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
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EFFICACY
SAFETY
SUITABILITY COST
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V. P Drug
Diltiazem
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
Basis
Subjective Lightheadedness, palpitations, & shortness of breath Objective Rate irregularly irregular Enlarged atria & mild left ventricular hypertrophy History of Hypertension and Rheumatic Heart Disease
Etiology
Hypertension Coronary Artery Disease Ischemic or nonischemic cardiomyopathy Mitral or tricuspid valvular disorders Hyperthyroidism Binge alcohol drinking (holiday heart)
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
Pharmacologic Agents
Calcium Channel Blockers Efficacy +++ BetaAdrenergic Receptors +++ Sodium Channel Blockers +++ Potassium Channel Blockers +++
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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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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
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.
Pharmacologic Therapy
Drug
Major indications
Mechanism of action
HMG-CoAreductase inhibitor
Elevated LDL-c
Dec cholestrol Inc hepaticLDLrecep tor,dec VLDL production De intestinal cholestrol absorption
Elevated LDL-c
Elevated LDL-c
Nicotinic 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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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
Thank you