CARDIO DRUGS

sustained and reproducible increase in blood pressure;

incidence increases with age; can lead to cardiovascular problems,

renal diseases, and blindness; leads to an increase in mortality rate;

approach is both pharmacologic and nonpharmacologic (approach

depends on age and situation; as you age, it is mostly pharmacologic);

silent killer (some individuals are not aware that they are hypertensive,

they would only be aware if a symptom would occur; one must know

his/her base blood pressure; associated with metabolic abnormalities;

more on sympathetic affectation).

Hypertension -

is a type of hypertension however, common cases occur with the aging population.

Juvenile HP

Optimal

< 120 < 80

Prehypertension

120-139 80-89

Hypertension Stage 1

140-159

Hypertension Stage 2

≥160 90-99 ≥ 100

normally maintained by complex interaction of several physiologic systems; control primarily by baroreceptor reflex (monitors and corrects changes in BP by altering the CO and PVR).

Blood Pressure -

essential HPN; 95% of hypertensive; no clear

discernible cause; exact cause is unknown.

○ May be associated with:

■ Strong family history.

■ Environmental factors.

● Primary Hypertension -

5% of hypertensive patients; attributed to specific

abnormalities such as renal stenosis, endocrine, catecholamine

producing tumors, cerebral tumors; treatment is aimed at targeting the

underlying cause.

● Secondary HPN -

External factors of HTN

○ Diet.

○ Stress.

○ Cigarette smoking (nicotine effects).

○ Alcohol.

○ Obesity (medical imbalance).

EFFECTS OF HYPERTENSION

● Associated with metabolic abnormalities:

○ Impaired glucose metabolism.

○ Hyperinsulinemia.

○ Dyslipidemia.

○ Abdominal obesity.

increase the formation and excretion of urine; used as anti

HPN due to their ability to increase renal excretion of water and sodium;

decrease the volume of fluid within the vascular; appears to have a

direct effect on BP due to the fluid excretion; often uses as the 1st type to

treat HPN; relatively inexpensive but works well with mild to moderate

HPN.

Diuretics -

○ Mainstay in the treatment of HPN.

DIURETICS

THIAZIDE DIURETICS EXAMPLE DRUGS

CHLOROTHIAZIDE

HYDROCHLOROTHIAZIDE

LOOP DIURETICS EXAMPLE DRUGS

FEROMESIDE

POTASSUM SPARING DIURETICS EXAMPLE DRUGS

SPIRONOLACTONE

WHAT ARE THE TYPES OF DIURETICS

THIAZIDE DIURETICS

LOOP DIURETICS

POTASSIUM SPARING DIURETICS

- share a common chemical nucleus and made of

action; act primarily on the early portion of distal tubule of nephron

where it inhibits sodium reabsorption; most frequently used type of

diuretic for hypertension.

○ More sodium is retained within the nephron with water creating

an increase in osmotic force then ultimately excreted from the

body.

Thiazide Diuretics

acts primarily on ascending loop of Henle; inhibits the reabsorption of sodium and chloride same with water.

Loop Diuretics -

prevents the secretion of K into the distal

tubule; K spared from secretion while Na remains in the tubule then

excreted; produce diuretic effectless than other diuretic drug and spared

potassium thereby reducing risk of hypokalemia (can lead to paralysis).

○ Normally: Na-K exchange occurs in distal tubule (Na is

reabsorbed and K is secreted).

Potassium Sparing Diuretics -

ADVERSE EFFECT OF DIURETICS

FLUID DEPLETION AND ELECTROLYTE IMBALANCE

● Classified according to where and how they interrupt sympathetic activity.

SYMPATHOLYTIC DRUGS

- used extensively to decrease BP (slows down the

heart rate to reduce pressure); one of the mainstay of anti-HPN therapy;

exerts primary effect on the heart to decrease HR and force myocardial

contraction; lowers BP by slowing down the HR and reducing CO.

○ Produces a general decrease in sympathetic tone (heart rate).

○ Compliments the effect of other anti-HTN meds (diuretic, ACE

inhibitors).

Beta Blockers (-olol)

EXAMPLE DRUGS OF BETA ADRENERGIC BLOCKERS

Pindolol and Acebutolol (PiAc)

Labetalol and Propranolol (LaPro)

Carvedilol and Nebivolol (CaNe)

block catecholamines.

○ Membrane stabilizing activity (normalizes the excitability of

cardiac cell membrane).

■ Pindolol and Acebutolol (PiAc) -

normalize

excitability of cardiac cell.

■ Labetalol and Propranolol (LaPro) -

- produces peripheral

vasodilation and cardiac beta blockade to decrease BP

Carvedilol and Nebivolol (CaNe)

blocks the alpha-1–adrenergic receptor on vascular smooth muscle promoting a decrease in vascular resistance; advantage in treating HPN including the ability to improve blood lipid profile and a favorable effect on glucose metabolism and insulin resistance; used also to treat symptoms of benign prostatic hypertrophy by decreasing sympathetic mediated contraction of smooth muscle in the prostate gland (patients with increasing sugar or dyslipidemia).

Alpha Blockers -

ALPHA BLOCKERS EXAMPLE DRUGS

PRAZOSIN AND TERAZOSIN

ADVERSE EFFECTS OF ALPHA BLOCKERS

REFLEX TACHYCARDIA

ORTHOSTATIC HYPOTENSION

one of the primary effect due to the fall of

peripheral vascular resistance where baroreceptor reflex responds by a

compensatory mechanism of increasing the HR.

● Reflex Tachycardia -

blockage of alpha1 receptors in peripheral

arteries and veins promotes pooling of blood in the LE when a px stands

up.

Orthostatic Hypotension -

inhibit sympathetic discharge from the

brainstem (2 types of neuronal receptors); characterized as agonists for

either one of the 2 receptors.

Centrally Acting Drugs -

What are the 2 neuronal receptors of CENTRALLY ACTING DRUGS

ALPHA 2 ADRENERGIC RECEPTORS

IMIDAZOLINE TYPE II RECEPTORS

EXAMPLE DRUGS OF CENTRALLY ACTING DRUGS

CLONIDINE

METHYLDOPA

- not commonly used for hypertension; block synaptic transmission at autonomic ganglia that will dramatically and effectively reduce blood pressure by decreasing systemic sympathetic activity; are essentially nicotinic cholinergic antagonists which block transmission at the junction between presynaptic and postsynaptic neurons in sympathetic and parasympathetic pathways; reduce blood pressure in hypertensive emergencies.

Ganglionic Blockers

EXAMPLE DRUGS OF GANGLIONIC BLOCKERS

MECAMYLAMINE

TRIMETAPHAN

First line of treatment in pregnant women especially during severe preeclampsia

- directly vasodilate the peripheral vasculature producing

an anti-hypertensive effect by decreasing peripheral vascular

resistance; exert an inhibitory effect directly on vascular smooth-muscle

cells; believed to inhibit smooth-muscle contraction by increasing the

intracellular production of second messengers such as cyclic guanosine

monophosphate (cGMP)

○ Increased amounts of cGMP inhibit the function of the contractile

process in the vascular smooth-muscle cell thus leading to

vasodilation.

Vasodilators

Primary vasodilators used: ___

■ Not usually the first medications used in patients with

hypertension.

■ Used to lower blood pressure in emergency situations

such as severe preeclampsia(pregnant) or malignant

hypertension.

Hydralazine and minoxidil.

ADVERSE EFFECT OF MINOXIDIL

Increase hair growth on face, ears, and forehead (MINOXIDIL).

○ Discontinued in women.

○ Men uses it cutaneously to treat baldness.

- drugs that inhibit the enzyme that converts

angiotensin I to angiotensin II; limits the production of angiotensin II

causing a decrease in BP.

● ACE Inhibitors (-pril)

- drugs that blocks the

angiotensin II receptors to negate the harmful effects of angiotensin II on

the vascular tissues.

○ Both drugs appear to have several advantages over other

antihypertensives.

○ Lower incidence of cardiovascular side effects.

○ Less reflex tachycardia and orthostatic hypotension.

○ Inhibit angiotensin II-induced vascular hypertrophy and

remodeling is an important benefit.

○ Beneficial in decreasing morbidity and mortality associated with

congestive heart failure.

● Angiotensin II Receptor Blockers (-tan)

EXAMPLE DRUGS OF ACE INHIBITORS

CAPTOPRIL

ENALAPRIL

EXAMPLE DRUGS OF ANGIOTENSIN II RECEPTOR BLOCKERS

IRBESARTAN

LOSARTAN

TELMISARTAN

- selectively block calcium entry into

vascular smooth-muscle cells; originally developed to treat certain

forms of angina pectoris and cardiac arrhythmias; beneficial in the

treatment of essential hypertension; decrease heart rate and

myocardial contraction force, and some of their antihypertensive

properties may derive from their inhibitory effect on the heart; help

preserve renal function.

Calcium Channel Blockers

EXAMPLE DRUGS OF CALCIUM CHANNEL BLOCKERS

AMLODIPINE

DILTIAZEM

FELODIPINE

NICARDIPINE

NIFEDIPINE

pain that occurs in the chest region during ischemic

heart disease; attacks begin suddenly; described as a sensation of

intense compression and tightness in the retrosternal region.

○ Pain sometimes radiating to the jaw or left arm.

○ Episodes of angina pectoris are precipitated by physical

exertion.

○ Can occur spontaneously even when the patient is at rest or

asleep.

○ Basic problem: supply of oxygen to the heart is insufficient to

meet myocardial demands at a given point in time resulting to

an imbalance between myocardial oxygen supply and demand

leading to myocardial ischemia.

● Angina Pectoris -

- have the ability to dilate vascular smooth muscle

(decrease workload increase oxygen supply); drug precursors

(prodrugs) that become activated when they are converted to nitric

oxide within vascular smooth muscle; relieve angina attacks by dilating

the coronary arteries; ↑ blood flow to the myocardium to ↑ the

myocardial oxygen supply; exert their primary antianginal effects by

producing a general vasodilation in the vasculature throughout the body

and not just in the coronary vessels.

organic nitrates

causes vasodilation by increasing the production

of cyclic guanosine monophosphate (cGMP) within the muscle

cell.

○ Nitric Oxide -

acts as a second messenger that inhibits smooth

muscle contraction.

○ Cyclic GMP -

most well known antianginal drug; most common

organic nitrate; administered for both the prevention and treatment of

anginal attacks and is available in oral, buccal, sublingual, and

transdermal forms.

Nitroglycerin -

best method to treat an acute

attack of angina; rapidly absorbed through the oral mucosa into

the systemic circulation; therapeutic effects usually begin within

2 minutes; spared from the first-pass effect.

○ Sublingual administration:

favorable due to ease and convenience;

prevents the onset of anginal episodes in many pxs.

○ Transdermal patch:

used for the treatment of acute

episodes of angina as well as for the prevention of anginal attacks;

longer effect of antianginal and hemodynamic; classified as a long

acting nitrate.

Isosorbide Dinitrate/Mononitrate -

supplied in small ampules that can be broken open to

inhale during anginal attacks; nasal membrane to cause peripheral

vasodilation to decrease preload and afterload.

● Amyl Nitrite -

- most common form of ischemic heart disease;

frequently referred to as effort or exertional angina since attacks are

usually precipitated by a certain level of physical exertion; coronary

arteries are unable to deliver the oxygen needed to sustain that level of

myocardial function; inability of the coronary arteries to adequately

deliver oxygen is usually caused by some degree of permanent coronary

artery occlusion (coronary artery atherosclerosis or stenosis).

○ Primary problem: myocardial oxygen demand greatly exceeds

oxygen supply.

○ Treatment:

■ Mainly consists of beta blockers and organic nitrates

■ Beta blockers (often the first drugs used in the long-term

management of stable angina because they decrease

the workload of the heart limiting myocardial oxygen

demand).

■ Organic nitrate (nitroglycerin for acute attacks

(sublingual)).

stable angina

- Prinzmetal Ischemia; can occur even when the patient

is at rest.

○ Primary problem: oxygen supply to the myocardium decreases

because of coronary artery vasospasm.

○ Vasospasm causes oxygen supply to decrease even though

oxygen demand has not changed.

○ Coronary arteries are sensitive to endogenous vasoconstrictive

agents, variety of emotional triggers.

○ Treatment:

■ Calcium channel blockers (drugs of choice in treating

the variant form of angina; limit the entry of calcium into

the coronary vessels to attenuate or prevent vasospasm

underlying variant angina; if cannot be tolerated, long

acting nitrates can be of use).

VARIANT ANGINA

severe form of angina; often initiated by sudden

rupture of atherosclerotic plaques within the coronary arteries; results to

coronary vasoconstriction and thrombus formation; also associated with

thrombosis and increased platelet aggregation in the affected coronary

arteries; often a precursor to acute myocardial infarction; regarded as

the most serious and potentially dangerous form of angina.

○ Plaque rupture can be brought on by exertion, or it may occur

spontaneously when the patient is at rest.

○ Primary problem: decrease in myocardial oxygen supply.

UNSTABLE ANGINA