CV drugs and antihypertensives 53/54/55 Flashcards Preview

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Flashcards in CV drugs and antihypertensives 53/54/55 Deck (88):
1

anti-HTN:

Diuretics
Beta blockers
Calcium channel blockers
RAAS inhibitors

2

Antihyperlipidemics

Bile acid binding resins
HMG-CoA reductase inhibitors
Fibrates
Niacin

3

Antidiabetics

Insulin
Sulfonylureas
Biguanides
Thiazolidinediones

4

Antianginals

Nitrates
Calcium channel blockers
Beta blockers

5

Drugs for CHF

Cardiac glycosides
Non-glycoside inotropes
ACE inhibitors
Diuretics
Vasodilators
Beta blockers

6

Antiarrhythmics

Sodium channel blockers
Potassium channel blockers
Calcium channel blockers
Beta blockers

7

Hydrochlorothiazide (Microzide)

thiazide Diuretic

8

Chlorthalidone (Thalitone)

thiazide Diuretic

9

Indapamide

thiazide Diuretic

direct dilator action on vascular smooth muscle

lesser propensity to raise serum cholesterol (even though it is longer acting)

10

Furosemide (Lasix)

loop diuretic

short-acting. Often given two or three times a day

11

Triamterene (Dyrenium)

K+ sparing diuretic

inhibitor of renal Na+ channels

12

Spironolactone (Aldactone)

K+ sparing diuretic

competitively block binding of aldosterone

interferes with sex-steroid receptors (non-sp)

13

Eplerenone (Inspra)

K+ sparing diuretic

competitively block binding of aldosterone

14

Reserpine

Peripheral Adrenergic Neuron Blocker

Depletes storage of the *peripheral neurotransmitter: NE* in vesicles of sympathetic nerve endings, thereby reducing amount of NE released with each nerve impulse

dec. both CO and TPR-->dec. BP
*irreversible*: persistent effect, need to make new vesicles
-do not get rebound HTN

used in standard HTN pt: cheap!

15

Methyldopa

Central Adrenergic Neuron Blocker

prodrug which is converted into methylnorepinephrine

alpha2 adrenergic AGONIST in the central vasomotor centers, dampening sympathetic neural outflow

*dec. in TPR*- main effect
dec. in renin
dec. in CO


*HTN during pregnancy*
not used as much anymore

16

Clonidine (Catapres)

Central Adrenergic Neuron Blocker

sim. to Methyldopa, influence CNS imidazoline rec

patch for transdermal absorption: moother BP control with fewer side effects although many show local skin reactions

*primary HTN*

17

Prazosin (Minipress)

α1-Adrenergic Receptor Blocker
3x day
more severe first-dose postural hypotension

18

Doxazosin (Cardura)

α1-Adrenergic Receptor Blocker
1x day

19

Terazosin (Hytrin)

α1-Adrenergic Receptor Blocker
1x day

20

important pgs to learn

skip pgs 5-7 (mostly pathology)

know pgs: 11-25
sections 13-23

after: sections 24-34 not as important

36-38: important tables

21

Propranolol (Inderal-LA)

β1 and 2-Adrenergic Receptor Blocker

22

Nadolol (Corgard)

β1 and 2-Adrenergic Receptor Blocker

23

Timolol

β1 and 2-Adrenergic Receptor Blocker

24

Pindolol

β1 and 2-Adrenergic Receptor Blocker (with ISA)

*partially stimulates B2, so contributes to vasodilation, lowering TPR-->lowering BP

25

Atenolol (Tenormin)

β1-Adrenergic Receptor Blocker

26

Metoprolol (Toprol-XL)

β1-Adrenergic Receptor Blocker

27

Acebutolol (Sectral)

β1-Adrenergic Receptor Blocker

28

Labetalol (Trandate)

α1/β1,2 Blocker

partial agonist @ B2
BP falls mainly from a decrease in peripheral resistance (due to the alpha block, partial vascular beta-2 stimulation and less renin release) but with some decrease in CO

severe primary HTN (oral)
HTN emergency (IV)

29

Nebivolol (Bystolic)

NO-releasing β1 Blocker

"vasodilating powerhouse" (Also decreases NO degradation)

decrease in BP is due to vasodilator effect (dec. TPR) as well as dec. CO:
β 1 -blocking action decreases renin release, HR and contractility
Increase in endothelial NO dilates vascular smooth muscle

good for HTN pts w. imparied endothelial cell function
good for mild-mod primary HTN


30

Hydralazine

Direct Arteriolar Dilator

release NO from arteriole endothelium-->vasodilate-->dec. TPR

partly inactivated by acetylation in the liver: "rapid" acetylators in the population show much smaller drug effects than "slow" acetylators (adjust dosing)

added as 3rd drug if not responding to diuretic and 2nd drug (i.e. B-blocker), but being used less due to SEs

SE: lupus-like rxn (also edema described elsewhere)

31

Minoxidil

Direct Arteriolar Dilator

opens ATP-sensitive K+ channels in arteriolar smooth muscle cells (via active sulfate metabolite)

added as 3rd drug if not responding to diuretic and 2nd drug (i.e. B-blocker), but being used less due to SEs

use for severe HTN
esp. effective treating renal insufficiency (good renal arteriolar dilator)

SE: hair growth (also edema described elsewhere)

32

Verapamil (Calan)

Calcium Channel Blocker (CCB)
-block in heart

older: short acting (3x/day)

33

Diltiazem (Cardizem)

Calcium Channel Blocker (CCB)
-block in heart

older: short acting (3x/day)

SEs: nausea, headache
directly suppressed heart rate and A-V conduction

34

Nifedipine (Procardia - XL)

Calcium Channel Blocker (CCB)
-block in vasculature

older: short acting (3x/day), original prototype, pts were dying from rapid effects

*tx for primary pulmonary HTN*

35

Felodipine

Calcium Channel Blocker (CCB)
-block in vasculature

longer-acting with slow onset (safer)

36

Amlodipine (Norvasc)

Calcium Channel Blocker (CCB)
-block in vasculature
only "dipine" not effected/enhanced by grapefruit juice (metabolism in liver)

longer-acting with slow onset (safer)

37

Captopril (Capoten)

ACE Inhibitor

prototype ACE inhibitor (NOT prodrug)

SEs: sulfydryl group: rash, loss of taste, and possibly (though seldom) some renal abnormalities causing loss of protein in urine.

38

Enalapril (Vasotec)

ACE Inhibitor

prodrug that is activated by deesterification to enalaprilat (need adequate liver function)

39

Lisinopril (Prinivil, Zestril)

ACE Inhibitor

active derivative to enalaprilat (NOT prodrug)

40

Fosinopril (Monopril)

ACE Inhibitor

long-acting, prodrug activated primarily by *liver

"smartdrug":
Active liver metabolite which has balanced route of elimination which shifts toward liver if the kidneys are damaged (useful in HTN pts with renal insufficiency)

41

Quinapril (Accupril)

ACE Inhibitor

long-acting, prodrug activated primarily by *liver

42

Ramipril (Altace)

ACE Inhibitor

long-acting, prodrug activated primarily by *liver

43

Losartan (Cozaar)

Angiotensin II Receptor Blocker (ARB)

44

Valsartan (Diovan)

Angiotensin II Receptor Blocker (ARB)

45

Candesartan (Atacand)

Angiotensin II Receptor Blocker (ARB)

46

Aliskiren (Tekturna)

Renin Inhibitor

47

HTN def

sustained systemic arterial blood pressure (BP) levels above 140/90 mmHg (systolic/diastolic)
>1 reading

Isolated systolic hypertension (ISH), usually seen over age 65, is defined by some as a systolic blood pressure (SBP) > 160.

(mostly concerned with large arteries, capillaries and veins also involved)

48

?? may be the most popular drugs for therapy of chronic primary hypertension

Thiazides and thiazide-like drugs (e.g. hydrochlorothiazide, chlorthalidone, indapamide)

indapamide with a lesser propensity to raise serum cholesterol

49

thiazide diuretic mechanism in HTN

In lowering BP, initially diuretics induce a natriuresis which shrinks blood volume thus reducing cardiac output (within 2-3 days).
[This activates mechanisms responsible for maintenance of fluid volume, particularly (RAAS) which may then limit the degree of volume reduction and the degree of ↓ BP]. -->tends to eventually return to normal

Continued diuretic use leads to a fall in TPR (and return of cardiac output toward normal, within 6-8 weeks), which is the reason for continued antiHTN effect. This may be due to an autoregulatory phenomenon and/or to direct relaxant actions of the drugs on vascular smooth muscle (*indapamide* may do the latter via calcium channel blockade)- direct dilator action (as well as inhib. Na+ retention)

50

autoregulatory phenomenon

decreased perfusion leading to vasodilation

51

thiazides have ??? on BP and blood chemistry

flat dose response curve
i.e. increasing dose does not significantly increase therapeutic response
-typically good enough for mild hypertensive pts

52

HTN pts may have
high-normal or
low-normal renin

why would it be low?

tx these pts with what ??

it is suppressed

makes sense to tx these high volume pts with diuretics ("volume dependent" HTN)
i.e. elderly, Afr. Americans

53

Resistance to thiazides

Overly vigorous diuretic therapy may *activate the RAAS excessively*-->pressure-raising mechs
-vasoconstrictive effect of angiotensin and aldosterone-mediated exchange of K for Na (tending to retain Na and waste more K)

overwhelming load of *dietary Na* or an intrinsically *impaired renal capacity* to excrete Na to begin with

the reduction in BP by *direct vasodilation*-->inc. hydrostatic press-->edema
may lead to intense Na retention, mandating use of additional diuretic

54

Thiazide SEs

Hypokalemia: K+ wasting
-->ventricular ectopic activity, sudden cardiac death

Hypercholesterolemia (be careful in high cholesterol pts)

Glucose Intolerance with hyperglycemia (be careful with DM pts)

55

how to minimized hypokalemia from thiazides

use of small doses and/or use of only moderately long-acting diuretics rather than very long-acting ones

combine K+ sparers with the diuretic and/or add drugs that suppress the RAAS.

reduce dietary Na+ intake and increase dietary K+ intake

56

loop diuretic: Furosemide

loop diuretics may exert a natriuretic effect near 25 percent of the filtered Na load (much more than thiazide diuretics) by blocking NaCl reabsorption in the thick ascending limb of the loop of Henle

better for v. low GFR and severe edema

indicated for patients with reduced renal Na excretory function

57

Reserpine SEs

sedation, migraine and mental depression: depletes NT; deplete serotonin (does get into brain!)

postural hypotensive symptoms (deplete NE in vasc. smooth musc)
bradycardia (deplete NE in SA node)
systemic fluid retention
nasal congestion

GI: PUD, diarrhea (unopp. parasymps)

58

Methyldopa SEs

peripheral fluid retention
and centrally-mediated sedation and dry mouth.

"autoimmune" disorders and may cause
parkinsonian signs (possibly due to accumulation of methyldopamine in CNS dopamine neurons) not seen with the other central alpha2 drugs.

surprisingly not much postural hypotension

not much rebound HTN as it is a pro-drug, so active form takes time to disappear

59

clonidine SEs

patch may cause local skin reactions

rebound hypertension may occur (though less with patch vs. oral drug)

60

a1-adrenergic receptor blockers:
doxazosin, prazosin and terazosin

Blockade of arterial vascular alpha1- receptors competitively inhibits binding of sympathetically-released NE-->dec. vasoconstriction-->dec. TPR-->dec. BP

*primary HTN*

affects vv as well as aa (some dec. in CO as well)

may improve glucose tolerance (but don't want to use in pts with autonomic neuropathy-->impaired postural reflex)

lower cholesterol and triglyceride levels, increase HDL

61

a1-adrenergic receptor blocker SEs

severe first-dose postural hypotension
postural dizziness

stress-induced urinary incontinence (esp. old ladies)

Reflex tachycardia and systemic fluid retention (less than other vasodilating drugs)

62

B-blockers reduce BP how ??

B1 action:

reduce CO (↓ contractility and possibly by ↓ HR)

inhibit the release of renin from the renal JG cells

63

non-selective (B1 and B2) blockers

remove the normal physiologic level of beta2-mediated vasodilation

tends to offset the decrease in total peripheral vascular resistance expected from the inhibition of renin release, thus limiting the overall antihypertensive effectiveness

*but work well, so still used*

64

metabolism of B-blockers

more lipid soluble-->metabolized by liver and more enters brain

less lipid soluble-->excreted thru kidney, less enters brain (less CNS effects, better pt compliance)

65

B blockers won't work as well in ??



useful in pts with ??

elderly and African- American patients
pts with lower plasma renin

Chinese pts are MORE sensitive

HTN associated with tachycardia and high CO
HTN accompanied by other cardiovascular conditions which can also be tx with B-blockers: e.g. angina, arrhythmia

66

B-blocker CV SEs

(less SEs with partial agonist activity (ISA))

bradycardia (if little/no ISA) -20% lower!

reduced exercise ability and easier fatigue

slow A-V conduction and suppress ventricular contractility too much

Rebound HTN

67

B-blocker pulmonary SEs

(less SEs with partial agonist activity (ISA) and with selective B1 blockers)

Bronchoconstriction

inhibition of airway β2 receptors (Especially a problem in patients who need to inhale beta2-agonists to maintain open airways) (try to chose a more selective B1 blocker for these pts)

68

B-blocker metabolic SEs

(less SEs with partial agonist activity (ISA) and selective B1 blockers)

insulin-induced hypoglycemia may be longer in duration and/or more severe in the presence of especially nonselective beta-blockers without ISA

ALL B-blockers mask an important warning sign of such hypoglycemia, i.e. tachycardia (sweating still occurs)

aggravate insulin resistance with glucose intolerance

Hypertriglyceridemia and a fall in HDL-cholesterol

69

B-blocker central SEs

Bad dreams, even hallucinations
-much less likely with lipid insoluble agents

70

combined a1/B adrenergic receptor blocker (Labetalol) SEs

a-blockade:
postural dizziness which B- blockade can not correct

B-blockage:
bradycardia
A-V block at high doses Obviously, little chance of reflex tachycardia otherwise expected with regular alpha-1 blockers!

71

NO-releasing B1 receptor blocker (Nebivolol) SEs

Similar to other β 1 -blockers though less rebound HTN upon sudden complete withdrawal

headache and fatigue (FYI- due to inc. NO in cerebral blood vessels (paradoxical?))

72

selective arteriolar vasodilators:
(Hydralazine, Minoxidil) major SE

if taken ALONE: markedly dilate resistance arterioles leading to ↑ capillary hydrostatic pressure with ↑ filtration of fluid into the interstitial spaces (edema) plus renal retention of Na and H2O

fall in arterial BP markedly activates sympathetic and renal compensatory reactions causing considerable release of catecholamines and renin resulting in stimulation of the heart and much more retention of Na and water

*use with B-blocker and diuretic to inhibit compensatory reactions*

don't effect vv as much, so little postural hypotension

73

CCBs that end in "dipine" block Ca2+ channels in the ??

vasculature

*not pure distinction, some crossover at high doses

74

dihydropyridine ("dipines") CCB actions

reduce calcium entry into arterial vascular smooth muscle cells through arterial L-type calcium channels
-->decrease in free intracellular calcium -->reduces arterial vascular tone-->dec. TPR and BP

(little suppressive effect upon ventricular contractility at
standard therapeutic doses)

intrinsic natriuretic capability (not as much edema)

75

Diltiazem and *verapamil* actions

↓ calcium entry through ventricular L-type calcium channels-->reduces ventricular contractility-->suppresses CO

May be some ↓ in HR and some ↓
arterial tone, via inhibition of similar channels in cardiac SA node and arterial smooth
muscle

76

CCBs are used for ??


particularly useful for ??

virtually all types of primary systemic hypertension (versatile)

elderly and African-American hypertensive patients
also work well in the face of high Na intake, irrespective of the degree of Na sensitivity.

77

dihydropyridine CCB SEs

reflexively (indirectly) increased heart rate due to peripheral vasodilation-->increased risk MI (incr. sympathetic activity)

nausea, headache, tachycardia, slight postural dizziness, ankle edema

78

Verapamil SEs

nausea, headache, *constipation*
directly suppressed heart rate and A-V conduction
(verapamil > diltiazem)
serious myocardial depression like excessive bradycardia and excessive A-V nodal dysfunction

79

ACE inhibitors end in ??

action ??

"pril"

inhibit production of the active form of angiotensin (angiotensin II)

inactivates the vasodepressor hormone bradykinin
-->increase availability of bradykinin and related PG vasodilators which can further ↓ BP by ↓ TPR

80

ACE inhibitors are eliminated primarily by the ??; dose should be reduced in patients with ??

kidneys

renal insufficiency

(also note the prodrugs are metabolized/activated by the liver)

81

MOA of RAAS inhibitors:
Renin inhibitors (prevent angiontensinogen-->AngI)
ACE inhibitors
ARBs

Ang-II mediated vasoconstriction is obviously overcome and TPR and BP then falls

A-II mediated synthesis of aldosterone is inhibited, thereby Na and H2O retention potentially reduced

also inhibits positive feedback of RAAS

82

good candidates for of RAAS inhibitors

“normal renin” as well as in “high renin” patients with primary HTN and/or with diuretic-induced renin-related resistance

HTN secondary to diabetic nephropathy

83

pts who should not get RAAS inhibitors

patients with fully established *bilateral (efferent and afferent) renovascular hypertension* (GFR is very low) , wherein abnormally “super” high levels of A-II keep renal GFR from falling too low beyond the stenoses by constricting the efferent arterioles; these patients may experience *more loss of GFR with these drugs*

(still sometimes used in these pts because of v. high systemic HTN)

84

AngII is more effective at vasoconstricting the ?? arterioles

efferent (vs. afferent)

therefore RAAS inhibitors decrease GFR by preventing efferent vasoconstriction

85

RAAS inhibitor SEs:
higher bradykinin levels with ACE inhibitors (less with ARBs or the renin inhibitor), may cause ??

nonproductive cough

Angioedema: localized, potentially fatal (asphyxiation)

86

RAAS inhibitor SEs

*hyperkalemia* (may become worse with addition of a K-sparing diuretic or K supplements)

too much hypotension
teratogenic!!
hepatotoxicity

87

??These drugs?? may impair the antihypertensive effects of ACE inhibitors by blocking ??

NSAIDs

bradykinin-mediated vasodilation because it is, at least in part, prostaglandin mediated

88

CASE: middle-aged male, HTN, start on diuretic hydrochlorothiazide (25mg: intermediate dose)
-adequately maintained
-comes in few mos later with severe hypokalemia, what is next most appropriate step??

a. lowering dose of hydrochlorothiazide
b. add on captopril (ACE inhib)
c. add on K+ sparing diuretic
d. add on other powerful diuretic

a. NO: would increase BP
b. NO: while it would raise the K+, it would lower BP too much (he is currently adequately controlled)
c. YES: would raise K+ without affecting BP much (these are weak diuretics, less effect on BP)
d. NO: would lower BP too much (remember: he is adequately controlled)