BMP Reference Range
1. Sodium (Na) 135-145 mEq/L - hyponatremia vs. hypernatremia
2. Potassium (K) - 3.3-4.9 mEq/L - hyperkalemia vs. hypokalemia
3. Serum Creatinine (SCr) 0.6- 1.1 mEq/L - several limitations to interpret kidney function
(see GFR)
4. Glomerular Filtration Rate (GFR) >60 mL/min –estimated calculation uses Scr + other
variables
5. Chloride (Cl) 97-110 mEq/L
6. Carbon Dioxide (CO)22-30 mEq/L
7. Blood Urea Nitrogen (BUN) 8-25 mg/dL
8. Blood Glucose (BG) 65-109 mg/dL
9. Calcium (Ca) 8.6-10.3 mg/dL
10. *AST - ASpartate Transaminase (aka SGOT) 11 - 47 IU/L
11. *ALT - ALanine Transaminase (aka SGPT) 7 - 53 IU/L
12. Serum Creatinine (SCr) – reference range 0.6- 1.1 mEq/L may or may not be “normal”
clinically
1. Value can be non-predictable, vary with patient factors (e.g., age, muscle mass,
weight, race, gender)
2. Value in reference range may appear “normal”; with low Glomerular Filtration
Rate (GFR) there if kidney dysfunction
13. Blood Urea Nitrogen (BUN) – high levels may indicate kidney and/or liver dysfunction
14. Glomerular Filtration Rate (GFR) – normal GFR ≥ 60mL/min (no kidney dysfunction)
15. Lab calculation to estimate patient’s renal function (mdrd.com algorithm)
16. Standardizes interpretation of kidney function without reliability solely on SCr
17. Creatinine Clearance (CrCl or CLCr) - Manual calculation (various formulas) to estimate
kidney function – normal typically >90 mL/min
1. Recommended drug adjustment for renal impairment may include CrCl (some
may include SCr and/or GFR instead)
2. Example formula to estimate kidney (renal) function: Cockcroft-Gault equation
18. Albumin-Creatinine Ratio (ACR) - normal ACR < 30 mg/g (NO proteinuria is normal;
proteinuria suggests kidney dysfunction
1. Proteinuria recommended terminology – includes microalbuminuria +
macroalbuminuria
19. Chronic Kidney Disease (CKD) - usually GFR < 60mL/min (with or without proteinuria) various stages
BRADYCARDIA
• Resting Heart Rate (HR) < 60 BPM [beats per minute]
• Symptoms may include: Fatigue, Dizziness/Lightheadedness, Syncope
TACHYCARDIA
• Resting Heart Rate (HR) >100 BPM
• Symptoms may include: Dizziness/Lightheadedness, rapid heartbeat or palpitations,
chest pain (angina), shortness of breath (SOB)
Clinical Manifestations of ASCVD
Coronary Artery Disease (CAD)
 AKA Ischemic Heart Disease (IHD)
 AKA called Coronary Heart Disease (CHD)
 Chronic Stable Angina
 Myocardial Infarction (MI)
 Acute Coronary Syndrome (ACS) / unstable angina
 Surgical revascularization of Coronary Artery
- e.g., Coronary Artery Bypass Graft (CABG) – “bypass surgery”
- e.g., Percutaneous Coronary Intervention (PCI) - coronary stent
“angioplasty”
Non-Coronary Vessel Disease
 Ischemic stroke - “Cerebrovascular Accident” (CVA)
 Transient Ischemic Attack (TIA) – “mini–stroke”
 Renal artery stenosis
 Mesenteric artery disease -” bowel infarction”
 Abdominal Aortic Aneurysm (AAA) - “triple A”
 Peripheral Vascular Disease (PVD)
- e.g., Peripheral Artery Disease (PAD) “intermittent claudication”
 Surgical revascularization of non-coronary artery (E.g., AAA repair)
Identification
Primary Prevention
Secondary Prevention
No Clinical manifestations
of ASCVD exist
Clinical manifestation(s)
of ASCVD exist
Clinical Goals
Prevent ASCVD
diagnosis & related
morbidity/mortality
Prevent ASCVD
progression & related
morbidity/mortality
Therapeutic Targets
Interventions to
reduce ASCVD risk
Interventions to
reduce ASCVD risk
Risk
Estimation
-10yr risk score
-30 yr risk score
-Risk enhancing factors
-Coronary calcium score
Can be estimated
 Pooled Cohort Equation*
estimates risk to guide
decisions on preventative
interventions
Already known (high risk)
 INVALID to use Pooled
Cohort Equation
 Decisions on interventions
are clear
Primary prevention:
 Assess traditional CV risk factors
 20-39 YO: Assess Q4-6 years
 40-75 YO: Assess “routinely”
 Estimate 10-year ASCVD risk score routinely between 40-75 YO
 If 10yr ASCVD risk 5% to 19.9%
 Consider Risk Enhancing Factors (REF)
 May consider Coronary Artery Calcium (CAC) score if risk-based
decisions remain uncertain after discussing above factors
 May consider 30-yr ASCVD risk score if 40-59 YO & 10-yr risk < 7.5%
 Recommend risk modification with lifestyle + drug therapy if indicated
Secondary prevention:
 Routinely assess traditional CV risk factors
 Recommend aggressive risk modification with lifestyle + drug therapy
 Invalid to use any ASCVD risk score, REF, or CAC
Traditional CV risk factors:
1. Age ≥55 YO for males / ≥ 65 YO for females
2. *Hypercholesterolemia (Dyslipidemia)
3. *Hypertension (HTN) - High Blood Pressure (BP)
4. *Diabetes mellitus (DM) - Type 1 or Type 2
5. Current cigarette (tobacco) use (only count if any in last 30 days)
6. *Obesity
7. *Physical Inactivity
Pooled cohorts equation:
 Validated in primary prevention ONLY
 Validated in select age groups
 10-year risk estimate valid for ages 40-79YO (guideline: to 75 YO)


 30-year risk estimate valid for ages 40-59 YO
Validated in Non-Hispanic White & African-American
 May underestimate ASCVD risk in patients from:
 South Asia (e.g., India, Pakistan); American Indian; Puerto Rico
 May overestimate ASCVD risk in patients from:
 East Asia (China; Japan); Mexico
Inaccuracies (e.g., socioeconomic or preventative care levels)
10 yr ASCVD risk “Short-Term”
 <5% - Low
 5% to 7.4% - Borderline
 7.5% to 19.9% - Intermediate
 ≥20% - High
30 yr (lifetime) ASCVD risk “Long-Term ”
 Compares risk with vs. without optimal risk factor management – e.g., 35% vs. 50%
8 Risk Enhancing Factors (REF) for Primary Prevention of ASCVD
Family history of premature ASCVD
1st degree relative (parent, child, sibling) had
early age ASCVD (male <55YO or female <65 YO)
High-risk race/ethnicity/ancestry
•
South Asian, American Indian, Puerto Rican
High LDL-Cholesterol (primary)
•
160–189 mg/dL
Elevated biomarker levels
(these may ↑ ASCVD risk; cannot
precisely assess impact)
•
•
•
•
•
Elevated TG - persistently ≥175 mg/dL
Elevated CRP (FYI: risk ≥2.0 mg/L) – C reactive protein
Elevated Lp(a) (FYI: risk ≥50 mg/dL) – Lipoprotein(a)
Elevated ApoB (FYI: risk ≥130 mg/dL) – Apoprotein-B
Low ABI ratio (FYI: <0.9 indicates PAD risk) - Ankle
brachial index (ankle vs. upper arm blood pressure)
Metabolic syndrome
•
FYI: at least 3 of 5 criteria: low HDL cholesterol;
Elevated waist circumference; high triglycerides;
high Blood Pressure; High blood glucose
Chronic Kidney Disease (CKD)
(DO NOT count if dialysis or kidney transplant)
Chronic inflammatory conditions
•
•
•
•
Psoriasis
Rheumatoid Arthritis
Lupus
HIV/AIDS
Premature menopause or pregnancyassociated conditions
•
•
Menopause under age 40
Pre-eclampsia during pregnancy
HTN dx:
 If not hypertensive: monitor BP annually
 Initial diagnosis of HTN: Based on average of ≥2 careful readings of high SBP and/or high
DBP from ≥2 clinical setting encounters
 HTN control is regularly assessed
 Based on average of careful, accurate readings
 Medical office/clinical setting – repeat if high
 Home/non-clinical setting – if needed/available
 Controlling BP to target does not remove HTN dx
Evaluating BP Trends
No hypertension
Non-clinical / Home/
Ambulatory Monitor
Setting
No hypertension
Hypertension
Hypertension
No hypertension
Hypertension
Hypertension
No hypertension
Medical Office/Clinical
Setting
Normotensive
Hypertension
(Sustained)
Masked hypertension
White Coat
hypertension
Primary causes (Primary, essential or benign HTN)
 Most common >90% of cases

Risk factors may exist, such as:
o older age (especially for isolated Systolic HTN)
o overweight or obese
o genetic pre-disposition
o race (e.g., higher rates in Black vs White or Hispanic population)
Secondary causes
 Less common < 10% of cases
 Due to drug or disease
 May cause abrupt, symptomatic, severe HTN
 May complicate primary HTN
Drug Induced HTN:
Alcohol abuse
Amphetamines – e.g., methylphenidate, methamphetamine
Anabolic steroids (androgens) – e.g., testosterone
Antidepressants – e.g., venlafaxine; desvenlafaxine; bupropion
Atypical antipsychotics – e.g., clozapine; olanzapine
Cocaine
Dietary supplements – e.g., St John’s Wort; Bitter Orange; Guarana; Kava
Erythropoeitin (and related agents)
Immunosuppressants – e.g., tacrolimus, cyclosporine
NSAIDs - e.g., ibuprofen; naproxen; high-dose aspirin (not low dose 81mg)
Oral contraceptives
Oral decongestants - e.g phenylephrine; pseudoephedrine
Systemic glucocorticoids (steroids) - e.g., prednisone
Tyramine-containing foods when on MOAI therapy (wine, aged cheese, etc)
Abruptly stopping *chronic beta-blocker (including alpha/beta)
Abruptly stopping *chronic central acting alpha-agonist
Abruptly stopping *chronic opioid – e.g., morphine, oxycodone
Abruptly stopping *chronic benzodiazepine – e.g., alprazolam, diazepam
HTN Treatment Approach
BP
CV Risk
NOT HIGH
Recommend
nonpharmacological therapy
 Reassess in in 3-6 months
HIGH
• Existing CVD
• High CV risk
nonpharmacological therapy
+ antihypertensive therapy
 Reassess in 1 month, repeat until BP at
goal then follow-up in 3-6 mo.
Elevated
or Stage 1 HTN
Stage 1 HTN
SBP ≥130-139 mm Hg +/- DBP
≥80-89 mm Hg
Stage 2 HTN
SBP ≥140 mm Hg +/-DBP ≥90
mm Hg
ANY
ANY
HTN Crisis
SBP ≥180 or
DBP ≥110 mm Hg
nonpharmacological therapy
+ antihypertensive therapy
 Prompt treatment, monitoring, primary care
referral if not currently managed
 Reassess in 1 month, repeat until BP at goal
then follow-up in 3-6 mo.
prompt evaluation
+ antihypertensive drug therapy
 HTN EMERGENCY: evolving TOD,
hospital/ICU care, manage over hours
 HTN URGENCY: no evolving TOD, outpatient
care, manage over days
Nonpharm:
Lifestyle Modification
Physical
activity
Healthy diet
Approach
(prevent or treat high BP)
Aerobic exercise;
isometric/dynamic
resistance
Follow *DASH diet
pattern
● 90–150 min/wk
● 65%–75% heart rate
Rich in fruits, vegetables, whole
grains, low-fat dairy; low saturated &
total fat (DASH - Dietary Approaches
to Stop Hypertension )
Weight loss
Assess
Best goal is ideal body weight; aim
Weight/body fat for at least 1kg reduction if
overweight (~1 mm Hg ↓ for every
1-kg weight ↓)
Sodium intake Lower
Optimal <1500 mg daily; *aim for at
dietary sodium
least 1000 mg per day reduction
Potassium
Adequate
Aim for 3500–5000 mg per day,
intake
dietary potassium prefer diet rich in potassium (unless
contraindicated – e.g., CKD or drugs
that reduce K+ excretion)
Moderate
Limit alcohol
Men ≤2 ; Women ≤1 “standard”
alcohol intake consumption
drinks daily
standard: 5oz, 12oz beer, 1.5oz
spirits
Adult
Existing
Clinical CVD
At High CVD risk*
NOT at
high CVD risk*
Approx. Impact on SBP*
Hypertension Normo-tension
-5/8 mm Hg -2/4 mm Hg
-11 mm Hg
-3 mm Hg
-5 mm Hg
-2/3 mm Hg
-5/6 mm Hg
(with aim*)
-4/5 mm Hg
-2/3 mm Hg
(with aim*)
-2 mm Hg
-4 mm Hg
-3 mm Hg
Patient History
• ASCVD – e.g., MI; Ischemic CVA or TIA, CABG or PCI surgery for
IHD
• NON-ASCVD– e.g., Heart failure, AFib
• 10-year ASCVD risk score ≥10%
• Diabetes Mellitus (DM)
• Chronic Kidney Disease (CKD)
• 10-year ASCVD risk score < 10%
• No existing clinical CVD
• No DM
• No CKD
Target BP & Threshold for adding drug
Target BP
(mmHg)
Threshold BP
(mmHg)*
< 130
<80
≥ 130
≥ 80
< 130
<80
May be
reasonable
≥ 140
≥ 90
COR
LOE
I
C-LD
IIa
C-EO
I
C-EO
Risk level
- Existing clinical CVD
- High risk for clinical CVD
if 65 YO+ non-institutionalized, ambulatory, communityliving adult use SBP only (not DBP)
for Target & Threshold
No additional markers of increased CVD risk
-No existing clinical CVD
-Not high risk for clinical CVD
Recommendations for Initial Drug Therapy
Most adults with hypertension, especially black adults,
will require ≥2 HTN drugs to achieve BP <130 / <80 mmHg
Stage 1 HTN and BP goal <130/80 mm Hg:
Initiate one(1) first-line antihypertensive using dosage titration + sequential
addition to achieve BP target.
* Stage2 HTN with BP > 20/10mmHg above goal:
Initiate two (2) first-line antihypertensives of different classes
either as separate agents or fixed-dose combination
HTN Treatment: Compelling Indications
overrides other first-line drug choice recommendations
Stable angina
MI or ACS
HF
For symptom
control:
1st line BB
2nd line CCB
(DHP w/BB)
For CV benefit:
ACEI
or
ARB
after sx control
ACEI
or
ARB
+
BB
+
ALDO ANTAG
in eligible patients
per GDMT
ACEI
or
ARB
+
BB
+
ALDO ANTAG
in eligible
patients
per GDMT
CKD
ACEI
or
ARB
DM
with
proteinuria
Ischemic CVA/
TIA
ACEI
or
ARB
ACEI
or
ARB
or
THZ
or
THZ + ACEI
HTN Treatment: Special Populations
Black +/- DM
o Typically require ≥2 drugs to achieve BP goal
(no HF or CKD)
o Initial regimen should include THZ or CCB
o If planning or pregnant, transition to preferred agent(s) labetalol,
Pregnancy
methyldopa, nifedipine XL
o AVOID ACEI, ARB, or DRI (teratogen)
o Clinical judgment re: comorbidities; life expectancy; patient
preference; age-related benefit vs. risks
o Examples include differences in:
• drug clearance (↓ with renal/hepatic impairment)
• volume of distribution (body fat: skeletal muscle)
≥ 65 YO
• drug-drug interaction potential (polypharmacy)
• side effect risks (e.g., falls; Beer’s Criteria drugs)
• impact w/ ↓ weight or dietary sodium (great SBP ↓)
• CV mortality w/ aggressive DBP↓ (↑ mortality risk)
• Inclusion of very old (≥ 80YO) in clinical trials (limited)
LOOP: Generally less effective than THZ for BP lowering unless fluid retention/volume overload
is involved
o Reserve use for managing HTN in the setting of edema due to:
 Heart Failure
 Chronic Kidney Disease (CrCl < 30mL/min)
 some specialists will use safe/effective THZ therapy at CrCl <30
mL/min for select patients though this offers less diuresis for
edema may be preferred if CKD and resistant hypertension
o - First line due to outcome data
o - Synergistic effects on BP ↓with other first line agents
BP lowering effects of ACEI, ARB, or DRI significantly increased with addition of CCB
or THZ
BB: Without compelling indication, monotherapy offers inferior protection from stroke relative
to 1st line agents
Alpha-1 blockers - Last line; AVOID monotherapy for HTN due to inferior outcomes
Central alpha-2 antag:
• Clonidine - role in HTN urgency or add-on alternative agent for Resistant HTN
• Methyldopa – a drug of choice for HTN in pregnancy (safety)
Resistant HTN:
Thiazide Diuretics:
• Chlorthalidone –QAM dosing
• Indapamide –QAM dosing
• Hydrochlorothiazide (HCTZ) 12.5mg or 25mg PO daily in the morning (AM)
 INITIATE low dose in higher risk persons e.g., Age 65 years; on concurrent ACE
or ARB or DRI
 E.g., start 12.5mg po daily & titrate to max 25mg daily to lower risk of
adverse effects
 HCTZ dose 50 to 100mg per day NOT recommended for HTN due to
adverse effects
 Available in various combination products
• Chlorthalidone most common in clinical trials, HCTZ most common in practice
• Caution with CrCl<30 mL/min
 Controversial: some specialists may consider continuing therapy on case-by-case
basis if safe/effective, monitoring electrolytes & GFR (CrCL)
Loop diuretics:
• Furosemide (Lasix)
– 20-80mg/day PO divided BID
– i.e., not dosed once daily for HTN
• Torsemide (Demadex) – once daily dosing
Potassium sparing diuretics w/o MRA:
• Amiloride
– LOW DOSE IF CRCL < 50mL/min
• Triamterene
– AVOID IF CRCL < 50mL/min
** avoid HCTZ ≥ 50mg/day to limit metabolic side effects
• Dyazide or Maxzide-25
o HCTZ 25mg + triamterene 37.5mg combination tablet or capsule
SIG: 1 pill PO DAILY in AM
• Maxzide
o HCTZ 50mg + triameterene 75mg combination tablet
**SIG: ½ tablet PO DAILY in AM
Aldosterone antag (potassium sparing diuretics with MRA:
• Spironolactone (ALDACTONE)
– HTN DOSING: 25mg PO ONCE DAILY initially, may ↑ to 50mg PO daily
• May titrate up to 100mg PO daily max for HTN, as tolerated
• Reduce dose if CrCl 31-50 mL/min
– CONTRAINDICATED if CrCl 30 mL/min or less
– Higher Gynecomastia risk vs. eplerenone
• Eplerenone (INSPRA)
– BID dosing frequency when used for HTN
–
–
–
Higher cost vs. spironolactone
Higher hyperkalemia risk vs. spironolactone
CONTRAINDICATIONS (FDA) * for hypertension
• K > 5.5 MEq/L
• SCr >2.0 mg/dL in males, >1.8 mg/dL in females
• CrCL <50 mL/min
• Type 2 diabetes with microalbuminuria (proteinuria)
• Concomitant potassium supplements or potassium-sparing diuretics
Diuretic ADEs:
• Urination
– ↑ Volume/frequency (esp. initially)
– Less pronounced with chronic use (except for LOOP)
– Dose in AM (+ late afternoon if BID)
• Dehydration/hypovolemia
• Orthostasis/dizziness
• Sulfonamide allergy cross-sensitivity possible with THZ or LOOPS
• Photosensitivity
• Erectile dysfunction
• Rare Nephrotoxicity (monitor SCr/GFR)
• Hyponatremia
• Hypokalemia (LOOP >> THZ risk)
• Hyperkalemia (ALDO ANT or K+ spar.)
• Hypomagnesemia (LOOP)
• Hypercalcemia (THZ)
• Hypocalcemia (LOOP)
• Hyperuricemia (Gout) – higher risk with THZ > LOOP
• Hyperglycemia (DM) - clinically significant with high dose THZ or LOOP
• Hyperlipidemia - clinically significant with high dose THZ or LOOP
Diuretic warnings:
• *Dehydration (hypovolemia)
o increased risk with higher doses
o use lower initial dose
• *Hypotension
o increased risk when added to existing HTN therapy especially ACEI, ARB, DRI
o use lower initial dose
• *Preexisting electrolyte imbalance
o increased risk with K+ sparing diuretic or ALDO ANTAG + ACEI, ARB, or DRI
• *CKD - generally AVOID at cutpoints (CrCL) – see slides
• Anuria (Absolute Contraindication)
• Severe hepatic disease
• Women of child-bearing age or lactation (benefit vs risk differs by agent)
Diuretic interactions:
• Use with other agents that cause hyperkalemia (AVOID or caution/monitor)
o ACEI; ARB; DRI; K+ sparing diuretic, ALDO ANT, KCL supplement
 Increased hyperkalemia risk with concomitant use
• Digoxin (LOOP >> THZ interaction)
o K+ wasting ↑ digoxin toxicity RISK and related cardiac arrhythmias
• Lithium (risk with THZ or LOOP – AVOID if possible)
o Reduced Lithium clearance –and related lithium toxicity
• Cholestyramine (for cholesterol lowering)
o 85% reduction of HCTZ absorption (cannot avoid w/ separated doses)
• Eplerenone
o 3A4 metabolism inhibitors may significantly increase exposure
o E.g., grapefruit or its juice (1 cup)  25% increase in eplerenone exposure
ACEi, ARB, DRI:
o Avoid concurrent use of ACEI, ARB, DRI
o Combination offers no additional CV benefit, more adverse risk
o NOTE: when ACEI or ARB are indicated, select either one
o Recommend lower initial dose if high risk for adverse effects
o Older persons
o On diuretic therapy
o Black patients may require titration to higher doses to control BP
o May need to use with THZ or CCB to optimize BP lowering
o NOTE: this does not limit use of drug class when indicated or compelling
ACE dosing:
• Lisinopril (Zestril, Prinivil) 10 - 40mg PO once daily
• Lisinopril + HCTZ (Prinzide, Zestoretic) 10/12.5mg, 20/12.5mg, 20/25mg PO once daily
• Enalapril (Vasotec) 5 - 40mg/day PO daily (divided QD or BID)
• Fosinopril (Monopril) 10 - 40mg QDay
• Ramipril (Altace) 2.5 -10mg/day given PO Qday (may divide BID for other uses)
• benazapril (Lotensin)
• benazapril + amlodipine (Lotrel)
• captopril
• quinapril (Accupril)
• quinapril+ HCTZ (Accuretic)
ARB dosing:
• Losartan (Cozaar) 25, 50 or 100mg/day PO once daily (may divide into BID)
• Irbesartan (Avapro) 75, 150, or 300mg PO once daily
• Valsartan (Diovan) 80, 160, or 320mg PO once daily
• losartan/HCTZ (Hyzaar)
• irbesartan/HCTZ (Avalide)
• valsartan/HCTZ (Diovan HCT)
EXCEPTION: Initiate lowest strength in patients with risk for depletion of intravascular
volume (e.g., concurrent diuretic therapy) or hepatic impairment
Do not initiate maximum strength dose; may titrate to maximum strength dose as tolerated,
as needed
Generally expect little gain in BP reduction with doubling of dose - “Flat dose-response”
DRI:





Aliskiren - Tekturna® (do not need to know dosing)
Little gain in BP reduction with doubling of dose - “Flat dose-response”
Generally well tolerated - Most common side effect: diarrhea (2.3%)
See ACE/ARB/DRI slides for class side effects/warnings
AVOID use with ACEI or ARB
ACE/ARB/DRI ADEs:
COMMON
• ACEI only - Dry non-productive COUGH (no phlegm, not wet)
o Up to 20% incidence (class effect) – no cough with ARB or DRI (not
clinically significant)
o Resolves upon d/c; not contraindicated with asthma (monitor for
cough)
• Hyperkalemia (↑ risk with CKD; KCL, K+sparing diuretic or ALDO ANTAG)
• Dizziness /Hypotension
o Higher risk if sodium or volume depleted (hypovolemic) or elderly
o Use very low dose initially, especially if high risk
• Slightly higher SCr less than ~ 30% reduction from baseline 
o Indicates predictable, stable hemodynamic auto-regulation due to
drug action
o Continue drug; accept slightly higher Scr as new baseline, continue to
monitor
RARE
• Acute Kidney Injury (AKI) – major ↑ SCr > 30% from baseline 
o Indicates ACUTE KIDNEY INJURY; must discontinue therapy if occurs
• Hepatoxicity
• Neutropenia
• Angioedema- RARE but serious hypersensitivity reaction
o ACUTE swelling of subcutaneous/submucosal tissues including face,
extremities, lips, tongue, glottis, and/or larynx that may occur at any
time during treatment
o Higher incidence in black patients, genetic predisposition; reported
with ACEI > ARB >DRI
 If reaction to any ACEI – avoid that class; same for ARB
 If ACEI angioedema, may try ARB ≥6 weeks after stop ACEI
(benefit vs. risk; monitor)
ACEI/ARB/DRI - Warnings:
CI:
• Known hypersensitivity
o E.g., life-threatening angioedema to any ACEI - AVOID rechallenge
o Cross-hypersensitivity risk may occur with ACEI, ARB, DRI classes
• Pregnancy– due to major risk of teratogenicity use requires adequate contraception
if childbearing age
• Severe renal artery stenosis (bilateral or in solitary kidney)
• Avoid dual RAAS agents
o No ACEI + ARB
o No ACEI +DRI
o No ARB + DRI
Precautions:
•
Volume depletion/Dehydration
• Correct imbalances before initiating
o Postural hypotension
• Start low dose if older, CKD, heart failure
o Pre-existing HYPERKALEMIA
o Women of child-bearing age
o Conditions that ↑ risk for AKI**
 Renal artery stenosis in 1 (of 2) kidneys
 Existing CKD
 Systolic heart failure
 Elderly
 Volume depletion (e.g., diarrhea/ vomiting)
 Concurrent drug that may be nephrotoxic
CCB:
•
DHP CCB
o Amlodipine
 Norvasc
 2.5 or 5mg po daily; up to 10mg PO Daily (max)
o Nifedipine extended-release
 Procardia XL, Adalat CC, Nifedical XL
 30 po daily initial; up to 60mg daily; max 90 mg PO Qdaily
 AVOID short-acting nifedipine (10mg po TID)
o Module drug list:
Amlodipine (DHP – CCB) +benazepril (ACEI)- Lotrel
• NON-DHP CCB
o Diltiazem long acting formulations
 120 (180mg)  240mg  360mg  480mg PO Qdaily
 Cardizem CD/Tiazac/Cartia XT
 Cardizem LA
 Cardizem SR (dosed BID)
o Verapamil long acting formulations
 180mg  240mg 360mg 480mg PO Qdaily
 Calan SR, Isoptin SR; Verelan -Sustained release
 Covera HS - Controlled release Verelan PM- Chronotherapeutic systemo Prefer once daily long-acting formulation over
immediate release [BID - TID dosing
 Some extended-release products costl
CCB ADEs:
DHP CCB
• PERIPHERAL EDEMA
– Common, dose related
– Eg. 3% vs. 11% incidence with amlodipine 5mg vs. 10mg
– NOT responsive to diuresis
• HEADACHE
– Dizziness/orthostasis
– Flushing
– GI – Nausea, Gastroesophageal reflux
– Gingival hyperplasia
NON-DHP CCB
• BRADYCARDIA
• Cardiac conduction abnormalities
– E.g., Atrial-Ventricular (AV) block
• Heart failure
– negative “inotropic” effects
• Constipation (most risk with verapamil)
• GI – Nausea, Gastroesophageal reflux
• Rare flushing, peripheral edema
CCB warnings:
• Hepatic/Kidney dysfunction
o Amlodipine – hepatic clearance
o Diltiazem – renal clearance
o Verapamil, Nifedipine– renal & hepatic clearance
• GI obstruction – for extended-release products
• Drug interactions:
• Verapamil, diltiazem, nifedipine are
o SUBSTRATEs for P450 3A4
 Grapefruit juice –may ↑ CCB levels
o INHIBITORS of P450 3A4
 CCB may increase ERYTHROMYCIN levels significantly– AVOID



CCB may increase DIGOXIN levels up to 50% - major
caution/monitor
SIMVASTATIN - not to exceed 20mg/day with concurrent
amlodipine
SIMVASTATIN - not to exceed 10mg/day with concurrent nonDHP
DHP
•
AVOID short-acting nifedipine
• may precipitate angina, MI, CVA (worse outcomes)
• NOTE: nifedipine XL ok
• AVOID in pregnancy/lactation
• NOTE: nifedipine XL ok
• Heart failure
• AVOID nifedipine XL
• NOTE: amlodipine ok
• Migraine
Non-DHP
• AVOID if cardiac conduction abnormality (e.g., AV block)
• AVOID concurrent BB due to risk of bradycardia, AV block
• AVOID in Heart failure
BB:
Cardioselective (Beta-1 selective)
atenolol (Tenormin)
 Typical initial dosing: 25- 50mg
po daily
 Typical dose range: 50-100mg
po daily
metoprolol (2 salt forms below)
 25- 50mg per day (total)
initially
 50-200mg per day dose range
for HTN
metoprolol tartrate po BID –
Lopressor
Alpha/Beta (non-selective)
 labetolol (Trandate) 100mg BID
increase every 2-3 day minimum
 HTN dose range 200-400mg BID
 carvedilol (Coreg) immediate release
tablets 3.125 or 6.25mg BID initially,
titrated to MAX 25mg BID
 carvedilol phosphate (Coreg CR)
extended release tablets - 20mg once
daily MAX 80mg Qday.
 Generally double dose q1-2
week
 $$$ vs. Immediate Release $
BB ADE:metoprolol succinate po daily -Toprol
XL
• Bradycardia
Non-cardioselective
(B1/B2; non-selective)
• Exercise Intolerance
 nadolol
(Corgard)
• Dizziness/Orthostatic
hypotension
 propranolol
(Inderal;
Inderal
LA)alpha/beta blocker
o Most significant with
• Bronchospasm
o Non-selective or Alpha/beta agents have higher risk than B1-selective agent
•
•
•
•
•
o B1-selectivity (Cardioselectivity) carry dose-dependent risk (lower risk at
lower doses)
 Risk vs. benefit with preexisting lung disease such as asthma or COPD
Diarrhea
o Especially alpha/beta blocker
Dyslipidemia
o Most impact with Non-selective
o Less impact with B1-selective blocker
o No impact with Alpha/beta blocker
Fatigue
o Especially Alpha/beta blocker
o Especially lipophilic propranolol
Weight Gain
Erectile Dysfunction
BB Diabetes ADEs:
1. Hyperglycemia: dose-related; ↑ risk with non-selective BB
• May impact existing diabetes or pre-diabetes glucose control
• Lowers insulin secretion; glycogenolysis (release glucose)
2. Hypoglycemia: dose-related; ↑ risk with non-selective BB
• May mask warning signs in persons at risk (e.g., on insulin)
• Block sympathetic response (e.g., no tachycardia, no
trembling)
• Only symptom may be sweating (parasympathetic)
• May prolong recovery from hypoglycemic episode
• Typically takes 15 minutes with 15g glucose
• May use BB for compelling indication or add-on HTN therapy in DM
• E.g., low dose, beta-1selective agent
• The key is benefit vs. risk; if used, patient education & monitoring
BB warnings:
• AVOID ABRUPT WITHDRAWAL
 MUST taper over 7-14 days if chronic use (at least 2 weeks of therapy)
 Risk of rebound HTN risk & risk of CAD exacerbation without taper
 Pre-existing lung disease
• Orthostatic Hypotension – esp. Alpha/Beta-blockers (vasodilatory effects)
• Bradycardia / cardiac conduction abnormality (AV BLOCK) - avoid with nonDHP CCB
• Heart failure – some BB may cause or worsen condition; avoid if decompensated
 Does NOT include agents with compelling use in systolic heart failure
• Uncontrolled DM – avoid use of high dose, non-selective BB
• CKD – AVOID, CAUTION or dose adjust w/ renally metabolized – e.g., atenolol, nadolol
• Hepatic disease – AVOID hepatically metabolized - e.g., propranolol, metoprolol,
carvedilol
• Drug interaction potential

CYP450 3A4 , 2D6 substrates- e.g., metoprolol, carvedilol
Alpha -1 blockers: prazosin (Minipress), doxazosin (Cardura), terazosin (Hytrin)
• Severe Orthostasis
o MAJOR risk of syncope and falls
o Take dose laying down at bedtime especially 1st dose or dose increase
• Systemic edema
o Sodium/water retention (non-pitting)
o Dose-related, may occur at low dose
• Systolic heart failure - cause/exacerbate
• Reflex tachycardia - palpitations
• CNS
o headache, vivid dreams
o Nasal congestion
o Erectile Dysfunction
o Priapism
• WARNINGS
o Beer’s list of Potentially Inappropriate drugs for older adults
o AVOID in heart failure
o Performing “hazardous tasks”
o Intraoperative “floppy iris syndrome”
o Moderate drug interaction potential
Central alpha -2 agonists
• Methyldopa
• Clonidine
• CATAPRES BID tablets
• CATAPRES TTS patch weekly
• Guanfacine (immediate release)
Central alpha- agonist ADEs:
 Bradycardia – may cause AV block
 Orthostasis
 Systemic edema
 Sodium/water retention (non-pitting)
 higher incidence with METHYLDOPA vs. CLONIDINE/GUANFACINE
 Anti-cholinergic: dry mouth, constipation, urinary retention, blurry vision
 Systolic heart failure – cause/exacerbate
 Acute withdrawal (requires taper to avoid) agitation, tremor, very high BP (rebound)
 CNS depression: sedation
 Headache
 Erectile dysfunction
 Rash (patch)
 Methyldopa ONLY: rare lupus, hemolytic anemia, hepatic dysfunction
Central alpha 2- agonist warnings:
 BRADYCARDIA: avoid use
 ELDERLY: Potentially inappropriate
 HEART FAILURE: avoid
 AVOID abrupt withdrawal
 CKD: Dose adjustment
 CONCURRENT BB: taper off BB therapy before clonidine taper to avoid HTN rebound
 Methyldopa: HEPATIC:
 Generally avoid in liver disease
 Check LFT baseline, periodically
 Transient increase in AST or ALT ok if < 3 x ULN.
 Taper off therapy ASAP if AST or ALT rises ≥ 3 x ULN
DVD –
 Hydralazine (QID to BID titration)
o COMMON: nausea, vomiting, diarrhea, anorexia
o RARE: hepatotoxicity; drug-induced lupus; drug fever, leukopenia
 Minoxidil (1 x daily dosing)
o BLACK BOX WARNING: limit use to RESISTANT HTN unresponsive to maximum
therapeutic doses of diuretic and 2 other HTN agents
o More side effects than hydralazine: e.g., reversible hirsutism; EKG changes;
pericardial effusion; skin reaction; hypernatremia
DVD ADE:
• Sodium/water retention
– hypernatremia, edema, heart failure
– More likely with MINOXIDIL vs. hydralazine
– Use concomitant diuretic therapy
• Initiate LOOP diuretic with minoxidil
• Initiate THZ diuretic with hydralazine
• Reflex tachycardia
– palpitations, angina, tachyarrhythmia
– More likely with HYDRALAZINE vs. minoxidil
– Use concomitant BB (or NON-DHP CBB)
• Hypotension/Dizziness
• Headache
• CNS depression – e.g., sedation
DVD avoid:
• Heart failure
• Recent MI or in persons with angina
• CNS depression (and avoid alcohol)
• Cerebrovascular Disease (CVA, TIA)
• Pregnancy or lactation