CASE 2: HYPERTENSION (NEWLY DIAGNOSED) Problem 1: Hypertension (Newly Diagnosed) Basis for Diagnosis:

Blood pressure of 146/94 mmHg

Repeat BP 144/92

Family history of hypertension Case Learning Objectives:

1. Classify Blood Pressure Levels Vital signs:

BP -146/94 mmHg Repeat BP 144/92 mmHg

BP CLASSIFICATION SBP mmHg DBP mmHg

Normal < 120 160 120

Classification: Stage 1 hypertension Target BP goals:

2. Identify the goals of therapy for HTN

To obtain target BP goals of

MEDICATIONS USED IN THE MANAGEMENT OF HYPERTENSION

Drug Class Efficacy Safety Suitability Cost

ACE inhibitors +++ +++ +++ + ARBs +++ +++ ++ ++ CCBs ++ + ++ +++

Thiazide Diuretics + + + ++

DRUG OF CHOICE: ACE Inhibitors

The drug of choice is ACE inhibitors because it inhibits conversion of Angiotensin I to Angiotensin II, which is a potent vasoconstrictor. It will result to decrease in aldosterone level, which is responsible to sodium retention and potassium excretion leading to decrease blood volume going back to the heart (decreases preload). It decreases systemic vascular resistance without increasing the heart rate. It is appropriate in preventing the progression of complications of hypertension by lowering the preload and preventing cardiac remodeling caused by angiotensin II. It is effective in the treatment of hypertension, decrease mortality and morbidity in heart failure and left ventricular dysfunction and myocardial infarction. ACE inhibitors causes cough, hyperkalemia, and angioneurotic edema.

NOTES High serum sodium promotes water reabsorption and increases the sensitivity of

blood vessels for vasoconstriction. This event is prevented by ACEI as it inhibits the conversion of A1 A2, thereby

preventing the production of aldosterone. Why NOT THIAZIDE? This drug causes Hyperuricemia, that eventually leads to

Gout (px had gout in 2010). It also causes Dyslipidemia (Px has hx of dyslipidemia in 2006).

Why NOT CCB? This causes CHF and heart block, bradycardia, and in some cases palpitations. Verapamil causes constipation (px is presently constipated despite increase in fiber intake)

Why NOT ARBs? See table below Therefore ACEIs are more effective for post MI pxs and pxs with high risk for

coronary artery disease

ACE INHIBITORS

Drug Efficacy Safety Suitability Cost

Captopril +++ +++ +++ +

Enalapril +++ +++ +++ ++

Lisinopril ++++ +++ ++++ +++

DRUG OF CHOICE: LISINOPRIL

Mechanism of action: Prevents the conversion of angiotensin I to angiotensin II (a potent vasoconstrictor) through competitive inhibition of angiotensin-converting enzyme resulting in decreased plasma angiotensin II concentrations; blood pressure may be reduced in part through decreased vasoconstriction, increased renin activity, and decreased aldosterone secretion

Kinetics: Absorption

Bioavailability: 25% Onset: 1 hr (initial); 6 hr (peak) Duration: 24 hr Peak plasma time: 6-8 hr Therapeutic plasma concentration: 1-5 ng/mL

Distribution Protein bound: 25% Vd: 124 L

Metabolism Does not undergo metabolism

Elimination Half-life: 12 hr Renal clearance: 106 mL/min Total body clearance: 250 mL/min Excretion: Excreted unchanged entirely in the urine Dialysis: Removed by hemodialysis

Adverse effects: Most common AE is dizziness which accounts for about 5-12% of cases, cough (4-

9%), Headache (4-6%), Hyperkalemia (2-5%), Diarrhea (3-4%), Hypotension (1-4%), Chest pain (3%), Fatigue (3%), Nausea/vomiting (2%), Kidney disease, of AMI patients (2%), Rash (1-2%)

Drug-drug interactions:

Some products that may interact with this drug include: aliskiren, lithium, drugs that may increase the level of potassium in the blood (such as ARBs including losartan/valsartan, birth control pills containing drospirenone).

Drug-food interactions: It is recommended that if you are taking lisinopril you should be advised to avoid moderately high or high potassium dietary intake. This can cause high levels of potassium in your blood. Do not use salt substitutes or potassium supplements while taking lisinopril, unless your doctor has told you to. Avoid drinking alcoholic beverages when taking this medication.

Precautions: This drug may make you dizzy. Do not drive, use machinery, or do any

activity that requires alertness until you are sure you can perform such activities safely. Limit alcoholic beverages. To reduce the risk of dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.

NOTES: Why Lisinopril It has longer half- life as compared to others ( 12 hrs) Can be taken Once/ day promotes compliance Renal and cardio protective properties Cheapest @ 6- 12 phppromotes compliance

Prescription

Remarks: Initial Therapy In Adults The recommended initial dose is 10 mg once a day. Dosage should be adjusted according to blood pressure response. The usual dosage range is 20 to 40 mg per day administered in a single daily dose. Doses up to 80 mg have been used but do not appear to give greater effect. MANAGEMENT

The treatment of hypertension requires a multimodal approach that encompasses the use of nonpharmacologic treatments such as weight reduction through appropriate physical activity and dietary habits, dietary sodium reduction, and moderation of alcohol consumption as well as individualized pharmacotherapy.

4. Monitoring, education and follow up plan:

State the goal blood pressure to the patient and ask if he agrees with it.

Advice patient to take his blood pressure daily so as to monitor presence of hypotension.

Explain to the patient that he may experience cough. But intractable, dry cough may warrant discontinuation.

Inform the patient regarding the other side effects of the drug, which includes taste disturbances and allergic skin rashes.

FEU-NRMF Medical Center Chester Joseph S. Alarilla, M.D.

Internal Medicine

Name: Jose Vasquez Sex: Male Age: 57 years old Date: 11/13/14

Rx Lisinopril 10mg tablet #7

(Zestril) Sig. Take one 10mg oral tablet once a day for 1 week

Follow up check- up after 1 week

Chester Joseph S. Alarilla, MD

Lic No. 123456 Ptr No. 654321

Inform the patient to avoid taking NSAIDs because it can impair the hypotensive effects of the ACEI.

Encourage lifestyle changes.

Explain to the patient the importance of compliance with his medications.

References: Helms, R. A., Quan, D. J., Herfindal, E. T., & Gourley, D. R. (2006). Textbook of Therapeutics: Drug

& Disease Management (8th Ed. ed.). Philadelphia: Lippincott Williams.

Katzung, B. G., Masters, S. B., & Trevor, A. J. (2012). Basic and Clinical Pharmacology (12th Ed.

ed.). McGraw-Hill.

Problem 2: Dyslipidemia

BASIS FOR DIAGNOSIS

History of hyperlipidemia for 8 years

Smoked 41 pack years

Family history of dyslipidemia

BMI:27.1 (Overweight)

Pertinent Labs:

Total Cholesterol: 240 mg/dl (high)

Triglycerides 180 mg/dl (borderline high)

LDL 167 mg/dl (high)

HDL 38 mg/dl (low)

Basis of Treatment

Patients LDL level

Risk factor status

Present of Known CHD or CHD risk equivalents

Framingham Risk Projection

Treatment Objectives

To lower the levels of cholesterol, triglyceride, and lipids within normal levels

To reduce the risk of developing coronary heart disease

Pharmacologic Therapy

Atorvastatin

Indication: reduction of total and LDL cholesterol, apolipoprotein B and triglycerides and

increase HDL cholesterol

Dosage: 10-80 mg once daily (start with 10 mg/day)

Administration: with or without food

Contraindication: active liver disease or elevated serum transaminases > 3x upper limit;

pregnancy and lactation

Special Precautions: monitor for creatine phosphokinase and transaminase elevations; avoid

alcohol consumption;

Adverse Reactions: gastrointestinal s/s, myalgia; hypo/hyperglycemia, anorexia;

thrombocytopenia, weight gain, dizziness, skin manifestations, etc.

Drug Interactions: risk of myopathy if taken with cyclosporin, fibric acid derivatives, niacin,

erythromycin; conc. w/ erythromycin, diltiazem HCl and grapefruit juice

Treatment

Dietary ( intake of sat fat and cholesterol, use plant sterols and fiber)

Weight Reduction

physical activity

Treat secondary causes of hyperlipidemia (hypothyroidism, diabetes) and measure impact of

treatment on lipid profile before starting hyperlipidemia treatment

Problem 3: Gout Basis for diagnosis:

Diagnosed with gout since 2010 Drinks alcohol 2-4 times a week Increased serum uric acid - 9mg/dL (NV: 3.5 mg 7.2 mg/dL)

Goals of therapy:

Terminate the pain and inflammation associated with an acute gout attack Limit and treat acute attack recurrences Reduce serum uric acid concentrations

Therapeutic plan Patient was taking Allopurinol 200 mg prior to losing insurance coverage.

Allopurinol

Allopurinol is currently the most commonly used agent for the long-term control of chronic gout.

Drug of choice in overproducers of uric acid and is effective in patients who are underexcretors as well.

Mechanism of Action It works by inhibiting xanthine oxidase, the enzyme that catalyzes the conversion of xanthine to uric acid and hypoxanthine to xanthine; therefore, it decreases the concentrations of both serum and urinary uric acid

Pharmacokinetics

Approximately 80% of the drug is absorbed after oral administration

It has a terminal serum half-life of 12 hours

It is metabolized by xanthine oxidase, but the resulting compound, alloxanthine, retains the capacity to inhibit xanthine oxidase

Has a long enough duration of action so its given only once a day

Pharmacodynamics Dietary purines are not an important source of uric acid. Quantitatively important amounts of purine are formed from amino acids, formate, and carbon dioxide in the body. Those purine ribonucleotides not incorporated into nucleic acids and derived from nucleic acid degradation are converted to xanthine or hypoxanthine and oxidized to uric acid. Allopurinol inhibits this last step, resulting in a fall in the plasma urate level and a decrease in the overall urate burden. The more soluble xanthine and hypoxanthine are increased.

Indications

Allopurinol is generally recommended for patients with tophaceous gout

Patients with increased uric acid production or nephrolithiasis

Patients who cannot tolerate or do not respond to uricosuric agents

Patients with renal insufficiency

Patients older than 60 years of age

Also used for the prevention of acute urate nephropathy in patients receiving cytotoxic therapy for malignancies

It reduces the chances of the patient developing secondary uric acid nephropathy from myeloproliferative neoplastic diseases

Adverse Effects

GI intolerance including nausea, vomiting, and diarrhea

Peripheral neuritis

Necrotizing vasculitis

Bone marrow suppression

Aplastic anemia (rare)

Cataracts (rare)

Hepatic toxicity and interstitial nephritis have been reported.

Allergic skin reaction, pruritic maculopapular lesions occurs in 3% of patients

Isolated cases of exfoliative dermatitis have been reported.

Drug-Drug Interaction

When chemotherapeutic purines (Azathioprine) are given concomitantly with allopurinol, their dosage must be reduced by about 75%.

Allopurinol may also increase the effect of cyclophosphamide.

Allopurinol inhibits the metabolism of probenecid and oral anticoagulants and may increase hepatic iron concentration.

Dosage

Allopurinol is generally dosed orally at 100 to 300 mg per day

Serum uric acid levels begin to decline within 1 to 2 days after starting allopurinol therapy, it reaches a nadir within 7 to 14 days

Along with this reduction in serum urate there is a decrease in urinary uric acid excretion.

The average dosage for an adult with normal renal function is 300 mg OD, which results in a normalization of uric acid levels in approximately 85% of patients

For some patients, 100 to 200 mg per day may be adequate

With impaired renal function, allopurinol and oxypurinol may accumulate, and the daily dose should be reduced

Allopurinol therapy should be started at 50 to 100 mg per day and slowly increased over 3 to 4 weeks until the recommended target dose is reached to reduce the risk of precipitating an acute gouty attack

REFERENCES:

Katzung, B. G., Masters, S. B., & Trevor, A. J. (2012). Basic and Clinical Pharmacology (12th Ed.

ed.). McGraw-Hill.

Helms, R. A., Quan, D. J., Herfindal, E. T., & Gourley, D. R. (2006). Textbook of Therapeutics: Drug

& Disease Management (8th Ed. ed.). Philadelphia: Lippincott Williams.

Problem 4: Seasonal Allergic Rhinitis since childhood Goals of therapy:

Explain to the patient to take the medication only when needed.

Continue to take Loratadine 10mg PRN

LORATADINE (Second Generation H1 Receptor Antagonist), these are mainly used for treatment of allergic rhinitis and chronic urticarial. It acts as a selective inverse agonist of peripheral histamine H1-receptors. Histamine is responsible for many features of allergic reactions.

It is given orally, is well absorbed from the gastrointestinal tract, and has rapid first-pass hepatic metabolism; it is metabolized by isoenzymes of the cytochrome P450 system, including CYP3A4, CYP2D6, and, to a lesser extent, several others. Loratadine is almost totally (9799%) bound to plasma proteins. Its metabolite desloratadine, which is largely responsible for the antihistaminergic effects, binds to plasma proteins by 7376%.

Loratadine's peak effect occurs after one to two hours, and its biological half-life is on

average 8 hours (range 3 to 20 hours) with desloratadine's half-life being 27 hours (range 9 to 92 hours), accounting for its long-lasting effect. About 40% is excreted as conjugated metabolites

into the urine, and a similar amount is excreted into the feces. Traces of unmetabolised loratadine can be found in the urine.