Function: prevents conversion from angiotensin I to angiotensin II - captoPRIL - benazaPRIL - enalaPRIL - fosinoPRIL - lisinoPRIL - quinaPRIL - ramiPRIL

- hypotension - hyperkalemia NO cough (different from an ACE)

1. hydrochloroTHIAZIDE (HCTZ) 2. chloroTHIAZIDE 3. chlorthalidone 4. indapamide 5. metolazone

- very potent "thiazide-like" diuretic - not common for HTN in general pop.

Antihypertensives Flashcards by Caitlyn O'Brien

First Line Drug Classes

ACES
ARBS
Thiazide Diuretics
Calcium Channel Blockers

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Examples of Rx-induced causes of HTN

amphetamines
corticosteroids
NSAIDs
estrogen-containing oral contraceptives
anabolic steroids
tacrolimus, cyclosporine - calcineurin inhibitors (transplant)
venlafaxine (Effexor) or desvenlafaxine (Pristiq) (antidepressants)
oral decongestants – pseudoephedrine/phenylephrine
abruptly stopping BETA-blocker therapy
abruptly stopping central acting, ALPHA- antagonist therapy

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Examples of non-Rx-induced causes of HTN

drugs of abuse
cocaine/cocaine withdrawal, nicotine withdrawal, narcotic withdrawal, phencyclidine (PCP)
dietary supplements/foods
sodium intake, alcohol (ethanol) intake, dietary supplements (ex. St. Johns Wort; herbal ecstacy, bitter orange, guarana, kava, high dose licorice), tyramine-containing foods (wine, aged cheese, etc) with “MOA inhibitors” (antidepressant)

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ACE inhibitors

Function: prevents conversion from angiotensin I to angiotensin II

captoPRIL
benazaPRIL
enalaPRIL
fosinoPRIL
lisinoPRIL
quinaPRIL
ramiPRIL

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Direct renin inhibitor

Medication
Side effects

aliskiren

Side effects: hyperkalemia, hypotension

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Side effects of ACE inhibitors

hypotension
hyperkalemia
cough

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Side effects of ARBs

hypotension
hyperkalemia

NO cough (different from an ACE)

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Among the first line Rxs, avoid the combination of THESE THREE DRUGS due to _____________

DRI, ACEs, ARBs

due to dual RAAS blockage

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Adverse Effects of ACE/ARB/DRI + patient populations to watch out for

dizziness/hypotension
- be careful with HYPOVOLEMIC and ELDERLY patients
hyperkalemia
- be careful with ELDERLY, DM, CKD patients
non-productive dry cough (ACE ONLY)
- common; resolves upon d/c; drug class intolerance > don’t rechallenge
increased SCr
- expect to see increase SCr with decrease GFR 5-14 days initiation/dose increase
- should rise <30%, anything over indicates unstable progressive renal damage/AKI

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RARE Adverse Effects of ACE/ARB/DRI

hepatoxicity, neutropenia, angioedema

serious hypersensitivity (allergic) rxn > consider allergy across ALL of ACEs/ARBs/DRIs
occurs more frequently in black pts
more common with ACEs

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Contraindications of ACE/ARB/DRI

known hypersensitivity
pregnancy!!!!!
bilateral renal artery stenosis

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Precautions of ACE/ARB/DRI

volume depletion/dehydration (correct before initial dosage)
pre-existing hyperkalemia
women of child-bearing age
risk for acute renal injury
existing CKD
renal artery stenosis, systolic HF, volume depletion (concurrent diuretics), concurrent nephrotoxicity risks (NSAIDs including HIGH dose aspirin)

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Monitoring ACE/ARB/DRI

1-2 weeks initial impact (esp. high risk)
4 weeks for full BP lowering impact

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Thiazide diuretics

hydrochloroTHIAZIDE (HCTZ)
chloroTHIAZIDE
chlorthalidone
indapamide
metolazone

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Calcium channel blockers

DHP
- amloDIPINE
- feloDIPINE
- israDIPINE
- nifeDIPINE
- nicarDIPINE

non-DHP
- verapamil
- diltiazem

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Thiazide diuretics that DON’T have the same endings

chlorthalidone
indapamide
metolazone

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non-DHP drugs

verapimil
diltiazem

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metolazone

very potent “thiazide-like” diuretic
not common for HTN in general pop.

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For thiazide diuretics, you should generally avoid CrCl of ______ mL/min

<30 mL/min

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DHP vs. Non-DHP

DHP
- nifedipine, amlodipine
- more potent peripheral vasodilators
- common side effects = peripheral edema, headache
- uncommon = dizziness/orthostasis, flushing, nausea, GERD, gingival hyperplasia, REFLEX tachycardia (esp with nifedipine)

Non-DHP
- verapamil, diltiazem
- less potent peripheral vasodilators
- common side effects = bradycardia, potential cardiac conduction abnormalities, systolic HF (AVOID USE EF <40%) due to negative inotropic effects, constipation
- uncommon: nausea, GERD, headache, dizziness, flushing (less vs. DHP)

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CCB Adverse Effects

pregnancy/lactation (avoid lactation)
hepatic/renal dysfunction

NON-DHP only
- beta blocker, cardiac conduction abnormalities, systolic HF/LV dysfunction

DHP only
- AVOID short-acting release nifedipine – risk of severe reflex tachycardia/rebound HTN with risk of MI/CVA
- nifedipine XL - avoid in systolic HF/LV dysfunction – AMLODIPINE OK
- migraines (worsen)

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Avoid Non-DHP with __________

beta-blocker

WHY?
- additive risk for bradycardia + AV block
- reserve use for specialists

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Major P450-drug interactions

Verapamil, diltiazem, + nifedipine = 3A4 inhibitors
- increase erythromycin
- increase digoxin levels by 50%
- major interactions with simvastatin
20 mg/day with amlodipine
10 mg/day with verapamil or diltiazem
- drug-food/drug-herb interactions
> 1L/day grapefruit juice

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How would you check the efficacy of your ACEi/ARB/DRI ?

By monitoring the systolic and diastolic BP

How would you check the *safety* of your ACEi/ARB/DRI ?

By monitoring the SCr, K+ (via BMP or CMP)

Elevated SCr indicates what?

Elevated SCr = >30-35% indicates unstable, progressive renal damage OR acute kidney injury (AKI)

Diuretics used for HTN

1. thiazide (first line) 2. loop 3. K+ -sparing 4. aldosterone-antagonist (ALDO antagonists)

Which subclass + med causes the risk of severe reflex tachycardia/rebound HTN with risk of MI/CVA?

Subclass = DHP (CCB) Med = nifedipine (amlodipine OK)

What first line class of meds are preferred for African Americans?

THZ + CCB

What first line class of meds are preferred for people with comorbidities including CAD, CKD, DM, prior stroke, systolic HF?

ACEi + ARB

Which diuretics are reserved use for HTN?

Loop + K+ sparing diuretics

What class of non-first line meds are preferred for people with comorbidities including CAD and systolic HF?

What class of non-first line meds are preferred for people with comorbidities including systolic HF and post-MI with LVD?

ALDO antag

Can you use a CCB in someone with systolic HF?

YES as long as 1. it's not nifedipine 2. EF >40%

Which CCB would be okay to use in someone with systolic HF/LV dysfunction?

Amlodipine

When would you want to use a loop diuretic over a THZ?

2 populations where you need to retain fluid/sodium 1. Ppl with CKD with CrCl < 30 mL/min - THZ not as good at < 30 mL/min 2. Ppl with systolic HF + edema - provides more diuresis than a THZ

Loop diuretic endings

-mide - furosiMIDE - torseMIDE - bumetanIDE - ethacrynic acid

If you have an allergy to sulfas, what drug class should you avoid?

loop diuretics *with the exception of ethacrynic acid*

Which diuretic is NOT GOOD for long term use?

loop diuretics - caps over time thiazides are better in conjunction with ACEi/ARB

Another name for K+ sparing diuretics

Aldosterone antagonist

Examples of K+ sparing diuretics

- spironolactONE - eplerenONE - triamterene - amiloride

When would you use a K+ sparing diuretic?

RESERVED USE - an option to limit hypokalemia - in combo with THZ - offers relatively WEAK anti-HTN - increased hyperkalemia risk when used with ACEi

Gynecomastia is a side effect of which drug?

spironolactone - preferred in women

Spironolactone vs. eplerenone

spironolactone preferred - cheaper - reduce dose if CrCl 31-50 mL/min - avoid if CrCl < 30 mL/min - effective ADD-ON eplerenone - less side effects - avoid if CrCl < 50 mL/min - more expensive

Metabolic adverse effects of diuretics

ALL: hyponatremia loop>THZ: hypokalemia, hypomagnesemia K+: HYPERkalemia high dose THZ or loop: - hyperglycemia - hyperlipidemia

Agents with NO impact on cholesterol

indapamide and K+ sparing (ALDO ANTAG)

Absolute contraindication of diuretics

anuria

You should be especially careful with loop diuretics because of ...

ototoxicity, dehydration (hypovolemia)

What diuretic puts you at risk for gout?

THZ

At high dose THZ or loop, you should be careful of...

hyperglycemia, uncontrolled lipid levels

General warnings of diuretics

- Preexisting electrolyte imbalance - CKD - severe hepatic disease - women of childbearing age / lactation

Combining WHAT drugs raises potassium levels

KCL; ACEI; ARB; DRI; K+ sparing/

Interaction between digoxin and diuretics

K+ wasting diuretics make digoxin more toxic; related to cardiac arrhythmias loop>>>THZ

This metal should be avoided with THZ/loop

lithium - reduces lithium clearance - risk of lithium toxicity

What causes an 85% reduction of HCTZ absorption?

cholestyramine

Which drug causes a clinically significant increase in hyperkalemia risk with 1 grapefruit or 1 cup of juice?

eplerenone

Serum levels of the diuretics

All: ↓ Na+ Loop>>THZ: ↓ K+, Mg2+ Loop: ↓ Ca2+ THZ: ↑ Ca2+ THZ>loop: ↑ uric acid - GOUT Loop/THZ: ↑ glucose, lipids (high dose) K+ sparing: ↑ K+ ↑ THZ (except K+, Mg2+) ↓ Loop (except glucose/lipids)

Lupus is associated with what drug?

Methyldopa