Chapter 17 to 19 Flashcards
Defined as either a sustained systolic blood pressure of greater than 140 mm Hg or a sustained diastolic blood pressure of greater than 90 mm Hg.
Hypertension
This results from increased peripheral vascular arterioral smooth muscle tone, which leads to increased peripheral vascular arteriolar resistance and reduced capacitance of the venous system.
hypertension
Have a higher incidence of hypertension than do both non-hispanic whites and Hispanic whites
Non-hispanic black
What controls cardiac output and peripheral resistance
Baroreflexes and the renin angiotensin aldosterone system
Most antihypertensive drugs lower blood pressure by (increasing, reducing) cardiac and/or (increasing/decreasing) peripheral resistance
Reducing, decreasing
Reducing cardiac output - slowing the heart rate
Decreasing peripheral resistance - relaxing blood vessels
Arterial blood pressure is (indirectly, directly) proportional to cardiac output and peripheral vascular resistance
Directly
Acts by changing the activity of the sympathetic nervous system
Baroreflexes
Responsible for the rapid, moment-to-moment regulation of blood pressure
Baroreflexes
How does sympathetic nervous system respond to a drop in blood pressure
Vasoconstriction and increased cardiac output
Provides long-term control of blood pressure by altering the blood volume
kidney
In response to reduced arterial pressure, baroreceptors in the kidney releases what enzyme
renin
What increases renin releases
Low sodium intake and greater sodium loss
Converts angiotensinogen to angiotensin I
renin
Is a potent circulating vasoconstrictor, constricting both arterioles and veins, resulting in a increase in blood pressure
Angiotensin II
Lowering of even moderately elevated blood pressure significantly (increases reduces) cardiovascular disease
reduces
Start two antihypertensives simultaneously when
Patients with systolic blood pressure greater than 160 mmHg or diastolic blood pressure greater than 100 mm Hg
Most common reasono for failure of antihypertensive therapy
Lack of patient compliance
B-blockers can cause adverse effects in male like
Sexual dysfunction
Can be used as initial dug therapy for hypertension unless there are compelling reasons to choose another agent
Thiazide diuretics
Lowers blood pressure initially by increasing sodium and water excretion
This causes a decrease in extracellular volume, resulting in a decrease cardiac output and renal blood flow
Thiazide diuretics
Can induce hypokalemia, hyperuricemia and hyperglycemia in some patients
Hyperuricemia - high level of uric acid in blood
Thiazide diuretics
Act promptly by blocking sodium and chloride reabsorption in the kidneys, even in patients with poor renal function or those who have not responded to thiazide diuretics
Loop diuretics
Cause decreased renal vascular resistance and increased in renal blood flow
Loop diuretics
Unlike thiazides, this diuretics can increase the Ca2+ content of urine
Loop diuretics
Thiazide diuretics decrease the Ca2+ content of urine
These are rarely used alone to treat hypertension, but are commonly used to manage symptoms of heart failure and edema
Loop diuretics
Edema - build up of fluid on the body
This diuretics reduce potassium loss in the urine
Potassium sparring diuretics
Aldosterone receptor antagonist
Are sometimes used in combination with loop diuretics and thiazides to reduce the amount of potassium loss induced by these diuretics
Potassium-sparring diuretics
These are treatment option for hypertensive patients with concomitant heart disease or heart failure
B-blockers
Concomitant - accompanying
What is the action of b-blockers as antihypertensives
– reduce blood pressure by decreasing cardiac output
- may also decrease sympathetic outflow from the CNS
- inhibit release of renin from the kidneys, thus decreasing the formation of angiotensin II and secretion of aldosterone
– Beta-blockers inhibit renin release from the kidneys, which reduces the production of angiotensin II.
- Decreasing formation of angiotensin II = less aldosterone secretion
- Less aldosterone secretion, so the body excretes more sodium and water, reducing blood volume and further lowering blood pressure.
- Too much aldosterone can cause high BP
Which drug acts as both b1 and b2 blcoker
Propranolo
Nonselective blockers like propranolol and nadolol, are contraindicated in patients with asthma due to their blockade of b2-mediated bronchodilation.
B-blockers should be used cautiously to patients with aute heart failure or peripheral vascular disease
What are some selective b1 blockers
Metoprolol
Atenolol
MANBABE
This two are among the most commonly prescribed b-blockers
A selective b1 blockers that also increases the production of nitric oxide, leading to vasodilation.
Nebivolol
Is the only drug in ACE inhibitor class available intravenously
Enalaprilat
True or false
Dry cough side effect of ACE inhibitors occurs more frequently in men
FALSE
## footnote
It occurs requetly in woman
An adverse effect of ACE inhibitors which occurs in up to 10% patients, that is thought to be due to increased levels o bradykinin and subtance P in the pulmonary tree
Dry cough
Hypertension with no identifiable cause
Essential hypertension
Can induce fetal malformations ad hsoldnot be used by pregnant women
ACE inhibitors
These are alternatives to ACE inhibitors
ARBs (angiotensin II receptor blockers)
ARBs pharmacological effects are similar to those of ACE inhibitors
ARBs do not increase bradykinin levels.
A rare but potentially life-threatening reaction that may also be due to increased levels of bradykinin
angioedema
The adverse effects of ARBs is similar to ACE inhibitors although the risk of _______ are decreased
Cough and angioedema
Can ARBs and ACE be combined to use as treatment?
No, due to similar mechanisms and adverse effects
Directly inhibits renin
Aliskiren
Acts earlier in the renin angiotensin aldosterone system than ACE inhibitors and ARBs
B-blockers that are available in intravenousformultions
Esmolol
Metoprolol
Propranolol
This can also cause cough and angioedema but less often than ACE inhibitors
Aliskiren - renin inhibitor
Aliskiren is metabolized by
CYP 3A4
Are recommended treatment option in hypertensive patients with diabetes or angina
calcium channel blockers
Angina - chest pain
Three classes of calcium channel blockers
Diphenylalkylamines
Benzothiazepines
Dihydropyrodines
It is the least selective of any calcium channel blockers and has significant effects on both cardiac and vascular smooth muscle cells
Verapamil
It is also use to treat angina and supraventricular tachyarrhythmias and to prevent migraine and cluster headaches
it is the only member of benzothiazepines that is currently approved in United States
Diltiazem
Like verapamil, Diltiazem also affects both cardiac and vascular smooth muscles. What is their difference
Diltiazem is less negative inotropic effect on the heart compared to that of verapamil. It has also favorable side effect profile.
Diltiazem has a weaker negative inotropic effect than Verapamil, making it a safer option in patients who need calcium channel blockers but cannot tolerate strong heart suppression.
The prototype b blocker is
propranolol
The prototype of dihydropyridine calcium channel blockers
Nifedipine
Have much greater affinity for vascular calcium channels than for calcium channel in the heart they are, therefore, Beneficial in treating hypertension
Dihydropyridines
Have the advantage in that they show little interaction with other cardiovascular drugs .
Block the inward movement of calcium by binding to L-type calcium channels in the heart and in smooth muscle of the coronary peripheral arteriolar vasculature
Calcium channel antagonists
May be administered cautiously to hypertensive patients with asthma
Selective b-blockers
This type of dosage form of b-blockers may take several weeks to develop their full effects
Oral b-blockers
What are some common adverse effects of b-blockers
May cause
- bradycardia
- hypotension
- CNS side effects like fatigue, lethargy, and insomnia
- decrease libido
- cause eretile dysfunction
Bradycardia - slow heart rate
Hypotension - low BP
Libido - sexual drive
What b-blockers may disturb lipid metabolism?
Noncardioselective b-blokers
Are recommended as first-line treatment of hypertension in patients with a variety of compelling indications, including stroke, diabetes, heart failure
ACE inhibitors
This drugs lower blood pressure by reducing peripheral vascular resistance without reflexively increasing cardiac output
ACE inhibitors
Increased PVR → Higher Blood Pressure (seen in hypertension).
Decreased PVR → Lower Blood Pressure (caused by vasodilators or exercise).
Block the enzyme ACE which cleaves angiotensin I to form the potent vasoconstrictor angiotensin II
ACE inhibitors
ACE - ACE is an enzyme that converts angiotensin I into angiotensin II, which narrows blood vessels (vasoconstriction) and increases blood pressure. It also stimulates aldosterone release, leading to water and sodium retention, further raising blood pressure.ACE is an enzyme that converts angiotensin I into angiotensin II, which narrows blood vessels (vasoconstriction) and increases blood pressure. It also stimulates aldosterone release, leading to water and sodium retention, further raising blood pressure.
A peptide that increases the production of nitric oxide and prostacyclin by the blood vessels
bradykinin
What does ACE inhibitor decrease that results to decreased sodium and water retention
Secretion of aldosterone
What are the first-line drugs for treating hear failure hypertensive patients with chronic kidney disease, and patients at increased risk of coronary artery disease?
ACE inhibitors
All ACE inhibitors except ____ and _____ undergo hepatic conversion to active metabolites.
Captopril and Lisinopril
This agents may be preferred in patients with severe hepatic impairment
What is the only ACE inhibitor that is not eliminated primarily by the kidneys and does not require dose adjustments in patients with renal impairment
Fosinopril
Renal impairment - decline in kidney
What is the role of intracellular concentrations of calcium
Maintaining the tone of smooth muscle and in the concentration of the myocardium
Calcium enters the muscle cell through
Special voltage sensitive calcium channels
Does calcium channel blockers dilate vevins?
No they dont
They are useful for hypertensive patients who also have asthma,diabetes, or peripheral vascular diseasee
calcim channel blockers
Unlike b-blockers, they do not have the potential to adversely affect these conditions
All CCBs are useful for the treatment of angina. _____, ____, are used in the treatment of atrial fibrillation.
Diltiazem and verapamil
This CCB has a very long half life and does not require a sustained release formulation
amlodipine
Nifedipine and other dihydropyridine may cause
Gingival hyperplasia
Gingival hyperplasia is the overgrowth or enlargement of the gum tissue.
What diverse effects are more frequent in dihydropyridines?/
Dizziness
Headache
Feeling of fatigue caused by decrease blood pressure
They decrease peripheral vascular resistance and lower arterial blo0d pressure by causing relaxation of both arterial and venous smooth muscle.
A-adrenocceptor-blocking agents
Increased PVR → Higher Blood Pressure (seen in hypertension).
Decreased PVR → Lower Blood Pressure (caused by vasodilators or exercise).
These drugs produce a competitive block of a1-adrenoceptors
Prazosin
Doxazosin
Terazosin
These druugus block a1, b1 and b2 receptors
Labetalol
Carvedilol
This may be an effective antihypertensive, it is mainly use in the treatment of heart failure
Carvedilol
These have been shown to reduce morbidity and mortality associated with heart failure
Carvedilol
Metoprolol succinate
Bisoprolol
Morbidity - worsening of the disease
Mortality - risk of death
Is used in the management of gestational hypertension and hypertensive emergencies
Labetalol
Gestational hypertension - high blood pressure that develops during pregnancy
Acts centrally as an a2 agonist to produce inhibition of sympathetic vasomotor centers, decreasing sympathetic outflow o the periphery
Clonidine
This leads to reduced total peripheral resistance and decreased blood pressure.
Clonidine is absorbed well after oral administration and is excreted by the kidney it is also available in ____
Transdermal patch
Is an a2 agonist that is converted to methyl norepinephrine centrally to diminish adrenergic outflow drom the CNS
methyldopa
Most common side effect of methyldopa are
Sedation and drowsiness
Where is methyldopa mainly used
Mainly used for management of hypertension in pregnancy
its use is limited due to adverse effects and the need for multiple doses
Used primarily fr the treatment of hypertension that has not responded adequately to treatment with two or more drugs
Clonidine
Is almost always administered in combination with a b-blcoker, such as propranolol, metroplol or atenolol (to balance the reflec tachycardia) and a diuretic (to decrease sodium retention)
Hydralazine
The three drugs decrease cardiac output, plasma volume, and PVR
What syndrome can ccur in high dosages of hydralazine
Lupus-like syndrome
Causes hypertrichosis (growth of body hair)
This drugs is used topically to treat male pattern baldness
Minoxidil
Is a rare but life threatening situation characterized by severe elevations in blood pressure with evidence of impending or progressive organ damage
Hypertensive emergency
A severe elevation in blood pressure without evidence of target organ damage is considered a
Hypertensive urgency
Is defined as blood pressure tht remains elevated despite administration of an optimal three-drug regimen that includes a diuretic
Resistant hypretension
Common causes of resistant hypretension
Poor compliance
Excessive ethanol intake
Concomitant conditions
Concomitant medications
Use of drugs with similar MOA
May lower blood pressure quickly with minimal adverse effects
Combination therapy with separate agents or a fixed -dose combination pill
A man is n hypertension therapy and developed a dry cough which is most likely responsible for this side effect?
A. Enalapril
B. Losartan
C. Nifedipine
D. Prazosin
E. propranolol
A
The cough is most likely an adverse
effect of the ACE inhibitor enalapril. Losartan is an ARB that has the same beneficial effects as an ACE inhibitor but is less likely to produce a cough. Nifedipine, prazosin, ang propranolol do not cause this side effect.
A 48-year-old hypertensive patient has been
successtully treated with a thiazide diuretic for the last 5 years. Over the last 3 months, his diastolic pressure has steadily increased, and he was started on an additional antihypertensive agent. He complains of several instances of being unable to achieve an erection and not being able to complete three sets of tennis as he once did. Which is the likely second antihypertensive
medication?
A. Captopril.
B. Losartan.
C. Metoprolol.
D. Minoxidil.
E. Nifedipine.
Correct answer = C. The side effect profile of B-blockers,
such as metoprolol, is characterized by interference with sexual performance and decreased exercise tolerance. None of the other drugs is likely to produce this combination of side effects.
are drugs that increase the volume of urine excreted
diuretics
Five functional zones along the nephron
Proximal convoluted tubule - acetazolamide
Descending loop of Henle
Ascending loop of Henle - loop diuretics
Distal convoluted tubule - thiazide an thiazide like
Collecting tubule and duct - spironolactone, amiloride, triamterene
Located in the cortex of the kidney
Proximal convoluted tubule
The site or the organic acid and base secretory systems
Proximal tube
Located in the middle-third of the proximal tubule that Secretes a variety of organic acids, such as uric acid, antibiotics and diuretics from the blood stream into the proximal tubular lumen
Organic acid secretor system
What interferes with penicillin secretion
Probenecid
Located in the upper and middle segments of the proximal tubule and is responsible for the secretion of creatinine and choline
Organic base secretory system, located n the upper an middle segments
Osmotic diuretics exet part f their action in this region
Descending loop of henle
A diluting region of the nephron and major site for salt reabsorption
Ascending loop of henle
Ca2 excretion is regulated by parathyroid hormone in this porrtrion of the tubule
Distal convoluted tubule
Sodium enters the principal cells through channels that are inhibited by
Amiloride and triamterene
Promote the reabsorption of water from the collecting tubules and ducts
Antidiuretic hormone
Most widely used diuretics
Thiazides
Sometimes called low ceiling diuretics
Thiazide
It is because increasing the dose above nomarl dose does not promote further diuretic response
First orally active diuretic that was capable of affecting the severe edema often seen in hepatic cirrhosis and heart faulire with minimal side effects
Chlorothiazide
3 thiazide like diuretics
Chlortalidone
Indapamide
Metolazone
They containe sulfonamide residue and their MOA is similar but they are not truly thiazides
Where do thiazide like diuretics mainly act
Cortical region of the ascending loop of Henle and the distal convoluted tubule
They have leesser effect in the proximal tubule
The efficacy of thiazide agents may be diminished with concomitant use of NSAIDS like
Indomethacin - inhibits production of renal prostaglandins, reducing renal blood flow
Action of thiazide
Cause diuresis with increased Na and Cl excretion which can result in the secretion of very hyperosmolar urine
Hyperosmolar - concentrated
This effect is unique as other diuretics are unlikely to produce a hyperosmolar urine
With the chronic use of thiazide diuretics what is required
Magnesium deficiency requiring supplementation
Are the diuretics of choice in reducing extracellular volume in heart failure
Loop diuretics
In treating idiopathic hypercalcuria this can be used
Thiazides
Thiazides inhibit urinary Ca excretion , beneficial for patients with calcium oxalate stones in the urinary tract
Thiazides can substitute ADH in the treatment of
Nephrogenic diabetes insipidus
Most frequent adverse effect of thiazides
Hypokalemia
K deficency - hypokalemia can be overcome by
Spironolactone which interferes with aldosterone action
Or Triamterene or amiloride to retain K
## footnote
Increased aldosterone contributes to urinary K losses
Hyponatremia may develop due to elevation of ADH as a result of
hypovolemia
A nonthiazide derivative that is like hydrochlorothiazide
Chlorthalidone
- long duration of action and is only once daily
More potent than thiazides, causes Na excretionan even in advanced renal failure
Metolazone
