Anti-hypertensive Drugs Flashcards
1
Q
What is the average efficacy of diuretics’ ability to lower blood pressure when administered alone
A
about 10-15 mmHg
2
Q
In what context of hypertension are diuretics used for
A
mild to moderate hypertension with normal cardiac/renal function
3
Q
In what patients are the thiazides not particularly effective
A
patients with renal insufficiency
4
Q
What are the 8 classes of drugs used to treat hypertension
A
- Diuretics
- Calcium channel blockers (CCBs)
- Centrally acting agents
- Alpha adrenergic blockers
- Beta adrenergic blockers
- Vasodilators
- Angiotensin converting enzyme inhibitor (ACE-I)
- Angiotensin receptor blockers (ARBs)
5
Q
Of the 8 classes of drugs used to treat hypertension which 4 are considered to be the first line drugs of choice
A
- Diuretics
- CCBs
- ACE-Is
- ARBs
6
Q
generally (not including the K+ sparing diuretics) what are the side effects of the diuretics
A
Hyponatremia, HYPERGLYCEMIA, Increased LDL/HDL ratio, HYPOKALEMIA, and metabolic alkalosis
7
Q
What is the MOA of the thiazides
A
inhibits Na+/Cl co transporter
8
Q
How do the thiazides decrease blood pressure
A
- Decreases fluid volume by preventing the reabsorption of Na+ in the DCT
- Stimulated PG production leading to vasodilation
9
Q
What drugs can interfere with the ability of thiazides to treat hypertension
A
NSAIDs (interfere with the anti-hypertensive effect of PGs)
10
Q
What drugs can be used with the thiazides to prevent hypokalemia
A
BB, ACEI, or ARBs (diminish K loss by blunting diuretic induced rise in renin and aldosterone levels)
or use with a K+ sparing diuretic
11
Q
What class of drug will exacerbate the hyperlipidemic and hyperglycemic effects of the thiazides
A
Beta Blockers
12
Q
Contraindication of the thiazides
A
existing hypokalemia
13
Q
Relative contraindication of the thiazides
A
Pregnancy
14
Q
What is the MOA of the loop diuretics
A
inhibits the Na+/K+/2Cl- co-transporter in TAL of hence
15
Q
What is the prototype loop diuretic
A
furosemide
16
Q
What are the differences in efficacy between the thiazide s and the loop diuretics
A
Furosemide has a short duration of action than thiazide, less effective in patients with normal renal function (due to rebound sodium retention)
17
Q
What patient population are the loop diuretics usually reserved for
A
Patients refractory to thiazides, pts with moderate to severe renal insufficiency or CHF
18
Q
What are the major side effects of the loop diuretics
A
Hyponatremia, HYPOKALEMIA, impaired diabetes control, increased LDL/HDL, REV. OTOTOXICITY
19
Q
What drug can interfere with the ability of the loop diuretics to treat hypertension
A
NSAIDs (interfere with the anti-hypertensive effect of PGs)
20
Q
What drug is to be avoided taken with the loop diuretics to avoid toxicities
A
Aminoglycosides (enhance ototoxicity and nephrotoxicity)
21
Q
What are the 2 types (MOAs) of the K+ sparing diuretics
A
Aldosterone receptor antagonist (Spironolactone and eplerenone) and ENaC blocker (triamterene and amiloride)
22
Q
In what context are the K+ sparing diuretics used to treat hypertension
A
NOT used alone for treatment, used in combo with other diuretics (usually to correct hypokalemia)
23
Q
Generally adverse effect of the K+ sparing diuretics
A
HYPERKALEMIA
24
Q
Adverse effect of spironolactone
A
gynecomastia
25
Contraindications of K+ sparing diuretics
any state that can lead to hyperkalemia, combination with drugs that inhibit the RAS (ACE-I, ARBs, BBs)
26
Selected drug interaction of the K+ sparing diuretics
NSAIDs (PG synthesis), ACE-I, ARBs, BBs
27
What is the common MOA of the Calcium channel blockers
1. inhibit Ca2+ influx into vascular smooth muscle thru L-type Ca channels
2. relax peripheral arterial vascular smooth muscle and decrease TPR (due inhibition of MLCK activity due to decrease in Ca-calmodulin)
28
What are the 2 main types of Ca Channel blockers
dihydropyridines and non-dihydropyridines
29
What differentiates dihydropridines and non-dihydropyridines
Non-dihydropyridines also reduce Ca current in CARDIAC pacemaker cells and reduce conduction in AV node --> lower HR and contractility (due to decrease Ca-induced Ca release from myocyte SR) --> reduce cardiac output
30
MOA of Nifedipine (prototype)
Dihydropyridine --> selective vasodilator of vascular smooth muscle
31
How is Nifedipine metabolized? How does that impact who is administered it?
P450 system - avoid in patients with liver disease and consider drug interactions that interfere with P450 system
32
Side effects of Nifedipine
acute tachycardia (reflex sympathoexcitation), peripheral edema (arteriolar dilation > ventilation)
33
MOA of Diltiazem
non-dihydropyridine --> inhibits sinus node as well as L-type Ca channels of myocytes and vascular smooth muscle --> reduces both cardiac output and peripheral resistance
34
Side effects of Diltiazem
bradycardia (slowed rate and conduction)
35
MOA of verapamil
non-dihydropyridine --> potent effect of the heart with more pronounced reduction of currents --> reduces both cardiac output and resistance
36
Side effects of verapamil
constipation and bradycardia
37
Relative contraindication for CCBs
pts with liver failure (drugs are metabolized by liver) and patients with SA or AV node conduction disturbances should NOT be given verapamil nor diltiazem (caution in pts on BBs for this reason)
38
MOA of the sympatholytic drugs to treat hypertension
reduce sympathetic drive to the heart and/or blood vessels --> decreased venous return, cardiac output, TPR, and renin release
39
MOA of the centrally acting agents for treating hypertension
reduce sympathetic output from the vasopressor centers in the brainstem
40
MOA of Clonidine (prototype)
alpha2 agonist at medullary cardiovascular regulatory centers --> decreases symp. outflow from CNS to vascular smooth muscle
41
Side effects of Clonidine
sedation, dry mouth, contact dermatitis (due to transdermal patch)
42
Why is Guanfacine a better choice over clonidine
has a longer half-life, less chance of rebound (hypertensive crisis)
43
What are the significant dangers when a patient misses a dose of Clonidine or abruptly stops taking it
rebound hypertension
44
MOA of methyldopa
crosses BBB and in converted to methyl-NE and acts as alpha2 agonist as well as competes with L-DOPA for DOPA decraboxylase preventing the production of dopamine and NE or EPI in peripheral nerves
45
What medication with methyldopa interfere with
L-DOPA for parkinsons
46
What are the side effects of methyldopa
Sedation
47
Contraindication for methyldopa
liver disease
48
In what specific condition is methyldopa used most extensively in
Hypertension during pregnancy
49
What is the MOA of reserpine
blocks VMAT vesicular transporter, prevents storage of NE centrally and peripherally
50
How is reserpine generally administered to treat hypertension
Given in combination with diuretics (side effects are significant in doses used for monotherapy)- low dose combo is highly efficacious with minimal side effects
51
Side effects of reserpine
DEPRESSION, nasal congestion
52
Selected drug interactions of reserpine
potentiates effects of CNS depressants and MOAI (counteract the effects of reserpine)
53
MOA of alpha adrenergic antagonists
act at post synaptic receptors to block arterial and venous constriction
54
MOA of phenoxybenzamine
non-selective alpha adrenergic antagonist
55
Indications for phenoxybenzamine
used exclusively for htn due to pheochromocytoma
56
Side effects of phenoxybenzamine
tachycardia (baroreflex)
57
MOA of prazosin (prototype)
selective a1 adrenergic antagonist
58
what are the advantages of terazosin and doxazosin over prazosin
longer half life, terazosin and doxazosin can be dosed once/day
59
Side effects of Prazosin
Hypotension (1st dose), fluid retention (best results obtained when taken with a diuretic)
60
Benefits of Prazosin/other selective a1 antagonists
do not impair exercise tolerance, less tachycardia than direct vasodilators or non-specific a-antagonists, DECREASES LDL/HDL
61
MOA od BBs
B-adrenergic antagonist: decrease myocardial contraction and CO, decrease renin secretion (and ATII), reduce sympathetic action thru CNS effects (lipophilic ones)
62
MOA of propanolol (1st gen)
Non-selective BB, lipophilic, short half life
63
Indications for propanolol
mild to moderate hypertension, used as an adjust to prevent reflexive tachycardia from direct vasodilators, MI or arrhythmia
64
Indication for Prazosin/Terazosin/Doxazosin
Second line for chronic hypertension
65
MOA of nadolol
non-selective BB
66
Advantage of nadolol over propanolo
longer half life, allows single daily dosing, hydrophilic
67
MOA of pindolol
non selective B-antagonist with partial B-agonist activity
68
Advantages of pindolol over other BBs
produces less bradycardia than other BBs (potentially eliminated some of the side effects of BBs)
69
Indication for pindolol
chronic hypertension, pts with symptomatic bradycardia or postural hypotension
70
MOA of metoprolol
B1 selective antagonist (fewer respiratory effects), lipophilic (so may have central sympatholytic effect)
71
Indication for metoprolol
Hypertension, long term angina rx
72
MOA for atenolol
B1 selective antagonist, hydrophilic
73
Indications for atenolol
Chronic hypertension, MI, angina, HF
74
MOA for labetolol
mixed alpha/beta adrenergic receptor antagonist
75
Side effect of labetolol
lipophilic, higher incidence of orthostatic hypertension
76
MOA of Carvedilol
non-selective alpha receptor and beta blocker and NO generator (vasodilatory), lipophilic
77
General side effects of beta blockers
ALL: bradycardia, increased serum TGs, decreased HDL levels, hyperglycemia (less so with cardioselective), low exercise tolerance
Non-selective: increased airway resistance
Lipophilic: insomnia, mild chronic fatigue, depression
78
Drug interactions with the BBs
CCB's increase the risk of conduction disturbances (reduces contractility and conduction)
79
What are the contraindications for the BBs
cardiogenic shock, sinus bradycardia, ASTHMA, severe congestive heart failure (protective in compensated heart failure)
80
Why should you taper a patient off a BB
rebound tachycardia
81
What should you worry about with a diabetic patient on a BB
BB can mask and prolong insulin induced hypoglycemia
82
What patient populations are BB mono therapy less efficacious in
African Americans and the elderly
83
MOA of Hydralazine
vasodilator of small vessels (primarily arterioles)
84
Indications for hydralazine
Drug resistant hypertension and emergencies
85
Side effects of hydralazine
tachycardia, angina aggravation (reduced venous return can compromise coronary blood flow), fluid retention, lupus-like syndrome
86
What drug will interfere with hydralazine efficacy
NSAIDs (probably due to PGs synthesis)
87
MOA of Minoxidil
vasodilator of arterioles via K+ channel opener
88
Indications for Minoxidil
drug resistant hypertension
89
Side effects of Minoxidil
tachycardia, angina aggravation (reduced venous return can compromise coronary blood flow), fluid retention, hypertrichosis
90
MOA of Nitroprusside
vasodilation of small vessels (primarily arterioles and veins), does not stimulate increase cardiac work
91
Indications for Nitroprusside
Emergencies: immediate onset brief duration
92
Side effects of Nitroprusside
cyanide poisoning
93
Contraindication for hydralazine
coronary artery disease (vasodilation in unobstructed coronary vessels "steal" blood from obstructed regions)
94
MOA of the ACE-Is
blocks production of angiotensin II and Ang-II mediated vasoconstriction: decreases TPR, increases bradykinin --> vasodilation, and reduces aldosterone secretion
95
MOA of captopril (Prototype)
ACE-I
96
MOA of Enalapril
ACE-I
97
MOA of Lisinopril
ACE-I
98
Why would you prescribe Lisinopril over captopril and enalapril
Captopril - has a shorter half life
Enalapril - longer half life BUT has to be converted to an active metabolite
Lisinopril - water soluble and excrete unchanged by the kidney, longer half life
99
Side effects of Lisinopril
DRY COUGH, hyperkalemia, angioedema (more common in african americans)
100
Drug interactions with Lisinopril
K+ sparing diuretics: can exacerbate hyperkalemia
101
Contraindications of Lisinopril
Pregnancy (Ang II in important in fetal renal development) and bilateral stenosis
102
Therapeutic benefits of lisinopril
prolongs survival in pts with HF or LV disfunction after an MI, preserves renal function in pts with diabetes
103
MOA of the ARBs
Bind to the angiotensin II receptors and inhibit there mediation of receptor vasoconstriction and sodium retention, but do not inhibit bradykinin metabolism (do not produce dry cough)
104
MOA of Losartan
ARB: selective AT1 receptor antagonist, short half life
105
Side effect of Losartan
Hyperkalemia
106
Contraindication for losartan
Pregnancy
107
Drug interactions for losartan
K+ sparing drugs (worsen hyperkalemia)
108
What patient population is losartan less effective in
Salt sensitive hypertensive pts (African americans)
109
What pt population should you reduce the dose of losartan
Liver disease (met by the liver) and hypovolemia
110
What drug(s) would be a good combination with the thiazides
K+ sparing diuretics and BBs
111
What drugs are a good combo with the CCBs
ACE-I
112
What are the bad combos of drugs
ACE-I/ARB and K+ sparing diuretics
| ACE-I and ARBs
113
What ant-hypertensive would be recommended for a diabetic patient
ACE-I or ARBs, AAs, CCBs (few effects on carb met)
114
What ant-hypertensive would be recommended for a pt with heart failure
ACE-I and diuretics
115
What ant-hypertensive would be recommended for a pt with MI
BBs, and ACE-I (prevent LV remodeling)
116
What ant-hypertensive would be recommended for a pregnant pt with hypertension
methyldopa
117
What ant-hypertensive would be recommended for an african american pt with uncomplicated hypertension
CCBs or diuretics as first line, or BBs, ACE-I, ARBs in combo with a diuretic
118
What ant-hypertensive would be recommended for a hyperlipidemic pt
Alpha blockers (decrease LDL/HDL ratio), CCBs, ACE-I, ARBs have little effect on lipid profile
119
What drug should be avoid in obstructive airway disease
BBs
120
At what blood pressure should you treat a pt under 60 without diabetes with anti-hypertensives
140/90
121
At what blood pressure should you treat a pt over 60 without diabetes with anti-hypertensives
150/90
