This case presentation discusses a 57-year-old male patient admitted to the hospital with dyspnea and a diabetic foot ulcer. The patient was diagnosed with severe calcific aortic stenosis along with comorbidities of hypertension, diabetes, and pleural effusion. Laboratory tests confirmed Klebsiella pneumonia as the cause of the foot ulcer. The patient is being treated with medications including amlodipine, pantoprazole, metronidazole, levofloxacin, furosemide, insulin, and N-acetylcysteine to manage his conditions while addressing any drug interactions and monitoring his health indicators.

1. A CASE PRESENTATION ON SEVERE
CALCIFIC AORTIC STENOSIS
PRESENTED BY
M.ARUMUGAVIGNESH
REG.NO: 381610805
PHARM D FIFTH YEAR
ARULMIGU KALASALINGAM COLLEGE OF
PHARMACY

2. SUBJECTIVE EVIDENCE
• Name: Mr. Zxy
• Age: 57 years
• Gender: Male
• I.P. No: 3796
• Ward: Male medical ward
• Date of admission: 25/02/2020
• Patient chief complaints: dyspnoea for four days
and right leg diabetic foot ulcer for the past one
week
• Final diagnosis: Calcific aortic stenosis

3. • The patient also has the co morbid conditions like
systemic hypertension, type 2 diabetic mellitus and
pleural effusion. The condition of severe calcified
aortic stenosis is diagnosed by Coronary Artery graft
coronary Angiography.
• Lab report of swab culture confirms that Klebseilla
pneumonia is the causative organism for right leg
diabetic foot ulcer.
• The general physical examination by physician reveals
that the lungs show bilateral pleural effusion.

4. OBJECTIVE EVIDENCE
SYSTEMIC EXAMINATION :
• CVS : S1S2 NORMAL HEART SOUND HEARD
• RS : Normal vesicular breath sound
• CNS : Non focal neurological deficit
• Abdomen : P/A soft

5. CLINICAL LAB PROFILE
CLINICAL PARAMETER OBSERVED VALUE NORMAL RANGE
Pulse rate 90/minute 60-100/minute
SPO2 98% 95-100%
Blood pressure 140/100mmHg 120/80mmHg
Haemoglobin 10.8g% 14-19g%
Fasting blood glucose 200mg/dL 70-110mg/dL
Red blood cells 3.84million/cu.mm 4.3-5.9million/cu.mm
Urea 132mg/dL 5-20mg/dL
Creatinine 1.9mg/dL 0.2-1.2mg/dL
Sodium 139mEq/L 135-145mEq/L
Potassium 4.9mEq/L 3.5-5mEq/L
Chlorine 108mEq/L 95-105mEq/L

6. Total cholesterol 180mg/dL Below 200mg/dL
Triglycerides 119mg/dL Below 150mg/dL
HDL 37mg/dL Above 40mg/dL
LDL 119mg/dL 70-160mg/dL
VLDL 24mg/dL 2-30mg/dL

7. ASSESSMENT
Calcific aortic stenosis (AS)
 It is more prevalent heart valve disorder among urban
populations. It is characterized by an obstinate fibro-calcific
remodeling and thickening of the aortic valve leaflets that, over
years, evolve to cause severe obstruction to cardiac blood flow.
 In developed countries, AS is the third-most frequent cardiovascular
disease after coronary artery disease and systemic arterial
hypertension, with a prevalence of 0.4% in the general population
and 1.7% in the population >65 years old. Congenital abnormality
(bicuspid valve) and older age are prominent risk factors for calcific
AS.

8.  Recently, multiple researchers have identified the insulin
resistance/metabolic syndrome as a major cardiovascular
risk factor. The metabolic syndrome (MetS) is clinically
manifested by the presence of a combination of features,
including central adiposity, dyslipidemia, hypertension,and
impaired fasting glucose.
 Metabolic syndrome and an elevated plasma level of
lipoprotein(a) have also been associated with increased risk
of calcific AS. The pathophysiology of calcific AS is
complex and involves genetic factors, lipoprotein deposition
and oxidation, chronic inflammation, osteoblastic transition
of cardiac valve interstitial cells and active leaflet
calcification.

9.  The promising therapeutic targets for reducing the
progression of AS include lipoprotein(a), the renin–
angiotensin system, receptor activator of NF-κB
ligand (RANKL; also known as TNFSF11) and
ectonucleotidases.
 As of now, aortic valve replacement (AVR) remains
the only effective treatment for severe AS.

10. CURRENT THERAPY
DRUG DOSE ROUTE FREQUENCY
Tablet
Amlodipine
10mg Oral 1-0-0
Tablet
Pantoprazole
40mg Oral 1-0-0
Inj.
Metronidazol
e
500mg I.V 1-1-1
Inj.
Levofloxacin
750mg I.V 1-0-0
Inj.
Furosemide
40mg I.V 1-1-0
Inj. Human
Insulin
10-10-8 units Sub
cutaneous
1-1-1
Tablet
N.Acetylcystei
ne
600mg Oral 1-0-1

11. DRUG INFORMATION
1. Amlodipine
Class : calcium channel blocker
Indication : Hypertension
Contraindication : aortic valve stenosis, cardiogenic shock ,
hypersensitivity
MOA : Reduces the tone of myometrium & opposes contraction
Side effects : cough , dyspnea, MI ,aplastic anaemia

12. 2. Pantoprazole
Class: Proton pump inhibitor
Indication: Peptic ulcer prophylaxis
Contraindication: interstitial nephritis, lupus erythematosus
M.O.A: It inhibits the final step in gastric acid production. In the
gastric parietal cell of the stomach, pantoprazole covalently
binds to the H+/K+ ATP pump to inhibit gastric acid and basal
acid secretion.
Side effects: Itching, constipation, facial puffiness

13. 3. Furosemide
Class : loop diuretics
Indication : Pleural effusion, hypertension, kidney injury
Contraindication : anuria, hypersensitivity
MOA : Blocking the absorption of Na & Cl in kidney tubules
- increases urine output
Side effects : pancreatitis , thrombocytopenia

14. 4. Metronidazole
Class: Anti-parasitic, antibiotic
Indication: Diabetic foot ulcer
Contraindication: seizures, alcoholism, meningitis
M.O.A: Metronidazole diffuses into the organism, inhibits protein
synthesis by interacting with DNA and causing a loss of helical
DNA structure and strand breakage. Therefore, it causes cell death
in susceptible organisms.
Side effects: heartburn, constipation, metallic taste, dizziness

15. 5. Levofloxacin
Class: Fluroquinolone antibiotic
Indication: Diabetic foot ulcer
Contraindication: seizures, low blood sugar, low potassium
M.O.A: The mechanism of action of levofloxacin and other
fluoroquinolone antimicrobials involves inhibition of bacterial
topoisomerase IV and DNA gyrase (both of which are type II
topoisomerases), enzymes required for DNA replication, transcription,
repair and recombination.
Side effects: headache, hunger, sweating, irritability

16. 6. Insulin
Class: Hormonal preparation, antihyperglycemic
Indication: Type- II diabetes mellitus
Contraindication: Hypoglycemia, hypokalemia
M.O.A: Insulin initiates its action by binding to a glycoprotein
receptor on the surface of the cell. This receptor consists of an
alpha-subunit, which binds the hormone, and a beta-subunit, which
is an insulin-stimulated, tyrosine-specific protein kinase.
Side effects: tachycardia, blurred vision, increased appetite

17. 7. N-acetylcysteine
Class: Prostaglandin analogue
Indication: kidney injury
Contraindications: asthma, GI bleeding, heart failure
M.O.A: acetylcysteine is a vasodilator as well as an antioxidant, it
works in two distinct ways, by preventing reduction in renal blood
flow and also prevents oxidative damage
Side effects: bronchospasm, drowsiness, fever, nausea

18. STANDARD TREATMENT
• Aortic valve replacement surgery is the best treatment for
calcific aortic stenosis.
• Insulin is the correct drug of choice for diabetes mellitus.
• Levofloxacin is the correct drug of choice for diabetic foot
ulcer.

19. PLAN
PHARMACIST INTERVENTION
 Aortic stenosis and diabetes mellitus are both ongoing diseases
which, if not treated, result in significant morbidity and
mortality. There is evidence that the prevalence of type 2
diabetes is considerably increased in patients with aortic
stenosis.
 The patients having aortic stenosis along with diabetes have
high rates of progression from mild to severe aortic stenosis.
There are good evidences supporting the hypothesis that aortic
stenosis and diabetes mellitus are correlated with diabetes
mellitus being inimical towards the quality of life and survival
of patients.

20.  Thus, a complete understanding of the pathogenesis of both of
these diseases and the correspondence between them helps in
framing appropriate preventive and therapeutic approaches.
 Systemic hypertension is nowadays a frequent detection in
patients with AS.
 An increase in blood pressure may not only disguise the
investigative findings of AS, but can also modify the
haemodynamic parameters used to assess the severity of the
disease. These facts are needed to be considered for an
adequate management of patients with AS.

21.  Lab report of swab culture reveals that the diabetic foot ulcer
is infected with Klebseilla pneumonia. Klebseilla shows high
sensitivity towards Levofloxacin ( 90.8% ) and it was
administered intravenously to the patient.
 Monotherapy of intravenous antibiotic is efficient for treating
this foot ulcer condition. Combination is needed only when the
organism becomes multi drug resistant.
DRUG – DRUG INTERACTIONS
 So Metronidazole is not conducive for this patient. In addition,
concomitant administration of Levofloxacin and
Metronidazole poses severe drug – drug interaction.
Concomitant administration of these two drugs increases the
risk of QT interval prolongation and arrhythmias.

22.  Insulin is given subcutaneously to treat uncontrolled type 2
diabetes mellitus. However concomitant use of Insulin and
Levofloxacin also poses severe risk of Hypo or
Hyperglycemia. Close monitoring of blood glucose level and
dose adjustment of Insulin is necessary. Concomitant use of
Insulin and Furosemide also increases the risk of
hyperglycemia.
CONTRAINDICATION
 Amlodipine is contraindicated for aortic stenosis condition.
Previously, antihypertensive treatment in severe aortic
stenosis was considered a relative contraindication. However,
recent studies have shown that antihypertensive treatment
may be safe and even effective in terms of reducing the
development of left ventricular pressure overload and even
subside the progression of valvular aortic stenosis.

23.  Renin-angiotensin system (RAS) are upregulated in AS and have been
shown to be involved in valve calcification and progression in both
experimental models and in human trials. As such, theoretically, RAS
inhibition would have benefit in retarding the progression of valvular
stenosis as well as have benefit in left ventricle remodeling. Recent clinical
studies are indeed showing that use of RAS inhibition may be beneficial in
patients with Aortic Stenosis. Hence instead of Amlodipine, ACE inhibitor
is beneficial to treat hypertension in this patient.
 The same Klebseilla pneumonia may be the cause of pleural effusion in this
patient. This infection may be hospital acquired. Furosemide can improve
pleural effusion condition in this patient. Levofloxacin is also helpful in
eradicating Klebsiella pneumonia.
 Furosemide as a diuretic also aids in the mitigation of kidney injury related
oedema and hypertension.

24.  Urea and Creatinine levels are also high in this patient. It
shows acute kidney injury. Hypertension and Diabetes mellitus
are the predictive risk factors for kidney injury in this patient.
 N-Acetylcysteine administered orally to this patient is a
potential therapy to treat iatrogenic acute kidney injury or slow
the progression of chronic kidney disease.

25.  This case of severe calcific aortic stenosis along with various
comorbid conditions highlights the rational use of antibiotic
for Klebseilla pneumonia infection and also highlights the
need for necessary precautions to prevent hospital acquired
infections. It also intensifies the need to establish therapeutic
guidelines for treating hypertension in patients with calcific
aortic stenosis.
 There is a need for a more reliable and sensitive diagnosis of
anemia in these kinds of government hospital settings.

26.  This case presentation also upholds the need to monitor drug-
drug interactions. The topic of drug– drug interactions has now
received much attention from the regulatory, scientific, and
health care settings worldwide.
 Pharmacists must play a key role in monitoring drug
interactions and in notifying the physician and patient about
potential problems.

27. MONITORING
For disease:
 Blood pressure
 Electrolytes
 Blood glucose level, HbA1c.
For drugs:
• Blood glucose level should be monitored while giving insulin.
• Liver functions should be monitored while giving amlodipine.
• Serum electrolytes should be monitored while giving
furosemide.

28. PATIENT COUNSELLING
• Salt restriction in diet is necessary due to hypertension.
• Avoid foods rich in fat and cholesterol.
• Restrict the intake of protien and sweets due to the condition
of kidney injury and diabetes respectively.
• Take bed rest.
• Avoid the habit of smoking and alcoholism.

29. PUBLICATION

30. THANK YOU