antihypertensives

Question 1

when does hypertension occurs

Answer 1

when systolic blood pressure
exceeds 130 mm Hg or diastolic blood pressure exceeds 80mm Hg on at least two occasions.

Question 2

what diseases results in hypertension

Answer 2

increased peripheral vsm tone

Question 3

what are the complications of HTN

Answer 3

heart disease,strokes,HF,and chronic kidney disease

Question 4

what are the HTN stages

Answer 4

normal—-<120 sys——<80 dia

elevated ——120-129 sys—–80-89 dai

stage 1 ———130-139 sys——–80-89 dia

stage 2——— >140 sys——->90 dia

Question 5

what is the etiology of HTN

Answer 5

◼

More than 90% of patients have essential HTN.

◼

A family history of HTN increases the likelihood that an individual will develop HTN.
◼

Its prevalence increases with age
◼

Non-Hispanic blacks have a higher incidence of HTN than do both non-Hispanic whites and Hispanic whites .
◼

Persons with diabetes, obesity, or disability status are more likely to have HTN.
◼

Environmental factors, such as a stressful lifestyle, high dietary intake of Na+, & smoking, may further predispose an individual to HTN.

Question 6

what is the MOA for controling bp

Answer 6

two main mechanisms: baroreflexes (sympathetic) and RAAS(renin-angiotensin-aldsterone system)

Question 7

what are the goals of HTN treatment

Answer 7

reduce CV and renal morbidity and mortality

the systolic should be less tha 130 and diastolic less than 80

Question 8

what should we think about when choosing the treatment for HNT

Answer 8

◼
If BP is inadequately controlled, a second drug should be added, with the selection based on minimizing the adverse effects if the combined regimen and achieving goal BP.
◼
Patients with systolic BP greater than 20 mm Hg above goal or diastolic BP more than 10 mm Hg above goal should be started on two antihypertensives simultaneously.
◼
Combination therapy with separate agents or a fixed-dose combination pill may lower BP more quickly with minimal adverse effects.
◼
A variety of combination formulations of the various pharmacologic classes are available to increase ease of patient adherence to treatment regimens that require multiple medications.

Question 9

how do diuretics work for HTN

Answer 9

by reducing the blood volume therefore the BP

Question 10

how does thiazide diuretics work?

Answer 10

hydrochlorothiazide and chlorthalidone lower bp by increasing NA and water excretion

they are the initial drug

they are useful with B blockers, ACEI , ARBS, Potassium-sparing diuretics

may cause hypokalemia, hyperuricemia, and
hyperglycemia.

Question 11

why isnt metolazone useful as a thiazide diuretic in combinations

Answer 11

because its not effective with inadequate kidney function patients

Question 12

how do loop diuretics work in HTN

Answer 12

The loop diuretics (furosemide, torsemide, bumetanide &ethacrynic acid) act promptly by blocking Na and Cl
reabsorption in the kidneys, even in patients with poor renal function or who have not responded to thiazides diuretics.
◼
Rarely used in HTN, mostly for HF and edema

Question 13

what are the uses of potassium sparing diuretics for HTN

Answer 13

Amiloride and triamterene (inhibitors of epithelial Na transport at the late distal and collecting ducts) as well as spironolactone and eplerenone (aldosterone antagonists) reduce potassium loss in the urine.
◼
Aldosterone antagonists have the additional benefit of
diminishing the cardiac remodeling that occurs in HF.
◼
Used in combination with diuretics to reduce K loss

Question 14

what are the pharmacokinetics of Beta blockers

Answer 14

orally active

◼ Propranolol undergoes extensive and highly variable
first-pass metabolism.
◼ Oral β-blockers may take several weeks to develop
their full effects.
◼Esmolol, metoprolol, and propranolol are available
in intravenous formulations

Question 15

what are the side effects of beta blockers

Answer 15

◼
Alterations in serum lipid patterns:noncardioselective β-blockers may disturb lipid metabolism, decreasing HDL cholesterol and increase triglycerides.
◼
Drug withdrawal: Abrupt withdrawal may
induce HTN, angina, MI, and even sudden
death in patients with IHD. Therefore, these
drugs must be tapered over a few weeks in
patients with HTN and IHD.

Question 16

how do beta blockers reduce bp

Answer 16

by reducing the activation of beta 1 adrenoceptors on the heart

by reducing the release of renin

Question 17

how do ACEI like enalapril and lisinopril

Answer 17

by inhibiting angiotensin I from converting into angiontensin II

Question 18

what are the actions of ACEI

Answer 18

increase in bradykinin which increase the production of NO and prostacyclin

decrease in ang-II

reduce preload and afterload therefore the cardiac work

Question 19

what are the therapeutic uses of ACEI

Answer 19

ACE inhibitors & ARB slow the progression of diabetic
nephropathy and decrease albuminuria.
◼
ACE inhibitors are a standard in a patient following MI and first line in patients with systolic dysfunction.
◼
Chronic treatment achieves sustained BP reduction, regression of left ventricular hypertrophy, and prevention of ventricular remodeling after a MI.
◼
These are first-line drugs for treating HF, hypertensive patients with chronic renal disease, and for patients with increased risk for coronary artery disease.

Question 20

what are the pharmacokinetics of ACEI

Answer 20

the are all prodrugs that undergo hepatic metabolism except captopril and lisinopril

fosinopril is the only one that doesnt undergo elimination by the kidneys

Question 21

what are the side effects of ACEI

Answer 21

◼
The dry cough, which occurs in up to 10% of patients,
is thought to be due to increased levels of bradykinin and substance P in the pulmonary tree
it occurs more frequently in women.
The cough resolves within a few days of discontinuation.
◼

Angioedema is a rare but potentially life-threatening reaction
that may also be due to increased levels of bradykinin
◼
Potassium levels must be monitored due to hyperkalecima
◼
potassium supplements, high- potassium diets and use of potassium-sparing diuretics should be used with caution.
◼
ACE inhibitors can induce fetal malformations and should not be used by women who are pregnant

Question 22

how are ARBS used in HTN

Answer 22

ARBS such as losartan and irbesartan

◼
These drugs block the AT1 receptors, decreasing the
activation of AT1 receptors by angiotensin II
◼
Their pharmacologic effects are similar to ACE inhibitors.
◼
ARBs do not increase bradykinin levels.
◼
ARBs used as first line in HTN.
◼
Adverse effects are similar to those of ACE inhibitors, although the risks of cough and angioedema are significantly decreased.
◼
ARBs are also teratogenic.

Question 23

how are renin inhibitors used for HTN

Answer 23

A selective renin inhibitor, aliskiren, is used for the treatment of HTN.
◼
It directly inhibits renin and, thus, acts earlier in the RAAS thanACE inhibitors or ARBs.
◼
It lowers BP effectively as ARBs, ACE inhibitors, and
thiazides.
◼
Aliskiren can cause diarrhea, cough and angioedema but
probably less often than ACE inhibitors.
◼
The drug is contraindicated during pregnancy

Question 24

when do we use and not use CCBs

Answer 24

They are effective in treating HTN in patients
with angina or diabetes.

◼ High doses of short-acting CCBs should be
avoided because of increased risk of MI due to
excessive vasodilation and marked reflex
cardiac stimulation.

Question 25

what are the different classes of CCBs

Answer 25

1) diphenylalkylamine (verapamil)
is the least selective CCB and has
significant effects on both cardiac and
VSMCs.
It is used to treat angina, supraventricular
tachyarrhythmias, and to prevent
migraine headache.

2)benzothiazepine (diltiazem)
◼
affects both cardiac and VSMCs, but it has
a less pronounced negative inotropic
effect compared to that of verapamil.
◼
Diltiazem has a favorable side-effect
profile(less side effects)

3) dihydropyridines (nifedipine, amlodipine, felodipine, isradipine, nicardipine, and nisoldipine.
)

All dihydropyridines have a much greater affinity for
vascular Ca channels than for Ca channels in the heart.
◼
They have the advantage in that they show little interaction with other CV drugs, such as digoxin or warfarin, which areoften used concomitantly with CCBs.

Question 26

what are the actions of CCBS

Answer 26

◼ Ca-channel antagonists block the inward movement
of Ca by binding to L-type Ca channels in the
heart and in smooth muscle of the coronary and
peripheral vasculature.
◼ This causes vascular smooth muscle to relax, dilating
mainly arterioles.

Question 27

what aare the therapeutic uses of CCBS

Answer 27

These agents are useful in the treatment of
hypertensive patients who also have asthma,
diabetes, angina, and/or peripheral vascular
disease.
◼ All CCBs are useful in the treatment of angina.
◼ Diltiazem and verapamil used in the treatment of
atrial fibrillation.

Question 28

what are the pharmacokinetics of CCBs

Answer 28

Most of these agents have short half-lives (3–8
hours) following an oral dose.
◼ Sustained-release preparations are available and
permit once-daily dosing.
◼ Amlodipine has a very long half-life and does
not required a sustained-release formulation.

Question 29

what are the side effects of CCBS

Answer 29

AV block and constipation are common side effects of
verapamil.
◼
Verapamil and diltiazem should be avoided in patients with HF or with AV block due to its negative inotropic and
dromotropic (velocity of conduction) effects.
◼
Dizziness, headache, and a feeling of fatigue caused by a
decrease in BP are more frequent with dihydropyridines.
◼
Nifedipine may cause gingival enlargement.

Question 30

what are alpha-blockers agents

Answer 30

Prazosin, doxazosin, and terazosin produce a
competitive block of α1-adrenoceptors.
◼ They decrease peripheral vascular resistance and
lower arterial BP by causing relaxation of both arterial
and venous smooth muscle.
◼ Due to weaker outcome data and their side effect
profile, α-blockers are no longer recommended as
initial treatment for hypertension but may be used
for refractory cases

Question 31

Labetalol and carvedilol block α1, β1 and β2
receptors.
◼ Carvedilol is mainly used in the treatment of
HF.

both are mixed blockers

Question 32

what is Clonidine

Answer 32

Centrally Acting Adrenergic Drug
◼
α2-agonist that diminishes central adrenergic outflow,
decreasing the firing rate of the sympathetic nerves and the
amount of norepinephrine release.
◼
It is used primarily for the treatment of HTN that has not
responded adequately to treatment with two or more drugs

Question 33

what is alpha methyldopa

Answer 33

Centrally Acting Adrenergic Drug
α2-agonist that is converted to methylnorepinephrine
centrally to diminish the adrenergic outflow from the
CNS.
◼ The most common side effects are sedation and
drowsiness.
◼ It is mainly used for management of HTN in
pregnancy

Question 34

what are vasodilators

Answer 34

◼
The direct-acting smooth muscle relaxants, such as
hydralazine and minoxidil, are not used as primary drugs to treat HTN.
◼
Act by producing relaxation of VSM, which decreases
resistance and BP.
◼
Both agents produce reflex stimulation of the heart,
resulting in increased myocardial contractility, HR, and
oxygen consumption.
These actions may prompt angina pectoris, MI or
HF in predisposed individuals.
◼ Vasodilators also increase plasma renin
concentration, resulting in Na and water retention.

◼ These undesirable side effects can be blocked by
concomitant use of a diuretic and a β-blocker.

◼ The 3 drugs decrease CO, plasma volume, and
peripheral vascular resistance

◼
Hydralazine monotherapy is an accepted medication for
controlling BP in pregnancy-induced HTN.
◼
Adverse effects include headache, tachycardia, nausea,
sweating, arrhythmia, and precipitation of angina.
◼
A lupus-like syndrome can occur with high dosage, but
it is reversible on discontinuation of the drug.
◼
Minoxidil treatment also causes hypertrichosis, it is
now used topically to treat male pattern baldness

Question 35

what is hypertensive emergency?

Answer 35

◼ Hypertensive emergency is a rare but life-threatening
situation
◼ characterized by severe elevations in BP (SBP >180
mm Hg or DPB >120 mm Hg)
◼ with evidence of impeding or progressive target
organ damage (e.g., stroke, MI).
◼ It require timely BP reduction by IV administration to prevent or limit organ damage.

Question 36

what meds do we use for hypertensive emergency

Answer 36

CCBs (nicardipine and clevidipine),

NO vasodilators (nitropruside and nitroglycerin),

adrenergic receptor antagonists (phentolamine,
esmolol, and labetalol),

vasodilator hydralazine,

dopamine agonist fenoldopam

Question 37

what is resistant hypertension

Answer 37

◼
It is defined as BP that remains elevated (above goal) despite administration of an optimal three-drug regimen that includes a diuretic.
◼
The most common causes of resistant HTN:
◼
poor compliance, excessive ethanol intake,
◼
concomitant conditions (diabetes, obesity, sleep apnea,
hyperaldosteronism,
◼
high salt intake, and/or metabolic syndrome),
◼
concomitant medications (sympathomimetics, NSAIDs, or antidepressant medications),
◼
insufficient dose and/or drugs, and use of drugs with similar mechanisms of action.