Zikra Zulfiqar
Riphah Institute of Pharmaceutical Sciences, Riphah International University, G7/4,7th Avenue, Islamabad, Pakistan.
Keywords: Blood pressure, diabetes, COPD, metabolic syndrome, pharmaceutical care

High blood pressure is regarded as “the silent killer” because it often has no warning signs or symptoms. About 60% of people who have diabetes also have high blood pressure. Diabetes mellitus and metabolic syndrome are common in patients with chronic obstructive pulmonary disease (COPD) because COPD directly increases the insulin resistance. Insulin resistance commonly occurs with obesity, dyslipidaemia and hypertension. Together these make up the ‘metabolic syndrome’, which is a major determinant of cardiovascular morbidity and mortality. Thus; the purpose of this case study is to understand the complexity of diseases that can arise problems in treatment regimes to avoid clinical errors for optimizing the therapy plans. A 58 year old male was presented in the medical ward of semi-private hospital, Rawalpindi, Pakistan with chief complaints of acute exacerbation of COPD, uncontrolled hypertension, known carotid artery stenosis and left sided chest pain. On the basis of his medical investigation, the physician prescribed him tablet Theograde(theophylline) 350mg ½ BID( twice a day), tablet Rast (rosuvastatin) 10mg 1 × HS (at night), Tablet Lasix (furosemide) 40mg 1 × O.D (once a day), tablet Minipress (prazosin) , tablet Panadol (paracetamol) 2× TDS(three times a day), tablet Famot (famotidine) 40mg 1 × O.D, Atem (Ipratropium bromide) nebulization three times a day, Ventolin (salbuatamol) nebulization four times a day, Brufen (ibuprofen) cream, steam inhalation three times a day and Injection Leflox(levofloxacin) 500mg IV × O.D. vital signs showed temperature 99°F, respiratory rate 21 breaths/ minute, Blood pressure 150/105, pulse 86/minute and PEFR 250 L/minute. Cyanosis and edema were observed. CVS= S1+S2+ loud R2. There were certain clinical and pharmaceutical inaccuracies were noted during the treatment. Thus; a rational clinical practice needed to implement health care system. Specially; the avoidable clinical errors are required to be addressed to optimize the regimens. The need of hour is a qualified pharmacist side by side with an experienced prescriber which will help to avoid the undesired health related consequences.

Article Information

Identifiers and Pagination:
First Page:124
Last Page:130
Publisher Id:JAppPharm (2012 ). 4. 124-130
Article History:
Received:November 19, 2011
Accepted:January 7, 2012
Collection year:2011
First Published:January 20, 2012


Blood pressure is the force of blood against the artery walls as it circulates through the body. High blood pressure or hypertension is the constant pumping of blood through blood vessels with excessive force. It can harden the arteries, decreasing the flow of blood and oxygen to the heart. This reduced flow can cause angina, heart failure, heart attack. [1]

Although no direct cause has been identified, there are many factors such as sedentary lifestyle, [2] smoking, stress, potassium deficiency [3] (hypokalemia), obesity [4], salt (sodium) sensitivity [5], alcohol intake [6], and vitamin D deficiency [7] that increase the risk of developing hypertension. Hypertension can be hereditary.

Hypertension is usually without any symptoms, but could give rise to early-morning headache, nosebleed, irregular heartbeats and buzzing in the ears. Other Symptoms of include tiredness, nausea, vomiting, confusion, anxiety, and chest pain and muscle tremors. [1]

Globally, nearly one billion people have high blood pressure (hypertension); of these, two-thirds are in developing countries.[1] High blood pressure is one of the common cardiovascular risk factors in Pakistan affecting one in three individuals over the age of 45 years.The National Health Survey of Pakistan (NHSP-1990-94) shows that 5.5 million men and 5.3 million women were hypertensives. [8] According to a cross-sectional survey of Gulshan-eSikanderabad, a squatter settlement situated near Ziauddin Medical University (ZMU), Karachi. Blood pressure was measured in 63 (38%) males and 135 (83%) females.Out of which, 11 (17.5%) males and 19 (14%) females were screened hypertensives. Hypertensives were older as compared to normotensives. Hypertensives were 9.7 times more likely to be diabetic as compared to normotensives in this study. [9]

Diabetes is a chronic disease that occurs either when the pancreas does not produce enough insulin or when the body cannot effectively use the insulin it produces. Insulin is a hormone that regulates blood sugar. It is classified into Type 1 diabetes (insulin dependent) whose symptoms include: excessive excretion of urine (polyuria), thirst, constant hunger, weight loss, and fatigue and type 2 diabetes (non-insulin-dependent) and is largely the result of excess body weight and physical inactivity. Symptoms may be similar to those of Type 1 diabetes, but are often less marked. [10]

Currently DM affects 240 million people worldwide and this number is projected to increase substantially to 380 million by 2025, with 80% of burden in low and middle income countries

[11]. Pakistan currently ranks at 7th position in the list of countries with major burden of DM. Pakistan belongs to high prevalence area, currently having 6.9 million affected people, with projected estimates expected to double by 2025 and affect 11.5 million people[12].

Chronic obstructive pulmonary disease (COPD) is a lung ailment that is characterized by a persistent blockage of airflow from the lungs- it is more than a “smoker’s cough”. It is not one single disease but an umbrella term used to describe chronic lung diseases that cause limitations in lung airflow. [13]The primary cause of chronic obstructive pulmonary disease (COPD) is tobacco smoke (80-90%) [14][15].Other factors include Occupational dusts and chemicals, [16] [17] [18] air pollution, [19] [20], and frequent lower respiratory infections. The most common symptoms of COPD are breathlessness, abnormal sputum, wheezing, chest tightness, tiredness and a chronic cough. [13]

Diabetes mellitus and metabolic syndrome are common in patients with chronic obstructive pulmonary disease (COPD). COPD may directly increase insulin resistance through effects of chronic inflammation on insulin receptor signalling and through chronic hypoxia and systemic corticosteroid treatment. COPD patients with diabetes have increased risk of pulmonary infection, structural lung damage, hospitalisation and death. Insulin resistance commonly occurs with obesity, dyslipidaemia and hypertension. (Makarevich AE, et al.,2007).An estimated 64 million people have COPD worldwide in 2004.More than 3 million people died of COPD in 2005.Almost 90% of COPD deaths occur in low- and middle-income countries. According to new estimates for 2030, COPD is predicted to become the third leading cause of death. [13]



A 58 year old male was presented in the medical ward of semi-private hospital, Rawalpindi, Pakistan with chief complaints of acute exacerbation of COPD, uncontrolled hypertension, known carotid artery stenosis and left sided chest pain. His physical examination showed temperature 99°F, respiratory rate 21 breaths/ minute, Blood pressure 150/105, pulse 86/minute and PEFR 250 L/minute.  Cyanosis and edema were observed. CVS= S1+S2+ loud R2. Abdomen= soft, tendor left hypochondrium (LHC). Chest bilateral crackles and bronchi observed.  Sputum was decreased in quantity and whitish in color. He was belonging to a middle class family. His diagnosis showed that he was a patient of diabetes mellitus, hypertension, COPD and IHD.

Patient history showed that he was an Ex-smoker and quit smoking 1 year back (smoking period=30-45 years). His history of present illness (HOPI) showed that the patient was alright 1 year back when he starts developing shortness of breath. It was moderate in intensity and was mildly relieved on taking inhaler. There was also associated productive cough. No history of fever. No history of TB. No orthopenia. Patient also complained of left sided chest pain, raditory to left arm. Pain was aggravated in exertion and relieved on rest. He was taking sublingual Angisid. He was also taking medicines for COPD, hypertension and IHD for one year. Patient was adviced Thallium seen for IHD.

On the basis of his medical investigation (primary diagnosis), the physician prescribed him tablet Theograde(theophylline) 350mg ½  BID( twice a day), tablet Rast (rosuvastatin) 10mg 1 × HS (at night), Tablet Lasix (furosemide) 40mg 1 × O.D (once a day), tablet Minipress (prazosin) , tablet Panadol (paracetamol) 2× TDS(three times a day), tablet Famot (famotidine) 40mg 1 × O.D, Atem (Ipratropium bromide) nebulization three times a day, Ventolin (salbuatamol) nebulization four times a day, Brufen (ibuprfen) cream, steam inhalation three times a day and Injection Leflox(levofloxacin) 500mg IV × O.D. on 2nd day of therapy , patient was complaint of left sided chest pain.his vital signs showed temperature 99°F, blood pressure 160/100, pulse 85/min and shortness of breath.the physician continued the treatment.  On 3rd day, patient complained of body aches and shortness of breath.the Blood pressure was 140/100 with left sided chest pain, pulse 82/min, temperature 98°F and respiratory rate 20breath/min with persistant bronchi bilateral. On 5th day of therapy, shortness of breath was improved and one chest physiotherapy session was done.  Vital signs showed temperature 98°F, blood pressure 150/100, pulse 86/min and respiratory rate 22 breath/min with Persistant bronchi bilateral.thus; the treatment continued.



The  BNF  (British  National  Formulary)  is  one  the  standard  books  used  to  design  the  treatment plans. The dose regimen of Tablet Rast, Tablet Famot, tablet Lasix and tablet Panadol prescribed according to the specifications but; the dose of tablet Theograde was noticed lower than the recommended dose. The doses of Ventolin nebulization, Atem nebulization and tablet Minipress were not mentioned in the treatment regimen.

Cui H et al, (2011) reported the highest prevalence of hypertension (40.3%) among 4960 COPD patients, followed by diabetes/impaired glucose tolerance (18.8%) [21]

The concomitant administration of theophylline, levofloxacin and salbutamol causes hypokalemia that may prone to cause myalgias (body aches) and ventricular fibrillation and thus requires intensive electrolytes monitoring but; he was also prescribed furosemide that also causes hypokalemia and also no potassium supplements were prescribed.  Along with hypokalemia, furosemide also causes hypocalcaemia, hypomagnesaemia, hyponatraemia, and hyperglycemia. [22]

Besides this, concomitant administration of levofloxacin and theophylline increases the risk of convulsions because levofloxacin inhibits the metabolism of theophylline by inhibiting CYP2D6 enzyme thus increases concentration of theophylline. Also levofloxacin injection must be given over atleast 60minutes for 500mg to avoid transient hypotension and counsel the patient to avoid a dairy product which was not followed. [22]

The patient history showed that he is also diabetic but no anti-diabetic drug was prescribed. Moreover; salbutamol increases blood glucose level and should be used with caution in diabetes and hypertension and requires regular monitoring of blood glucose level but; the frequency of nebulization was QID. [22]

Also furosemide and prazosin are prone to cause increase hypotensive effect especially 1st dose hypotension so there concomitant use should be avoided. In addition, drugs like theophylline, salbutamol, furosemide and levofloxacin also cause hypotension and should be monitored (blood pressure) time to time.

This study is substantiated by Kushner, Peckman and Snyder (2001) who reported two cases of seizures following administration of levofloxacin. They reported that after five doses, patient experienced seizures. [23] While Moorthy, Raghavendra and Venkatarathnamma (2008) reported

Levofloxacin-induced acute psychosis in 50-year-old man, with uncontrolled diabetes mellitus and hypertension on 3rd day of therapy following administration of oral levofloxacin (500 mg/day) [24].

This study is further substantiated by Whyte, Reid, Addis, Whitesmith, Reid (1988) who reported salbutamol induced hypokalemia due to stimulation of  the beta-2 adrenergic receptor linked to a membrane bound Na+/K+ ATPase pump which transfers potassium into cell(Struthers & Reid, 1984) in combination with theophylline in a single-blind, randomized and placebo controlled clinical trials. They reported that theophylline significantly increases salbutamol induced hypokalemia and tachycardia while in some individuals profound hypokalemia (< 2.5 mmol 1-1) was observed with relatively low doses of salbutamol and theophylline. [25] While Lai, Legge, Friend (1991) reported hypokalemia and tachycardia in 9 patients with severe COPD due to air-driven nebulised high-dose salbutamol combined with oral theophylline.[26] In addition, Zuccalà, G (2000) reported that loop diuretics are one of the factors that cause hypokalemia in patients along with age and diabetes in a multicentre survey. [27]




The rational therapy of multiple diseases is a serious issue and need unusual intention of health professionals. Specially; the avoidable clinical errors are needed to be addressed for optimizing the therapy plans. There is also a need of degree holder competent pharmacists in hospitals in Pakistan who can help physician in selecting the rational therapy. The need of hour is a qualified pharmacist side by side with an experienced prescriber. Therefore; the comprehensive clinical examination and pharmaceutical care will help to avoid the undesired health related consequences.



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Welcome to the research group of Prof. Dr. Cornelia M. Keck in Marburg. Cornelia M. Keck is a pharmacist and obtained her PhD in 2006 from the Freie Universität (FU) in Berlin. In 2009 she was appointed as Adjunct Professor for Pharmaceutical and Nutritional Nanotechnology at the University Putra Malaysia (UPM) and in 2011 she obtained her Venia legendi (Habilitation) at the Freie Universität Berlin and was appointed as a Professor for Pharmacology and Pharmaceutics at the University of Applied Sciences Kaiserslautern. Since 2016 she is Professor of Pharmaceutics and Biopharmaceutics at the Philipps-Universität Marburg. Her field of research is the development and characterization of innovative nanocarriers for improved delivery of poorly soluble actives for healthcare and cosmetics. Prof. Keck is executive board member of the German Association of Nanotechnology (Deutscher Verband Nanotechnologie), Vize-chairman of the unit „Dermocosmetics“ at the German Society of Dermopharmacy, active member in many pharmaceutical societies and member of the BfR Committee for Cosmetics at the Federal Institute for Risk Assessment (BfR).

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