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RCS > L14, L16- Antihypertensive Drugs > Flashcards

L14, L16- Antihypertensive Drugs Flashcards

1
Q

list the classifications of HTN

A
  • Normal: <120/<80
  • Elevated: 120-129/<80
  • Stage 1 HTN: SP 130-139, or DP 80-89
  • Stage 2 HTN: SP >140, or DP >90
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2
Q

although most cases of HTN have a (1) cause, the mechanism is the same, described as (2)

A

1- unknown

2- inc peripheral vascular smooth muscle tone –> inc arteriolar resistance + dec capacitance of venous system

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3
Q

BP control is dependent on (1) which is controlled by (2) and (3) which is dependent on (4).

A

1- arterial BP (proportional to CO, PVR)
2- SNS, RAAS

3- CO, PVR
4- baroreceptors / ANS, RAAS

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4
Q

the main compensatory responses to decreased BP and adverse effects of antihypertensives are….

A

-tachycardia
-Na/H2O retention
(both aim to inc BP)

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5
Q

Stage 1 HTN is treated with (1) and Stage 2 with (2). (3) is recommended for both.

A

1- single drug
2- multiple drugs
3- lifestyle recommendations

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6
Q

list the 1st line HTN agents

A
  • ACE inhibitors / ARBs
  • Ca channel blockers
  • thiazides
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7
Q

list the 2nd line HTN agents

A
  • β-blockers

- aldosterone antagonists (K+ sparing diuretics)

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8
Q

list the 3rd line HTN agents

A
  • loop diuretics
  • α-blockers, central α2-agonists
  • direct vasodilators
  • renin inhibitors
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9
Q

list the main ACE inhibitors

A
  • lisinopril
  • enalapril
  • captopril
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10
Q

ACE inhibitors are (1st/2nd/3rd) line HTN drugs, and are preferred in (2) patients. Its use will result in decreased (3) and increased (4). (5) is also an important absent reaction seen with these drugs.

A

1- 1st
2- DM, CKD Pts (over thiazides, Ca-channel blockers)
3- PVR, Na/H2O retention
4- bradykinin
5- no barorecptor reflex => inc HR/contractility (SV)/CO

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11
Q

renin release occurs in response to the following….

A
  • dec renal perfusion
  • renal SNS activity
  • dec GFR
  • β-agonists, PG-I2
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12
Q

compare renin, angiotensin I, angiotensin II levels in ACE inhibitors vs ARBs

A

ACE: inc renin, inc angio-I, dec angio-II

ARBs: inc renin, inc angio-I, inc angio-II

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13
Q

ACE inhibitors are more effective in (1) patients, but if combined with (2) it will equally effective in (3) patients. It is used in (4) patients because it will (5).

A

1- white, young patients
2- diuretic
3- black/all patients

4- DM, CKD
5- preserve renal function (no glomerular HTN)

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14
Q

in addition to HTN, ACE inhibitors are effective treatments for….

A
  • chronic HF

- post-MI MI prevention (no acute action, but prevents recurrence)

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15
Q

describe the effect of ACE inhibitors and ARBs on GFR

A

dec GFR: causes efferent arteriole dilation

-usually a benign or insignificant effect unless patient has previous kidney disease history

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16
Q

list the adverse effects of ACE inhibitors

A
  • dry hacking cough (via bradykinin)
  • hyperkalemia (via dec Na retention via dec aldosterone)
  • hypotension
  • angioedema (bradykinin, rare)
  • ARF in patients with bilateral RAS
  • rash, fever, altered taste
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17
Q

list the contraindications for using ACE inhibitors

A
  • Pregnany: congenital malformation in 1st trimester, fetal hypotension, anuria, renal failure in 2nd/3rd
  • Pts with bilateral RAS
  • Pts with previous h/o angioedema
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18
Q

the main ARBs are….

A
  • losartan

- valsartan

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19
Q

ARBs are (1st/2nd/3rd) line agents in HTN treatment, and are alternatives to (2) because of (3). They function by blocking (4) leading to decreased (5), and importantly unchanged (6) which is increase with (2) use.

A

1- 1st line
2- ACE inhibitors
3- intolerance, usually cough via bradkinin
4- angiotensin-II type 1 receptors
5- dec BP (via arteriolar, venous dilation), dec Na/H2O retention, dec diabetic nephropathy
6- bradykinin levels (unchanged)

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20
Q

list ARB’s adverse effects

A
  • hyperkalemia (via dec Na retention via dec aldosterone)
  • hypotension
  • ARF in patients with bilateral RAS
  • rash, fever, altered taste
  • angioedema (rare + lower than in ACEI use)
  • losartan: reduces [uric acid] in plasma (via URAT1 transporter inhibition) –> useful in, but not a Tx for, gout

(NO dry hacking cough via bradykinin)

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21
Q

list the contraindications for ARB use

A
  • pregnancy

- patients with bilateral RAS

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22
Q

the main renin inhibitor is (1), which inhibits renin so (2) cannot occur, and has (3) as the end result

A

1- Aliskiren
2- conversion of angiotensinogen (via liver) to angiotensin-I
3- inhibits angiotensin-II and aldosterone

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23
Q

what are the adverse effects of Aliskiren

A

(renin inhibitor)

  • hyperkalemia (via dec Na retention via dec aldosterone)
  • hypotension
  • ARF in patients with bilateral RAS
  • rash, fever, altered taste

-angioedema (rare + lower than in ACEI use)

(NO dry hacking cough via bradykinin)

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24
Q

list the Ca channel blockers by class

A
  • Non-dihydropyridines: verapamil, diltiazem

- Dihydropyridines: nifedipine, amlodipine

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25
Q

Ca channel blockers are (1st/2nd/3rd) line drugs for HTN treatment, mainly for (2) patients

A

1- 1st

2- black, elderly patients (since ACEI’s are more effective in young, white people)

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26
Q

Verapamil is a (1) type antihypertensive which has effects on (2) and is used to treat (3)

A

1- Ca channel blocker, non-dihydropyridine
2- cardiac and vascular smooth muscle (inhibits contraction??)
3- angina, suprventricular tachyarrhythmias, HTN, migraines, cerebral vasospasm

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27
Q

Diltiazem is a (1) type antihypertensive which has effects on (2) and is used to treat (3). It is also useful because of (4).

A

1- Ca channel blocker, non-dihydropyridine
2- cardiac and vascular smooth muscle (inhibits contraction??)
3- angina, suprventricular tachyarrhythmias, HTN, cerebral vasospasm
4- good side-effect profile

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28
Q

Amlodipine is a (1) type antihypertensive which has great effects on (2) in comparison to (3). It functions to reduce (4), causing (5). It is also used to treat (6).

A

1- Ca channel blocker, dihydropyridine
2- vascular smooth muscle Ca channels
3- cardiac smooth muscle Ca channels
(non-dihydropyridines (diltiazem, verapamil) have equal affinities)
4/5- dec Ca entry into smooth muscles –> coronary / peripheral vasodilation –> low BP
6- n/a, primarily for HTN

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29
Q

Nifedipine is a (1) type antihypertensive which has great effects on (2) in comparison to (3). It functions to reduce (4), causing (5). It is also used to treat (6).

A

1- Ca channel blocker, dihydropyridine
2- vascular smooth muscle Ca channels
3- cardiac smooth muscle Ca channels
(non-dihydropyridines (diltiazem, verapamil) have equal affinities)
4/5- dec Ca entry into smooth muscles –> coronary / peripheral vasodilation –> low BP
6- n/a, primarily for HTN

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30
Q

Ca channel blockers specifically inhibit (1) channels to limit entry of Ca. Ca normally has (2) function in the cell membrane of smooth muscle cells and (3) function elsewhere. Overall, Ca channel blockers function to cause (4) in smooth muscle cells.

A

1- V-gated Ca channels, L-type (long-lasting)
2- inc Ca (out) / Na (in) exchange [rapid Ca out or into SR dec refractory period, inc HR + contractility] –> inc Na (out) / K (in) exchange
3- inc quantity of Ca release from –> inc free Ca
4- inc myofibril vascular relaxation by dec free Ca in cytoplasm

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31
Q

Ca channel blockers are used clinically for…

A
  • HTN (1st line in black, elderly patients)
  • intrinsic natriuretic effect –> no need for diuretic
  • angina
  • cardiac arrhythmias (nondihydropyridine: verapamil, diltiazem
32
Q

A key risk of high doses of (1) type Ca channel blockers is (2) due to (3)

A

1- short-acting dihydropyridines (amlodipine, nifedipine)
2- inc risk of MI
3- excessive vasodilation –> reflex cardiac stimulation

(therefore sustained release preparations / formulations are used)

33
Q

verapamil adverse effects

A

(non-dihydropyridine Ca channel blocker)

-constipation (7%), negative ionotropic effects, gingival hyperplasia

34
Q

diltiazem adverse effects

A

(non-dihydropyridine Ca channel blocker)

-negative ionotropic effects

35
Q

dihydropyridines adverse effects

A

(amlodipine, nifedipine)

  • hypotension
  • peripheral edema (feet/ankles)
  • dizziness, HA, fatigue
  • gingival hyperplasia
  • flushing
  • reflex tachycardia (short-acting preparations –> inc risk of MI)
36
Q

what are the contraindications of Ca channel blockers

A

(just non-dihydropyridines: verapamil, diltiazem)

  • Pts on β-blockers
  • Pts with 2nd/3rd degree AV block
  • Pts with severe L ventricular systolic dysfunction
37
Q

(1) diuretics are the 1st line treatments in HTN, especially for (2) patients

A

1- thiazides (DCT)

2- black, elderly

38
Q

what is the other function of thiazides in HTN patients

A

counteracts Na/H2O retention caused by other anti-hypertensives

39
Q

list the thiazide adverse effects

A
  • hypokalemia, hypomagnesium
  • hyperuricemia, hyperglycemia, hypercholesterolemia
  • sexual dysfunction
40
Q

loop diuretics are used often for (1) because of (2); therefore they are mostly used in (3) patients

A

1- prompt diuresis in patients with poor renal functions, HF
2- more potent than other diuretics (also more adverse effects)
3- patients not responding to thiazides
(dec renal vascular resistance –> inc RBF)

41
Q

(1) is an aldosterone antagonist diuretic often used in (1st/2nd/3rd) HTN therapy and in patients with (3). The biggest risk with using (1) is (4).

A

1- spironolactone (K+ sparing)
2- 1st line (in adjunct with thiazides mostly, maybe loop diuretics)
3- HF / severe L ventricular dysfunction
4- hyperkalemia (b/c dec aldosterone)

42
Q

β-blockers are used as (1) in reference to HTN therapy, and are first line drugs for the following, (2).

A

(propanolol, metoprolol, atenolol, pindolol)
1- add-on therapy to first line HTN drugs
2- CAD, HF, post-MI

43
Q

______ is the preferred β-blocker for pregnant women

A

pindolol, non-selective partial β agonist

44
Q

describe the MOA of β-blockers

A
  • reduce BP via dec CO, contractility, HR
  • blunts SNS response with exercise
  • inhibits NE and renin release => dec angiotensin II and aldosterone secretion
45
Q

describe the pharmacokinetics of β-blockers in terms of starting and finishing regimen

A
  • when starting, it may take several weeks to develop full effects
  • abrupt drug withdrawal –> induces angina, MI, sudden death in HD Pts (due to β-receptor upregulation) // must be tapered off
46
Q

list the adverse effects of β-blockers

A
  • bradycardia, hypotension
  • dec libido, impotence
  • disturbed lipid metabolism (dec HDL, inc TAGs - Pt is usually on statin anyway)
  • hypoglycemia
  • CNS: fatigue, lethargy, insomnia, hallucinations
47
Q

The main α1-blockers are (1) and work by using (2) inhibition. There main effects on BP is (3) and have (4) effects on the heart. In addition, (5) also occurs, and is relevant to BP changes.

A

1- prazosin, doxazosin
2- competitive
3- dec PVR, dec BP via arterial and venous dilation
4- minimal changes (no-long term tachycardia)
5- Na/H2O retention

48
Q

list the uses of α1-blockers

A

MAINLY: BPH

  • sometimes HTN, although many side-effects and not for essential HTN
  • occasionally HF
49
Q

list the adverse effects of α1-blockers

A
  • orthostatic HTN –> syncope (first and large doses)
  • dizziness, drowsiness, HA, lack of energy, nausea, palpitations
  • β-blocker use to blunt short-term tachycardia
  • Doxazosin known to inc rate of congestive HF
50
Q

(1) is a the commonly used mixed α-/β-blocker. It is administered via (2) for HTN management in (3) and it is administered via (4) for HTN emergencies.

A

1- labetalol
2- oral/parenteral
3- pregnancy
4- IV (–> rapid BP reduction)

51
Q

describe the MOA of a mixed α-/β-blocker

A

Dec BP:

  • α1 blockade –> vasodilation
  • β1 blockade –> no associated reflex tachycardia or inc in CO
52
Q

the main adverse effect of mixed α-/β-blockers is…..

A

orthostatic HTN upon first or large doses

-NOTE: plus the other adverse effects of α-/β-blockers

53
Q

Clonidine is a (1) type drug which has a (2) MOA in order to lower BP. It also has a (3) effect on RBF/GFR. It is used to treat (4).

A

1- central α2 agonist
2- activates α2 on presynaptic / postganglionic SNS neurons –> dec SNS output (=> dec PVR, CO)
3- no effect (doesn’t lower RBF or GFR)
4- HTN management and crises

54
Q

list the adverse effects of clonidine

A
  • dizziness, drowsiness, HA
  • dry mouth
  • sexual dysfunction

-rebound HTN with abrupt withdrawal – avoid use with β-blockers

55
Q

Methyldopa is a (1) type drug which has a (2) MOA in order to lower BP. It also has a (3) effect on RBF/GFR. It is used to treat (4).

A

(must be converted to α-methyldopamine –> methylnorepinephrine)
1- central α2 agonist
2- activates α2 on presynaptic / postganglionic SNS neurons –> dec SNS output (=> dec PVR, but CO unchanged)
3- no effect (doesn’t lower RBF or GFR)
4- HTN management mainly in pregnancy

56
Q

list the adverse effects of methyldopa

A
  • sedation, drowsiness, dizziness, HA, nausea, weakness, fatigue
  • nightmares, mental depression, vertigo
  • sexual dysfunction
  • (10-20%) –> hemolytic anemia, hepatitis, drug fever after long-term Tx (>1 yr)
57
Q

(1) are direct vasodilators used as (2) drug in HTN treatment . They act by (3), which will also produce (4) and (5). There side-effects are usually managed by (6).

A 
1- hydralazine, minoxidil
2- not 1st line HTN drug
3- direct smooth muscle relaxants
4- reflex tachycardia (baroreceptors)
5- inc renin (RAAS) --> inc Na/H2O retention
6- combined with diuretic or β-blocker
58
Q

Hydralazine is a (1) type drug that is administered via (2). It is used to treat (3).

A

1- vasodilator – arterioles mostly
2- oral, IV
3- pregnancy induced HTN (pre-eclampsia) OR last line HTN therapy

59
Q

list the adverse effects of hydralazine

A
  • fluid retention or reflex tachycardia (administer with thiazide and β-blocker)
  • reversible lupus-like syndrome
  • HA, nausea, sweating, flushing
60
Q

Minoxidil is a (1) type drug used to treat (2). Since (3) are the main adverse effects, (4) are usually also given. It also causes (5), therefore it is a treatment for (6).

A 
1- vasodilator -- arterioles
2- severe malignant HTN (orally)
3- reflex tachycardia, fluid retention
4- loop diuretic, β-blocker
5- hypertrichosis
6- male pattern baldness, topical use
61
Q

list the 3 main drugs used in treating pulmonary HTN

A
  • PGs: epoprostenol
  • Endothelin synthesis / action inhibitors: bosentan
  • Vasodilators: sildenafil (viagra)
62
Q

Epoprostenol is a (1) type drug that is administered via (2) in order to decrease (3). Its adverse effects are (4).

A

1- PG-I2
2- IV, continuous infusion
3- peripheral, pulmonary, coronary resistance (treats pulmonary HTN)
4- flushing, HA, jaw pain, diarrhea, arthralgias

63
Q

Bosentan is a (1) type drug that will block (2) and (3) responses in order to treat (4). Its main adverse effect / contraindication is (5).

A 
1- nonselective endothelin receptor blocker
2- initial transient depressor (ET-a)
3- prolonged pressor (ET-b)
4- pulmonary HTN
5- pregnancy: category X
64
Q

Sildenafil will inhibit (1) in order to induce (2) and is used to treat (3). It has (4) as adverse effects and is contraindicated with (5).

A 
1- phosphodiesterase 5 (PDE5)
2- inc cGMP --> smooth muscle relaxation
3- impotence, pulmonary HTN
4- HA, flushing, dyspepsia, cyanopsia (vision changes)
5- nitrates (=> severe hypotension)
65
Q

HTN crisis = ……

A
  • acute BP elevation: diastolic BP >120 mmHg
  • => vascular injury + organ damage

(either an emergency or an urgency)

66
Q

compare a HTN emergency and urgency

A

Both: HTN crises with acutely high BP

Emergency:

  • signs of target organ damage: brain, CVS, kidneys
  • BP reduction via IV drugs required
  • DBP >150 + SBP >210 in healthy person
  • DBP >120 in person with pre-existing complications

Urgency: w/o target organ damage // start Pt on 2-drug oral combination for BP reduction and outpatient monitoring

67
Q

list the many causes of HTN emergencies

A
  • essential HTN
  • pregnancy / eclampsia
  • renal parenchymal disease
  • renovascular disease
  • Endocrine: pheochromocytoma, cushing’s, renin producing tumors
  • CNS: disorders: injury, stroke, tumor
  • ANS hyperreactivity
  • Drugs: cocaine, crack, amphetamines, MAOIs, tyramine
  • Drug withdrawal: clonidine, nifedipine
68
Q

list the many drugs that can be used to treat HTN emergencies

A
  • Na nitroprusside
  • labetalol
  • fenoldopam
  • nicardipine
  • nitroglycerin
  • diazoxide
  • phentolamine
  • esmolol
  • hydralazine
69
Q

describe the use of sodium nitroprusside in a HTN emergency

A

-given IV (oral is poisonous) via continuous infusion (half-life in 1-2 mins)
-prompt vasodilation + reflex tachycardia
(peripheral vasodilation by direct effects on arterial/venous smooth muscle)

70
Q

list adverse effects of sodium nitroprusside

A
  • hypotension (overdose), HA, goose bumps
  • abdominal crampings, n/v
  • cyanide toxicity (rare) – treated via sodium thiosulfate infusion (=> nontoxic thiocynate)
71
Q

describe the use of labetalol in a HTN emergency

A
  • mixed α-/β-blocker
  • IV bolus or infusion, half-life 3-6 hrs
  • NO reflex tachycardia
  • NOT USED in Pts with: asthma, COPD, 2nd/3rd degree AV block, bradycardia
72
Q

describe the use of fenoldopam in a HTN emergency

A
  • peripheral D1 receptor agonist –> arteriolar dilation
  • IV infusion, half-life 30 min
  • maintains/inc renal perfusion as BP lowers –> promotes naturesis
  • very safe (best for renal insufficiency Pts), only exception is glaucoma
73
Q

describe the use of nicardipine in a HTN emergency

A
  • Ca channel blocker
  • IV infusion, half-life 30 min
  • => reflex tachycardia
74
Q

describe the use of nitroglycerin in a HTN emergency

A
  • Vasodilator: veins > arteries
  • Best Choice for patients with cardiac ischemia, angina, post-by-pass surgery
  • 2-5 min half life
  • SE: hypotension
75
Q

describe the use of diazoxide in a HTN emergency

A
  • arteriolar dilator: prevents contraction by opening K+ channels (efflux) –> stabilizing membrane potential
  • half life 24 hrs
  • SE: hypotension, reflex tachycardia, Na+/H2O retention

-NOTE: inhibits insulin release, used to treat hypoglycemia secondary to insulinoma

76
Q

(1) treats HTN emergency related to catecholamines
(2) treats HTN emergency related to pregnancy / eclampsia
(3) treats HTN emergency in aortic dissection / post-operative HTN

A

1- phentolamine (reversible competitive non-selective α-agonist)

2- hydralaxine (direct acting vasodilator)

3- esmolol (non-selective β-blocker, short acting)

RCS (29 decks)

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