Fcm - Hypertension Pharmacology

Front 1

Baroreceptor reflex (BRR)

Back 1

Regulates blood pressure very well, but only in the short term (minutes). It tends to accommodate to altered blood pressure over time, so it's role in long term blood pressure regulation is low.

Decreases in blood pressure decrease sympathetic afferent input into the brain stem which releases inhibitory control on the sympathetic effectors in the cardiovascular system. Total peripheral resistance and cardiac output increase (via increases in heart rate and stroke volume).

Front 2

Total Peripheral Resistance

Back 2

The sum of the resistance of all peripheral vasculature in the systemic circulation.

An increase in total peripheral resistance can lead to hypertension. TPR increases with norepinephrine, epinephrine, and angiotension II. Can also be modified by the baroreceptor reflex.

Front 3

What percentage of hypertensives have a know etiology?

Back 3

10%

Front 4

Renin

Back 4

Decreases in blood pressure increase renin release from the juxtoglomerular apparatus in the kidney. Renin is not stored in the secretory cells, so decreases in blood pressure require time (hours) for renin synthesis and release to occur. It is not effective in the short-term regulation of blood pressure but is exquisitely effective in regulating blood pressure in the long-term.

Renin release is always on and regulated by blood pressure as well as beta adrenergic controls. It regulates blood pressure by adjusting blood volume and by adjusting total peripheral resistance through direct vasoconstrictor effects of angiotension II. The angiotensinogen gene is over-expressed in many, but not all, salt-sensitive hypertensives.

Front 5

Angiotensinogen

Back 5

It is produced constitutively and released into the circulation mainly by the liver. It is converted by renin into angiotensin I.

The angiotensinogen gene is over expressed in many, but not all, salt-sensitive hypertensives.

Front 6

Angiotensin converting enzyme (ACE)

Back 6

Cleaves the 2 terminal amino acids off angiotensin I to form angiotensin II.

Front 7

Diuresis

Back 7

Increased production of urine by the kidney.

Front 8

Essential hypertension

Back 8

Essential hypertension (also called primary or idiopathic hypertension) is the form of hypertension that by definition, has no identifiable cause. Is is the most common cause of hypertension (90%).

It is polygenic in origin with requisite environmental factors (salt, stress, etc.) contributing as well. It is also racially asymmetrical with a much higher incidence in African American (frequently preceded by insulin resistance).

Front 9

Renovascular hypertension

Back 9

A syndrome which consists of high blood pressure caused by narrowing of the arteries supplying the kidneys (renal artery stenosis). It is a form of secondary hypertension - a form of hypertension whose cause is identifiable.

Front 10

Sympatholytics

Back 10

Interrupt sympathetic communication to effector tissues in one way or another. These include ganglionic blockers, alpha adrenergic blockers, and beta adrenergic blockers.

Sympatholytics disrupt the baroreceptor reflex and this contributes to their side effects; e.g. orthostatic hypotension, reflex bradycardia, etc.

Front 11

What are the 3 routes to hypertension?

Back 11

Increased cardiac output, increased total peripheral resistance, and increased blood volume

Front 12

Beta blockers

Back 12

Effective in hypertension management since inhibiting sympathetic access to the myocardium reduces cardiac output and this reduces blood pressure.

At least part of their antihypertensive effects appear to be mediated by blocking renin release. Proven to reduce mortality in patients with heart failure, beta blockers are of special interest in treating hypertension in patients with heart failure as well.

Side effects: sinus bradycardia, exercise intolerance, and asthmatic symptoms.

Front 13

Are beta blockers less or more effecting in African Americans compared to Caucasians?

Back 13

Beta blockers are less effective in African Americans.

Front 14

Propanolol

Back 14

Inderal; 60-240 mg/d

Non-selective B1/B2 antagonist. Useful in the treatment of mild to moderate hypertension. Part of effects due to its blocking renin release.

Propanolol cross the blood brain barrier, where it can cause nightmares, depression, insomnia, etc. May also increase plasma triglycerides and reduce HDL.

Non-selective beta blockers slow the rate of recovery in acute hypoglycemia caused by insulin, and they can mask the symptoms of hypoglycemia. Use with caution in diabetic patients.

Front 15

Atenolol

Back 15

Tenormin; 25-100 mg/d

Selective B1 antagonist. Useful in the treatment of mild to moderate hypertension.

Front 16

Carvedilol

Back 16

Coreg; 12.5-50 mg/d

Selective B1 antagonist with a1 blocking properties as well. Useful in treatment of mild to moderate hypertension.

Does NOT push the patient towards insulin resistance. For this reason, Carvedilol is the preferred beta blocker for most applications.

Front 17

Alpha blockers

Back 17

Antagonize the alpha adrenergic actions of sympathetic stimulation of the peripheral vasculature.

Side effects: mild but may include reflex tachycardia. Alpha-blockers can produce first dose hypotension, potentially leading to syncope.

Prazosin, Doxazosin

Front 18

Prazosin

Back 18

Alpha blocker. Selective a1 antagonist. Useful in the treatment of mild to moderate hypertension and preferred over nonselective alpha blockers since it produces less reflex tachycardia (a2 not blocked).

Also used in benign prostatic hypertrophy since it dilates the urethra.

Front 19

Metoprolol

Back 19

Beta blocker. Selective B1 antagonist. Useful in treatment of mild to moderate hypertension and acute MI.

Front 20

Doxazosin

Back 20

Alpha blocker. Selective a1 antagonist. Also used in benign prostatic hypertrophy.

Front 21

Central acting adrenergic blockers

Back 21

Central acting adrenergic blockers stimulate neuronal (brain stem) cells and decreases sympathetic outflow. They usually do not interfere with the baroreceptor reflex control of blood pressure. These drugs are not widely used in antihypertensive therapy, but may offer options in difficult to manage patients.

Side effects: these drugs cross the BBB; nightmares, depression, insomnia, etc.

Clonidine, Methyldopa

Front 22

Clonidine

Back 22

Central acting adrenergic blocker. Alpha antagonist with partial alpha agonist activity.

Adverse reactions: rebound hypertension

Front 23

Methyldopa

Back 23

Central acting adrenergic blocker. Alpha 2 antagonist that stimulates neuronal (brain stem) cells and decreases sympathetic outflow. Has partial alpha agonist activity and causes an early rise in blood pressure followed by a prolonged decrease.

Front 24

Side effects of alpha blockers

Back 24

First dose hypotension (and syncope), elevated LDL, and heart failure

Front 25

NE depleting agents

Back 25

NE depleting agents are taken up into the adrenergic nerve terminals where they enter the presynaptic vessels and displace NE. This results in sympathectomy-like toxicities.

They often have severe and widespread side effects and are not widely used in clinical practice.

Reserpine

Front 26

Reserpine

Back 26

NE depleting agent. Of historical significance only. Depletes vesicular NE stores and produces chemical sympathectomy in large doses. Crosses BBB and reduces amine stores there too.

Front 27

ACE inhibitors mechanism of action

Back 27

Angiotensin converting enzyme inhibitors are competitive antagonists of ACE, reducing the ability of ACE to cleave the 2 terminal amino acids off angiotensin I to form angiotensin II. Angiotensin levels are reduced and circulating aldosterone levels, Na+ retention, and fluid retention are also reduced. ACE inhibitors also inhibit the degredation of bradykinin.

Some ACE inhibitors work at the cellular level (vascular smooth muscle myocytes and ventricular myocytes), giving them efficacy in co-morbid conditions (HF and medial hypertrophy). ACE inhibitors also suppress vascular smooth muscle superoxide anion generation and cellular hypertrophy (medial hypertrophy seen in hypertension).

Front 28

What is the most common side effect of ACE inhibitors?

Back 28

Dry cough caused by increased levels of bradykinin.

Other side effects include angioedema, first-dose hypotension, and hyperkalemia.

ALL ACE INHIBITORS ARE CONTRAINDICATED IN PREGNANCY. Less effective in African Americans.

Front 29

Captopril

Back 29

The first ACE inhibitor introduced for treatment of hypertension. Effective in the management of mild to severe hypertension and in CHF.

Toxicities include loss of taste sensation.

Front 30

Which ACE inhibitors are lipophilic? Why does it matter?

Back 30

Enalopril, Quinopril, and Ramipril

Lipophilic ACE inhibitors are effective on tissue ACE.

Front 31

Enalopril

Back 31

ACE inhibitor. A prodrug that is converted by de-estrification to enaloprilat, a potent ACE inhibitor. Effective in the management of mild to severe hypertension and in CHF.

Effective on tissue ACE.

Front 32

Lisinopril

Back 32

ACE inhibitor. A lysine derivative of enalopril. Effective in the management of mild to severe hypertension and in CHF.

Front 33

Quinopril

Back 33

More recent long acting entry to ACE inhibitor class. Lipophilic and thus active against tissue ACE.

Front 34

Ramipril

Back 34

More recent long acting entry to ACE inhibitor class. Lipophilic and thus active against tissue ACE.

Front 35

Antiotension receptor blockers (ARBs)

Back 35

Competitively antagonize angiotension II receptors on the adrenal cortical cells and on blood vessels. These drugs do not alter kinin metabolism and thus do not stimulate NO or prostacyclin.

Side effects: no dry cough or angioedema; contraindicated in pregnancy

Less effective on African Americans

Losartan, Candesartan, and Valsartan

Front 36

Mechanism of action of diuretics

Back 36

Diuretics increase urinary output in excess of that which would otherwise occur and reduce total body water.

Diuresis pulls on the interstitial fluid compartment which, in turn pulls on the intracellular (dehydration) compartment and blood volume (volume constriction). In this way, modest diuresis reduces blood volume and therefore CO and BP. However, after several days on diuretic therapy, blood volume and CO return to normal, but BP stays lowered. Diuretics may dilate the arteriolar resistance vasculature by altering the cellular Na balance in the vascular smooth muscle myocytes.

Front 37

Thiazide diuretics

Back 37

Inhibit the Na/Cl co-transporter in the luminal membrane of the distal convoluted tubule. Increases loss of Na+ and Cl- and increases urine output by osmotic drag.

Thiazide diuretics are mild diuretics and are currently recommended for first line therapy for hypertension.

Can deplete K+, which is important in patients with renal disease and/or on digitals.

Hydrochlorothiazide, Chlorothiazide

Front 38

Hydrochlorothiazide

Back 38

Thiazide diuretic. Also used in relieving bloating in premenstrual syndrome.

Front 39

Chlorothiazide

Back 39

Thiazide diuretic.

Front 40

Loop diuretics

Back 40

Inhibit the Na/K/Cl co-transporter in the luminal membrane of the thick ascending loop of Henle. Increases loss of Na+, K+, and Cl- and increases urine output by osmotic drag.

Loop diuretics are strong diuretics and are not used widely in antihypertensive therapy. Can deplete K+, which is important in patients with renal disease and/or on digitals.

Primarily used to relieve edema and are recommended only as tertiary options in antihypertensive therapy.

Furosemide

Front 41

Furosemide

Back 41

Loop diuretic. Toxicity includes dose-related and irreversible hearing impairment.

Front 42

Potassium-sparing diuretics

Back 42

Induce diuresis without depleting K+. They have been given in combination with thiazide and loop diuretics and the result is improved diuresis without altering K+ balance.

Aldosterone antagonist: spironolactone

Na channel blockers: amiloride and triamterene

Front 43

Spironolactone

Back 43

Potassium-sparing diuretics - aldosterone receptor antagonist. Blocks upregulation of Na/KATPase in the epithelial cells of the collecting duct. Na reabsorption and K secretion are decreased thereby increasing urinary output (osmotic drag). Promotes natriuresis, diuresis, and potassium retention.

Front 44

Amiloride

Back 44

Potassium-sparing diuretic - Na channel blocker. Blocks inward movement of Na and efflux of K at the luminal membrane of the collecting duct.

Not recommended as monotherapy, but used in combination with thiaizide diuretics to offset K+ loss.

Front 45

Triamterene

Back 45

Potassium-sparing diuretic - Na channel blocker. Blocks inward movement of Na and efflux of K at the luminal membrane of the collecting duct.

Not recommended as monotherapy, but used in combination with thiaizide diuretics to offset K+ loss.

Front 46

Calcium channel blockers

Back 46

Block L type calcium channels in cardiac and vascular myocytes. Reducing calcium influx decreases cytoplasmic calcium levels in these cells and reduces contractile strength. Vascular selectivity over cardiac effects is important.

Short acting CCBs have been linked to increased mortality. With the exception of amlodipine, CCBs are contraindicated in patients with CHF.

Side effects: decreases CO and BP, so serious hypertension can occur. Cimetidine slows CCBs metabolism by cytochrome P450, increasing CCBs toxic effects.

Front 47

Amlodipine

Back 47

Long acting dihydropyridine calcium channel blocker with good selectivity for vascular relaxation without myocardial effects.

Only CCB show to reduce atherogenic activity in humans. Does NOT increase mortality in patients with CHF.

Front 48

Nifedipine

Back 48

Short acting calcium channel blocker. Extended release formulation available.

Front 49

Diltiazem

Back 49

Short acting calcium channel blocker. Extended release formulation available.

Front 50

Verapamil

Back 50

Short acting calcium channel blocker. Extended release formulation available.

Can cause severe constipation.

Front 51

Hydralizine

Back 51

Direct vasodilator. Arteriolar dilator thta effectively lowers blood pressure. Tachyphylaxis develops rapidly when used alone. This outcome led to its use in combination with other antihypertensive preparations particularly in severe hypertension.

Used for treatment of eclampsia.

Front 52

Nitroprusside

Back 52

Powerful vasodilator that relaxes both arterioles and veins thereby reducing both blood pressure and venous return (afterload and preload). In the blood, it releases large quantities of NO which increases cGMP and promotes vasorelaxation.

Useful in the management of of hypertensive crises.

Front 53

Nitroglycerine

Back 53

Powerful vasodilator that relaxes both arterioles and veins thereby reducing both blood pressure and venous return (afterload and preload). In the blood, it releases large quantities of NO which increases cGMP and promotes vasorelaxation.

Most commonly used for angina, but its use as an antihypertensive is mainly for the management of hypertensive crises.

Front 54

Caduet

Back 54

Poly pill (amlodipine + atorvastatin) used for comorbid hypertension and hypercholesterolemia. It's the first pill with two drugs for two different diseases. Given once a day.

Front 55

When are beta blockers contraindicated?

Back 55

Patients with asthma, AV block, or uncompensated heart failure.

Front 56

When are ACE inhibitors contraindicated?

Back 56

Patients with severe renovascular disease.

Front 57

When are Thiazide diuretics contraindicated?

Back 57

Patients with severe renal failure or gout.

Front 58

When are calcium channel blockers contraindicated?

Back 58

Nondihydropyridine calcium channel blockers are contraindicated in patients with bradycardia, sick sinus syndrome, AV block, and should be given with care in severe aortic stenosis.

All CCBs except amlodipine are contraindicated in heart failure.

Front 59

What is the initial drug therapy for stage 1 hypertension?

Back 59

Thiazide-type diuretics.

In practice, ACE inhibits or ARB would be first line for hypertension stage 1. Isn't medicine fun?

Front 60

What is the initial drug therapy for stage 2 hypertension?

Back 60

Two-drug combination for most (usually thiazide-type diuretic and ACEI or ARB or BB or CCB)

Front 61

What page were those charts on for drug treatments for heart failure, postmyocardial infarcton, diabetes, ect.?

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