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Anti HTN Drugs I & II

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xibocutie's version from 2017-03-19 09:29

Section 1

Question Answer
What type of drug is Hydrochlorothiazide?Diuretic
What type of drug is Metolazone?Diuretic
What type of drug is Furosemide?Diuretic
What type of drug is Torsemide?Diuretic
What type of drug is Triamterene?Diuretic
What type of drug is Amiloride?Diuretic
What type of drug is Spironolactone?Diuretic
What type of drug is Captopril?ACE Inhibitor
What type of drug is Enalapril?ACE Inhibitor
What type of drug is Losartan?Angiotensin receptor blocker
What type of drug is Aliskiren?Renin Inhibitor
What type of drug is Nifedipine?Calcium channel blocker
What type of drug is Verapamil?Calcium channel blocker
What type of drug is Diltiazem?Calcium channel blocker
What type of drug is Hydralazine?Direct vasodilator
What type of drug is Minoxidil?Direct vasodilator
What type of drug is Sodium Nitroprusside?Direct vasodilator
What type of drug is Metoprolol?Sympatholytic
What type of drug is Prazosin?Sympatholytic
What type of drug is Clonidine?Sympatholytic
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Section 2

Question Answer
Diuretic Section
Thick ascending loop of henle actively reabsorbs how much Na via what transporter?25% Na reabsorbed here via Na/K/2Cl symporter
Distal Convoluted Tubule reabsorbs how much Na via what transporter?only 5% of filtered Na, via Na/Cl symporter
Late Distal Tubule and Collecting Duct: how much Na reabsorbed and what is secreted actively here?Na reabsorb via renal-specific Na channels, only 1-2% of filtered Na reabsorbed, K and H ions actively secreted in this segment
Water moves in kidney how?Transcellular and paracellular pathways, follows concentration of solutes
Diurectics block water reabsorption how?By blocking solute reabsorption (usually Na), blocks formation of gradient, inhibits the pull of water of of the nephron. Diuretics cause diuresis (increase urine volume) and natriuresis (excretion of sodium in the urine)
Which are the most powerful diuretics?Loop diuretics (Na/K/2Cl) symport inhibitors. Agents that act beyond the Loop of Henle (thiazides and K-sparing diuretics) cause a milder diuresis bc most of Na has already been reabsorbed
Increased delivery of Na to the distal tubule will cause what distally?Will cause increased excretion of K+ (kaliuresis). Thus, non-K sparing diuretics often cause hypokalemia.
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Section 3

Question Answer
Thiazides
Name 2 Thiazide drugsHydrochlorothiazide and Metolozone
What is the target/MOA of Thiazide drugs?Na/Cl symporter in the DCT, inhibit symporter in luminal membrane and block reabsorption of sodium and chloride
Thiazides cause increased delivery of Na to distal tubule, thus it causes what?Increased excretion of K+ and H+ ions in distal tubule
Chronic administration of thiaziades has the benefit of what?Decreases excretion of Ca2+ (reabsorbed more, good to use in post-menopausal women with HTN at risk for osteoporosis and in HTN pts with risk of kidney stones due to Ca)
How do thiazides get into kidney?Via organic acid transporter in PCT, interacts with gout drug probenecid
What are some of the fluid and electrolyte adverse effects that thiazides can cause?Volume depletion, Hypotension, hyponatremia, hypokalemia, hyperurecemia
At high doses, what are some of the metabolic adverse effects that thiazides can cause?Hyperglycemia, hyperlipidemias, increased LDL levels, orthostatic hypotension. Decrease glucose tolerance and can unmask latent diabetes mellitus. Low dose thiazides generally don't cause this.
What is the medical use for thiazides?Tx HTN, edema due to CHF/liver disease/renal disease, reduce Ca2+ excretion in calcium nephrolothiasis and osteoporosis
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Section 4

Question Answer
Loop diuretics
Name two loop diureticsFurosemide and torsemide most common. Others are bumetanide and ethacrynic acid
How do loop diuretics get into the nephron?Via organic acid transporter in PCT, interacts with gout drug probenacid
Site of action of Loop DiureticsNa/K/2Cl symporter in TAL of Loop of Henle, inhibit it. Indirectly also inhibit Ca and Mg reabsorption in TAL by reducing the lumen-positive transepithelial potential difference that drives reabsorption of these positively charged ions
Loop diuretics cause increased distal delivery of Na, thus cause increased excretion of what?Increased excretion of K and H ions distally
Loop diuretics also block Na reabsorption in macula densa of TAL thus cause what?activate the macula densa pathway in a similar fashion as low sodium delivery, powerful stimulators of renin release, cause reflex sympathethic stimulation due to volume depletion
Fluid and electrolyte adverse effects of loop diurects?Hyponatremia, hypokalemia, hyperurecemia, ototoxicity, hyperglycemia
Drug interactionsOther diurectics and probenecid
Clinical use of loop diurectics?Acute pulmonary edema, chronic CHF, HTN (but not diuretic of first choice), used to mobilize edema due to cardiac, hepatic, or renal disease
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Section 5

Question Answer
Potassium-Sparing Diuretics
Name two K-sparing diuretics?Triamterene and amiloride
Where do Potassium Sparing Diuretics act on?Principal cells in the late distal tubule and cortical collecting duct in the kidney
What is the normal function of principal cells in kidney usually?Secrete K out into lumen and reabsorb Na
What is the MOA of potassium sparing drugs?Inhibit Na channels in the luminal membrane and decrease sodium transport. Thus this decreases the transluminal electrical potential, which is the driving force for K+ secretion. Thus, less K+ is secreted.
How is K+ spared?K+ Sparing Diuretics inhibit the ENaC channels in principal cells, the potential is the lumen stays more positive, thus the driving force to attract K is decreased thus less K is secreted
In addition to K+ sparing, what other ions are spared from being excreted?Ca and Mg. Decreased excretion of Ca an Mg
How do they drugs get into the kidney?Glomerular filtration into nephron. Excreted into urine. Renal failure, which causes decreased excretion of the drug, can enhance toxic effects.
Triamterene is metabolized where?Liver. Thus, liver disease can also decrease clearance of triamterene.
What is the most dangerous adverse effect of K+ Sparing Diuretics?Hyperkalemia (High concentration of potassium in serum)
K+ Sparing drugs are contraindicated in what pts?In pts at risk for developing hyperkalemia (renal failure, taking K+ supplements, ACE inhibitors, or other K+ sparing diuretics)
Clinical use of K+ sparing diuretics?Mild natriuresis thus seldom used alone. Usually used in combo with other diuretucs to enhance efficacy and inhibit the K+ secretion induced by other drugs. Used in edema and HTN.
Aerolized triamterene used where?In cystic fibrosis: the inhibition of Na absorption in airway epithelium augments hydration of respiratory secretions and improves mucociliary clearance
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Section 6

Question Answer
Aldosterone antagonists
Name the important aldosterone antagonistSpironolactone. (another one is eplerenone)
MOA of aldosterone antagonistsAlso K+ Sparing drugs. Site of action is late distal tubule and collecting duct. Bind to mineralcorticoid receptor and inhibit aldosterone binding. Thus inhibits the normal action of aldosterone to promote K+ excretion.
Aldosterone normally causes what?retention of salt and water, increased excretion of K+ and H+ ions.
MOA of AldosteroneEnters epithelial cells, binds to mineralcorticoid receptor in the cytoplasm. The hormone-receptor complex then translocates itself to the nucleus where it binds to DNA and induces expression of aldosterone-induced proteins. Net effect increases Na reabsorption and increased Na/K ATPase pump activity. The increase in the lumen-negative potential causes driving force for K+ secretion.
Adverse effect of aldosterone antagonistsHyperkalemia is the most serious adverse effect (can be life threatening). Contraindicated in pts at risk for hyperkalemia
Clinical use of aldosterone antagonistsCo-administered with thiazides or loop diuretics. for tx of edema and HTN. Very effective for treating hyperaldosteronism and refractory edema associated with secondary aldosteronism (cardiac failure, hepatic cirrhosis, nephrotic syndrome, severe ascites). Diuretic of choice in hepatic cirrhosis.
Long term benefit of aldosterone antagonistsShown to have the benefit when used long term of slowing the progression of heart failure
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Section 7

Question Answer
Angiotensin Converting Enzyme Inhibitors
In response to decreased "effective" blood volume, what important system kicks in?Renin-Angiotensin-Aldosterone System. Important regulator of blood pressure. Activated in response to low blood volume, blood loss, low sodium diet, congestive heart failure. Major effector is Angiotensin II which does several things to raise BP.
What is the rate limiting enzyme and the enzyme that determines how much Ang II is produced?Renin
ACE enzyme cleaves what two proteins?Ang I to Ang II and Bradykinin to inactive
Renin is released from where?From juxtaglomerular cells in the kidney
Renin release is controlled by what 3 factors?1. Rate of Na reabsorbption by macula densa in TAL of nephron. Low reabsorption stiumulates renin release from juxtaglomerular cells. 2. Blood pressure in the pre-glomerular vessels. Decreased pressure in afferent arterioles stiumulates renin release via baroreceptor response. 3. Sympathethic nervous system. NE--> + B1 receptors on Juxtaglomerular cells--> + renin release
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Section 8

Question Answer
There are two types of Angiotensin II receptors:AT1 and AT2
Most of the actions of Angiotensin II are mediated by what receptor?AT1
Angiotensin II receptors are expressed where?Vascular SMCs, adrenal cortex, kidney, heart, brain
AT1 receptors couple to what?Gq--> + PLC--> IP3 + DAG --> inc intracellular Ca --> rapid constriction of smooth muscle
Longer term effects of Angiotensin II to alter gene transcription are mediated by what receptors/signaling mechanisms?JAK-STAT pathways
What are the 3 Major Effects of Angiotensin II?1. Altered Peripheral resistance 2. altered renal function 3. altered cardiovascular structure
Angiotensin II's effect on peripheral resistance causes what?Vasoconstriction, rapid pressor response
Angiotensin II's effect on renal function causes what?Aldosterone, increased Na reabsorption, slow pressor response
Angiotensin II's effect on cardiovascular structure causes what?gene regulation/transcription, increased afterload, increased wall tension, Vascular and Cardiac Hypertrophy and Remodeling
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Section 9

Question Answer
Name two ACE InhibitorsCaptopril and Enalapril
ACE inhibitor drug names end in what?-pril (ie enalapril and ramipril)
MOA of ACE InhibitorsHighly selective inhibitors of ACE enzyme. prevent ang I to ang II. Reduce the levels of circulating Ang II
What happens to bradykinin in presence of ACE inhibitors?Builds up, doesn't get broken down, vasodilator (good), may cause cough due to accumulation (bad)
ACE inibitors lower blood pressure by decreasing what?Decrease peripheral vascular resistance. Do not cause reflex sympathetic activation. Can be used in patients with ischemic heart disease.
How are ACE inhibitors cleared from the body?Via secretion into kidney. Thus, contraindicated in impaired renal function.
Adverse Effects of ACE Inhibitors?Hypotension, Cough, Hyperkalemia, Acute Renal Failure (esp in bilateral renal stenosis bc AngII needed to maintain GFR), Fetopathic potential in 2nd and 3rd trimesters
Clinical Use of ACE Inhibitors?HTN, CHF, Left Ventricular Systolic Dysfunction, HF,MIs, diabetics
ALL patients with left ventricular systolic dysfunction should be treated with what?ACE Inhibitors
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Section 10

Question Answer
Name an Angiotensin II Receptor AntagonistLosartan
Angiotensin II Receptor Antagonists names end in what?-sartan
MOA of Angiotensin II Receptor Blockers aka ARBsCompetitive antagonists of Type I angiotensin II (AT1) receptors. Block the ability of Ang II to bind to AT1 in VSMC and other sites
How are ARB effective?Block the actions of Ang II
What is one beneficial thing that makes ARBs different from ACE Inhibitors?ARBs do NOT cause cough bc they don't block the breakdown of bradykinin. Also, do not have the adverse effect of angioneurotic edema.
Adverse effect of ARBsHypotension and Hyperkalemia
Clinical Use of ARBsHTN, ARBs have protective effects in pts with LVH and are renal protective similar to ACE inhibitors
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Section 11

Question Answer
Name a renin inhibitor drugAliskiren
What is the first (and currently only) renin inhibitor?Aliskiren
MOA of AliskirenCompetitive inhibitor of the active site of renin. Aliskiren inhibits conversion of angiotensinogen to angiotensin I. Reduces production of angiotensin II. Typical reductions in plasma renin activity are 50 to 80%
What effects are seen in the body by using aliskiren?Same as ACE inhibitors and ARBs. Lowers systolic and diastolic BP.
How is aliskiren different from ACE inhibitors or Angiotensin II Receptor Blockers?Unlike ARBs or ACE Inhibitors, renin inhibitors DO NOT cause elevation of Ang I, Ang II, or bradykinin. In addition, even though they increase circulating amounts of renin, this renin is neutralized by the inhibitor.
Adverse effects of renin inhibitorssame as ACEIs and ARBs, increased serum and potassium HYPERKALEMIA and others, lower risk of cough, similar risk of angioedema, increases uric acid in serum, irritates GI tract, diarrhea
Clinical use of AliskirenMonotherapy use for HTN and in combo. Use in high renin pts and pts resistant to ACEI and ARBs
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Section 14

Section 15

Section 16

Section 17

Section 18