Case 9 HYPERTENSION

Presenters
Arisepogu, Ritesh Babcock, Michelle Ines, Lafayette Rose

Problem:

Hypertension

I. Basis
PMH: Hypertension for 20 years Rx: Lisinopril (anti-HPN: ACEI) Furosemide (anti-HPN: Loop diuretic) PE BP: 145/90 stage I HPN HEENT: Mild AV nicking Echo: mild Left Ventricular Hypertrophy

II. Treatment Objectives

Lower blood pressure to at least 140/90. Improve quality of life Prevention of short-term and long-term complications. Prevention of catastrophic events in advanced disease. Provide education to ensure appropriate management.

III. Non-Pharmacological and Pharmacological therapy

Non-Pharmacological therapy
Weight reduction to normal. DASH eating plan rich in fruits, vegetables, and low-fat dairy products with a reduced content of saturated fat and total fat. Reduce dietary sodium intake. Limit alcohol consumption to no more than two drinks per day for men and one drink per day for women. Engage in regular aerobic physical activity such as brisk walking.

III. Non-Pharmacological and Pharmacological therapy

Pharmacological therapy

IV. Table of drug classes/drugs

Anti-Hypertensive Drugs
Diuretics b-blockers Renin Inhibitors ACEI CCBs ARBs Adrenergic Blockers

a1

EFFICACY

SAFETY
SUITABILITY COST

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IV. Table of drug classes/drugs

Calcium Channel Blockers
DILTIAZEM EFFICACY SAFETY SUITABILITY COST +++ +++ +++ ++ VERAPAMIL +++ +++ +++ ++ DIHYDROPYRIDINE + + + ++

V. P Drug

Diltiazem

VI. P Drug info

MOA
Inhibits the movement of calcium ions across the membranes of cardiac and arterial muscle cells, resulting in the depression of impulse formation in specialized cardiac pacemaker cells, slowing of the velocity of conduction of the cardiac impulse, depression of myocardial contractility* and dilation of coronary arteries and arterioles and peripheral arterioles*

VI. P Drug info

MOA
These effects lead to decrease cardiac work, decreased cardiac energy consumption, and in patients with vasospastic (Prinzmetals) angina, increased delivery of oxygen to myocardial cells.

 Pharmacodymics
ROUTE ONSET PEAK

Oral
SR, ER IV

30 60 min
30 60 min Immediate

2 3 hr
6 11 hr 2 3 min

 Pharmacokinetics
Distribution: crosses placenta, enters breast milk Metabolism: Hepatic Half-life: 3.5-6 hr; 5-7 hr (Sustained Release) Excretion: Urine

 Indications
Essential hypertension Systolic Hypertension Atrial Fibrillation, atrial tachycardia and flutter Advanced age Angina pectoris due to coronary artery spasm (prinzmetals variant angina)

 Contraindications
Allergy to diltiazem Impaired hepatic or renal function, sick sinus syndrome, heart block (second or third degree), lactation.

 Adverse Effects
The most common side effects are:
headache, peripheral edema, bradycardia, and Constipation.

 Adverse Effects
Other Adverse effects are:
dizziness GI disturbances AV block Congestive heart failure Urinary frequency

 Drug Interactions
Drug-drug:
increased serum levels and toxicity of cyclosporine if taken concurrently with diltiazem. Possible depression of myocardial contractility, AV conducton if combined with beta blockers; Use caution and monitor patient closely

 Drug Interactions
Drug-food: Decreased metabolism and increased risk of toxic effects if taken with grapefruit juice; avoid this combination.

Atrial Fibrillation

By: Michelle Babcock

Basis
Subjective Lightheadedness, palpitations, & shortness of breath Objective Rate irregularly irregular Enlarged atria & mild left ventricular hypertrophy History of Hypertension and Rheumatic Heart Disease

Atrial Fibrillation (AF)

Atrioventricular conduction system is bombarded with many electrical stimuli which causes an inconsistent impulse transmission and an irregular ventricular rate
Ventricles may beat 100-175 beats a minute in contrast to the normal rate of 60-100 beats a minute.

Etiology
Hypertension Coronary Artery Disease Ischemic or nonischemic cardiomyopathy Mitral or tricuspid valvular disorders Hyperthyroidism Binge alcohol drinking (holiday heart)

Table 233-1. Risk Factors for Stroke in Atrial Fibrillation

History of stroke or transient ischemic attack Mitral stenosis Hypertension Diabetes Mellitus Age >75 years Congestive heart failure Left ventricular dysfunction Marked left atrial enlargement (>5.0 cm)

Adopted from Harrisons 18th ed.

Classification
Paroxysmal atrial fibrillation Symptoms can be mild or severe which stop within a week or in most cases less than 24hrs

Persistent Atrial Fibrillation Abnormal heart rhythm continues for >1wk Permanent Atrial Fibrillation Normal heart rhythm cannot be restored with treatment.

Clinical Manifestations
Asymptomatic Palpitations Vague chest pain Symptoms of Heart failure (weakness, lightheadedness, dyspnea)

Diagnosis
irregular heart rhythm tachycardia often associated with palpitations (acute onset) or fatigue (chronic) high incidence and prevalence in the elderly population

Treatment Objectives
Establish rate control Rhythm control

Prevention of thromboembolism

Non-Pharmacologic Healthy diet (decrease sodium intake to aid in regulating BP) Reducing stress Avoid alcohol/caffeine intake Continue exercising

Non-Pharmacologic & Pharmacologic Management

Pharmacologic Rate control- Anti Arrhythmics Rhythm control- Anti Arrhythmics Prevention of thromboembolismAnticoagulants

Pharmacologic Agents
Calcium Channel Blockers Efficacy +++ BetaAdrenergic Receptors +++ Sodium Channel Blockers +++ Potassium Channel Blockers +++

Suitability

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Safety

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Cost

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Pharmacologic Agents
Diltiazem Verapamil Nifedipine Bepridil

Efficacy

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Suitability

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Safety

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Cost

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Diltiazem
MOA: Inhibits extracellular calcium ion influx across membranes of myocardial cells and vascular smooth muscles, without changing serum calcium concentrations, resulting in inhibition of cardiac and vascular smooth muscle contraction and dilating main coronary and systemic arteries.

Diltiazem
Pharmacokinetics: T - 3-4 hours (IV) / 3-4 hours (oral, immediate release) Metabolized in the liver Primarily excreted in the feces

Diltiazem
Side Effects: Edema Headache

Contraindications: Hypersensitivity 2nd/3rd degree heart block Co-administration with beta blockers

Dizziness

Dr. Michelle Babcock 123 McArthur Highway Marulas, Val. City Tel No. 09265555555 October 9, 2011 Rx Diltiazem 20mg Bolus (Cardizem) #1 Bolus

Sig Infuse one bolus intravenously over 2 minutes. M. Babcock M.D. Lic. No. 123456 PTR no. 987654

Name of Patient: CC Age: 62 y.o. Address: Tampoy 2, Valenzuela City

Warfarin (Coumadin)
Goal: International Normalized Ratio (INR) target 2.03.0
Needs to be maintained for patients with at least one risk factor

Used to decrease the tendency of thrombosis formation or for prevention of further episodes for individuals that have already formed a blood clot Indicated in patients with atrial fibrillation where there are increased instances of pooling of blood.

PROBLEM 3: HYPERLIPIDEMIA
ARISEPOGU, RITHESH

saturated fat :
A fat with a triglyceride molecule containing three saturated fatty acids. All carbon atoms in the fatty acid chains of saturated fats are connected by single bonds. Most fats derived from animal sources are saturated fats. Eating foods high in saturated fats can lead to elevated

unsaturated fat

A triglyceride fat containing at least one unsaturated fatty acid. Fats derived from plants are often unsaturated fats. Eating foods high in unsaturated fats can reduce the amount of

 Hyperlipidemia : a condition of abnormally elevated levels of any or all lipids and/ or lipoproteins in the blood. A risk factor for cardiovascular disease LDL: BAD cholesterol it is the form of cholestrol that is delivered to peripheral tissue from liver

 LDL-c : LDL receptors occurs on the cell surface in pits that are coated on the cytosolic side of the cell membrane with a protien like clathrin
HDL: GOOD cholesterol mobilizes cholesterol from tissue & transports it to liver for excretion in the bile

 Chylomicrons : Chylomicrons are large lipoprotein particles that consist of triglycerides (85-92%), phospholipids (6-12%), cholesterol (1-3%) and proteins (1-2%). They transport dietary lipids from the intestines to other locations in the body. Chylomicrons are one of the five major groups of lipoproteins

 Very-low-density lipoprotein (VLDL) is a type of lipoprotein made by the liver. That enable fats and cholesterol to move within the water-based solution of the bloodstream. VLDL is assembled in the liver from triglycerides, cholesterol, and apolipoproteins. VLDL is converted in the bloodstream to lowdensity lipoprotein (LDL). VLDL particles have a diameter of 30-80 nm. VLDL transports endogenous products, whereas chylomicrons transport exogenous (dietary) products.

Problem basis
Past medical history of hyperlipidemia for 5 years Smoked 15 pack years ; quit 5years ago(Smoking :hypoxia and vasoconstriction results in endothelia BMI weight status damage which results in increase vldl) Below 18.5 Under weight 18.5-24.9 BMI is : 25.3kg/m Normal
25-29.9 30 & above OVERWEIGHT Obese

Problem basis
Given values Cholesterol 6.2 mmol/L Normal values <5.2 mmol/L

Triglycerides
LDL HDL

2.03 mmol/L
4.4 mmol/L 0.88 mmol/L

<1.86 mmol/L
<3.4 mmol/L >0.90 mmol/L

Treatment Objectives:
To reduce the cholesterol levels. To modify the current medication. To reduce cardiovascular risk.

Non- Pharmacologic Therapy

Exercise Diet low in saturated fat and cholesterol Patient should avoid high alcohol intake.

Pharmacologic Therapy

DRUG CLASSES FOR HYPERCHOLESTEROLEMIA

3-hydroxy-3-methyl glutaryl-coenzyme A (HMG CoA)reductase inhibitors-the statins Bile acid-binding resins

Nicotinic acid (niacin)

Fibric acid derivatives

The cholesetrol absorption inhibitor ezetimibe

Drug

Major indications

Mechanism of action

HMG-CoAreductase inhibitor

Elevated LDL-c

Dec cholestrol Inc hepaticLDLrecep tor,dec VLDL production De intestinal cholestrol absorption

Cholestrol absorption inhibitor

Elevated LDL-c

Bile acid sequestrants

Elevated LDL-c

Inc bile acid excretion & inc LDL receptor

Dec VLDL hepatic synthesis

Nicotinic acid

Elevated LDL-c,low HDLc, elevated TG Elavated TG,elevated remanants elevatedTG

Fibric acid derivative

Inc LPL,decVLDL synthesis

Omega 3 fatty acid

Inc TG catabolism

Drug Classifications
HMG-CoA REDUCTASE INHIBITORS NIACIN (NICOTINIC ACID) BILE ACID BINDING RESINS FIBRIC ACID DERIVATIVES (FIBRATES)

Efficacy

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Safety

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Suitability

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Cost

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HMG-CoA reductase inhibitors

SIMVASTATIN (Afordel) efficacy safety +++ ++ ATORVASTATIN (Lipitor) +++ ++ ROSUVASTATI N (Crestor) +++ ++

suitability
Cost

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DRUG OF CHOICE
SIMVASTATIN ( AFORDEL) 10mg, 20mg & 40mg tablets

PHARMACOKINETICS:
Metabolism
First pass in the liver Converted to maximally active simvastatin acid by nonenzymatic pathways & nonspecific enzymes Simvastatin acid also converted to other active metabolites by CYP3A4

Elimination: Excreted primarily in the feces 60%; urine 13% (inactive forms) Absorption: absorbed from the GIT and is hydrolyzed to its active -hydroxyacid form. Bioavailability 5% Peak plasma concentration 1.3-2.4 hr Onset 2 wk Maximum effect 4-6 wk Half-life: 1.9 hrs Distribution: Protein bound 95%

Mevolanate pathway

Mechanism of action
Reduction of LDL levels through mevalonic acid like moiety that competitively inhibits HMGCoA reductase By reducing the conversion of HMGCoA to mevolanate ;statins inhibit an early &ratelimiting step in cholestrol biosynthesis
Affects blood cholesterol by Inhibits hepatic cholestrol synthesis result in increased LDL receptor gene

 In response to reduced free cholesterol content w/n hepatocytes ,membrane bound SREBPs (sterol regulatory element binding proteins) are cleaved by protease & Translocated to the nucleus The transcription factor then bind the sterol responsive element of the LDL receptor gene enhancing transcription and increase the synthesis of LDL receptor

 Degradation of LDL receptor is also reduced the greater number of LDL receptor on the surface of hepatocytes results in increase removal of LDL from the blood ,there by lowering LDL level

INDICATION: Treatment of hypercholesterolemias particularly type IIa & IIb hyperlipoproteinemias Treatment of hyperlipidemia, ischemic heart disease, CHD & severe renal impairment. DRUG INTERACTIONS: Increased risk of myopathy if certain drugs eg, immunosuppressants, fibric acid derivatives or nicotine acid are given concurrently with statins. Bleeding and increases in prothrombin time have been reported in patients taking simvastatin with coumarins.

 ADVERSE DRUG REACTIONS: GI disturbances headache, dizziness, blurred vision skin rashes insomnia dysgeusia an abnormal taste (metallic, foul etc) Myopathy characterized by myalgia & muscle weakness.

Oct 8, 2011

Rx

Simvastatin (Afordel) 10-20 mg # 7 tabs

Sig. Taken 10mg/tab once in the evening for seven days

A.Rithesh MD Lic. No. 007 PTR. No. 420 Name of Patient: CC Age: 62 Address: QC

Thank you