Chapter 28 - Hypertension Flashcards
1
Q
Uncontrolled hypertension makes the patient at greater risk for:
A
- Heart disease
- Stroke
- Kidney disease
(HTN is mostly asymptomatic)
2
Q
Lifestyle management:
A
■ Weight loss (1kg of weight loss decreases BP 1 mmHg)
■ A heart-healthy diet
- The DASH eating plan (Dietary Approaches to Stop Hypertension)) that is high in fruits, vegetables, fiber and low-fat dairy products, and low in saturated fats and sugar
■ Adequate dietary K intake or supplementation, unless CI (chronic kidney disease)
■ Reducing sodium intake to < 1,500 mg daily
■ Routine physical activity
■ Limiting alcohol consumption to 1 drink daily for women and 2 drinks daily for men
■ Tobacco cessation
■ Controlling blood glucose and cholesterol to reduce cardiovascular disease risk
3
Q
Patho of HTN (Primary and Secondary)
A
1) Primary, or essential, hypertension: (95%)
- Unknown cause
- Combination of risk factors:
– Obesity, sedentary lifestyle, excessive salt intake, smoking, family history, diabetes, dyslipidemia
2) Secondary hypertension can be caused by
- Renal disease (chronic kidney disease)
- Adrenal disease (excess aldosterone secretion)
- Obstructive sleep apnea
- Drugs
- There is increased activity of the sympathetic nervous system (SNS) and the renin- angiotensin-aldosterone system (RAAS), leading to increased levels of neurohormones (norepinephrine, angiotensin II, aldosterone) that can increase blood pressure.
4
Q
SCREENING AND DIAGNOSIS
A
- Average of at least two readings on two separate occasions
- BP at Dr’s clinic tend to be higher –> inaccurate
American College of Cardiology/American Heart Association (ACC/AHA):
■ Normal: SBP < 120 mmHg and DBP < 80 mmHg
■ Elevated: SBP 120 -129 mmHg and DBP < 80 mmHg
■ Hypertension:
– Stage 1: SBP 130-139 mmHg or DBP 80 - 89 mmHg
– Stage 2: SBP >= 140 mmHg or DBP >= 90 mmHg
5
Q
How does the BP vary during the day?
A
BP usually decreases during the night and increases again in the early morning.
6
Q
Correct use of your blood pressure monitoring device
A
DO:
- Go to the restroom and empty the bladder
- Sit in a chair (feet on floor)
- Relax for at least 15 min
- Use the correct cuff size
- Support arm at heart level (on a desk)
- Wait 1-2 min in between measurements
DONT:
- Talk
- Sit or lie down on the examination table
- Drink caffeine, exercise or smoke for 30 min prior
- Use a finger or wrist monitor (less accurate)
Self-monitoring:
- Bring device and BP reading log to clinic visits
Ambulatory BP monitoring devices:
- Wear during daily activities; obtains readings every 15-60 minutes, day and night
Home BP monitoring devices:
- Record the average of 2-3 readings in the morning and/or evening before eating or taking any medications
7
Q
DRUGS THAT CAN INCREASE BLOOD PRESSURE
A
- Amphetamines and ADHD drugs
- Cocaine
- Decongestants (pseudoephedrine, phenylephrine)
- Erythropoiesis-stimulating agents
- lmmunosuppressants (cyclosporine)
- NSAIDs
- Systemic steroids
Others:
- Alcohol (excessive)
- Appetite suppressants (phentermine)
- Caffeine
- Herbals (ma huang, licorice, yohimbine)
- Oral contraceptives
- Select oncology drugs (bevacizumab, tyrosine kinase inhibitors)
- Antidepressants (TCAs, SNRls, MAO inhibitors)
8
Q
Natural Products
A
(not recommended by guidelines but have some evidence for reducing blood pressure and overall cardiovascular risk)
- Fish oil
- Coenzyme QlO
- L-arginine
- Garlic
!!!! Patients should be advised that fish oil and garlic can increase bleeding risk !!!!
9
Q
TREATMENT PRINCIPLES
A
1) Lifestyle modifications
2) Once daily meds (better for adherence)
3) 4 preferred drug classes:
- ACE inhibitors
- ARBs
- CCBs
- Thiazide diuretics
4) Most pts will require 2 or more drugs but Do not combine ACEI and ARBs
5) When titrating meds, adding a 2nd drug before reaching max doses of the 1st med can be more effective and cause fewer SE
6) Pts with HTN & comorbid conditions (HF, ischemic heart disease) should be treated according to the specific disease-state
10
Q
PREGNANCY AND HYPERTENSION
1- What drugs have bbw in preg
2- In what conditions can you use antihypertensive drugs during pregnancy?
A
1- BBW for fetal toxicity in preg - Stop!:
– ACEis
– ARBs
– Direct renin inhibitor (aliskiren)
2- Antihypertensive drugs can be used during preg to treat:
– Preeclampsia
– Gestational hypertension (HTN that develops during pregnancy)
– Chronic hypertension (HTN before pregnancy)
11
Q
Preeclempsia
- When does it occur?
- Who is at risk of developing it?
- What should you recommend pts at high risk?
A
- Preeclampsia occurs after week 20 of the preg & is evident by:
– Elevated BP & proteinuria - Pts at risk:
– Overweight
– Have pre-existing HTN
– Renal Dx
– Diabetes
–> Recommend daily low-dose aspirin after the 1st trimester
12
Q
1- When should pregnant patients with chronic hypertension receive drug treatment?
2- What drug does the ACOG recommend?
3- At what level should the BP be maintained at?
A
1- If SBP is > 160mmHg or DBP is > 105mmHg
2- The American College of Obstetricians and Gynecologists (ACOG) recommend as first-line treatments:
– Labetalol
– Nifedipine extended- release
- Methyldopa is recommended but may be less effective at BP lowering.
3- The BP should be maintained between 120 - 160 mmHg systolic and 80 - 110 mmHg diastolic
13
Q
COMBINATION BLOOD PRESSURE DRUGS:
- ACEi or ARB + DIURETIC:
1) Zestoretic
2) Hyzaar
3) Benicar HCT
4) Diovan HCT
Tip: the brand names of many diuretic combinations end in HCT, -ide or -etic
A
ACEi:
- Lisinopril/ Hydrochlorothiazide (Zestoretic)
ARB:
- Losartan/ Hydrochlorothiazide (Hyzaar)
- Olmesartan/ Hydrochlorothiazide (Benicar HCT)
- Valsartan/ Hydrochlorothiazide (Diovan HCT)
Others:
- Azilsartan/Chlorthalidone (Edarbyclor)
- Benazepril/Hydrochlorothiazide (LotensinHCT)
- Candesartan/Hydrochlorothiazide
- Captopril/Hydrochlorothiazide
- Enalapril/Hydrochlorothiazide (Vaseretic)
- Fosinopril/Hydrochlorothiazide
- lrbesartan/Hydrochlorothiazide (Avalide)
- Moexipril/Hydrochlorothiazide
- Quinapril/Hydrochlorothiazide (Accuretic)
- Telmisartan/Hydrochlorothiazide (MicardisHCT)
14
Q
ACEi or ARB+ CCB
- Lotrel
- Exforge
A
ACEi:
- Benazepril/ Amlodipine (Lotrel) (To know)
- Perindopril/Amlodipine (Prestalia)
- Trandolapril/Verapamil (Tarka)
ARB:
- Valsartan/ Amlodipine (Exforge) (To know)
- Olmesartan/Amlodipine (Azor)
- Telmisartan/Amlodipine (Twynsta)
15
Q
DIRECT RENIN INHIBITOR + DIURETIC
A
Aliskiren/ Hydrochlorothiazide
(Tekturna HCT)
(ali ski ren- bt ren bl dayne so renin. w tekturna huwe kawkab)
16
Q
ALPHA-2 AGONIST + DIURETIC
A
Methyldopa/ Hydrochlorothiazide
17
Q
BETABLOCKER + DIURETIC
A
- Atenolol/Chlorthalidone (Tenoretic)
- Bisoprolol/Hydrochlorothiazide (Ziac)
- Metoprolol Tartrate/Hydrochlorothiazide (Lopressor HCT)
- Metoprolol Succinate/Hydrochlorothiazide (Dutoprol)
- Nadolol/ Bendroflumethiazide
- Propranolol/ Hydrochlorothiazide
18
Q
K-SPARING + THIAZIDE-TYPE DIURETIC
A
- Triamterene/ Hydrochlorothiazide
(Maxzide, Maxzide-25, Dyazide) (To know) - Amiloride/ Hydrochlorothiazide
- Spironolactone/ Hydrochlorothiazide
(Aldactazide)
19
Q
TRIPLE COMBINATIONS (Ens)
A
- Olmesartan/ Amlodipine/ Hydrochlorothiazide
(Tribenzor) - Valsartan/ Amlodipine/ Hydrochlorothiazide (Exforge HCT)
20
Q
THIAZIDE-TYPE DIURETICS
1- Characteristics
2- When are loop diuretics primarily used?
3- MOA
A
1- Characteristics:
- Inexpensive
- Effective
- Mild SE
2- (Loop diuretics are used primarily in HF)
3- Thiazides and thiazide-type diuretics:
- Inhibit Na reabsorption in the distal convoluted tubules
- Causing increased excretion of:
– Na
– Cl
– Water
– K
21
Q
Chlorthalidone
- Dose
A
- Thiazide like diuretic
- 12.5 - 25 mg PO daily
22
Q
Hydrochlorothiazide
- Dose
A
- Thiazide Diuretic
- 12.5 - 50 mg PO daily
23
Q
List the thiazide type diuretics
A
1- Thiazides are Benzothiadazine derivatives:
- Hydrochlorothiazide
- Chlorothiazide (only IV one in class)
2- Thiazide-like diuretics are sulfonamide derivatives:
- lndapamide
- Metolazone
- Chlorthalidone
- Less potent than loop diuretics but are much longer lasting
- Chlorthalidone may be preferred over hydrochlorothiazide due to longer duration
(if a patient is doing well on hydrochlorothiazide, no need to switch)
24
Q
What are the 3 types of diuretics?
A
- Thiazide
- Loop
- Potassium sparing
25
CI of thiazide type diuretics
- Hypersensitivity to sulfonamide-derived drugs (not likely to cross-react)
- Anuria (Failure of kidneys to produce urine)
26
Warning with thiazide type diuretics (to read)
- Severe renal disease (can precipitate azotemia)
- Progressive liver disease (fluid and electrolyte changes can precipitate hepatic coma)
- Can precipitate or exacerbate conditions such as systemic lupus erythematosus (SLE), gout and diabetes
- Transient myopia or acute angle-closure glaucoma (hydrochlorothiazide)
27
SE of thiazide-type diuretics
- Dec electrolytes: K, Mg, Na
- Inc electrolytes/labs: Ca, UA, LDL, TG, BG
- Photosensitivity (including a small inc risk of non-melanoma skin cancer)
- Impotence
- Dizziness
- Rash
28
Monitoring of thiazide type diuretics
- Electrolytes
- Renal function
- BP
- Fluid status (input and output, weight)
- BG (in diabetes)
29
Are thiazides effective in all CrCl levels or renal functions?
Thiazides are not effective when CrCI < 30 ml/min
Except: Metolazone
- which may work with reduced renal function or diuretic resistance
30
- At what time of the day should you take diuretics
- How can you avoid hypokalemia?
- Take early in the day to avoid nocturia
- Hypokalemia can be avoided with regular intake of potassium-rich foods or potassium supplements
31
Thiazide-Type Diuretic Drug Interactions
■ Monitor BP with other antihypertensive drugs.
■ Do not use in combination with NSAIDs:
- can cause Na and water retention
- can decrease the effectiveness of antihypertensive meds
■ Do not use with LITHIUM:
- Thiazide diuretics can dec LITHIUM renal clearance
- Inc the risk of lithium toxicity
■ Do not use with DOFETILIDE:
- Thiazide diuretics can inc DOFETILIDE serum concentrations
- Inc risk of QT prolongation
32
- What are the 2 types of CCB?
- List drugs & brands.
1- Dihydropyridines (DHP) (-dipine)
- Amlodipine (Norvasc)
- Nicardipine IV (Cardene IV)
- Nifedipine ER (Adalat CC, Procardia XL)
- Felodipine
- lsradipine
- Nisoldipine
- Clevidipine
2- Non-dihydropyridines (non-DHP)
- Diltiazem
- Verapamil
33
Can you switch between generics and brands CCBs?
- Not all generic products are therapeutically equivalent to the brand-name products
- Check the Orange Book and choose a generic product that is AB-rated to the brand product
34
Nicardipine CI
Advanced aortic stenosis
35
Warning with DHP CCB
- Hypotension (especially with severe aortic stenosis)
- Worsening angina and/or Ml
- Severe hepatic impairment
- Use caution in HF
-- (This is because CCBs can cause an increase in the filling pressure of the heart, which can make it harder for the heart to pump blood effectively. This can lead to a worsening of heart failure symptoms such as shortness of breath, fatigue, and fluid buildup)
Nifedipine IR:
- Do not use for chronic hypertension or acute BP reduction in non-pregnant adults (profound hypotension, Ml and/or death has occurred)
36
SE with DHP CCB
- Generally well-tolerated
- Can cause peripheral edema/ headache/ flushing/ palpitations/ reflex tachycardia/ fatigue (worse with nifedipine IR), nausea, gingival hyperplasia (more gingival hyperplasia with non-DHPs)
37
Monitoring with CCB DHP
- Peripheral edema
- BP
- HR
38
DHP CCB
1) Which CCB is considered the safest if a CCB must be used to lower BP in HFrEF?
2) What is the drug of choice in pregnancy?
3) What is another indication for CCB DHP (Nifedipine ER)?
4) Counseling tip on Adalat CC and Procardia XL (Nifedipine)
1) Amlodipine
2) Nifedipine ER
3) DHP CCBs (nifedipine ER) are used to prevent peripheral vasoconstriction in Raynaud's (cold/blue fingers)
4) Adalat CC and Procardia XL (Nifedipine):
- OROS/gel matrix formulations can leave a ghost tablet (empty shell) in the stool
39
Clevidipine
- Class
- CI
- Warnings
- SE
- Monitoring
- Notes
- How many kcal per ml?
- DHP CCB
CI:
- Allergy to soybeans, soy products or eggs;
- Defective lipid metabolism (lipoid nephrosis, hyperlipidemia with acute pancreatitis)
- Severe aortic stenosis
WARNINGS
- Hypotension
- Reflex tachycardia
- Infections
SIDE EFFECTS
- Hypertriglyceridemia
- Headache
- Atrial fibrillation
- Nausea
MONITORING
BP, HR
NOTES
- A lipid emulsion (provides 2 kcal/ml); it is milky-white in color
- Use strict aseptic technique due to infection risk; maximum time of use after vial puncture is 12 hrs
40
CASE SCENARIO:
- TW is a 54-year-old female admitted to the medical ICU with a hypertensive emergency.
- She is receiving clevidipine 50 mg/100 ml at a rate of 3 mg/hr.
- The bottle has 52 ml remaining at 1400 .
1) How many calories per day is TW receiving from clevidipine?
2) At what time should the bottle of clevidipine be removed and replaced?
3) What other drugs may require similar calculations?
1) 3mg/hr x 24 hrs/day x 100 ml/50mg x 2kcal/ml = 288 kcal/day
2) Should be changed 12 hrs after its open
48 ml of clevidipine have been used. First, calculate how long the bottle has been hanging.
48ml x 50mg/100ml x 1hr/3mg = 8 hrs
The bottle needs to be replaced every 12 hours (or in 4 more hours). It is currently 1400.
A new bottle should be hung at 1800.
3) Propofol (Diprivan) is another lipid emulsion that provides calories (1.1 kcal/ml) and requires tubing/vial changes every 12 hours
41
NON-DIHYDROPYRIDINE CCBs moa
- Mainly on heart
- The non-DHP CCBs, verapamil and diltiazem, are primarily used to control HR in certain arrhythmias (atrial fibrillation) and are sometimes used for HTN & angina.
- They inhibit Ca ions from entering vascular smooth muscle and myocardial cells, but they are more selective for the myocardium than the DHP CCBs.
- The decrease in BP produced by non-DHP CCBs is due to
-- Negative inotropic (dec force of ventricular contraction)
-- Negative chronotropic (dec HR) effects
42
Diltiazem brand
- Cardizem
- Tiazac
43
Verapamil
Calan SR
(Vera btaate calin)
44
NON-DIHYDROPYRIDINE CCBs CONTRAINDICATIONS
- Hypotension (SBP< 90 mmHg) or cardiogenic shock;
- 2nd or 3rd degree AV block or sick sinus syndrome (unless has a functioning artificial ventricular pacemaker)
- Diltiazem
-- Acute Ml
-- Pulmonary congestion
- Verapamil
-- Severe left ventricular dysfunction
-- Atrial flutter or atrial fibrillation
-- Accessory bypass tract
45
WARNINGS of nonDHP ccb
- Heart failure (may worsen symptoms)
- Bradycardia
- Hypotension
- Acute liver injury/ inc LFTs
- Cardiac conduction abnormalities (diltiazem)
- Hypertrophic cardiomyopathy (verapamil)
46
SE of Non-DHP CCB
- Edema
- Constipation (more with verapamil)
- Gingival hyperplasia
- Headache
- Dizziness
47
MONITORING of Non-DHP CCB
BP, HR, ECG, LFTs
48
NOTES of Non-DHP CCB
- IV: PO dose conversions are not 1:1
- Non-DHP CCBs are used to reduce rapid heart rate in atrial fibrillation
49
CCB Drug Interactions
■ Use caution with other drugs that dec HR, including beta-blockers, digoxin, clonidine, amiodarone & dexmedetomidine (Precedex).
■ All CCBs are major substrates of CYP450 3A4.
Use caution with strong CYP3A4 inducers and inhibitors, and in some cases, do not use in combination.
- Do not use with grapefruit juice.
■ Diltiazem and verapamil are substrates and inhibitors of P-gp and moderate inhibitors of CYP3A4, increasing the concentration of many other drugs.
- Patients who take statins should use lower doses of simvastatin or lovastatin or use a statin that is not metabolized by CYP3A4 (pitavastatin, pravastatin, rosuvastatin).
50
RENIN-ANGIOTENSIN ALDOSTERONE SYSTEM INHIBITORS moa
- Angiotensin II causes vasoconstriction and increased release of aldosterone; this results in sodium and water retention.
- RAAS inhibitors decrease BP by inhibiting the effects of Ang II.
Some drugs (ACEi and ARBs) have been shown to slow the progression of kidney disease in patients with albuminuria (due to diabetes, HTN).
- Ang II constricts the efferent arterioles of the nephron, causing increased workload in the glomeruli; over time, this results in kidney damage.
- Blocking Ang II causes efferent arteriole vasodilation and decreases glomerular filtration pressure.
In HF, ACEi and ARBs protect the myocardium from the remodeling effects of Ang II.
- RAAS inhibitors should not be used in combination (ACE inhibitor ± ARB ± aliskiren ± ARNI) due to an increased risk for adverse effects.
- Angioedema is a potentially fatal adverse effect that can occur with the use of any drug.
It is more common with ACEi than ARBs or aliskiren, and black patients have a higher risk.
- For testing purposes, if a patient develops angioedema with any RAAS inhibitor, other RAAS inhibitors should be avoided.
51
ANGIOTENSIN-CONVERTING ENZYME INHIBITORS moa
- End in" -pril."
- Block the conversion of angiotensin I (Ang I) to Ang II, resulting in dec vasoconstriction and dec aldosterone secretion.
- Block the degradation of bradykinin, which is thought to contribute to the vasodilatory effects (and SE of a dry & hacking cough and angioedema).
52
Benazepril brand
Lotensin
53
Enalapril brand
Vasotec
54
Enalaprilat brand
Vasotec IV
55
Lisinopril brand
Prinivil
Zestril
56
Quinapril brand
Accupril
57
Ramipril brand
Altace
Rami al tes
58
List the other ACEi drugs
- Captopril
- Fosinopril
- Moexipril
- Perindopril
- Trandolapril
59
BOXED WARNINGS of ACEi
- Can cause injury and death to the developing fetus when used in the 2nd and 3"' trimesters
- Discontinue as soon as pregnancy is detected
60
CI of ACEi
- History of angioedema
- Within 36 hrs of sacubitril/ valsartan (Entresto)
- With aliskiren in diabetes
61
WARNINGS of ACEi
- Angioedema
- Hyperkalemia
- Hypotension
- Renal impairment
- Bilateral renal artery stenosis (avoid use)
62
SE of ACEi
- Generally well-tolerated
- Can cause cough
- Hyperkalemia
- Inc SCr
- Hypotension/dizziness [inc risk if volume-depleted (with concurrent diuretic)]
- Headache
63
Monitoring of ACEi
BP, K, renal function, s/sx of angioedema
note: Once-daily drugs can be used BID if needed
64
ANGIOTENSIN RECEPTOR BLOCKERS moa
- ARBs end in "sartan."
- They block Ang II from binding to the angiotensin II type-1 (ATl) receptor on vascular smooth muscle
65
lrbesartan brand
Avapro
ava pro
66
Losartan brand
Cozaar
67
Olmesartan brand
Benicar
68
Valsartan brand
Diovan
69
Sacubitril/valsartan brand
Entresto
70
ARBs SE, Warnings,
Same as ACE inhibitors except:
- Less cough
- Less angioedema
- No washout period required with sacubitril/valsartan (Entresto)
Olmesartan: sprue-like enteropathy - severe, chronic diarrhea with substantial weight loss; can occur months to years after drug initiation
Azilsartan: keep in original container to protect from light and moisture
71
DIRECT RENIN INHIBITOR
- Drug name and brand
- Moa
- CI
- Aliskiren (Tekturna)
- Aliskiren directly inhibits renin, which is responsible for the conversion of angiotensinogen to Ang I.
- A decrease in the formation of Ang I results in a decrease in the formation of Ang II.
- CI: Do not use with ACE inhibitors or ARBs in patients with diabetes
72
RAAS INHIBITOR DRUG INTERACTIONS
■ All RAAS inhibitors inc the risk of hyperkalemia.
- Other medications that inc K (K-sparing diuretics) should be used cautiously.
- Patients should avoid salt substitutes that contain potassium chloride (instead of sodium chloride).
■ Do not use more than one RAAS inhibitor together (ACE inhibitor± ARB± aliskiren ± ARNI) due to an inc risk of renal impairment, hypotension & hyperkalemia.
- Aliskiren in combination with an ACEi or ARBis specifically contraindicated in pts with diabetes.
■ ACEi and ARBs should not be used in combination with sacubitril/valsartan (Entresto).
- If switching from an ACEi to Entresto, or vice versa, a 36-hour washout period is required.
■ ACEi and ARBs can inc lithium renal clearance and inc the risk of lithium toxicity.
73
POTASSIUM-SPARING DIURETICS
- Drugs
- Characteristics
- When are they used?
- Drugs: triamterene and amiloride
- Have minimal BP-lowering effects
- Used in combination with hydrochlorothiazide (Maxzide) to counteract the mild K losses seen with thiazide diuretics.
- The aldosterone receptor antagonists, spironolactone and eplerenone, are the preferred add-on drugs in resistant hypertension (uncontrolled BP despite maximum tolerated doses of a CCB+ thiazide diuretic + ACEi or ARB), and they are commonly used in heart failure.
- Spironolactone is a non-selective aldosterone receptor antagonist (also blocks androgen), while eplerenone is a selective aldosterone receptor antagonist that does not exhibit endocrine SE.
- These meds compete with aldosterone at receptor sites in the distal convoluted tubule and collecting ducts of the nephron, increasing sodium and water excretion and conserving potassium.
74
POTASSIUM-SPARING DIURETICS
- List drugs and brand
- Triamterene (Dyrenium)
+ HCTZ (Dyazide, Maxzide, Maxzide-25)
- Spironolactone (Aldadone)
- Amiloride
- Eplerenone
75
BBW with Amiloride and triamterene:
- Hyperkalemia (K > 5.5 mEq/L)
--- More likely in patients with diabetes, renal impairment, or elderly patients
76
CI, SE, Monitoring with K sparing diuretics
CI:
- Hyperkalemia
- Severe renal impairment
- Addison's dx (spironolactone)
- Taking strong CYP3A4 inhibitors (eplerenone)
SE:
- Hyperkalemia, inc SCr, dizziness, hyperchloremic metabolic acidosis(rare)
- Spironolactone: gynecomastia, breast tenderness, impotence, irregular menses, amenorrhea
- Eplerenone: i TGs
Monitor:
- BP, K, renal function, fluid status, s/sx of HF
77
Potassium-Sparing Diuretic Drug Interactions
■ Potassium-sparing diuretics inc the risk of hyperkalemia.
Additive potassium accumulation can occur when these medications are used with other potassium-sparing drugs
■ Diuretics can dec lithium renal clearance and inc the risk of lithium toxicity.
■ Eplerenone is a major substrate of CYP3A4; do not use with strong CYP3A4inhibitors (ketoconazole, itraconazole, clarithromycin, ritonavir).
78
BETA-BLOCKERS
1- When are they recommended?
2- On what will the selection of a specific beta-blocker depend on
3- MOA
4- What drugs are beta-blockers with alpha-1 blocking properties?
5- How do alpha1 blockers work?
6- What drugs are Beta-blockers with intrinsic sympathomimetic activity (ISA) & how do they work? When are they not recommended?
7- If a beta-blocker is needed in a patient with bronchospastic disease (Asthma, COPD), what bb is preferred?
1- They are no longer recommended 1st line for treating HTN unless the pt has a comorbid condition for which BB are indicated:
- Post-MI
- Stable ischemic heart disease
- Heart failure
2- Selection of a specific beta-blocker will depend on the condition being treated.
- Ex: bisoprolol, carvedilol or metoprolol succinate should be used if treating chronic heart failure.
3- BBs dec BP by competitively blocking beta-1 and/or beta-2 adrenergic receptors, resulting in dec in HR and myocardial contractility.
4- Carvedilol and labetalol
5- Alpha-I blockers decrease peripheral vasoconstriction, lowering BP.
6- BB with intrinsic sympathomimetic activity (ISA) (acebutolol, penbutolol and pindolol) partially stimulate beta receptors while blocking the effects of catecholamines (norepinephrine).
- They do not dec HR to the same degree as BB without ISA
- They are not recommended in post-MI pts.
7- If a BB is needed in a patient with bronchospastic disease (Asthma, COPD), a beta-1 selective agent is preferred.
79
List the Beta-1 Selective Blockers and their brands
- Atenolol (Tenormin)
- Esmolol (Brevibloc) IV
- Metoprolol tartrate (Lopressor)
- Metoprolol succinate extended release (Toprol XL)
- Acebuolol
- Betaxolol
- Bisoprolol
Remember:"AMEBBA''
80
BB 1 BBW
- Do not discontinue abruptly (particularly in patients with CAD/I HD)
- Gradually taper dose over 1-2 weeks to avoid acute tachycardia, hypertension, and/or ischemia
81
CI in BB 1
- Severe bradycardia
- 2nd or 3rd degree AV block or sick sinus syndrome (unless a permanent pacemaker is in place)
- Overt cardiac failure or cardiogenic shock
- Esmolol: pulmonary hypertension; use of IV non-DHP CCBs
82
Warning with BB1
- Use caution in pts with diabetes:
-- Can worsen hyperglycemia or hypoglycemia and mask hypoglycemic sx
- Use caution with bronchospastic dx (Asthma, COPD), beta-1 selective preferred
- Use caution with Raynaud's other peripheral vascular dx, pheochromocytoma and HF (slow dose titration required if used in these conditions)
- Can mask signs of hyperthyroidism (tachycardia), can worsen CNS depression
83
SE & Moniotoring of BB1
SIDE EFFECTS:
- Bradycardia
- Fatigue
- Hypotension
- Dizziness
- Depression
- Impotence (less than thiazides)
- Cold extremities (can exacerbate Raynaud's)
MONITORING:
- HR (dec dose if HR < 55 BPM)
- BP
84
Notes with bb1
- Oral drugs: titrate doses every 1-2 weeks (as tolerated), take without regard to meals (except Lopressor and Toprol XL should be taken with or immediately following food)
- Metoprolol tartrate IV is not equivalent to PO (IV:PO ratio is 1:2.5)
- When switching from metoprolol tartrate to metoprolol succinate, the same total daily dose of metoprolol should be used
85
Beta-1 Selective Blocker with Nitric Oxide-Dependent Vasodilation:
- Drugs & Brand
- CI
- SE
- Notes
- Nebivolol (Systolic)
- CI: Severe liver impairment (Child-Pugh > class B)
- SE: Fatigue, nausea, inc TGs, dec HDL
- NOTES: Nitric oxide causes peripheral vasodilation
86
Beta-Blocker Drug Interactions
■ Monitor blood glucose in diabetes.
- Beta-blockers can enhance the hypoglycemic effects of insulin and sulfonylureas
- Mask some of the sx of hypoglycemia (shakiness, palpitations, anxiety);
- Sx of sweating & hunger are not masked
- BB can dec insulin secretion, causing hyperglycemia
■ Use caution when administering other drugs that dec HR, including diltiazem, verapamil, digoxin, clonidine, amiodarone and dexmedetomidine (Precedex)
■ Carvedilol, propranolol and metoprolol are major substrates of CYP2D6, & nebivolol is a minor substrate of CYP2D6. Monitor for drug interactions.
■ Carvedilol & propranolol are inhibitors of P-gp and can inc the serum [ ] of P-gp substrates (cyclosporine, dabigatran, digoxin, ranolazine).
87
CENTRALLY-ACTING ALPHA-2 ADRENERGIC AGONISTS MOA
- These drugs decrease BP by stimulating alpha-2 adrenergic receptors in the brain and reducing sympathetic outflow of norepinephrine, which decreases SVR and HR.
- Clonidine is commonly used for resistant hypertension and in patients who can not swallow (due to dysphagia, dementia) since it is available as a patch formulation.
- Since the patch is changed weekly, it can help with adherence.
88
List CENTRALLY-ACTING ALPHA-2 ADRENERGIC AGONISTS
Clonidine:
- Catapres, Catapres-TTS patch
- Kapvay- for ADHD
Guanfacine
- IR (Tenex')
- Guanfacine ER: lntuniv- for ADHD
Methyldopa
89
CI, SE & Warning of Methyldopa
CI:
- Concurrent use with MAO inhibitors
- Active liver disease
Warning:
-Risk for hemolytic anemia (detected by a positive Coombs test)
- Hepatic necrosis
SE:
- Hypersensitivity reactions [drug-induced lupus erythematosus (DILE)]
- Edema or weight gain (control with diuretics)
- Inc prolactin levels
Methyldopa is a preferred drug in pregnancy
90
WARNINGS of CENTRALLY-ACTING ALPHA-2 ADRENERGIC AGONISTS
- Do not discontinue abruptly (can cause rebound hypertension, sweating, anxiety, tremors);
- Must taper gradually over 2-4 days
91
SE of CENTRALLY-ACTING ALPHA-2 ADRENERGIC AGONISTS
- Dry mouth
- Somnolence, fatigue, dizziness
- Constipation
- Dec HR, hypotension
- Impotence
- Depression, behavioral changes (irritability, confusion, anxiety, nightmares)
92
Monitoring of CENTRALLY-ACTING ALPHA-2 ADRENERGIC AGONISTS
- BP
- HR
- Mental status
93
What should you counsel a patient that is on a clonidine patch?
- Apply weekly to a clean, dry and hairless area of skin on the upper outer arm or upper chest
- Remove before MRI; can apply the adhesive cover over the patch if it loosens
94
DIRECT VASODILATORS MOA
- These drugs cause direct vasodilation of arterioles, with little effect on veins.
- The result is a decrease in SVR and a reduction in BP.
95
Hydralazine
- Class
- CI
- Warning
- SE
- Monitoring
- DIRECT VASODILATORS
- CI: Mitral valvular rheumatic heart disease, CAD
- WARNINGS: Drug-induced lupus erythematosus (DILE - dose and duration related), peripheral neuritis, blood dyscrasias, hypotension
- SE: Peripheral edema/ headache/ flushing/ palpitations/ reflex tachycardia, N/V
- MONITORING: HR, BP, ANA titer
96
Minoxidil
- Class
- BBBW
- CI
- SE
- DIRECT VASODILATORS
- OTC topical for hair growth
- BBW: Potent antihypertensive - can cause pericardia effusion and angina exacerbations; administer with a beta-blocker and loop diuretic
- CI: Pheochromocytoma
- SE: Fluid retention, tachycardia, hair growth
97
ALPHA-BLOCKERS MOA
- Alpha-blockers (doxazosin, prazosin, terazosin) bind to alpha-1 adrenergic receptors, which results in peripheral vasodilation of arterioles and veins.
- They are not recommended for HTN but may be used in men who have hypertension and benign prostatic hyperplasia
98
HYPERTENSIVE CRISES: URGENCIES AND EMERGENCIES
- A hypertensive crisis is defined as a rapidly accelerating BP (>= 180/120 mmHg).
- The two types of crises are:
1) Hypertensive emergency:
- Acute target organ damage that may be life-threatening
- Encephalopathy, stroke, acute kidney injury, acute coronary syndrome, aortic dissection, acute pulmonary edema
o Treat with IV meds (The key iv htn meds)
o Dec BP by no more than 25% (within the first hour), then if stable, decrease to 160/100 mmHg in the next 2- 6 hrs.
2) Hypertensive urgency:
- No evidence of acute target organ damage.
o Treat with any oral med that has a short onset of action (15- 30 minutes)
o Dec BP gradually over 24 - 48 hours
99
Key IV HTN meds
- Chlorothiazide
- Clevidipine
- Diltiazem
- Enalaprilat
- Esmolol
- Hydralazine
- Labetalol
- Metoprolol tartrate
- Nicardipine
- Nitroglycerin
- Nitroprusside
- Propranolol
- Verapamil
100
ALL HYPERTENSION PRODUCT counseling
■ Can cause orthostasis.
■ Check your blood pressure regularly.
■ Take this medication as directed, even if you feel well.
o Lowering blood pressure helps dec risk of complications such as:
- Heart disease
- Kidney disease
- Stroke
101
Thiazide-Type Diuretics counseling
■ Take this medication early in the day (no later than 4 PM) to avoid getting up at night to go to the bathroom.
■ Can cause:
o Hyperglycemia.
o Photosensitivity.
o Sexual dysfunction.
102
Calcium Channel Blockers counseling
■ Can cause:
o Peripheral edema
o Gingival hyperplasia
■ Take Adalat CC on an empty stomach.
■ Ghost tablet in stool (Adalat CC and Procardia XL).
103
ACE Inhibitors, ARBs and Aliskiren counseling
■ Avoid in pregnancy (teratogenic)
■ Allergy/anaphylaxis (angioedema)
■ ACEi: dry, hacking cough
104
Beta-Blockers counseling
■ Do not abruptly discontinue without consulting your healthcare provider.
■ This medication can mask symptoms of low blood sugar. If you have diabetes, check blood sugar if you notice symptoms of sweating or hunger.
■ Can cause sexual dysfunction.
■ Take Coreg/CoregCRwith food.
■ Take Lopressor/ToprolXL with or immediately after meals.
105
Clonidine counseling
■ Do not abruptly discontinue without consulting your healthcare provider.
■ Patch: apply weekly to upper outer arm or chest.
- The white adhesive cover can be applied over the patch to keep it in place.
- Remove before an MRI.
■ Can cause sexual dysfunction.
