Master Module 3 Pharm

Antihypertensive therapy goal

The reduction of cardiovascular and renal morbidity and mortality.

Stage 1 hypertension guideline

Drug therapy should be started if the patient's $10$ year cardiac and stroke risk assessment is greater than $10\%$. If the risk is less than $10\%$, lifestyle changes are recommended with reassessment in $3-6$ months.

Stage 2 hypertension guideline

Patients should be started on lifestyle changes and two different classes of medications from the start.

Cardiovascular risk assessment factors

Cardiovascular history, family history, diet, exercise, blood pressure, cholesterol, smoking history, and the presence of diabetes.

First-line treatments for hypertension

The four main classes considered first-line treatment include (1) Thiazide Diuretics, (2) ACE-inhibitors, (3) ARBs, and (4) Calcium channel blockers.

Thiazide Diuretics

Medications that increase salt excretion from the kidney and long-term reduce sodium concentration in cells to reduce sensitivity to vasoconstrictors, gradually reducing peripheral resistance.

Thiazide Diuretics Adverse Effects

Low potassium, which can lead to dehydration, muscle weakness, and fatigue.

Renin-angiotensin-aldosterone mechanism (RAA)

The pathway where ACE-inhibitors, ARBs, and direct renin inhibitors act to reduce the amount of angiotensin II produced.

ACE-Inhibitors

Angiotensin Converting Enzyme inhibitors that inhibit the enzyme converting angiotensin I to angiotensin II, leading to decreased aldosterone and antidiuretic hormone release and causing vasodilation.

ACE-inhibitor Unique Adverse Events

A dry cough and angioedema (swelling of the face and oral cavity).

Angiotensin II Receptor Blockers (ARBs)

Medications that bind to the angiotensin-1 receptor to prevent angiotensin II from binding, inhibiting vasoconstriction effects.

Calcium Channel Blockers

Medications that block calcium channels in cardiac and vascular smooth muscles to induce arteriolar vasodilation.

Non-dihydropyridines

A group of calcium channel blockers, including $verapamil$ and $diltiazem$, that decrease heart rate, conduction, and contractility.

Dihydropyridines

A group of calcium channel blockers, including $amlodipine$ and $nifedipine$, that have no direct actions on the heart.

Angioedema

A life-threatening adverse event associated with ACE-inhibitors involving the swelling of the face and oral cavity, requiring the medication to be stopped.

Blood pressure

The pressure exerted against the walls of blood vessels as blood circulates through the body.

Sphygmomanometer

An instrument used to measure blood pressure, also commonly known as the blood pressure cuff.

Millimeters of mercury ($mm/Hg$)

The units in which blood pressure measurements are recorded.

Brachial artery

The artery from which blood flow is cut off by a blood pressure cuff during measurement.

Korotkoff sound

The first sound heard through a stethoscope when releasing cuff pressure, indicating blood flow is no longer completely restricted.

Systolic value

The top number of a blood pressure reading corresponding to the first $Korotkoff$ $sound$.

Diastolic value

The bottom number of a blood pressure reading, occurring when the sounds disappear and the brachial artery is completely open.

Hypertension

A persistent systolic blood pressure of greater than $130\,mm/Hg$ and/or a diastolic blood pressure greater than $80\,mm/Hg$.

Essential hypertension

Also known as primary hypertension; a condition where the cause of the increased blood pressure is unknown.

Secondary hypertension

Elevated blood pressure that is caused by another underlying disease.

Orthostatic hypotension

A sudden drop in blood pressure occurring when a patient changes positions, such as moving from a seated to a standing position.

Cardiac output

The amount of blood ejected from the heart's left ventricle, determined by heart rate ($beats\,per\,minute$) and stroke volume.

Stroke volume

The volume of blood pumped per contraction of the heart.

Systemic Vascular Resistance (SVR)

The resistance to blood flow determined by the diameter and musculature nature of the blood vessel.

Normotensive

A blood pressure classification defined as less than $120/80\,mm/Hg$.

Elevated Blood Pressure

A blood pressure classification defined as $120-129/<80\,mm/Hg$.

Hypertensive Stage 1

A blood pressure classification defined as $130-139/80-89\,mm/Hg$.

Hypertensive Stage 2

A blood pressure classification defined as greater than $140/90\,mm/Hg$.

Peripheral resistance

The resistance generated by the flow of blood through the arteries.

Renin

An enzyme released by the kidney that leads to vasoconstriction, water and sodium retention, and an increase in blood pressure.

Angina Pectoris

Chest pain that occurs when the heartɹs supply of blood carrying oxygen is insufficient to meet the demands of the heart.

Coronary Artery Disease (CAD)

A condition due to atherosclerosis and insufficient blood supply to the heart.

Coronary arteries

The specific arteries that deliver oxygen to the heart.

Ischemia

Damage to the tissues or cells because of a lack of oxygen delivery.

Ischemic heart disease

A condition where the heart is the specific organ damaged by ischemia; it is the number $1$ killer in the US today.

Atherosclerosis

The primary cause of ischemic heart disease involving fatty plaques that develop in the arteries, making them narrower and decreasing the supply of oxygen rich blood to the heart.

Myocardial infarction (MI)

Also known as a heart attack, it occurs when blood flow in one or more of the coronary arteries is completely blocked causing part of the heart muscle to receive no oxygen.

Nitrates Mechanism of Action

Relaxing vascular smooth muscle by converting nitrate ions to nitric oxide, which is a potent vasodilator.

Nitroglycerin

A nitrate medication available in both rapid acting and long acting dosage forms.

Isosorbide mononitrate

A nitrate medication available in a long acting dosage form.

Beta Blockers Mechanism of Action

Work by blocking beta-$1$ receptors in the heart, leading to a decrease in heart rate and the force of the heartɹs contraction.

Preferred Beta Blockers for Angina

Nadolol, propranolol, atenolol, and metoprolol.

Calcium Channel Blockers (CCB) Mechanism of Action

Blocks calcium from entering the vascular smooth muscle, leading to vasodilation, reduced blood pressure, and a lower overall workload of the heart.

Non-dihydropyridines

Specific calcium channel blockers, including verapamil and diltiazem, that work directly on the heart by blocking calcium in the heart muscle itself.

CCBs used for Angina

Verapamil, diltiazem, amlodipine, nifedipine, and nicardipine.

Verapamil Adverse Event

Specifically known to cause constipation.

Chronic heart failure (CHF)

A condition in which the heart is unable to pump sufficient blood to the tissues of the body, leading to blood build-up in the heart and overflow into the lungs and body.

Pulmonary edema

Fluid in the lungs, often a symptom of chronic heart failure when blood overflows from the heart.

Peripheral edema

Fluid in the body, often occurring in the lower extremities, commonly seen in patients with chronic heart failure.

Ejection Fraction

The proportion of blood that is ejected during each contraction of the heart compared with the total volume of blood within the ventricle of the heart.

Left ventricular end diastolic volume

The total amount of blood in the ventricle right before it contracts, also known as the preload.

NYHA Functional classes

A historical classification system created by the New York Heart Association that focuses on the severity of a patient's symptoms.

NYHA Class I

No limitations on physical activity; normal physical activity does not cause symptoms.

NYHA Class II

Slight limitations on physical activity; the patient is comfortable when at rest, but ordinary activity causes symptoms.

NYHA Class III

Marked limitation of physical activity; the patient is comfortable at rest, but less than ordinary activity causes symptoms.

NYHA Class IV

The patient is unable to have physical activity without symptoms or experiences symptoms at rest.

ACCF/AHA Staging

A recent system developed by the American College of Cardiology Foundation/American Heart Association focusing on disease progression and structural changes to the heart.

ACCF/AHA Stage A

At high risk but no symptoms or structural heart disease.

ACCF/AHA Stage B

Structural heart disease is present but there are no signs or symptoms.

ACCF/AHA Stage C

Structural heart disease with past or current symptoms.

ACCF/AHA Stage D

Refractory heart failure requiring interventions.

Digoxin

A cardiac glycoside originally obtained from the digitalis plant (foxglove) used as a positive inotrope in heart failure treatment.

Positive inotrope

A substance that increases the force of the heart's contraction.

Low therapeutic index

A characteristic of a drug, like Digoxin, where drug concentrations must be monitored closely due to the narrow window between therapeutic and toxic levels.

Tachycardic

An increased heart rate; in CHF, the heart beats faster to try and meet body demands, which often makes the efficiency worse.

Preferred Beta blockers for CHF

Metoprolol, bisoprolol, nebivolol, and carvedilol.

ACE-Inhibitors/ARBs mechanism in CHF

Prevents sodium and water from being reabsorbed into the body to decrease blood volume, blood return to the heart, preload, and workload.

Nephron

The main structural component of the kidney and the primary site of filtration.

Glomerulus

The site of blood filtration marking the beginning of the nephron, located proximal to the proximal convoluted tubule.

Glomerular filtration rate (GFR)

The rate at which filtering occurs in the kidney, used by clinicians to estimate how well the kidneys are functioning.

Proximal convoluted tubule

The part of the nephron immediately after the glomerulus where close to $70\%$ of filtered sodium and water is reabsorbed.

Loop of Henle

The part of the nephron between the proximal and distal tubules where $25\%$ of sodium reabsorption occurs.

Distal convoluted tubule

The segment of the nephron where the final $5\%$ of sodium reabsorption occurs and where Thiazides and potassium sparing diuretics exert their effect.

Antidiuretic hormone (ADH)

A hormone released within the brain that acts on the collecting tubule to reabsorb water back into the bloodstream to regulate water balance.

Osmotic Diuretics

Non-absorbable diuretics that increase the pressure of the glomerular filtrate to pull fluid into the nephron, primarily used for Acute Renal Failure.

Carbonic Anhydrase Inhibitors

Diuretics that inhibit the enzyme responsible for making hydrogen available for sodium and water reabsorption; used for high-altitude sickness and edema from CHF.

Acetazolamide

A specific Carbonic Anhydrase Inhibitor used when other diuretics have not worked for fluid accumulation caused by CHF.

Loop Diuretics

Potent diuretics structurally related to sulfa antibiotics that block chloride and sodium reabsorption in the ascending limb of the loop of Henle.

Thiazide Diuretics

Sulfa-related diuretics that work in the distal tubule to inhibit electrolyte reabsorption and directly relax small blood vessels to reduce SVR.

Potassium Sparing Diuretics

A class of diuretics that reduces the amount of potassium excreted in the urine by blocking sodium reabsorption in the distal tubule and collecting duct.

Spironolactone

A potassium sparing diuretic that binds to aldosterone receptors; its specific adverse event is gynecomastia.

Mannitol

The drug example provided for the class of Osmotic Diuretics.

Bumetanide, furosemide, and torsemide

Specific drug examples categorized as Loop Diuretics.

Amiloride and triamterene

Potassium sparing diuretics that do not bind to aldosterone receptors but instead inhibit aldosterone-induced sodium reabsorption.

SVR (Systemic Vascular Resistance)

A factor reduced by Thiazide diuretics through the direct relaxation of small blood vessels, aiding in the treatment of hypertension and heart failure.

Hypercholesterolemia

A condition characterized by higher than normal amounts of cholesterol in the blood, which may lead to atherosclerosis and coronary heart disease.

Cholesterol

A fat-soluble steroid found in animal fats, oils, and egg yolks, as well as various organs; it is necessary for making steroid hormones, cell membranes, and bile acid.

Plaque

A substance containing cholesterol, dead cell products, and calcium that accumulates in the innermost layer of the arteries.

Lipoprotein

A combination of a lipid and a lipid-carrying protein that allows for the transport of lipids via the blood.

Low density lipoprotein (LDL)

Commonly known as ‘bad cholesterol’; the typical recommended level is less than $100\,mg/dL$.

High Density Lipoprotein (HDL)

Known as ‘good cholesterol’ because it removes cholesterol from the blood and returns it to the liver; the typical recommended level is greater than $40\,mg/dL$.

Triglycerides (TG)

A fat formed by three fatty acids that supplies energy to muscle cells; the typical recommended level is less than $150\,mg/dL$.

Statins (HMG-CoA reductase inhibitors)

The drug of choice for treating hyperlipidemia; they work by inhibiting the rate-limiting enzyme in cholesterol synthesis within the liver.

HMG-CoA reductase

The rate-limiting enzyme responsible for cholesterol synthesis within the liver.

Atorvastatin (Lipitor)

A high-intensity statin with a typical dose range of $40-80\,mg$.