Term
|
Definition
| Stroke volume x heart rate |
|
|
Term
| What two things does stroke volume depend on? |
|
Definition
1. Muscle stretch (after-load, preload, blood volume)
2. Inherent contractility |
|
|
Term
| What controls vascular tone? |
|
Definition
1. sympathetic nerve activity (including that initiated by baroreceptor activity)
2. Endogenous constrictors, dilators (nitric oxide, endothelin, angiotensin, etc.). |
|
|
Term
| What three things relate to total peripheral resistance? |
|
Definition
1. Vascular tone
2. Structural hypertrophy in vascular smooth muscles and cardiomyocytes
3. Blood volume |
|
|
Term
| What organs can affect blood pressure? |
|
Definition
| Brain, heart, kidney, arterial and venous vasculature, baroreceptors |
|
|
Term
| What primarily controls blood volume? |
|
Definition
| Handling of sodium ion by the kidney |
|
|
Term
| List the seven major sites of action for antihypertensive agents |
|
Definition
1. Vasomotor center
2. Sympathetic nervous system
3. Vascular smooth muscle
4. Renal tubular cells
5. Renin-angiotensin system
6. Aldosterone receptor antagonists
7. Endothelin receptor antagonists |
|
|
Term
| What drugs work on the vasomotor center to lower drug pressure? |
|
Definition
| adrenergic α2-agonists; methyldopa |
|
|
Term
| How would you lower blood pressure via the sympathetic nervous system? |
|
Definition
1. Substitute or displace norepinephrine
2. Sympathetic ganglia blockers (risky)
3. β-adrenoceptor antagonists on heart
4. α1-adrenoceptor antagonists on vascular smooth muscle |
|
|
Term
| What drugs work on the vascular smooth muscle to lower drug pressure? |
|
Definition
| A number of direct vasodilators (including nitric oxide [NO] and generators of NO), and those drugs which affect cellular influx of calcium ion (calcium channel blockers). |
|
|
Term
| List four categories of drugs that lower blood pressure through the renin-angiotensin system |
|
Definition
1. β-adrenoceptor antagonists
2. Angiotensin-converting enzyme (ACE) inhibitors
3. Direct angiotensin receptor antagonists (ARBs)
4. Direct renin antagonists |
|
|
Term
| What pathology are endothelin receptor antagonists approved to treat? |
|
Definition
|
|
Term
| What are neprilysin antagonists? |
|
Definition
| Drugs that degrade naturetic factors to lower drug pressure (under current study) |
|
|
Term
| What three categories of diuretic drugs are effective for HTN? |
|
Definition
1. Thiazides
2. Loop diuretics
3. Potassium sparing diuretics
(Carbonic anhydrase inhibitors and osmotic diuretics are not considered effective) |
|
|
Term
| How long do thiazide diuretics take to work? Why? |
|
Definition
Over a period of several weeks:
Initially, BV decreases which lowers CO. They both return to normal due to compensation via the renin-angiotensin system.
After this, continued sodium loss decreases vascular resistance for continued lower blood pressure |
|
|
Term
Why are loop diuretics less popular than thiazides as a HTN diuretic?
When would a loop diuretic be used? |
|
Definition
Loop diuretics are used infrequently because of a short duration of action and modest effects of blood pressure.
They are used in volume-expanded patients with chronic kidney disease. |
|
|
Term
| List six adverse effects of thiazide and loop diuretics |
|
Definition
1. Potassium less
2. Erectile dysfunction
3. Uric acid, gout
4. Changes in glucose tolerance
5. Changes in lipid profile
6. Hypoperfusion of placenta in pregnant women |
|
|
Term
| What drugs are contraindicated with thiazides? |
|
Definition
NSAIDs- will decrease the antihypertensive action of diuretics probably through their ability to inhibit the synthesis of renal prostaglandins
Lithium- will get too concentrated with a diuretic |
|
|
Term
| Describe the mechanism of α-methyl DOPA |
|
Definition
| In the CNS, is metabolized to α-methyl norepinephrine; to inhibit adrenergic neuronal outflow and lower blood pressure |
|
|
Term
| List adverse effects of α-methyl DOPA |
|
Definition
Sedation, dry mouth, reduction libido, Parkinsonian signs, hyperprolactinemia which may cause gynecomastia and galactorrhea
Hepatotoxicity
Hemolytic anemia (rare) |
|
|
Term
| What is the antihypertensive drug of choice for pregnancy? |
|
Definition
|
|
Term
| What is the mechanism of action for clonidine for HTN? |
|
Definition
| Its action is at action at α2A-adrenoceptors in the brain stem which decreases sympathetic outflow |
|
|
Term
| Describe route of administration of Clonidine |
|
Definition
| Administered as a skin patch for a lower plasma concentration, watch for contact dermatitis |
|
|
Term
| List side effects of clonidine |
|
Definition
1. Sedation, dry mouth
2. Orthostatic hypertension
3. Impotence
4. Withdrawal syndrome with abrupt discontinuation
5. Mental depression |
|
|
Term
| What patient population would be given clonidine? |
|
Definition
| In problem patients not responding to other therapeutic combinations; also, patients should be treated concurrently with diuretics and/or direct vasodilators |
|
|
Term
|
Definition
| A rare drug used for HTN that works by blocking NE at sympathetic nerve terminals |
|
|
Term
|
Definition
Depletes nerve endings and CNS sites of NE and serotonin
Adverse effects* limit use, generally used in combination with a thiazide
(*Peptic ulcer, diarrhea, nasal congestion, depression, night terrors, bradycardia, water retention) |
|
|
Term
Which beta blockers are stronger at β1 than β2?
When would they be preferred? |
|
Definition
Metoprolol, atenolol
Better for asthma and diabetes |
|
|
Term
|
Definition
Stronger at β1 than β2
Unusual- exists as two isomers, one isomer blocks β1, the other releases NO from vascular endothelium.
Thus, this drug decreases peripheral vascular resistance whereas the other β-adrenoceptor blockers tend to increase vascular resistance |
|
|
Term
| Give four examples of long-acting β-adrenoceptor blockers which allows once daily dosing for hypertension |
|
Definition
| Nadolol, atenolol, betaxolol, bisprolol |
|
|
Term
| How do you choose between the long-acting β-adrenoceptor blockers for a patient? |
|
Definition
By liver and kidney health
Atenolol- excreted by kidney
Betaxolol/bisprolol- metabolized by liver |
|
|
Term
| What three drugs are partial agonists for the β1-receptor and have some agonist action at β2-receptors? |
|
Definition
1. Penbutolol
2. Pindolol
3. Acebutolol |
|
|
Term
| Why would you choose a partial agonist for the β1-receptor which has some agonist action at β2-receptors? |
|
Definition
| They have less effect on the plasma lipid profile and less effect on depression of cardiac contractility and AV block than the agents without ISA; thus, they may be useful for therapy in patients with significant bradycardia and/or peripheral vascular disease |
|
|
Term
| List adverse effects of beta blockers |
|
Definition
1. Bronchospasm
2. Masks hypoglycemia
3. Fatigue, sleep disturbances
4. Bradychardia, AV block
5. CHF worsens (but mortality decreases)
6. Increases triglycerides, lowers HDL
7. Cold extremities, impotence
8. Orthostatic hypotension
9. Angina or MI with quick stop |
|
|
Term
| What three mechanisms do beta blockers use to lower blood pressure? |
|
Definition
1. Decreased HR and contractility
2. Decreased renin secretion by JG apparatus
3. Decreased sympathetic outflow (but most don't enter CNS) |
|
|
Term
| What patient population responds best to beta blockers? |
|
Definition
| Patients with high renin concentrations in the plasma, i.e., those who are young and white generally speaking |
|
|
Term
| List three examples of alpha blockers |
|
Definition
| Prazosin, doxazosin, terazosin |
|
|
Term
| What is the MOA for alpha blockers? |
|
Definition
α1-adrenoreceptor inhibition causes decreased peripheral resistance and increased venous capacitance;
Heart rate is increased but less than for non-selective blockers
Plasma renin activity through increased sympathetic outflow |
|
|
Term
| List side effects of alpha blockers |
|
Definition
1. Marked hypotension, first dose syncope
2. Palpitations, headache, nervousness
3. Orthostatic hypotension |
|
|
Term
| What patient population would use alpha blockers exclusively for HTN? |
|
Definition
Only people who also have BPH
These drugs have a higher incidence of stroke and CHF, and are usually combined with a βblocker and diuretic |
|
|
Term
|
Definition
A direct vasodilator
(1) Dilates arterioles but not venous capacitance vessels; effect on arterioles due to decreased intracellular calcium; may release endothelial NO.
Rebound renin release can lead to salt/water retention |
|
|
Term
| Describe the pharmacokinetics of hydralazine |
|
Definition
| Acetylated by first pass metabolism (slow acetylators may have drug induced lupus syndrome) |
|
|
Term
| List side effects of hydralazine |
|
Definition
1. Marked hypotension (but little orthostatic hypotension)
2. Rebound renin release
3. Slow acetylators may have lupus-like syndrome or autoimmune reactions
4. Rapid acetylators may have hepatotoxicity
5. Pyroxidine deficiency |
|
|
Term
| Describe the therapeutic use of hydralazine |
|
Definition
Not first-line therapy and generally combined with beta blockers and/or diuretic agents.
Use with caution in elderly and coronary artery disease- decreases coronary perfusion |
|
|
Term
|
Definition
| A direct vasodilator which activates an ATP-dependent potassium channel (channel opener) which increases potassium efflux and causes subsequent hyperpolarization and relaxation |
|
|
Term
| Do minoxidil and hydralazine affect arterioles or veins more? |
|
Definition
|
|
Term
| Describe the pharmacokinetics of minoxidil |
|
Definition
(1) Minoxidil is a prodrug with the active metabolite being a sulfate ester
(2) Because of the formation of an active metabolite, the antihypertensive action is delayed relative to observed peak plasma concentrations of the parent drug. |
|
|
Term
| List side effects of minoxidil |
|
Definition
1. Hypotension-induced SNS activity
2. Sodium and water retention (low renal perfusion)
3. Flattened and inverted T waves
4. (4) Patients with left ventricular hypertrophy and diastolic dysfunction have problems with increased plasma volume
5. Hypertrichosis |
|
|
Term
| What is the therapeutic use of minoxidil? |
|
Definition
| Used only for treatment of severe hypertension and is combined with both a beta-blocker (to decrease myocardial ischemia) and diuretic agent (to help with fluid retention). |
|
|
Term
| Define sodium nitroprusside |
|
Definition
A direct vasodilator
(a) Metabolized to NO by both enzymatic and non-enzymatic processes and a different enzyme is involved than that for nitroglycerin. Unlike NTG, tolerance does not develop. |
|
|
Term
| What vessels do sodium nitroprusside dilate? |
|
Definition
| Both arterioles and capacitance venules |
|
|
Term
| How is cardiac output affected by sodium nitroprusside? |
|
Definition
| Decreases cardiac output in normal people because venous pooling is a larger determinant of output than is decreased afterload; however, the opposite is true in patients with left ventricular dysfunction; cardiac output is increased as afterload is decreased. |
|
|
Term
| How is sodium nitroprusside administered? |
|
Definition
It decomposes in alkali and when exposed to light
Given only by IV in an opaque bad, rapid onset. |
|
|
Term
| Describe the metabolism of sodium nitroprusside and a side effect that comes with it |
|
Definition
| Rapidly metabolized to cyanide which is converted to thiocyanate by hepatic rhodanase; after 24 hr. of infusion, the patient may have accumulated enough of these metabolites to produce toxic effects |
|
|
Term
| List side effects of sodium nitroprusside |
|
Definition
1. Marked hypotension
2. Accumulation of cyanide and thiocyanate, lactic acidosis, toxicity
3. Worsen atrial hypoxemia in COPD |
|
|
Term
| What is the therapeutic use of sodium nitroprusside? |
|
Definition
Hypertensive emergensies
For treatment of CHF when short-term reductions in preload and afterload are required, especially with pulmonary edema
Aortic dissection, but beta blocker given with it |
|
|
Term
|
Definition
| A direct vasodilator which activates ATP-dependent potassium channels causing hyperpolarization and relaxation of blood vessels |
|
|
Term
| How is diazoxide administered? What vessels does it affect |
|
Definition
Only by IV bolus.
Affects arterioles, but not capacitance veins |
|
|
Term
| List side effects of diazoxide |
|
Definition
1. Marked hypotension, precipitates strokes
2. Increases SNS activity, water retention
3. Hyperglycemia secondary to inhibitory effects on the pancreatic β-cell potassium channel causing inhibition of insulin release |
|
|
Term
| What are the therapeutic uses of diazoxide? |
|
Definition
Same as sodium nitroprusside but given only if that drug can not be used, i.e., when accurate pumps are not available or close monitoring of blood pressure is difficult.
Always used in combination with beta blockers |
|
|
Term
|
Definition
| A direct vasodilator; Dopamine-1 (D-1) receptor antagonist |
|
|
Term
| Describe the pharmacokinetics of Fenoldopam |
|
Definition
| Given IV, works within minutes, peak after 2 hours |
|
|
Term
| What is the therapeutic use of Fenoldopam |
|
Definition
| Treatment of individuals with severe HTN who also have substantially reduced renal function; it is considered to be better for this indication than nitroprusside because it causes naturesis, diuresis and increased CrCl |
|
|
Term
| Define calcium channel antagonists |
|
Definition
| Class of drugs used extensively to treat other cardiovascular problems including angina, arrhythmias and heart failure. |
|
|
Term
| What are the four chemical classes of calcium channel antagonists? |
|
Definition
a) Verapamil - phenylalkylamine
b) Diltiazem - benzothiazepine
c) Dihydropyridines (amlodipine, nifedipine, etc.)
d) Bepridil – diarylaminopropylamine (not used for hypertension) |
|
|
Term
| What is the mechanism of action for calcium channel antagonists? |
|
Definition
Block the pore of the L-type, voltage-dependent calcium channels thus decreasing calcium influx.
Lowers heart rate (negative ionotropic effect) |
|
|
Term
| Describe the specific effect of Verapamil on the heart |
|
Definition
| Substantial negative inotropic effect, substantial depression of AV conduction, low selectivity for vasodilatation. |
|
|
Term
| Describe the specific effect of Diltiazem on the heart |
|
Definition
| Milder negative inotropic effect, milder depression of AV conduction, low selectivity for vasodilatation. |
|
|
Term
| Describe the specific effect of Nifedipine and DHPs on the heart |
|
Definition
| Little or no negative inotropic effect, no depression of AV conduction, much better selectivity for vasodilatation |
|
|
Term
How can Verapamil be used in cancer therapy?
For heart failure? |
|
Definition
f) Verapamil blocks the activity of P-glycoprotein to cause the efflux of some drugs from cells and this action may result in a positive effect (decreased resistance) when used in conjunction with cancer chemotherapy
Same effect is toxic in heart failure |
|
|
Term
| Describe the pharmacokinetics of calcium channel blockers |
|
Definition
| Substantial first-pass metabolism and are substantially bound to plasma protein |
|
|
Term
| List side effects of dihydropyridines |
|
Definition
1. Peripheral edema (hemodynamic changes, arteriolar dilation NOT sodium retention)
2. Angina, aggravation of MI
3. Increased SNS activity |
|
|
Term
| List side effects of calcium channel blockers |
|
Definition
1. Bradycardia, cardiac depression
2. Cardiac failure due to increased venous return
3. Constipation, esophageal reflux due to relaxation of gastrointestinal smooth muscle |
|
|
Term
| List therapeutic uses of calcium channel blockers |
|
Definition
1. Angina
2. Cardiac arrhythmias
3. CHF
4. Low renin hypertension (elderly, African Americans)
5. Raynaud's |
|
|
Term
| How is angiotensin II formed? |
|
Definition
Renin cleaves angiotensinogen into angiotensin I.
Angiotensin converting enzyme, cleaves angiotensin I to angiotensin II |
|
|
Term
| What are the three major effects of angiotensin II? |
|
Definition
1. Rapid increase in TPR through CNS-induced vasoconstriction
2. Slow increase in BP
3. Cardiac hypertrophy |
|
|
Term
| What are the two major mechanisms of action of ACE inhibitors? |
|
Definition
1. Decreased formation of ANG II
2. Increased amount of bradykinin (because ACE breaks down this vasodilator) |
|
|
Term
| What are the three groups of ACE inhibitors? |
|
Definition
1) sulfhydryl-containing
2) dicarboxyl-containing
3) phosphorus-containing
All three are the same therapeutically |
|
|
Term
| Describe the pharmacokinetics of ACE inhibitors |
|
Definition
Ester-based ones are well absorbed by the GI
Eliminated by kidney |
|
|
Term
| List six side effects of ACE inhibitors |
|
Definition
1. Hypotension, dizziness
2. Chronic cough
3. Hyperkalemia
4. Acute renal failure if patient has compromised renal blood flow already
5. Fetopathic (contrainidicated in pregnancy)
6. Angioneurotic edema or laryngeal edema |
|
|
Term
| What are the therapeutic uses of ACE inhibitors? (What patients would we give an ACE inhibitor to?) |
|
Definition
1. Monotherapy in young/middle-aged caucasians
2. Drug of choice for diabetics, due to renoprotective action
3. Cardiac failure, MI, renal failure, cirrhosis patients |
|
|
Term
| What is the mechanism of action of angiotensin II receptor antagonists? |
|
Definition
| Block AT1 receptors in a competitive, but essentially irreversible manner |
|
|
Term
| Compare and contrast ACE inhibitors and ARBs |
|
Definition
1. ARBs reduce angiotensin activation more
2. ARBs only affect AT1 receptors, not AT2
3. ARBs do not increase bradykinin and thus do not produce cough or angioedema
4. ARBs are approved for diabetic nephropathy
5. An ARB in study blocks neprilysin, a protease that degrades natriuetic peptides |
|
|
Term
| List four groups of people who should not take ARBs |
|
Definition
1. Pregnany women
2. People with high renin related to volume depletion
3. People with renal disease (hyperkalemia, will decrease renal blood flow)
4. People with low renin, elderly and African Americans |
|
|
Term
| How long can an ARB take to work? |
|
Definition
|
|
Term
| Can NSAIDs be taken with an ARB? Why or why not? |
|
Definition
| They are discouraged because it can increase incidence of renal failure |
|
|
Term
| Define Aliskiren and describe its therapeutic use |
|
Definition
A direct inhibitor of renin
Containdicated in pregnancy, takes 2 weeks for full effect. Metabolized by CYP3A4.
Do not take with high fat meals. |
|
|
Term
|
Definition
An antagonist of the aldosterone receptor but is generally only referred to as a potassium-sparing diuretic agent
Generally not used due to poor efficacy and adverse reactions |
|
|
Term
|
Definition
An aldosterone antagonist more specific than spironolactone
Less sexual side effects, but still has K+ retention |
|
|
Term
| Why are endothelin receptor antagonists not commonly used? |
|
Definition
Both drugs have a substantial potential to produce liver injury and peripheral edema.
However, they can help patient mobility in pulmonary hypertension. |
|
|
Term
| Define ambrisentan and bosetan |
|
Definition
The only two endothelin receptor antagonists on the market right now,
Contraindicated in pregnancy. |
|
|
Term
| Give some examples of Thiazide diuretics |
|
Definition
Chlorothazide (Diuril)
Chlorthalidone (Generic)
Hydrochlorothiazide (Microzide, HydroDiuril)
Polythiazide (Renese)
Indapamide (Lozol)
Metolazone (Mykrox [5 times more bioavailable) or Zaroxolyn) |
|
|
Term
| Give some examples of loop diuretics |
|
Definition
Bumetanide (Bumex)
Furosemide (Lasix)
Torsemide (Demadex) |
|
|
Term
| Give some examples of potassium sparing diuretics |
|
Definition
Amiloride (Midamor)
Triamterene (Dyrenium)
Aldosterone receptor blockers Eplerenone (Inspra) Spironolactone (Aldactone) |
|
|
Term
| Give some examples of beta blockers used for hypertension |
|
Definition
Atenolol (Tenormin)
Betaxolol (Kerlone)
Bisoprolol (Zebeta)
Carteolol (Cartrol)
Esmolol (BreviBloc)
Metoprolol (Lopressor, also extended release Toprol XL)
Nadolol (Corgard)
Nebivolol (Bystolic)
Propranolol (Inderal)
Timolol (Blocadren) |
|
|
Term
| Give some examples of Beta-adrenergic blockers with intrinsic sympathomimetic activity (ISI) |
|
Definition
Acebutolol (Sectral)
Penbutolol (Levatol)
Pindolol (generic) |
|
|
Term
| Give some examples of Adrenergic blockers which inhibit both alpha and beta receptors |
|
Definition
Carvedilol (Coreg)
Labetalol (Normodyne, trandate) |
|
|
Term
| Give some examples of Angiotensin converting enzyme inhibitors (ACEIs) |
|
Definition
Benazepril (Lotensin)
Captopril (Capoten)
Enalapril (Vasotec)
Fosinopril (Monopril)
Lisinopril (Prinivil, Zestril)
Moexipril (Univasc)
Perindopril (Aceon)
Quinapril (Accupril)
Ramipril (Altace)
Trandolapril (Mavik) |
|
|
Term
| Give some examples of Angiotensin II antagonists (ARBs) |
|
Definition
Azilsartan medoxomil (Edarbi)
Candesartan (Atacand)
Eprosartan (Teveten)
Irbesartan (Avapro)
Losartan (Cozaar)
Olmesartan (Benicar)
Telmisartan (Micardis)
Valsartan (Diovan) |
|
|
Term
| Give some examples of Calcium channel blockers – nondihydropyridines |
|
Definition
Diltiazem extended release (Cardizem CD, Cardizem LA, Dilacor XR, Tiazac)
Verapamil immediate release (Calan, Isoptin)
Verapamil sustained release (Cardene SR)
Verapamil (Coer, Covera HS, Verelan PM) |
|
|
Term
| Give some examples of Calcium channel blockers – dihydropyridines |
|
Definition
Amlodipine (Norvasc)
Felodipine (Plendil)
Isradipine (Dynacirc CR)
Nicardipine sustained release (Cardene SR)
Nifedipine long-acting (Adalat CC, Procardia XL)
Nisoldipine (Sular)
Clevidine (Cleviprex) New short acting agent used only IV for emergency treatment |
|
|
Term
| List two direct vasodilators used for daily treatment of hypertension |
|
Definition
Hydralazine (Apresoline)
Minoxidil (Loniten) |
|
|
Term
| List three direct vasodilators used Intravenously for treatment of hypertensive emergencies |
|
Definition
Diazoxide (Proglycem)
Fenoldopam (Corlopam)
Nitroprusside sodium (Nipride) |
|
|
Term
| List two endothelin receptor blockers |
|
Definition
Ambrisentan (Letairis)
Bosentan (Tracleer) |
|
|
