HTN/HLD

LDL

“bad cholesterol”

• increased by cholesterol, saturated + trans fats

• primary target of these drugs

VLDL

“very low density lipoproteins”

• secreted by liver

• some convert to LDL

• increased by sucrose, fructose, excess calories

• also is the carrier of TGs to peripheral tissue

• bad in 3 freakin ways

triglycerides

• really high —> risk for pancreatitis

• increases after eating; so take labs BEFORE eating

• can be drug-induced (TPN, propofol, alcohol)

• increased by

  • total fat

  • alcohol

  • excess calories

HDL

“good cholesterol

• anti-atherosclerotic effect

  • bc takes cholesterol away from artery walls

HDL helps get rid of cholesterol!! so good for CV pts to have a lil high HDL

primary treatment algorithm (she will give this)

• if they already have CV disease, need to go to secondary to prevent further events

• first look at LDL

• check if they have DM

  • if no DM, look at framingham risk score to see if high mod or borderline risk

• anybody with intermediate risk or higher, DM, or CV event —> statin!!!

• do they have an event or not? what’s their LDL? do they have DM? what’s their framingham risk?

KNOW THE EXTREMES**

high intensity

• atorvastatin 40 or 80mg

• rosuvastatin 20 or 40mg

• this is the only way to to lower LDL by 50% or more

which patients have risks outweighing benefits for statins?

• maintenance HD

• LDL <70

• Class 2-4 HF

• risk for adverse effects too high

initial evaluation labs

fasting lipid panel:

• LDL, TG, ALT, CK (if indicated), A1C (statins increase risk for developing DM); Hx of prior/current muscle Sx

fasting lipid panel

to assess adherence and predicted response; repeat at 4-12 weeks then q 3-12 months

TG value to treat

>500***

LDL value to treat

>190

ALT

>3x upper limit of normal = contraindicated bc statins are highly metabolized by liver

baseline muscle pain

bc we might attribute it to the statin when it might have been underlying

all med categories

• HMG-CoA reductase inhibitors (statins)

• fibrates

• bile acid sequestrants

• sterol absorption inhibitor

• nicotinic acid

• omega-3 ethyl esters

• plant sterols/stanols

• red yeast Chinese rice

statins MOA

HMG-CoA is converted to cholestererol by HMG-CoA reductase inhibitors

• statins BLOCK this process —> reduces cholesterol synthesis

• upregulates LDL receptors on hepatocytes

  • recycling/removal the LDL already there

  • ULTIMATELY —> prevents more being made, removing what’s there

statins ADEs

• rare confusion state or memory impairment

• hepatic dysfunction

  • avoid in severe hepatic impairment

• myopathy

• rhabdomyolysis (increased CK)

• DM

• hemorrhagic stroke potential if plaque ruptures

• contraindicated in pregnancy/lactation!!

when are statins most effective?

in the evening because that’s when the most cholesterol is made

who’s at higher risk for adverse effects with statins?

• multiple comorbidities (renal/hepatic impairment)

• Hx muscle disorders

• unexplained ALT >3x ULN

• age >75 yrs

• genetic factors that decrease statin metab, clearance

• drug interaction risk bc lots of CYPs

lipophilic statins vs hydrophilic statins

• lipophilic more likely to cross into muscle than hydro

  • —> proteolysis & apoptosis —> muscle Sx

lipophilic statins

atorvastatin, simvastatin, lovastatin

hydrophilic statins

rosuvastatin, pravastatin

LESS muscle pain!!

if muscle symptoms happen, and if severe, ____

d/c statin; R/O other causes

it SHOULD be reversible else it’s something else

• if severe, check CK, creat, UA for myoglobinuria

  • checking for rhabdo

• more likely with lipophilic (atorva, simva, lovas)

mild-moderate muscle Sx: resolve and no contraindications

restart same statin or lower dose

mild-moderate muscle Sx: resolve so statin IS the cause

use low dose of different statin then increase as tolerated

mild-moderate muscle Sx: Sx unresolved after 2 months

identify other causes then restart same statin at same dose

high-intensity statins

atorvastatin (lipitor) and rosuvastatin (crestor— reduce with renal impair)

• both are CYPs

• <1L grapefruit juice daily

fibrates names

• lopid (gemfibrozil)

  • CYP!!

• tricor (fenofibrate)

fibrates MOA

• decreases VLDL secretion

• increases lipoprotein lipase (breakdown)

• increase HDL

fibrates ADEs

• dyspepsia, rash

• HYPOkalemia

• myopathy

• hepatic dysfunction

• gallstones

• rhabdo

• AVOID IN RENAL/HEPATIC impairment

• avoid in obesity bc inc risk gallstones

avoid using fibrates with statin because ___ unless ____

because increased risk for myopathy, rhabdo (same ADEs)

UNLESS TG >500!! can add to low or moderate intensity statin

ezetimibe MOA

• prevents absorption of cholesterol from gut into liver

• also inhibits reabsorption of cholesterol and decreases LDL

• cholesterol still being made, just won’t be absorbed

• in combo with statins

ezetimibe ADEs

rare hepatic dysfunction, myositis

ezetimibe monitoring

baseline LFTs

• contraindicated during pregnancy/lactation

• use with STATINS!!

bile acid sequestrants names

• colestid (colestipol)

• questrand (cholestyramine)

• welchol (colesevelam)

bile acid sequestrants MOA

• sequestering bile acid —> can’t absorb into intestinal lumen —> increase cholesterol breakdown

• also breaks down LDL receptors

• NEVER LEAVE THE GUT so no systemic SEs

bile acid sequestrants ADEs

constipation, bloating, heartburn, diarrhea, increased VLDL (only local effects)

bile acid sequestrants monitoring

fasting lipid banel at baseline, 3 months, q6-12 months

bile acid sequestrants considerations

• avoid in diverticulitis, TG >250 so NOT FOR TGs!!

• can impair vit K and folic acid absorption

• NEED to take with food

• other meds 1 hr before or 2 hours after

niaspan (nicotinic acid) other name + MOA

• aka Vitamin B3

• MOA

  • dec VLDL hepatic secretion

  • inc HDL, dec LDL/TG

nicotinic acid monitoring

• start low; titrate up

• fasting BG, A1C, LFTs, uric acid

nicotinic acid ADEs

• severe flushing so premedicate with ASA 325mg 30min prior to dose

• teratogenic!!

• also pruritis, rash, dry skin, N, abd discomfort, hyperBG, arrythmias

d/c nicotinic acid/niaspan/vit B3 IF

• persistent severe cutaneous Sx

• persistent hyperBG

• acute gout

• unexplained GI Sx

• new-onset afib or weight loss

omega-3 ethyl ester name

lovaza aka fish oil!

ONLY for TGS

lovaza MOA

• reduce hepatic synth of TGs

lovaza ADEs + monitoring

• pruritis, rash, dysgeusia, dyspepsia, constipation, LFTs abnormals

• may increase LDLs

• monitor for GI changes, skin changes, bleeding

when would we consider adding lovaza?

when TG >500

• can use with high-intensity statin (atorvastatin (lipitor) and rosuvastatin (crestor)

  • both CYPs

PCSK9 Inhibitors names

• praluent (alirocumab)

• repatha (evolocumab)

• only if they failed statin therapy

PCSK9 inhibitors use + ADEs

• technically the most effective for lowering LDL but they’re INJECTIONS q2-4weeks! and also very

• ADEs

  • rash, itchy, swelling, pain or bruising at injection site, flu, allergic rxns

which one doesn’t touch TGs?

bile acid sequestrants

HTN treatment + goals (she will give us this chart)

DUAL therapy— either ACE or ARB + Ca channel blocker or diuretic**

• prevents side effects of Ca channel blockers

• monotherapy if low risk

• can also use beta blockers as second drug or monotherapy

aim for BP control within ____

3 months

HTN drug classes

• thiazide/thiazide-like diuretics

• Ca channel blockers

• ACEi

• ARBs

do NOT use __ & __ together

ACEi & ARB because they work on the same RAAS system

thiazide names

• hydrochlorothiazide

• chlorTHALIDONE

• indapamide

• metolazone

thiazide MOA

• works in distal convoluted tubule for sodium reabsorption

• if i block sodium reabsorption and Na stays in urine, water stays in urine —> pee it out —> lowers BP

• eventually normalizes CO, decreases SVR

thiazide ADEs

• hypoNa

• hypoK BOTH low

• metab alkalosis

• photosensitivity

• hyperBG

• weakness

• monitor lytes, BP, fluid status

thiazides are less effective for who?

• renal pts

• won’t get to site of action in same amount

• it’s so far down the nephron

what’s one way to increase thiazide efficency?

give with a loop diuretic

RAAS general overview

• angiotensinogen is converted by renin (from kidneys) —> AG1

• AG2 UPs aldosterone —> more salt/water retention —> BP up

how do ACEi work?

stops AG1 —> AG2

how do ARBs work?

block receptor directly

this is also why we can use ONE OR THE OTHER, not both

ACEi names

-prils

ACEi oral formulations

prodrugs so need hepatic activation through hydrolysis NOT CYPs so not a lot of drug interactions

ACEi ADEs

• hyperK

• dry, hacking cough (can happen anytime)

  • can switch to ARB or try a different ACEi

• angioedema —> never use again!

  • switch to ARB

• rash

• dysgeusia

ACEi considerations

• avoid in pregnancy! esp 1st trimester

• hold in AKIs

• but actually helps stabilize CKD (dec proteinuria)

  • protective effect for neprhon bc vasodilates Efferent arteriole —> reduces pressure IN nephron

enalaprilat

IV formulation of enalapril

ARBs names

-sartans

which ARBs are CYPs?

• losartan

• irbesartan

ARB MOA

• blocks AG receptor

ARB ADEs

• fatigue

• diarrhea

• hyperK

• angioedema (not as often)

• NO dry cough

• contraindicated in pregnancy!

(ACEi/ARB) in volume depleted pts,

hypotensive— monitor BP especially with 1st dose

if angioedema,

life threatening!

• stop drug immediately

• do ARBs, CCB, or thiazide instead

monitoring hyperkalemia

• monitor K 1-2 wks after starting drug and with each titration

• know their baseline K

• advise about salt substitutes that have high K

CCB: Dihydropyridine names

• amlodipine (norvasc)

• nisoldipine (sular)

• nifedipine

  • immediate release

• nicardipine

• clevidipine

  • only IV, very short acting

• all -dipine

• all CYPS!!!

CCB: Dihydropyridine MOA

• potent peripheral vasodilation

• won’t affect HR or output

CCB: Dihydropyridine ADEs

• peripheral edema

• flushing

• h/a

• dizzy

which CCB is immediate release?

• nifedipine

• BLACK BOX WARNING**

• avoid using for acute Tx of HTN crisis

  • increased risk of MI, CVA, death

CCB: Nondihydropyridine names

• diltiazem

• verpamil

CCB: Nondihydropyridine MOA

• work on CC in HEART rather than periphery

• reduces HR, conduction rate —> lowers BP

CCB: Nondihydropyridine ADEs

• bradycardia**

• heart block

  • higher risk if used with BBs

• constipation (main effect)**

• peripheral edema

• also will inhibit PGP and CYP**

avoid diltiazem/verapamil in ___

HF 2/2 systolic dysfunction rt negative inotropic effects (weakens the force of muscular contractions)

• the NONdihydropyridine CCBs are really not for HTN, more for HR**

when do we use “alternative meds”?

• mostly for a patient who has another indication to need this med

• OR if difficult to treat HTN

• add on to 3 drug regimen or might be a substitute if indication

loop diuretic names

• alternative med bc don’t have best CV benefit compared to ACEi/ARBs

• lasix

• bumex

• torsemide

  • CYP

loop diuretics MOA

• works in LOOP of Henle

• blocks sodium/water reabsorption

• better than thiazides for CHF/CKD

loop diuretics ADEs

• hypoNa

• hypoK

• hypoMg

• dehydration

• ototoxicity (may not be reversible)

• photosensitivity

• rash

• all are sulfas (except edecrin)

K-sparing diuretics names + MOA

• amiloride

• triamterene

• MOA: epithelial sodium channel blocker

K-sparing diuretics ADEs

• hyPONa

• HYPERK

  • others bring both down; this brings K up

• metab acidosis

• dehydration

• kidney stones

• reduce dose in renal impairment

aldosterone antagonists names

• spirinolactone

  • NOT selective to aldosterone in kidney only, works everywhere (HRT, acne)

  • can also cause gynecomastia

• eplerenone

• -one

• both also K-sparing!!

aliskiren (Tekturna)

renin inhibitor (renin converts angiotenosigen into AG1)

BUT not very effective bc too far upstream

• avoid in pregnancy!

sympathoplegic: central-acting names

• clonidine

• methyldopa

clonidine

• MOA: central alpha-2 agonist —> dec sympathetic

  • inc PARASYMPH —> reduced peripheral vasc resistance, bradycardia —> reduced CO

• ADEs

  • sedation, depression, xerostomia, confusion, N/V

• abrupt withdrawal —> HTN crisis!!!!**

  • after missing only 1-2 doses

alpha-2 agonists

• negative feedback loop

• A2 receptors shut DOWN SNS —> reduce BP

methyldopa

• central-acting; reduces periph vasc resistance

• primarily used during pregnancy

beta blockers MOA

• beta 1 ANTAGonists

• dec HR, myocardial contractility, periph vasc resistance

• reduce renin release

beta blockers ADEs

• bradycardia

• bronchoconstriction (from beta 2 after losing selectivity)

• hypoglycemia unawareness

  • when you have low BG —> SNS activated; Sx being blocked with beta blockers

• sexual dysfunction

• depression

  • caution in depression, asthma pts

• abrupt dc —> rebound tachy**

beta 1 receptors vs beta 2; alpha vs beta

• 1 heart

• beta 2 lungs

• alpha = constrict

• beta = dilate

beta blockers are most effective when

used with a diuretic to combat compensatory mechanisms

alpha blockers names

• doxazosin (cardura)

• terazosin (Hytrin)

• prazosin (minipress)

• -azosin

alpha blockers MOA

• alpha 1 antag = constrict on heart antag —> directly vasodilates

alpha blockers ADE

• orthostatic hypotension**

• dizzy

• fatigue

• h/a

• rare priapism