Antihypertensives Flashcards
1
Q
What is the mechanism of action for the ACE-Inhibitors?
A
Angiotensin converting enzyme - Inhibitor
- Inhibits conversion of angiotensin-1 to angiotensin-2
- Causes vasodilation, decreased aldosterone levels, Na+ and fluid wasting and K+ retention
2
Q
What is considered a normal BP?
A
SBP = <80
3
Q
What BP would be considered to be prehypertension?
A
SBP = 120 - 139 or DBP = 80 - 89
4
Q
What BP is considered to be Stage I HTN?
A
SBP = 140 - 159 or DBP = 90 - 99
5
Q
What BP is considered to be Stage II HTN?
A
SBP = > or = to 160 or DBP = > or = to 100
6
Q
What is the BP goal for a patient without co-morbid conditions?
A
< 140/90
7
Q
What is the BP goal for a patient with diabetes, CKD, MI, angina, stroke, or heart failure?
A
< 130/80
8
Q
What is the goal BP for a patient with proteinuria?
A
< 125/75
9
Q
What is the goal BP for a patient with left ventricular hypertrophy?
A
< 120/80
10
Q
What is the goal BP for a patient with isolated systolic HTN?
A
Treat with usual BP goals…
For patients with SBP >180, first goal is to reduce to <160 and monitor closely for hypotension. Then, attempt to reduce BP to target goal.
11
Q
What are some drugs that may worsen HTN?
A
- Corticosteroids
- Oral contraceptives
- NSAIDs and COX-2 Inhibitors
- Erythropoietin
- Oral Decongestants
- Some antidepressants
- Cocaine and withdrawal from cocaine
- Nicotine and withdrawal from nicotine
- Amphetamines
12
Q
What are some lifestyle modifications that can be done to reduce BP in patients?
A
- Weight reduction
- Dietary approaches to stop HTN
- Physical activity
- Dietary sodium reductions
- Reduce consumption of alcohol
13
Q
What is the mechanism of action for the Alpha-2 Adrenergic Agonists?
A
Stimulates Alpha-2 receptors of the brain stem associated with autonomic regulation of CV system. Activation of Alpha-2 receptors causes neurons to quit releasing norepinephrine.
- Decreased sympathetic output
- Decreased BP
- Mildly decreases HR
14
Q
What are some therapeutic uses for Alpha-2 Adrenergic Agonists?
A
Not 1st line for HTN, does not reduce M/M
- Clonidine tabs effective for HTN urgencies
- Clonidine used in treatment of withdrawal symptoms of nicotine, opiates, benzos, and alcohol.
- Methyldopa is DOC in pregnancy induced HTN
15
Q
What are some adverse effects of the Alpha-2 Adrenergic Agonists?
A
- Orthostatic hypotension and dizziness, headache, and impaired ejaculation
- Anticholinergic: sedation, dry mouth, constipation, urinary retention, blurred vision
- Rebound fluid retention - add diuretic
- WARNING: Abrupt withdrawal causes severe rebound HTN. Taper over 3 - 4 days
16
Q
What is the mechanism of action for the Alpha-1 Blockers?
A
Competitive blocking of the alpha-1 receptors.
HTN: lowers BP by causing vasodilation. Relaxes both arterial and venous smooth muscle surrounding some blood vessels.
BPH: Relax smooth muscle of the bladder neck & prostate, which improves urine flow in BPH
17
Q
What are some therapeutic uses for Alpha-1 Blockers?
A
Not 1st line for HTN: does not reduce M/M
- Reduces BP well
- BPH: treats symptoms of urinary retention
- Raynaud’s disease
18
Q
What are some adverse effects of Alpha-1 Blockers?
A
- Orthostatic hypotension: FIRST DOSE EFFECT - syncope following 1st dose…give at bedtime
- Reflex tachycardia
- Sodium and water retention
- Dizziness, lack of energy, drowsiness, nasal congestion, headache, decreased libido
19
Q
What are some drug interactions of Alpha-1 Blockers?
A
- Use with vardenafil and sildenafil causes hypotension
- Alfuzosin is contraindicated with potent CYP3A4 inhibitors
20
Q
What are the Alpha-2 Agonist drugs?
A
- clonidine
- methyldopa
21
Q
What are the Alpha-1 Blocker drugs?
A
- doxazosin HTN/BPH
- alfuzosin BPH
- terazosin HTN/BPH
- tamsulosin BPH
- prazosin HTN
22
Q
What are the Beta-1 Blocker drugs?
A
A - O in alphabet
- acebutolol
- atenolol
- betaxolol
- bisoprolol
- metoprolol
- nebivolol
23
Q
What is the mechanism of action for the Beta-1 Blockers?
A
- Selectively block the Beta-1 receptors
- Higher affinity for Beta-1 receptors than Beta-2 receptors
- Decreased HR, decreased force of contraction
- Block juxtaglomerular cells - block renin release
24
Q
What are the therapeutic uses for Beta-1 Blockers?
A
Preferred drug for HTN in pts. with cardiac co-morbidities such as:
- chronic unstable angina
- acute coronary syndrome
- post-MI
- systolic and diastolic CHF to improve M/M
- Atrial fibrillation and tachycardia
25
What are some other, non-cardiac therapeutic uses for Beta-1 Blockers?
- Hyperthyroidism to protect heart from excess adrenaline in patients with poorly controlled hyperthyroidism.
- Essential tremor
- Autonomic nervous system overload (stage fright; PTSD)
26
What are some adverse effects of Beta-1 Blockers?
- Hypotension
- sexual impairment
- nightmares
- Transient decreased HDL & increased Tg
- Acute heart failure, reduced cardiac output
- Bradycardia and AV block
- May mask S/S or hypoglycemia in diabetics
- WARNING: risk of fatal rebound HTN, tachycardia, angina, and MI with abrupt withdrawal. Taper over 1 - 2 weeks
27
Which patients must you use caution in when prescribing Beta-1 blockers in?
- Uncompensated heart failure
- AV block
- Diabetes
- Cardioselective Beta-blockers are safer than non-selective agents in pts with diabetes, peripheral vascular disease, asthma, and COPD
28
What are some drug interactions of Beta-1 Blockers?
- Additive AV blocking when given with digoxin, verapamil, or diltiazem
29
Which drugs may have intrinsic sympathomimetic activity?
Beta-1 blockers
- These have partial agonist activity
- Have little effect on resting HR, cardiac output, and Tg levels.
- Do not reduce CV risk like other Beta-blockers and may be detrimental post-MI.
30
What are the non-selective Beta-blockers?
Pinched Paul's Nads
- propanolol
- nadolol
- pindolol
31
What is the mechanism of action for the non-selective Beta-blockers?
Same as Beta-blockers
- Selectively block the Beta-1, Beta-2, receptors
- Decreased HR, decreased force of contraction
- Block juxtaglomerular cells - block renin release
32
What are some therapeutic uses for the non-selective beta-blockers?
- chronic unstable angina
- acute coronary syndrome
- post-MI
- systolic and diastolic CHF to improve M/M
- Atrial fibrillation and tachycardia Cartelol and timolol are used as eye drops to treat glaucoma
- Hyperthyroidism to protect heart from excess adrenaline in patients with poorly controlled hyperthyroidism.
- Essential tremor
- Autonomic nervous system overload (stage fright; PTSD)
33
Which class of drugs may be used for migraine prophylaxis?
Non-selective beta-blockers
34
Which drugs may treat the following conditions?
- Hyperthyroidism to protect heart from excess adrenaline in patients with poorly controlled hyperthyroidism.
- Essential tremor
- Autonomic nervous system overload (stage fright; PTSD)
- chronic unstable angina
- acute coronary syndrome
- post-MI
- systolic and diastolic CHF to improve M/M
- Glaucoma
- Beta-1 Blockers
| - non-selective Beta-blockers
35
What are some adverse effects that may be seen with Non-selective beta-blockers?
- Hypotension
- sexual impairment
- nightmares
- Transient decreased HDL & increased Tg
- Acute heart failure, reduced cardiac output
- Bradycardia and AV block
- May mask S/S or hypoglycemia in diabetics
- WARNING: risk of fatal rebound HTN, tachycardia, angina, and MI with abrupt withdrawal. Taper over 1 - 2 weeks
- Peripheral vasoconstriction
- Bronchoconstriction
- Hypoglycemia
- USE CAUTION: in asthma, COPD, PVD, decompensated heart failure, AV-block or fragile diabetes
36
What are some drug interactions associated with non-selective beta-blockers?
- Additive AV blocking when given with digoxin, verapamil, or diltiazem
- May blunt the response to albuterol and other Beta-2 agonists
37
What are the alpha-1, beta-1, and beta-2 blocker drugs?
- carvedilol
38
What is the mechanism of action for the alpha-1, beta-1, and beta-2 blocker drugs?
- Selectively block the Beta-1, Beta-2, and alpha-1 receptors
39
What are the therapeutic uses for the alpha-1, beta-1, and beta-2 blocker drugs?
- Improves M/M in patients with CHF and post-MI
40
What are the adverse effects of the alpha-1, beta-1, and beta-2 blocker drugs?
- Similar to cardioselective Beta-1 blockers (except no change in lipid levels) plus...
- Similar to non-selective Beta-blockers plus...
- Similar to Alpha-1 blockers (except will not cause reflex tachycardia)
41
What are the therapeutic uses for ACE-I drugs?
- DOC for managing hypertension to improve M/M
- Diabetic neuropathy or persons with proteinuria: slows progression of renal failure in diabetics, even in diabetics without HTN
- Stroke prevention
- Improved M/M when administered with Beta-blocker in pts. with chronic stable angina, MI, and systolic heart failure
- Slows the progression of CHF and improves quality of life
- Acute MI
42
What are some dosing recommendations for patients taking ACE-I drugs?
- Test dose of captopril appropriate in pts with high level of RAA activity e.g.. hyponatremia, diuretic use, heart failure
- Reduce starting dose in pts. who are on diuretic, volume depleted, or at risk of orthostatic HTN, or elderly.
43
What are some adverse effects of ACE-I drugs?
- Hypotension
- Bradykinin related side effects:
- Dry, hacking cough
- Non-allergic rash
- Angioedema - immediately Dx use
- Hyperkalemia
- Acute reversible renal insufficiency: more likely to occur in people with renal artery stenosis, preexisting renal dx, or taking NSAIDs.
- Contraindicated in pregnancy.
44
What are some drug interactions of ACE-I drugs?
- Co-admin of NSAIDs in persons with underlying renal compromise may worsen renal function
- NSAIDs may diminish BP lowering effects of ACE-I
- Concurrent use with K+ sparing diuretics, ARBs, or K+ supplements may lead to hyperkalemia
- May cause alterations in lithium levels
45
Which molecule is the primary afferent vasodilator in the kidney?
Prostaglandin
46
Which molecule is a potent vasoconstrictor of the efferent arteriole in the kidney?
Angiotensin-2
47
What is the role of an ACE-I in regulation of kidney function?
- ACE-I will reduce ANG-2 levels, thus causing the efferent arteriole to vasodilate, which reduces the glomerular filtration pressure.
- In persons with bilateral stenosis or on NSAIDs, they may not be able to compensate for the reduction in pressure and suffer a dramatic decrease in glomerular filtration
- NSAIDs produce prostaglandins
48
What are the Angiotensin-2 Receptor Blocker (ARB) drugs?
- candesartan
- irbesartan
- olmesartan
- valsartan
- eprosartan
- losartan
- telmisartan
49
What is the mechanism of action for the ARBs?
- directly bind and block the angiotensin-2-receptor
- ACE-I block only one pathway of Ang-2 production, but reduce angiotensin-2 levels at all receptor sites.
- ARBs block only one type of angiotensin-2-receptor, but block it more completely
- Above is the difference between ACEs and ARBs
50
What are some therapeutic uses for ARBs?
Same as ACE-Is
- Where ACE-I are preferred, ARBs are an acceptable alternative in a pt. who cannot tolerate bradykinin-related side effects of an ACE-I
- May be equal to or superior to ACE-I in preventing diabetic nephropathy.
51
What are some adverse effects of the ARBs?
- Similar ADRs as ACE-I except...
- Less likely to cause cough and rash due to their lack of effects on bradykinin levels
- Hx of angioedema is a precaution rather than contraindication
- Contraindicated in pregnancy
52
What are some drug interactions associated with ARBs?
- Co-admin of NSAIDs in persons with underlying renal compromise may worsen renal function
- NSAIDs may diminish BP lowering effects of ACE-I
- Concurrent use with K+ sparing diuretics or K+ supplements may lead to hyperkalemia
- May cause alterations in lithium levels
53
What are the Calcium Channel Blocking (CCB) drugs?
```
Pines
- amlodipine
- felodipine
- isradipine
- nicardipine
- nifedipine
Cardiac
- diltiazem
- verapamil
```
54
What is the mechanism of action for the CCB drugs?
- Inhibits the entrance of Ca++ into the smooth muscle cells of the coronary and arterial vessels.
- All CCBs are vasodilators
- diltiazem and verapamil also act on the calcium channels of the heart causing them to have some Beta-1 blocker properties - negative inotropes and negative chronotrope
55
What are some therapeutic uses for CCBs?
- DOC for managing HTN to improve M/M
- Angina (chronic or exertional)
- Long-term benefits in diabetes have been shown
- Effective for isolated systolic HTN in elderly and in african americans
- Raynaud's
- Cardiac CCBs can be used to treat a-fib and tachycardia; however they are NOT cardioprotective in same way beta-blockers are in post-MI and heart failure
56
What are some adverse effects of CCBs?
All CCBs:
- vasodilators: dizziness, hypotension, flushing, peripheral edema, and headache
- especially verapamil: constipation
- Except amlodipine: have negative inotropic effect
- gingival enlargement
Pine CCBs:
- especially nifedipine & nicardipine: reflex tachy,
Cardiac CCBs:
- DO NOT cause reflex tachy
57
Why should immediate release nifedipine not be administered in patients?
- It is associated with dangerous, ping-ponging BP, relfex tachy, arrhythmias, MI, and death.
- Do NOT prescribe
58
What are some drug interactions associated with CCBs?
- Especially verapamil and diltiazem: cytochrome p450 interactions
- verapamil and diltiazem may also cause AV block if given with Beta-blockers
59
What is the mechanism of action by which the diuretics work within the kidneys?
- Block tubular reabsorption of Na+ and fluid at different sites within the nephron
- Water follows sodium: water passively follows Na+ concentration
60
At what location within the nephron do thiazide diuretics act?
distal convoluted tubule
61
How do thiazide and loop diuretics induce hypokalemia and acid/base imbalance?
- Urine that hits the Na/K/H channels at the end of the distal convoluted tubule is full of Na+
- Na/K/H channels sense increase and rev up to compensate
- When the channels absorb Na+, they must do so in exchange for either a K+ or H+ molecule
- Channels are not active enough to counteract diuretic, but active enough to cause hypokalemia or acid/base imbalance
62
What are the thiazide diuretic drugs?
- chlorothiazide
- chlorthalidone
- hydrochlorothiazide
- metolazone - thiazide like
- indapamide
63
What is the mechanism of action of the thiazide diuretics?
- Enter nephron via organic acid secretory pathway of proximal tubule and block tubular reabsorption of Na+ at early part of distal convoluted tubule
- Also posses some vasodilatory effects
64
Why are thiazides more effective than loop diuretics for chronic HTN?
- Thiazides do not cause rebound vasoconstriction as loops sometimes do.
- They also have direct acting vasodilatory properties
65
What are some therapeutic uses for thiazide diuretics?
- DOC for management of HTN to improve M/M
- Offer synergy when combined with and other antihypertensive
- Treat mild to moderate edema
- Minor uses: reduce amount of Ca++ excreted into urine; thus useful in tx of calcium-based kidney stones and reduction of risk of osteoporosis
66
What are some adverse effects associated with thiazide diuretics?
- Dehydration and electrolyte balance
- Hypokalemia
- May increase Tg & LDL
- Hypeeruricemia may produce Gout attacks
- High doses may cause hyperglycemia in some diabetics
67
What are some drug interactions associated with thiazide diuretics?
- Beta-blockers may increase hyperglycemic effects of thiazides in type II diabetics
- synergistic hypotension may occur when used with ACE-I or any other hypertensive
68
What are the loop diuretics?
Torch Fur with Butane
- furosemide
- bumetanide
- torsemide
69
What is the mechanism of action for the loop diuretics?
- Act in ascending limb of loop of hence
- Secreted into urine by organic acid pathway of proximal tubule
- Pts. with renal failure will require larger doses to be effective.
70
What are the therapeutic uses for loop diuretics?
- Edema associated with CHF or renal failure
- IV for acute pulmonary edema or acute decompensated heart failure
- Tx of HTN due to fluid overload in pts. with reduced ClCr
71
What are some adverse effects of loop diuretics?
- Orthostatic hypotension, dizziness, photosensitivity, rash, and hyperuricemia (gout)
- dehydration, hypokalemia, and electrolyte imbalance (pts. usually require K+ supplement)
- Ototoxicity- hearing can be affected, especially when used with aminoglycosides
- Prerenal azotemia- decreased kidney function due to over-depletion of blood volume
72
What are some dosing recommendations for loop diuretics?
- Dose at night when dosing twice daily
- Higher doses might be needed in patients with renal failure and heart failure to overcome diuretic resistance
- synergy with thiazides
73
What are some drug interactions that may be associated with loop diuretics?
- Hypokalemia; if pt becomes hypokalemic while on digoxin, toxicity may occur
Synergistic hypotension may occur with concomitant use of ACE-I or other anti-HTN
74
What are the potassium sparing diuretics?
- spironolactone
| - eplerenone
75
What is the mechanism of action for the potassium sparing diuretics?
- Synthetic aldosterone agonists. Competes with aldosterone at renal receptor sites.
- Aldosterone normally stimulates Na+ reabsorption and K+ elimination at the distal tubule
- Causes Na+ elimination and K+ reabsorption
76
What are the therapeutic uses of the Potassium sparing diuretics?
- Not powerful enough as a diuretic to be used alone to treat edema
- Improves M/M in left vent. systolic dysfunction
- Reduce portal vein HTN in liver failure pts. with ascites
- Used in combo with thiazides or loops to help retain K+ and prevent hypokalemia
- Resistant HTN, where pts. are already on 3 or more drugs
77
What are some adverse effects that may be associated with potassium sparing diuretics?
- Hyperkalemia: may be life threatening
| - Spironolactone - may cause gynecomastia in men and menstrual irregularities and deepening of the voice in women.
78
What are the contraindications and precautions associated with potassium sparing diuretics?
- Serum K+ > 5.5 at initiation or ClCr less than or equal to 30 ml/min
- Use EXTREME CAUTION in pts taking K+ supplements, ACE-Is, ARBs, or using salt substitutes
- Eplerenone use contraindicated with powerful CYP3A4 inhibitors, such as macrolides and azoles
79
What are some medications that may be used to treat orthostatic hypotension?
- midodrine: alpha-1 agonist
| - fludrocortisone: increases salt and water retention
80
What are some tips for preventing orthostatic hypotension in pts?
- Get up slowly from lying or seated position.
- Exercise calf muscles before sitting up
- Avoid bending at waist to pick stuff up
- Sit or lie down immediately after feeling light-headed
- Avoid alcohol
81
How should most patients with stage 1 HTN be treated initially?
- With a thiazide diuretic
82
How should patients with stage 2 HTN be treated initially?
- With combination therapy with one of the agents preferably being a thiazide diuretic
83
How should a patient with isolated Systolic HTN be treated initially?
- thiazide diuretics and CCBs seem to work well
84
What drugs are the drugs of choice in the management of HTN with or without compelling indications as they have the best evidence supporting benefits on Mortality and Morbidity
- Diuretics
- ACE-Inhibitors
- Angiotensin-2-Receptor Blockers (ARBs)
- Calcium Channel Blockers (CCBs)
85
What would be the best management of HTN in a patient with systolic heart failure / left vent. hypertrophy?
- ACE-I + diuretic (loop or thiazide depending on fluid issues)
- Also, beta-blockers, ARB, aldosterone agonist
86
What would be the best management of HTN in a patient who is post-MI?
- Beta-blocker + ACE-I
- Also aldosterone antagonist
- Propanolol, timolol, carvediolol, and metoprolol have all been proven beneficial in post-MI studies.
87
What would be the best management of HTN in a patient who have angina or acute coronary syndrome?
- Beta-blocker
88
What would be the best management of HTN in a patient who has diabetes?
- ACE-Is or ARBs
| - Also, thiazide diuretics
