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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
What group of patients are diuretics effective in?
- Isolated hypertension - elderly - black patients
26
ACEi MOA?
Block production of angiotensin II - vasodilation --> dec cardiac output --> dec BP
27
ACEi ADRs (5)
Hacking cough Angioedema (must d/c) HYPERkalemia Dec eGFR Hypotension, dry mouth, nausea, rash, muscle pain
28
ADRs difference between ACEi and ARBs
Same - ARBs have less chance of cough and angioedema
29
Contraindications of ACE and ARBs (3)
1. Renal artery stenosis (less lumen available for blood flow to kidneys) 2. History of angioedema 3. Hyperkalemia
30
What/When to monitor for ACE/ARB?
Check K and SCr - 1 week after starting - 4 weeks later - Then q3months
31
What did the ONTARGET trial show?
ACEi=ARBs
32
What was the proposed MOA of direct renin-inhibitors (aliskiren) but did not work?
- 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
33
CCB general MOA
inhibit the L-type calcium channel on cells - inhibit Ca2+ entry into excitable cells - inhibit the role of Ca2+ as an intracellular messenge
34
Dihydropyridines MOA Drugs?
Mainly vasodilation --> reduced TPR - Vaso selective - has some chronotropic (HR) + inotropic (contractility) effects but low Drugs - nifedeipine - amlodipine - felodipine
35
Non-dihydropyridines MOA Drugs
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
ADRs of DHP (4)
vasodilation effects - headache - lightheadedness - flushing - peripheral edema (up to 20% of patients)
37
ADRs of NDHP?
Reduced contractility effects - constipation (25%) - bradycardia (low HR) - worsening cardiac output
38
When are NDHPs contraindicated?
- using beta blockers - have heart failure with reduced ejection fraction - 2nd or 3rd degree atrioventricular block (afib)
39
What is edema the result from in DHP?
Due to disproportionate vasodilation betwen arteries and veins - causes increased permeability of capillaries - NOT a result of volume
40
How to manage edema in DHP CCB?
Dose dependant (not improved by diuretics) - reduce dose - switch to NDHP if indicated - add/replace with ACE/ARBs, reduce it
41
What do trials say about using short acting calcium channel blockers?
Do not use - increased risk of MI in HTN treatment
42
What are the major durg interactions with amlodipine?
CYP 3A4 subtrates - azoles - protease inhibitors - macrolides (azith) - Quinidine
43
When are beta-blockers first line therapy? (4)
With a compelling indication such as: - angina - MI - HF - Afib
44
What did ALLHAT trial show for alpha blockers?
Should not be used as first-line therapy - can be used if there is indication in hyperplasia BPH
45
When are central alpha-2 agonists used?
Not as first line - used for HTN urgencies OR - as an add-on medication
46
In a systematic review of effects of 10 mm Hg reduction in systolic, which drugs performed best for CV outcomes, stroke, heartfailure
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
In a systematic review for old drugs (Diuretics, B-blockers) vs new drugs (CCB, ACEi) which performed better?
CV events - new drugs did WORSE than old drugs CV mortality - no difference
48
What did the ALLHAT trial show us with chlorthalidone vs amlodipine vs lisnopril
Primary outcome - All drugs good for composite outcomes Secondary outcomes - Chlorthalidone better for stroke, heart failure
49
What were the shortcomings of the ALLHAT double-blinded RCT trial
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
Can you apply the allhat trial to other thiazide diuretics like HCTZ?
No
51
Thiazides systematic review Potency? BP lowering ability?
Potency? - indapamide most potent BP lowering ability? - cholorthalidone is the best
52
Clinical outcomes of thiazide-like vs thiazide-type? Shortcomings?
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
Renal decline in thiazide-like vs thiazide-type? Shortcomings?
worse renal function with chlorthalidone than HCTZ - (however, this is observational data, not very reliable) - "network meta analysis"
54
Is there evidence that HCTZ alone 12.5-25 mg/day reduces CV outcomes? What is used in RCTs?
No 12.5 - 25mg/day CTDN 1.25 - 5mg/day INDP
55
Should we switch patients who are already on HCTZ?
If patients meeting target goal for BP, keep it
56
What are safety issues with thiazides to monitor? When to check
Hypokalemia - more common in CTDN than HCTZ - Low Na diet reduces risk of hypokalemia - Check at 1-2 months after starting
57
When do patients need combination therapy?
If their BP is 20/10 mmHg above goal
58
ACCOMPLISH trial PICO
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
ACCOMPLISH outcomes found?
ACE + CCB is better for composite outcomes in these patients - no difference in mortality
60
ACCOMPLISH short comings? (3)
- 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
What drugs should be used INITIALLY for patients with diabetic nephropathy, CKD with proteinuria, HF, LV dysfunction, STEMI, NSTEMi
ACEi/ARB
62
What drugs should be used INITIALLY for patients who are black
CCB or thiazides
63
What are options for diastolic hypertension with or without systolic hypertension
All - thiazide - B-blockers - ACE/ARB - CCB or combo product
64
When are B-blockers not recommended
As monotherapy for 60+ yo - same as alpha blocker
65
What is the standard therapy for Coronary artery disease?
ACE/ARB + B-blockers or CCB (if stable angina)
66
What is the standard therapy for Recent MI?
ACE + B blockers - use ARB if ACE intolerant
67
What is the standard therapy for Heart Failure?
ACE + B-blockers - spironolactone (aldosterone antagonists) - Thiazide
68
What is the standard therapy for LVH Left ventricular hypertrophy?
- ACE/ARB - Long-acting CCB - Thiazides
69
What is the standard therapy for past stroke or TIA?
ACE + thiazide
70
What is the follow-up time for all BP treatment
F/U q1-2 months until BP are below their target in 2 consecutive visits
71
What are possible reasons for poor response to antihypertensive therapy?
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
Outcome of ASA in primary prevention
Benefits in non-fatal MI Minimal benefit in stroke No benefits in mortality
73
What are the 2 bleeding risks we are scared of with ASA
Major GI bleeding Hemorrhagic stroke
74
HOT trial PICO Outcome?
Population - DBP 100-115 I: set DBP targets at <80, <85, <90 No major differences in CV outcomes
75
Post-HOC subgroup HOT trial outcome?
Looked at subgroup of people with diabetes. Found that there was benefit at DBP <80 - lower statistical significance
76
HOT trial shortcoming
Problems: Study in 1988, only 7% on statin, way too many smokers, only 18% from North America
77
ACCORD-BP PICO
Population - Type II DM - primary (CV disease or 2+ risk factors) + secondary I: <140 vs <120 in diabetes
78
ACCORD outcome
No differences for primary, maybe a bit of benefit but more serious AE’s in intensive lower target tx
79
ACCORD vs HOT trial
Better than HOT, used prospective RCT. Newer (2010), 100% statins, less smokers, 100% North Americans
80
What is the grade A CHEP 2020 evidence with sodium consumption?
Consider reducing sodium intake to 2000mg/day
81
Were most under/over 50% of studies guided by pharmaceutical industry
over 50 - 51%
82
Which big trial was not funded by pharmaceutical industry?
ALLHAT

IPFC 3 Final (6 decks)

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