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IPFC 3 Final > Hypertension therapeutics > Flashcards

Hypertension therapeutics Flashcards

1
Q

What is the one goal of treatment for HTN

A

Reduce CV events

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2
Q

Are blood pressure goals surrogate or clinical outcomes?

A

Surrogate targets

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3
Q

What are the benefits of BP control
MI
Stroke/heart failure

A

MI: 20-25% RRR
Stroke/heart failure: 40-50% RRR

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4
Q

What are the 5 most effective lifestyle changes on BP?

A
  1. Dietary sodium reduction
  2. Weight loss
  3. Reduce alcohol
  4. Exercise
  5. Dietary modification
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5
Q

What are the benefits of salt reduction to 2000mg in diet?

A
  • Decrease blood pressure
  • improves response to ACE/ARBs
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6
Q

When should you increase potassium intake?

A

patients not at risk of HYPERkalemia
- increases BP

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7
Q

What are risk factors for hyperkalemia? aka, when is potassium not appropriate in? (4)

A
  • People on ACE
  • People on trimethoprin, sulfamethazole (anything similar to aldosterone)
  • CKD GFR <45
  • Baseline serum potassium > 4.5 mmol/L
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8
Q

When do you start treatment in the following groups? What is the BP target?
Low risk CVD
High risk CVD
Diabetes
Most

A

Low risk CVD:
- 160/100, <140/90

High risk CVD:
- 130 , <120

Diabetes
- 130/80, <130/80

Most
- 140/90, <140/90

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9
Q

Should low-risk patients be treated? NNT for CV events?

A

Yes
1/100 NNT

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10
Q

What type of HTN occur in most cases of elderly? Target?

A

isolated systolic hypertension
<140/90

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11
Q

When would you consider <120 BP (intensive target? When do you not?

A

high CV risk and NO diabetes

Do not consider
- patient unwilling/ not able to adhere
- standing SBP <110 hg (orthostatic)
- Inability to measure SBP accurately
- Known secondary causes of hypertension (Chronic kidney disease, Cushing’s syndrome, thyroid disease)

  • eGFR <20
  • HF, recent MI, stroke
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12
Q

What are high risk patients for CVD where you would target systolic <120? (4)

A
  1. 75+
  2. Clinical/subclinical CVD (previous MI, CV procedures, peripheral artery disease)
  3. FRS 15%+
  4. CKD GFR of 20-59 (non-diabetic nephropathy)
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13
Q

SPRINT trial
PICO

A
  • Increase CV risk (no previous event)
  • 75+
  • SBP 130+
  • NO diabetes
  • CrCl 20-59 by MDRD

I: <120 BP vs <140 BP

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14
Q

SPRINT trial
intensive therapy effect on kidneys?

A

Patients with CKD at baseline = no effect

Patients without CKD at baseline = suffered AKI

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15
Q

When would we consider single pill combinations?

A

In patients with stage 2 HTN 160/100+

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16
Q

What are compelling indications that require beta-blocker first line?

A

HF with reduced ejection fraction
Post-MI
Coronary artery disease
- Diabetes (add-on if needed for more control)

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17
Q

What is the general rule of treatment?

A

Degree of BP lowering not the choice of specific medication

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18
Q

MOA of diuretics

A

Causes inc renal excretion of Na + water
–> dec fluid volume –> VASODILATION

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19
Q

Thiazide type vs thiazide like drugs

A

Thiazide type: HCTZ
Thiazide like: Chlorthalidone, indapamide

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20
Q

When are potassium-sparing diuretics used?

A

Given in combo with thiazides to prevent potassium deficiency

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21
Q

Adverse effects of diuretics? (5)

A
  • Diuresis (AM dosing)
  • Hypotension
  • Weakness, muscle cramps
  • Electrolyte imbalance (HYPOKALEMIA, HYPONATREMIA)
  • reversible impotence and gout attacks
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22
Q

Difference of chlorthalidone vs HCTZ in ADRs

A

since chlorthalidone is more potent -> need lower dose -> less risk of side effects (but the same ones)

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23
Q

Monitoring for diuretics? Which drug is more urgent?

A

Monitoring: monitor serum potassium at 1-2 months (more urgent for chlorthalidone than HCTZ)

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24
Q

What CrCl are diuretics ineffective in?

A

<30-40 ml/min

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25
Q

What group of patients are diuretics effective in?

A
  • Isolated hypertension
  • elderly
  • black patients
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26
Q

ACEi MOA?

A

Block production of angiotensin II
- vasodilation –> dec cardiac output –> dec BP

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27
Q

ACEi ADRs (5)

A

Hacking cough
Angioedema (must d/c)
HYPERkalemia
Dec eGFR
Hypotension, dry mouth, nausea, rash, muscle pain

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28
Q

ADRs difference between ACEi and ARBs

A

Same
- ARBs have less chance of cough and angioedema

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29
Q

Contraindications of ACE and ARBs (3)

A
  1. Renal artery stenosis (less lumen available for blood flow to kidneys)
  2. History of angioedema
  3. Hyperkalemia
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30
Q

What/When to monitor for ACE/ARB?

A

Check K and SCr
- 1 week after starting
- 4 weeks later
- Then q3months

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31
Q

What did the ONTARGET trial show?

A

ACEi=ARBs

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32
Q

What was the proposed MOA of direct renin-inhibitors (aliskiren) but did not work?

A
  • block pro-renin activity (thought to have independent effects from its enzymatic activity and contribute to HTN)
  • avoiding the increased renin activity bc that can be potentially a result of ACEi and ARBs
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33
Q

CCB general MOA

A

inhibit the L-type calcium channel on cells
- inhibit Ca2+ entry into excitable cells
- inhibit the role of Ca2+ as an intracellular messenge

34
Q

Dihydropyridines MOA
Drugs?

A

Mainly vasodilation –> reduced TPR
- Vaso selective
- has some chronotropic (HR) + inotropic (contractility) effects but low

Drugs
- nifedeipine
- amlodipine
- felodipine

35
Q

Non-dihydropyridines MOA
Drugs

A

Slow cardiac contractility and conduction (dec CO)
- chronotropic (# of heart beats) and inotropic (speed of contractility) effects
- myocardial cells (cardio selective)
- still has vasodilation effects but low

Drugs
- Verapamil
- diltiazem (central effects)

36
Q

ADRs of DHP (4)

A

vasodilation effects
- headache
- lightheadedness
- flushing
- peripheral edema (up to 20% of patients)

37
Q

ADRs of NDHP?

A

Reduced contractility effects
- constipation (25%)
- bradycardia (low HR)
- worsening cardiac output

38
Q

When are NDHPs contraindicated?

A
  • using beta blockers
  • have heart failure with reduced ejection fraction
  • 2nd or 3rd degree atrioventricular block (afib)
39
Q

What is edema the result from in DHP?

A

Due to disproportionate vasodilation betwen arteries and veins
- causes increased permeability of capillaries
- NOT a result of volume

40
Q

How to manage edema in DHP CCB?

A

Dose dependant (not improved by diuretics)
- reduce dose
- switch to NDHP if indicated
- add/replace with ACE/ARBs, reduce it

41
Q

What do trials say about using short acting calcium channel blockers?

A

Do not use
- increased risk of MI in HTN treatment

42
Q

What are the major durg interactions with amlodipine?

A

CYP 3A4 subtrates
- azoles
- protease inhibitors
- macrolides (azith)
- Quinidine

43
Q

When are beta-blockers first line therapy? (4)

A

With a compelling indication such as:
- angina
- MI
- HF
- Afib

44
Q

What did ALLHAT trial show for alpha blockers?

A

Should not be used as first-line therapy
- can be used if there is indication in hyperplasia BPH

45
Q

When are central alpha-2 agonists used?

A

Not as first line
- used for HTN urgencies OR
- as an add-on medication

46
Q

In a systematic review of effects of 10 mm Hg reduction in systolic, which drugs performed best for CV outcomes, stroke, heartfailure

A

B-blockers
- less effective in CVD events, stroke, renal failure, all-cause mortality

CCB
- superior for stroke
- LESS effective for HF

Diuretics
- superior for heart failure

47
Q

In a systematic review for old drugs (Diuretics, B-blockers) vs new drugs (CCB, ACEi) which performed better?

A

CV events
- new drugs did WORSE than old drugs

CV mortality
- no difference

48
Q

What did the ALLHAT trial show us with chlorthalidone vs amlodipine vs lisnopril

A

Primary outcome
- All drugs good for composite outcomes

Secondary outcomes
- Chlorthalidone better for stroke, heart failure

49
Q

What were the shortcomings of the ALLHAT double-blinded RCT trial

A

90% were already on HTN (mostly diuretics)
- a randomization of switching vs. continuing diuretics
- patients with latent HF were taken off their diuretics

Differences in SBP of the groups, CCB & ACEi had a slightly higher SBP than CTDN…maybe increased risk of stroke

50
Q

Can you apply the allhat trial to other thiazide diuretics like HCTZ?

A

No

51
Q

Thiazides systematic review
Potency?
BP lowering ability?

A

Potency?
- indapamide most potent

BP lowering ability?
- cholorthalidone is the best

52
Q

Clinical outcomes of thiazide-like vs thiazide-type? Shortcomings?

A

there have been no head-to-head RCTs, so observational data has been used “network meta analysis”
- data showered no benefit
- much bigger group of patients on HCTZ

53
Q

Renal decline in thiazide-like vs thiazide-type? Shortcomings?

A

worse renal function with chlorthalidone than HCTZ
- (however, this is observational data, not very reliable)
- “network meta analysis”

54
Q

Is there evidence that HCTZ alone 12.5-25 mg/day reduces CV outcomes?
What is used in RCTs?

A

No

12.5 - 25mg/day CTDN
1.25 - 5mg/day INDP

55
Q

Should we switch patients who are already on HCTZ?

A

If patients meeting target goal for BP, keep it

56
Q

What are safety issues with thiazides to monitor? When to check

A

Hypokalemia
- more common in CTDN than HCTZ
- Low Na diet reduces risk of hypokalemia
- Check at 1-2 months after starting

57
Q

When do patients need combination therapy?

A

If their BP is 20/10 mmHg above goal

58
Q

ACCOMPLISH trial
PICO

A

Population:
- 60+ HTN with CV or renal disease or end organ damage + 1 OF THE FOLLOWING
- (previous MI, stroke, unstable angina, etc.. DM, renal events)

I: ACE + CCB vs
ACE + HCTZ

59
Q

ACCOMPLISH
outcomes found?

A

ACE + CCB is better for composite outcomes in these patients
- no difference in mortality

60
Q

ACCOMPLISH short comings? (3)

A
  • HF patients were excluded (and amlodipine did worse on HF outcome than chlorthalidone in ALLHAT)
  • Chlorothalidone should have been chosen instead of HCTZ (ALLHAT showed it is better)
  • BP measurement occurred in the morning (right after HCTZ was taken), did not give the drug a chance to work
61
Q

What drugs should be used INITIALLY for patients with diabetic nephropathy, CKD with proteinuria, HF, LV dysfunction, STEMI, NSTEMi

A

ACEi/ARB

62
Q

What drugs should be used INITIALLY for patients who are black

A

CCB or thiazides

63
Q

What are options for diastolic hypertension with or without systolic hypertension

A

All
- thiazide
- B-blockers
- ACE/ARB
- CCB

or combo product

64
Q

When are B-blockers not recommended

A

As monotherapy for 60+ yo
- same as alpha blocker

65
Q

What is the standard therapy for Coronary artery disease?

A

ACE/ARB + B-blockers or CCB (if stable angina)

66
Q

What is the standard therapy for Recent MI?

A

ACE + B blockers
- use ARB if ACE intolerant

67
Q

What is the standard therapy for Heart Failure?

A

ACE + B-blockers
- spironolactone (aldosterone antagonists)
- Thiazide

68
Q

What is the standard therapy for LVH Left ventricular hypertrophy?

A
  • ACE/ARB
  • Long-acting CCB
  • Thiazides
69
Q

What is the standard therapy for past stroke or TIA?

A

ACE + thiazide

70
Q

What is the follow-up time for all BP treatment

A

F/U q1-2 months until BP are below their target in 2 consecutive visits

71
Q

What are possible reasons for poor response to antihypertensive therapy?

A

Conditions
- Obesity
- Tobacco use
- Excessive alcohol
- Sleep apnea
- Chronic pain

Drug interactions
Suboptimal treatment regimens
Volume overload
- too much salt intake
- renal sodium retention

Secondary hypertension conditions (renal insufficiency, thyroid disease etc..)

72
Q

Outcome of ASA in primary prevention

A

Benefits in non-fatal MI

Minimal benefit in stroke

No benefits in mortality

73
Q

What are the 2 bleeding risks we are scared of with ASA

A

Major GI bleeding
Hemorrhagic stroke

74
Q

HOT trial
PICO
Outcome?

A

Population
- DBP 100-115

I: set DBP targets at <80, <85, <90

No major differences in CV outcomes

75
Q

Post-HOC subgroup HOT trial outcome?

A

Looked at subgroup of people with diabetes. Found that there was benefit at DBP <80
- lower statistical significance

76
Q

HOT trial shortcoming

A

Problems: Study in 1988, only 7% on statin, way too many smokers, only 18% from North America

77
Q

ACCORD-BP
PICO

A

Population
- Type II DM
- primary (CV disease or 2+ risk factors) + secondary

I: <140 vs <120 in diabetes

78
Q

ACCORD
outcome

A

No differences for primary, maybe a bit of benefit but more serious AE’s in intensive lower target tx

79
Q

ACCORD vs HOT trial

A

Better than HOT, used prospective RCT. Newer (2010), 100% statins, less smokers, 100% North Americans

80
Q

What is the grade A CHEP 2020 evidence with sodium consumption?

A

Consider reducing sodium intake to 2000mg/day

81
Q

Were most under/over 50% of studies guided by pharmaceutical industry

A

over 50
- 51%

82
Q

Which big trial was not funded by pharmaceutical industry?

A

ALLHAT

IPFC 3 Final (6 decks)

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