DISORDERS OF THE DIAPHRAGM

Unilateral diaphragmatic paralysis is usually asymptomatic and discovered incidentally on patients having imaging for some other reason. The

commonest cause is involvement of the phrenic nerve (C2-C4) in the thorax by a bronchial carcinoma. Chest X-ray shows an elevated hemidiaphragm on the affected side and the diagnosis is made on fluoroscopy (the diaphragm moves paradoxically upward during inspiration). Bilateral diaphragmatic weakness causes orthopnoea, paradoxical (inward) movement of the abdomi-nal wall on inspiration and a large fall in FVC on lying down. Causes include trauma or generalized muscular or neurological conditions (motor neurone disease, muscular dystrophy, Guillain-Barré syndrome). Treatment is either diaphragmatic pacing or night-time assisted ventilation.

THERAPEUTICS

Most drugs described in this section are used in the management of asthma and COPD. Drug inhalation delivers the drug directly to the airways; the dose is smaller than that for the drugs given by mouth, and side-effects are reduced. Metered-dose inhalers (MDI) are the method of first choice for drug delivery. An MDI with a spacer device removes the need to coordinate actua-tion of an MDI and inhalation, and may improve drug delivery for patients who have difficulty using a pressurized MDI. They increase airway drug deposition and reduce oropharyngeal deposition. Local adverse effects from inhaled corticosteroids, e.g. oropharyngeal candidiasis, are reduced and a spacer device should be co-prescribed with inhaled corticosteroids for chil-dren, patients on high doses and those with poor inhaler technique. Breath-activated inhalers or dry powder inhalers are also available. A nebulizer converts a solution of a drug into an aerosol for inhalation and delivers a higher dose of drug than is usual with standard inhalers. Nebulizers are used in the management of acute severe asthma, chronic persistent asthma and brittle asthma.

Bronchodilators

Short-acting selective β2-adrenoceptor stimulants
Mechanism of action

Interact with p-receptors on the surface of a variety of cells and lead to bronchial smooth muscle relaxation, decrease release of mediators from mast cells, inhibit neutrophil and eosinophil functional responses and increase mucociliary transport.

Indications

Inhalers used on an as required basis for relief of symptoms in mild asthma and on an as required or regular basis in COPD. Oral preparations are used by patients who cannot manage the inhaled route, and the intravenous route is used for acute severe asthma. In asthma patients using an inhaler on a daily basis, regular inhaled preventative corticosteroid treatment is given (Fig. 11.4).

Preparations and dose

Salbutamol By inhaler (MDI): 100 ựg/puff; Breath-actuated inhaler: 100 ựg/ puff; Tablets:2 mg, 4 mg; Oralsolution: 2 mg/5 mL; Nebules:2.5 mg/2.5 mL, 5 mg/2.5 mL; For infusion: 5 mg/5 mL.

Inhaled MDI or breath-actuated inhaler: one to two puffs inhaled when required up to three to four times daily.

Oral 4 mg three to four times daily. Elderly and sensitive patients 2 mg initially.

Nebules 2.5-5 mg inhalation of nebulized solution, repeated according to clinical need.

IV infusion Add 5 mg in 5 mL to a 500 mL bag of sodium chloride 0.9% or glucose 5%, to give a 10 μg/mL solution. Infuse at a rate of 5 μg per minute and adjust according to response. Usual maintenance: 3-20 μg/min.

Terbutaline Inhaler: 250 μg/puff; Dry powder inhaler: 500 μg/inhalation; Inịection: 500 μg/mL.

Inhaled

■ One to two puffs of inhaler when required up to three to four times daily

■ One inhalation of dry powder inhaler when required up to four times daily.

IV 250-500 μg up to four times daily. Give i.v. over 1-2 minutes or dilute

1.5-2.5 mg in 500 mL glucose 5% and give as a continuous infusion at a rate of 1.5-5 μg/min for 8-10 hours.

Side-effects

Fine tremor, tachycardia, palpitations, headache, disturbances of sleep. Hypokalaemia with high doses (monitor plasma potassium in severe asthma).

Cautions/contraindications

Caution in untreated/poorly controlled hyperthyroidism, arrhythmias.

Long-acting selective inhaled β2-adrenoceptor stimulants (LABA)

Mechanism of action

See short-acting selective β2-adrenoceptor stimulants.

Indications

LABA are added to existing inhaled corticosteroid therapy to prevent asthma attacks (Fig. 10.4). They are not used for an acute asthma attack. They are also used in COPD without inhaled corticosteroids.

Preparations and dose

Salmeterol Metered-dose inhaler: 25 ng/puff.

Two puffs inhaled twice daily.

Accuhaler (dry powder for inhalation): 50 μg/blister.

1 blister twice daily.

Diskhaler (dry powder for inhalation): 50 μg/blister.

1 blister twice daily.

Formoterol (eformoterol) dry powder: 6 and 12 μg/inhalation.

6-24 μg inhaled twice daily.

Side-effects

As above.

Cautions/contraindications

As above.

Antimuscarinic bronchodilators
Mechanism of action

Ipatropium (short acting) and tiotropium (long acting) antagonize the actions of acetylcholine by competition at the type 3 muscarinic receptor (M3) site located on airway smooth muscle. Antagonism of acetylcholine results in airway smooth muscle relaxation and bronchodilatation.

Indications

Ipatropium is used when there is a poor response to β-agonists and steroid in the emergency treatment of acute severe asthma. Antimuscarinics are not usually used as first-line bronchodilators to treat chronic asthma. Ipatropium is used for short-term relief of symptoms in COPD and tiotropium for main-tenance treatment.

Preparations and dose

Ipatropium bromide Metered-dose inhaler: 20 and 40 μg/puff.

20-80 μg inhaled three to four times daily.

Aerocaps (dry powder for inhalation): 40 μg.

20-80 μg inhaled three to four times daily.

Nebules: 250 μg/mL.

100-500 μg inhaled up to four times daily.

Tiotropium bromide Dry powder for inhalation: 18 μg.

18 μg inhaled once daily.

Side-effects

Dry mouth, nausea, constipation, tachycardia, headache, acute angle-closure glaucoma.

Cautions/contraindications

Use with caution in patients with myasthenia gravis, narrow-angle glaucoma (protect patient's eyes from nebulized drug), benign prostatic hypertrophy, bladder neck obstruction.

Theophylline
Mechanism of action

Inhibits phosphodiesterase-mediated hydrolysis and leads to an increase in intracellular concentration of cyclic nucleotides in airway smooth muscle and inflammatory cells. This in turn leads to smooth muscle relaxation and bronchodilatation. Theophylline also has anti-inflammatory/immunomodula-tory and bronchoprotective effects that may be mediated by other molecular mechanisms.

Indications

It is used occasionally:

■ In acute exacerbations of COPD

■ In patients with chronic asthma whose asthma is not adequately control-led with inhaled corticosteroids. A single dose at night can help control nocturnal asthma and early morning wheezing.

Preparations and dose

Aminophylline is a mixture of theophylline and ethylenediamine; the ethylenediamine confers greater solubility in water.

Theophylline SR capsules: 60 mg, 125 mg, 250 mg.

250-500 mg every 12 hours.

SR tablets: 200 mg, 300 mg, 400 mg.

200 mg every 12 hours, increased after 1 week to 300 mg every 12 hours. Patients over 70 kg: 200-300 mg every 12 hours, increased after 1 week to 400 mg every 12 hours.

Aminophylline Tablets: 100 mg; SR tablets: 225 mg; Inịection: 250 mg/10 mL.

Oral 100-300 mg three to four times daily, or SR 225-450 mg twice daily.
IV with cardiac monitoring Loading dose 5 mg/kg (250-500 mg) over 20 minutes and then maintenance dose of 0.5 mg/kg/hour (add 500 mg to 250-500 mL sodium chloride 0.9% or glucose 5%). Plasma theophylline levels are measured daily to maintain concentration of 10-20 mg/L (55110 μmol/L). In patients already taking oral theophylline omit the loading dose and check plasma levels before starting the maintenance infusion.

Side-effects

Tachycardia, palpitations, nausea and other gastrointestinal disturbances, headache, CNS stimulation, insomnia, arrhythmias and convulsions especially if given rapidly by intravenous infusion. There is a narrow margin between therapeutic and toxic dose.

Cautions/contraindications

All modified-release theophylline preparations should be prescribed by brand name as the bioavailability between different brands may vary. Plasma theo-phylline concentration should be monitored in patients on oral therapy (8-12 hours after the last dose) and on intravenous treatment for longer than 24 hours (stop infusion for 15 minutes before taking the blood sample). Plasma theo-phylline concentration for optimum response 10-20 mg/L (55-110 μmol/L).

Theophylline is metabolized in the liver; there is considerable variation in plasma-theophylline concentration particularly in smokers, in patients with hepatic impairment or heart failure, or if certain drugs are taken concurrently - check National Formulary for details.

Intravenous magnesium sulphate
Mechanism of action

Relaxation of bronchial smooth muscle leading to bronchodilatation.

Indications

A single dose of i.v. magnesium sulphate is given to patients with acute severe asthma, life-threatening or near fatal asthma (Emergency Box 11.1).

Preparations and dose

Magnesium sulphate 50% (Mg2+ approx. 2 mmol/mL): 2 mL (1 g), 5 mL (2.5 g), 10 mL (5 g) ampoule.

IV (Magnesium sulphate concentration should not exceed 20%; dilute 1 part of magnesium sulphate injection 50% with at least 1.5 parts of water for injection.) 1.2-2 g i.v. infusion over 20 minutes.

Side-effects

Nausea, vomiting, flushing, hypotension, arrhythmias, drowsiness and muscle weakness.

Cautions/contraindications

Profound hypotension reported with concomitant use of calcium-channel blockers.

Corticosteroids

Mechanism of action

The precise beneficial mechanism in asthma is not known. Corticosteroids induce the synthesis of inhibitory factor kappa B (IkB), a protein that traps and thereby inactivates nuclear factor kappa B. The latter protein activates cytokine genes, and thus steroids inhibit the synthesis of most cytokines. Steroids reduce airway inflammation and hence reduce oedema and secretion of mucus into the airway. Compound preparations that contain an inhaled corticosteroid and a long-acting β2 agonist (e.g. budesonide with formoterol) are used for patients stabilized on the individual components.

Indications

Inhaled For prophylactic treatment of asthma when patients are using a β2-agonist more than once daily. In patients with COPD who have an improve-ment in lung function after a trial of oral corticosteroids.

Oral Acute severe asthma and in patients with chronic asthma when the response to other anti-asthma drugs is small.

Parenteral Acute severe asthma.

Preparations and dose

Beclometasone Metered-dose inhaler: 50, 100, 200, 250 Ịj.g/puff.

200 μg inhaled twice daily, or for more severe cases up to 800 μg daily may be used.

Breath-activated inhaler: 50, 100, 250 μg/puff.

200 μg inhaled twice daily, or for more severe cases up to 800 μg daily may be used.

Dry powder for inhalation: 100, 200, 400 μg/puff.

400 μg inhaled twice daily.

Budesonide Metered-dose inhaler: 50, 200 ng/puff.

50 μg inhaled twice daily, or for more severe cases up to 400 μg twice daily.

Turbohale® (dry powder): 100, 200, 4001!g/inhalation.

100-800 μg inhaled twice daily.

Fluticasone Metered-dose inhaler: 50, 125, 250 μg/puff.

100-200 μg inhaled twice daily, increased up to 1 mg twice daily when necessary. Higher doses initiated by a specialist.

Dry powder for inhalation: 50, 100, 250, 500 ựg/blister.

100-200 μg inhaled twice daily, increased up to 1 mg twice daily when necessary. Higher doses initiated by a specialist.

Oral See page 663.

IV See page 663.

Side-effects

The adverse effects of oral corticosteroids are listed on page 665. Inhaled corticosteroids have far fewer side-effects than oral corticosteroids but adverse effects are reported. Hoarseness and oropharyngeal candidiasis are reduced by rinsing the mouth with water after inhalation of a dose and/or by using a spacer device. Higher doses of inhaled corticosteroids have the potential to induce adrenal suppression, and patients on high doses should be given a ‘steroid card' and may also need corticosteroid cover during an operation or illness. High doses may also reduce bone mineral density and the dose should be reduced when asthma control is good. There is a small increased risk of glaucoma.

Cautions/contraindications

Caution with inhaled corticosteroids in active or quiescent tuberculosis. Para-doxical bronchospasm may be prevented (if mild) by inhalation of a β2-agonist before corticosteroid treatment.

Ebook Essentials of Kumar and Clark's Clinical Medicine, 5e

1. Ethics and communication

Ethics and communication

2. Infectious diseases

Infectious diseases

3. Gastroenterology and nutrition

Gastroenterology and nutrition

4. Liver, biliary tract and pancreatic disease

Liver, biliary tract and pancreatic disease
LIVER BIOCHEMISTRY AND LIVER FUNCTION TESTS
SYMPTOMS AND SIGNS OF LIVER DISEASE
JAUNDICE
HEPATITIS
NON - ALCOHOLIC FATTY LIVER DISEASE (NAFLD)
CIRRHOSIS
COMPLICATIONS AND EFFECTS OF CIRRHOSIS
LIVER TRANSPLANTATION
TYPES OF CHRONIC LIVER DISEASE AND CIRRHOSIS
PRIMARY SCLEROSING CHOLANGITIS
BUDD - CHIARI SYNDROME
LIVER ABSCESS
LIVER DISEASE IN PREGNANCY
LIVER TUMOURS
GALLSTONES
THE PANCREAS
CARCINOMA OF THE PANCREAS
NEUROENDOCRINE TUMOURS OF THE PANCREAS

5. Haematological disease

Haematological disease
ANAEMIA
Assessment and treatment of suspected neutropenic sepsis
HAEMOLYTIC ANAEMIA
INHERITED HAEMOLYTIC ANAEMIAS
ACQUIRED HAEMOLYTIC ANAEMIA
MYELOPROLIFERATIVE DISORDERS
THE SPLEEN
BLOOD TRANSFUSION
THE WHITE CELL
HAEMOSTASIS AND THROMBOSIS
THROMBOSIS
THERAPEUTICS

6. Malignant disease

Malignant disease
MYELOABLATIVE THERAPY AND HAEMOPOIETIC STEM CELL TRANSPLANTATION
THE LYMPHOMAS
THE PARAPROTEINAEMIAS
PALLIATIVE MEDICINE AND SYMPTOM CONTROL

7. Rheumatology

Rheumatology
COMMON INVESTIGATIONS IN MUSCULOSKELETAL DISEASE
COMMON REGIONAL MUSCULOSKELETAL PROBLEMS
BACK PAIN
OSTEOARTHRITIS
INFLAMMATORY ARTHRITIS
THE SERONEGATIVE SPONDYLOARTHROPATHIES
Clinical features, Investigations
INFECTION OF JOINTS AND BONES
AUTOIMMUNE RHEUMATIC DISEASES
SYSTEMIC INFLAMMATORY VASCULITIS
DISEASES OF BONE
THERAPEUTICS

8. Water, electrolytes and acid–base balance

WATER AND ELECTROLYTE REQUIREMENTS
BODY FLUID COMPARTMENTS
REGULATION OF BODY FLUID HOMEOSTASIS
PLASMA OSMOLALITY AND DISORDERS OF SODIUM REGULATION
DISORDERS OF POTASSIUM REGULATION
DISORDERS OF MAGNESIUM REGULATION
DISORDERS OF ACID - BASE BALANCE
THERAPEUTICS

9. Renal disease

Renal disease
INVESTIGATION OF RENAL DISEASE
GLOMERULAR DISEASES
NEPHROTIC SYNDROME
URINARY TRACT INFECTION
TUBULOINTERSTITIAL NEPHRITIS
HYPERTENSION AND THE KIDNEY
RENAL CALCULI AND NEPHROCALCINOSIS
URINARY TRACT OBSTRUCTION
ACUTE RENAL FAILURE/ACUTE KIDNEY INJURY
CHRONIC KIDNEY DISEASE
RENAL REPLACEMENT THERAPY
CYSTIC RENAL DISEASE
TUMOURS OF THE KIDNEY AND GENITOURINARY TRACT
DISEASES OF THE PROSTATE GLAND
TESTICULAR TUMOUR
URINARY INCONTINENCE

10. Cardiovascular disease

COMMON PRESENTING SYMPTOMS OF HEART DISEASE
INVESTIGATIONS IN CARDIAC DISEASE
CARDIAC ARRHYTHMIAS
HEART FAILURE
ISCHAEMIC HEART DISEASE
RHEUMATIC FEVER
VALVULAR HEART DISEASE
PULMONARY HEART DISEASE
MYOCARDIAL DISEASE
CARDIOMYOPATHY
PERICARDIAL DISEASE
SYSTEMIC HYPERTENSION
ARTERIAL AND VENOUS DISEASE
ELECTRICAL CARDIOVERSION
DRUGS FOR ARRHYTHMIAS
DRUGS FOR HEART FAILURE
DRUGS AFFECTING THE RENIN - ANGIOTENSIN SYSTEM
NITRATES, CALCIUM - CHANNEL BLOCKERS AND POTASSIUM - CHANNEL ACTIVATORS

11. Respiratory disease


Respiratory disease
TUBERCULOSISnd
DIFFUSE DISEASES OF THE LUNG PARENCHYMA
OCCUPATIONAL LUNG DISEASE
CARCINOMA OF THE LUNG
DISEASES OF THE CHEST WALL AND PLEURA
DISORDERS OF THE DIAPHRAGM

12. Intensive care medicine

Intensive care medicine

13. Drug therapy, poisoning, and alcohol misuse

Drug therapy, poisoning, and alcohol misuse

14. Endocrine disease

Endocrine disease
PITUITARY HYPERSECRETION SYNDROMES
THE THYROID AXIS
MALE REPRODUCTION AND SEX
FEMALE REPRODUCTION AND SEX
THE GLUCOCORTICOID AXIS
THE THIRST AXIS
DISORDERS OF CALCIUM METABOLISM
DISORDERS OF PHOSPHATE CONCENTRATION
ENDOCRINOLOGY OF BLOOD PRESSURE CONTROL
DISORDERS OF TEMPERATURE REGULATION
THERAPEUTICS

15. Diabetes mellitus and other disorders of metabolism

DIABETES MELLITUS
DIABETIC METABOLIC EMERGENCIES
COMPLICATIONS OF DIABETES
SPECIAL SITUATIONS
HYPOGLYCAEMIA IN THE NON - DIABETIC
DISORDERS OF LIPID METABOLISM
THE PORPHYRIAS

16. The special senses

THE EAR
THE NOSE AND NASAL CAVITY
THE THROAT
THE EYE

17. Neurology

COMMON NEUROLOGICAL SYMPTOMS
COORDINATION OF MOVEMENT
THE CRANIAL NERVES
COMMON INVESTIGATIONS IN NEUROLOGICAL DISEASE
UNCONSCIOUSNESS AND COMA
STROKE AND CEREBROVASCULAR DISEASE
EPILEPSY AND LOSS OF CONSCIOUSNESS
NERVOUS SYSTEM INFECTION AND INFLAMMATION
HYDROCEPHALUS
HEADACHE, MIGRAINE AND FACIAL PAIN
SPINAL CORD DISEASE
DEGENERATIVE NEURONAL DISEASES
DISEASES OF THE PERIPHERAL NERVES
MUSCLE DISEASES
MYOTONIAS
DELIRIUM
THERAPEUTICS

18. Dermatology

Dermatology

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