woman brought into the opd complaining of loss of appetite and nausea for the preceding 2 days. She also reports hazy vision with "halos" but thinks that is due to her tiredness.

PastMedicalHistory : CHF, HTN.

Medications: Digoxin.

She recently started taking an angiotensin-converting enzyme Inhibitor (Ace-I) .

Case Conclusion :

Mrs X's presentation was consistent with digoxin toxicity. Labs returned with a normal potassium value (3.9 mEq/L) and a supratherapeutic digoxin level (2.6 microg/l). Her digoxin and ACE-I were immediately discontinued. Within 2 days. X was starting to feel like herself again. The ACE-I and oral digoxin were restarted (at lower doses)

Digoxin increases contractility of the heart muscle by inhibiting the Na+/K+ ATPase pump. In a normally functioning heart. intracellular calcium stored in the sarcoplasmic reticulum is released and activates the contractility of the muscle. The Na+/Ca2+ exchanger located in the cell membrane controls normal intracellular calcium levels. Exchangers use the Na+ ion gradient, maintained by the Na+/K+ ATPase, to move calcium ions out of the cell. when digoxin inhibits the Na '/K+ ATPase, intracellular sodium levels increase. This increase in sodium shifts the balance of the Na+/Ca2+ exchanger, leading to increased stores of intracellular calcium available in the sarcoplasmic reticulum and stronger contraction of the heart muscle.

When starting digoxin therapy, it is important to obtain baseline electrolyte levels and renal function. Electrolyte imbalances (hypokalemia, hypomagnesemia, or hypercalcemia) predispose patients to digoxin toxicity. When serum potassium is low, digoxin uptake increases because digoxin and potassium compete for the same site on the Na+/K+ ATPase. Increases in serum calcium can facilitate digitalis toxicity by causing overloading of intracellular calcium stores that can induce arrhythmias. Low magnesium also can contribute to toxicity. In addition, digoxin is cleared by the kidney; therefore. it is important to obtain baseline renal function values to determine if dose adjustments are necessary.

Because of digoxin's narrow therapeutic range, toxicity can often occur. especially in those who have predisposing factors, such as hypokalemia, concurrent therapy with potassium wasting diuretics, age (elderly and pediatrics), small body size. and drug interactions. Common signs of toxicity include GI complaints (nausea, vomiting, and anorexia). arrhythmias, and CNS effects (I.e., confusion, hallucinations. and visual disturbances).

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