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
Although no direct cause has been
identified, there are many factors such as sedentary lifestyle,  smoking, stress,
potassium deficiency  (hypokalemia), obesity , salt (sodium) sensitivity , alcohol
intake , and vitamin D deficiency  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. 
Globally, nearly one billion people have
high blood pressure (hypertension); of these, two-thirds are in developing countries. 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. 
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. 
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. 
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
. 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.
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. The
primary cause of chronic obstructive pulmonary disease (COPD) is tobacco smoke
factors include Occupational dusts and chemicals,    air pollution,  ,
and frequent lower respiratory infections. The most common symptoms of COPD are
breathlessness, abnormal sputum, wheezing, chest tightness, tiredness and a chronic
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
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.
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%) 
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. 
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. 
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. 
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.
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.  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)
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.  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. 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. 
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
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