•  mjr risk factor 4 CAD
•  homocysteine: intermed. product from met metab
•  pyridox. (B6)/cynocobala (B12)/folic acid= cofctrs.
• studies=> serum concentrations>15 mcmol/L= need tx-promote atherosclerosis by FX on the vascular endothelial cells, coag cascade & cytokines.
•  no studies 4 FX of vit suppl 4 vasc. dz outcomes.
• AHA says- screen high risk pnts: elderly, renal DZ, premature vasculature DZ
•  tx if homocysteine >10 micromoles/L (↑)
• ↑  intake of cfctrs √ in 1 mo ( B6 +B12+ folic acid.)
• still ↑, + an MVT and √ 1mo
• C-reactive protein: acute rxn release: response 2 inflam.
•  Causes of ↑: tobacco/obesity/abnrm firbinolytic activity, Subclin atherosclerosis
• RF for MI, stroke, & CV death
•  AHA/ CDC recom: 4 pnts @ risk- ↓ <1MG/L, ↑ >3mg/L.
  
•  acute phase react. (APR) -show infect. of inflam., ↑ as much as 500X or + during sev. infect. on inflam. Has pro-coag. FX as well.
  
•  can indicate long-standing inflam. (CAD or CHD), rather than recent illness.
• pnts w/ CRP has ↑er rates of: MI, angina, Stoke, PAD, sudden cardiac death.
  
• What↓ CRP? Exercise , fish oil (few studies) , possibly vitamin E, dark chocolate
  
• 2DARY CAUSES - Dz: hypothyroid, nephrotic synd, obstruct liver dz, DM. DRUGS: alcohol, progestins, β Block, thiazides, glucocort, cyclosporine.

• SCREENING 4 LIPID DISORDER: 20 or + yrs, q 5 yrs, FLP preferred
• if nonfast- get total/ HDL chl.
  
• Need full panel if: tot chl 200 mg/ dL or+ OR HDL <40mg/dL
  

•  LIPID ASSESS/GOALS: Step 1- dx hyperlipidemia: FLP on 2 sep. dys. WHAT DO WE WANT 4 TC<200=), 200-239=↑er, greater to or equal of 240=↑.
  
• LDL=tx guide. < 100= ;) 100-129 is near optimal/above optimal. 130-159= ↑er. 160-189=↑, ≥ 190 =very↑
•  HDL: <40=↓, ≥60=↑ (=D)
  
• LIPID GOALS-TC- goal < 200, HDL 4 men >40
• women > 50 HDL,
• LDL <100
• optional goal is <70(4 very↑risk pnts)
• TG<150.
  
• Step 2- other frms athersclerotic dz (PAD, ab aortic aneurysm, and symptomatic carotid artery disease) , DM, mult.RF's 4 a 10 yr risk 4 CHD >20%
  
• Step 3: cigs, htn (BP ≥140/90 or on antihtn ), low HDL (<40mg/dL).FH of premat. CHD. (CHD in female 1st deg rel <65 yrs/CHD in male 1st deg rel <55 yrs. Age (men ≥ 45, women ≥ 55)*HDL≥60 mg/dL =(-) RF- its removes 1 RF tot count
• count the mjr RF=4 pnts with mult (2+) rf- perform a 10-yr risk assess
• step 4:4 pts with a 0-1 RF. 10 year-not req. most pnts have a 10 year risk <10%.
•  Step 5- get LDL goal for therapeutic lifestyle Δs (TLC) and drug tx in diff. risk categories. (SEE CHART IN IMPORTANT DIAGRAMS)
•  Other tx issues: metabolic syndrome- step 8, ↑TG (step 9), ↓ HDL (step 9, appendix 2) Non-HDL goals: patient category: <2 risk factors- <190 (nonhdl), 2 risk=10 yr risk  <20%- <160, CHD or eq (10 yr risk >20%) <130. **Non-HDL= TC-HDL. Goals are 30 points above the LDL goals. **note someone with over 400 TG is when prof vivian would act with either 400 or 500.Atherosclerosis and diabetes you don't even have to calculate, the goal is less than 100.

• Statins= drug of choice for chl- study after study  shows
• Non-pharm tx step 6 in app 2. TCL diet: fat, chl, fiber issues. wgt manage- 15-25 # weight loss: ↓LDL 15-25 mg/dL. PhysAct: ↑ HDL, help w/wgt manage. moderation etoh: TG issue. margarine vs butter-stay away from sat fats, there are margarines that ↓LDL. polyunsat., monounsat., sat fats. trans-fatty acids/hydrogenated (tub/liquid margarine preferred) Margarine: ↓serum chl≈ 25 vs butter.Meats:  Best=boil/bake/grill meat vs fry. south states =↑er rates of obesity. use smaller portions- 6 -8 oz qd. lean meat&trim fat. Eggs:limit yolks + sub bake, egg whites↓ fat. Dairy- skim/ low-fat. skim milk cheeses =meat sub. sub low-fat frozen desserts for ice cream. Fats/oil- use ↓ amts of fats, popcorn- one that is↓ fat=best. fruit instead of chocolate, smaller serving of dessert. split it with a friend. ↓ fat mayo/ salad dressing. Processed foods/desserts: sub low-fat snack food (pretzels, air-popped popcorn, fruit) 4 deep fry snacks. dietary fiber-25% daily fiber intake should be soluble fiber. ones with good high in fiber is really good.

• Phys act.notes: aerobics, 30 minutes sustain heart rate elevation, most days qwk, start out slow. *for ↓HDL-aerobic exercise, weight loss, smoking cessation, alcohol use(?) *will be update of the ATP III report.
• COMBOS; statin+ fibrate, BAS< ezetimibe,. niacin+ bas, firbate + BAS.

• LP notation: TC/TG/HDL/ LDL.

•  Freidewald equation: TC=(TG/5)+HDL+LDL ,LDL= TC-{HDL + (TG/5)}
•  Why ↓chl? higher LDL asscociated with ↑risk of : CHD mortality, nonfatal MI, ravascularization (CABG, PTCA), stroke

• define lipoproteins: ↑mol. weight particles which transport np lipids (mostly TG & chl esters) in plasma. 
• structure: core- hydrophoib. lipids (TG, chl esters) surface- phopholipids, unesterified chol, apoproteins. 
• TG and  Free chl- source: dietary/endogenous hepatic synthesis.
• Chylmomicrons: frm exogenous (dietary)TG & chl; formed in intestinal epithelial cells. Absent in blood after 12-14 hour fast. 
• contain: mostly TG, some chol, apo E, metabolized in intestinal epithelium to remnants, free fatty acids, monoglycerides.
• Deliver TG to fat tissue and CHL to liver. Remnants: dervived from chylomicron metabolism. Contain: chl esters, Apo E and B48. Metabolized in liver to cholesterol: bile acids, VLDL. 
• VLDL: composition: TG >>cholesterol esters, apoproteins B100, catabolized to IDL.  IDL: derived from VLDL metabolism in tissue capillaries. 
• Catabolism: hepatic (minor amount), plasma- TG removed, apoproteins removed except B100. LDL: transformed from IDL (contains apo B100) cholesterol-rich(contain 75% total serum chl)
•  role: chl transport to periphery.
•  HDL: synthesized in periphery. Role: transport of chol from periphery to liver for elimination in bile. Apolipoprotein B (apo B)- non HDL Cholesterol= (TC-HDL), drugs and lifestyle changes often move cholesterol from one atherogenic particle to another without reducing coronary risk. until more widely available, a practical way to estimate apoB levels is to calculate non-HDL or N-HDL. Valid in non-fasting sameple. ATP III guidelines recommend non-HDL as a goal of therapy for patients with elevated triglycerides (>250mg/dL) * Lipoprotein-associated phospholipase a2 (LP-PLA2) - enzyme secreted by macrophages mediating plaque inflammatory processes. Elevated LP- PLA2 levels are higherly predictive of myocardial infartion and stroke, esp when combined with high-sensitivity C-reactive protein (HS-CROP) treatement of elevated Lp-PLA2 levels (>200ng/ml)- adjust LDL goals downawrd by 30 points. In patients with very high risk (LDL goal remains <70mg/dL), consider addition of agnets to modify other elements of the lipid profile, such as TG or HDL cholesterol.

MOA

• ↓LDL14-17%↑HDL22-26%, ↓TG28-35%; inhibits hepatic vldl syn. ↓LDL,
• inhib lipolysis in adipose tissue,
• ↑lipoprot. lipase activity, ↓esterify of TG in liver. 
• MOA=not understood. Covert vldl and ldl. NOT nicotinamide, nicotinic acid, niacor, nicolar, nicobid, niaspan, niaspan/lovastatin (advicor), niaspan/simvastatin.

ADR

flushing (women's hot flash), HA, urticaria, pruritus, anorexia, hyperuricemia/gout, skin discoloration. Hyperglycemia (relative) Serious/dangerous- hepatotox (esp with BID SR), gastritis, GI bleeding, myopathy, macular edema

CI

absolute: liver dz, active PUD. Relative: DM, active gout, hyperuricemia, PUD, statin. Statin: myopathy, rhabdomyolysis- sm broke down. Releases muscles+electrolytes frm inside muscle cells. Risk of rhabdo include muscle breakdown,hepatotoxicty.

Therapeutic Considerations

poor tolerability (acceptable for niacin) Lab tests: toxicity- lft(stop drug if 3X ULN) = baseline, 6-8wk, 12wks  Glucose- base, 6-8 wks, periodically.   check uric acid (-/+). Efficacy FLP- base, 4-8 wks after stable dose is reached. q 6 mo. *COUNSELING: titrate slowly, if flushing, return to prev.dose for additional week, take cf. Avoid hot beverages/soups. use of ASA or diphenhydramine if severe flushing. only qhs,Diet+exercise.

CONS

poor tolerability

MOA

↓LDL 17-62%, slight ↑HDL 5-10% (17% rosuvastatin) ↓tg 7-30%. The max is rosuvastatin 21-43%↓, good= atorvastatin 25% ↓, fair- simvastatin/pravastatin (10 to 15%↓), min- fluvastatin, lovastatin.

Classify

HMG-COa reductase. ↑LDL receptors, ↑LDL cl. ↓chl syn.

ADR

rare/well tolerated. CNS: HA, insomnia Gi: Epigas. discomf, flatulence, diarrhea, constipat. Serious: hepatitis, myopahty, rhabdomyolysis

CI

absolute: liver dz, preg/lactation. Relative: renal dz, hx liver dz, niacin, gemfibrozil, cyclosporine, erythromycin. Drug interactions: warfarin (dec INR), bile acid resins (adsorption), cyclosporine: rhabdomyolysis. Erythromycin: rhabdomyolysis. Gemfibrozil: rhabdomyolysis. niacin: myopathy or rhabdomyolysis.  CYP 3A4 inhibitors: itraconzole, ketoconazole, erthyromycin, clarithromycin, protease inhibitors (ritonavir), amiodarone, verapamil. diltiazem.  -WILL BE GIVEN DRUG INTERACTION CASE!!!!- hold the statin during the duration of therapy with the statin. if they are going to be on it long term?- look at the statin that are metabolized other than P450. grapefruit juice interactions (3A4) exception are pravastatin and rosuvastatin. (not a lot of grapefruit juice in nursing homes- not grapefruit because of interactions)

Therapeutic Considerations

good tolerability * lab monitoring: efficacy- FLP baseline at 6-12 weeks, after dose adjustments, every 6-12 months, once goal is reached. CK- if muscle pain or weakness or concurrent high risk drugs. FDA statin safety label. approved crucial changes to the safety label for statins.  based upon the FDA's further review of the data are are as follows: removing the recommendation for the periodic monitoring of liver enzymes. the FDA  recommends that liver enzymes should be preformed b4 starting statin. and as clinically therafter. Creatinine kinase if muscle pain/weakness or concurrent high risk drugs.  rare reports of serious liver problems. pnts should notify their healthcare professional right away if they have:unusual fatigue or weakeness. loss of appetitte, upper belly pain, dark-colored urine, or yellowing of the skin or the whites of the eyes.  (get liver function tests to see if has any affect on the liver) fatgue:might be indicative of muscle breakdown. other one is indicative of liver. creatine kinase of muscle pain or weakness. found in combinations . PEARLS* timing of the daily dose(some of the stronger ones can be made during the day but some others you should just take it at night, if they keep forgetting, they should just take it at night) , muscle pain and weakness, diet and exercise* ↓ morbidity and mortality of LDL and CV.****START WITH STATIN UNLESS THEY HAVE ELEVATED TRIGLYCERIDE**** Fluva<LOVA<pravaa/sima<atorva<rosuva. 

PROS

good tolerability

MOA

Ezetimibe: ↓LDL 18%, further ↓25% w/statin, minimal ↑HDL (1%), ↑3% with statin. ↓TG (8%) further ↓by 14% w/ statin. ↓intestinal cholesterol absorption by intestinal cells, glucruonidated, distributes into systemic circulation. Enterohepatic recirculation coordinated with meals.

 ADR

acute liver disease-LFT elevations. Diarrhea, potentially worsened diarrhea or↓ezetimibe efficacy.

CI

statins: 1.3 LFT↑w/combo therapy (vs 0.4% LFT↑ monotherapy) Cholestyramine:↓ezetimibe AUC by 55%. Fibrates:  cholelithiasis. Cyclosporine: case report of 12-fold↑ in serum ezetimibe.

Therapeutic Considerations

not monotherapy. good tolerability. further LDL ↓ with 25% w/statin- moderate FX alone.similar to placebo.Labs: as for statin in the combo.  **No dose adjustment for: mild hepatic, renal insuffieiency, Geriatic patients. PEARLS; w/or w/o food, combo for efficacy. Diet/exercise.

MOA

LDL 20%, modest ↑HDL 11%, ↓Tg 20-30%. ↓hepatic VLDL production, ↑lipoprotein lipase activity. ↑biliary chl excretion.

ADR

GI: epigastric discom (rare)  dyspepsia, ab PA, diarrhea. CNS; dizziness. Serious- cholelithiasis, myopathy, hepatitis, neutropenia.

CI

Relative: hepatic dz, sev.renal DZ, gallstones, concrrent statin therapy:myopathy, rhabdomyolysis, warfain: ↑INR.

Therapeutic Considerations

good tolerability. Lab- CBC base,6mo, 1yr, LFT: base, 3-6 months, 1 yr. Efficacy: FLP base @4,6,8,or 12wks, then every 6-12 months.

PROS

good tolerability

MOA

bind biles salts in GI- when the chylomicrons(in GI) move to the liver- ↑LD receptors. ↓LDL 9-28%, slight ↑HDL 4-8%, no Δ or slight↑TG 11-28%.

 ADR

constipation, bloating, nausea, epigastric fullness, flatulence

CI

major(adsorption) : thyroid, warfarin, statins, acet, fat sol vitamins, NSAIDs, digoxin, thiazides, beta blockers, corticosteroids, amiodarone, acetaminophen.  (sep.time you take these by a min of 2 HOURS) don’t take= preg, lactating, or constipated.

Therapeutic Considerations

Fair/poor tolerability. don’t use if TG >500, caution <200. monitor FLP&efficacy. √baseline &4-6 wks. Mix powders w/noncarb fluid/foods, mix in advances, titrate wkly, prevent constipation (water, stool softner, dietary fiber), space meds 1 to 2 hours before meds or 3-4 hours after meds.diet /exercise.max effect at 12 weeks.

MOA

FX on FLP: estrogen alone ↓LDL, ↑HDL and TG.

ADR

=(due to ↑risk of CHD, breast cancer, stroke, DVT.

Therapeutic Considerations

no longer recommemened 

MOA

flaxseed, canola oil, sardines. Fatty fish, salmon, mackerel,herring, sardine, trout, pilchard, kipper, seeds, nuts, flaxseed oil, canola oil, soybean oil, nuts. ↓TG, ↓HDL, min on LDL

  ADR

 bleeding, vita E deficiency, borborygmus, antinflamm FX.

Therapeutic Considerations

talk to them- switch of their oil= can influence vit. E absorb. While it ↓TG, might ↑LDL 44.5%, ↓0.7 when + statin. HDL↑ to 9.1, tg↓ 44.9

MOA

vit E and Vit C.may protect Ox chl damage in arteries

  Therapeutic Considerations

maybe associated ↑risk for HF, not recommended. Benefit theoretical: no studies. Dietary vs supplmental

Brand Name

Niaspan, niacor, nicolar, nicobid, niaspan/lovastatin,niaspan/simvastatin.

MOA

inhib. hepatic vldl syn. ↓LDL, inhib. lipolysis in adipose, ↑lipoproteins lipase, ↓esterification of TG in liver. MOA not fully understood. Inihib FA release frm adipose, ↓hepatic syn. of TG and secretion of VLDL, inihib conversion of VLDL to LDL.

Adverse effects

flushing(com), some women:hot flash (relieve= taking aspirin or food) can impair glucose tolerance for those with DM, for doses >1500 mg/day. PUD- protoglandin mediated  vasodialation. Gout- ↑uric acid levels w/ goat. Liver enzyme elevations (uncom)  IR=+++flush;+ hepatotox. SR + risk of flush, +++ hepatotox. Niaspan- ++flush, +hepatotox

Therapeutic Considerations

Conflicting results Coronary Drug Project vs AIM HIGH.studies suggest= niacin+statin-NOT improve than statin alone.Researchers hoped that adding niacin would lower CV risk by increasing HDL,but no.big question=niacin+ statin is beneficial if LDL NOT @ goal. Encourage ↑HDL w/ lifestyle:exercise etc. recommend a statin to↓LDL and CV risk. niacin 4 pnts who can't take a statin...or no LDL goal on a statin alone.  even though niacin or other add-ons (Zetia, etc) can improve lipid#'s...they not proven to↓CV risk* use IRNiaspan. Avoid the SR!!

Brand Name

Questran

Classification

Bile Acid resin

Brand Name

Colestid

Classification

Bile Acid resin

Brand Name

Welchol

Classification

Bile Acid resin

Brand Name

antara, lofibra, tricor, and triglide, trilipix

Therapeutic Considerations

ANTARA:w/ meals to optimize F. 1º hyperchl or mixed hyperlidpid- start @ 130. ↓dose start for hypertg and impaired renal func./elderly. TRILIPIX- can be w/o regard to meals. Range for hyperlipidemia, higher 4 primary hyperlipidemia or mixed dyslipidemia. for impaired renal func. start↓. ↑for co-admin therapy w/ statins 4dyslipid- may be taken @ same time as statin.  TRICOR- w/o regard to meals. ↑end for 1º hyperchl or mixed hyperlipid.↓for impaired renal and hypertriglyc. Fenofibrate- w/ meals to optimize F.↑range for hypertriglycerid.

MOA

↓lipid benefits @ 3 mo. ↓TC 6%, ↓LDL, tg, no ΔHDL. Unknown if benefit past 3 mo. No data on CV. Marginal dislipidemia- get a slight further↓. This would be a lifestyle change. All depends on the garlic clove=diff.conc. We don't actually know. . 

Classification

lignins, cellulose. Foods; bran cereal, whole grain bread, blackberries, parsnips, kidney beans, lentils, white beans, popcorn.

MOA

moves bulk through intestines. Controls/balances  PH (Acidity) in intestines.

Indication Dosing/Treatment

Benefits: promotes regular bowel mvmnt and prevent constipa. remove toxic waste through colon in ↓time.  optimal PH in intestines to prevent microbes from producing CA substances. Therefore prevent colon CA. 

FIX

 Classification

oats, psyllium, pectin, guar gum. Food- oranges, pinto beans, brown rice, apples.

MOA

↓TC+LDL. Binds w/FA. Prolong stomach empty:sugar is released/absorbed more slowly.

Indication Dosing/Treatment

insol.vs sol. 3 servings vs oatmeal=sig-↓dose statin.Ex. of insol- popcorn, bran cereal. Soluable- organes, brown rice Benefits of sol: ↓tot and LDL ↓ the risk of heart dz. reg. the BS for ppl w/ DM

Adverse effects

GI distress.

Therapeutic Considerations

RDA-20-35gm/day

Brand Name

 benecol, take control,cholox

 MOA

↓CHL absorb frm gut.↓LDL chl:10-15% w/o SE. neutaceutical- food as drug

Indication Dosing/Treatment

↓colon CA? This is very interesting.

Classification

red yeast from fermented rice. Or extract frm honeybee wax (policosanol)

MOA

inhib. HMG CO-a, ↓cL 25-40

Therapeutic Considerations

considered statin- toxic w/ more statin. Note- lova derived-yeast species.

Brand Name

advicor

Therapeutic Considerations

1g/day ↓mortality/CV. fishy tastes, GI upset. ↓TG +lipo-A. if concerned of rhabdomyolysis(statin+niacin or fibrate) you can try FO. Concerns of mercury w/ ↑fish: avoid swordfish. 2 avg meals of fish ↓in merc. (catfish etc)look @ the mercury levels.

 Some ↓TG. b4 meals(↓GI/fishy taste). DART- ↑fiber -get 29% ↓in CHD mortality w/ fish advice. FX- 30% ↓TG↓,↓LP by 14%

Brand Name

Caduet

Classification

red yeast frm fermented rice. There is some lovastatin

Classification

lovastatin+niacin

 Classification

atrovastatin+ amoldipine

Brand Name

Lopid

Therapeutic Considerations

30 min b4 meals, report unusual muscle PA/weakenss  diet + exercise

Brand Name

atromid-S

Brand Name

vascepa

  MOA

 only EPS (eicopentaenoic acid): NOT EPA+DHA (like lovaza/ most supple). ↓TG ≈ 27% in pnts w/very ↑ tg. Lovaza ↓tgs 45% BUT can ↑LDL 45%.

Contraindications

preg/children: merc.

Therapeutic Considerations

Concerns w/FO= ↑merc., polychlor. biphenyls, dioxins & other environ. contanmin. found in ↑pred fish. may be preg, preg women, nursing mothers and children=avoid some fish and eat ↓merc.no fish w/ ↑merc lvls.up to 12 oz of fish that are ↓in merc. OTC- manufac process of most fish may avoid  merc, lack of manufac regulation.  Save FO/fibrates/niacin til TG ≥500 mg/dl. no proof using these drugs ↓Tg improves CV outcomes. FO used- suggest Lovaza or vascepa.

Assessment

CLINICAL ASSSES OF XS BODY Na & ECF VOL.- ↑d BW(changes in TBW 1 liter about 1 kg), PE(not sensitive but can detect sig diff)- in adults-may be hard to detect Δs in ECF of >3L by PE, increased IFV-pitting edema (some swell on limb and press on w/ thumb=a dent in interstitial space,in areas w/the ↓places of gravity, ankles happen w/ ambul= pitting edema) , pulmon conges (dyspnea, orthopnea, crackles) ascites (accum in fld in ab cavity, lots of ppl with liver dz): lungs can develop 

Therapeutic Considerations

WATER vs SOLUTE= cell mem & capillaries freely perm 2 wtr- unrestrict flow=osmol in most body flds, cell mem have resctricted perm to most solute, capillaries-restricted perm to ↑mol-distrib of wtr=determined by the distrib of solute in various areas & vol of compart determined by the amnt of solute in the compart-can control vol in compart by +/- solute 

What is going on in the body

free wtr balance regs osmol

Distribution

intracell=2/3, extracell= 1/3, ISF(most variable) of ECF=3/4, circulate plasma=25 of ecf, L of wtr(in body would seek out where is wtr)- distrib same ratio as started(2/3 intra, 1/3 ECF)vs L wtr isoton(wtr stay in ECF since solute stays in ECF- give saline if have ↓BP, need 3X free wtr as will saline

Regulation

STIMULI FOR RELEASE- ↑ in osmol. (solute XS or free wtr deficit. ↓in cirulating vol or in BP  (hemodynamic Δ's associated with the hrt fail or liver fail=trigger mech. Other non-osmotic stimuli (ie pain, na, angiotensin II, acute psychosis, drugs) 

Presentation of Symptoms

body wtr not matched w/ body electrolyte solute= abnorm osmolaity of body flds. Free wtr imblances are distrb thru both ICF (2/3) & ECF (1/3), assessed as serum na conc (outside the norm range- 135-144 mMol/L (recog if free wtr imablance based on the value) 

Assessment

Ex- 73 yo male, complains SOB, orthopna, 2+ and 4+ putting edema on legs, recent wgt gain of 5 kg, JVD 3 cm above clavicle, + HJR, s-3 hrt sounds present, serum na 140 mMol/L

Treatments

5 kg wgt+ in ECF 5L XS ≈ 5mMol extra na- need more na excreted than intake- 0.5-1kg to drain edema- this means that has to excrete 70-140mMol/day na more than intake (therefore ↓his intake) - ↓ dietary na, diuretic therapy- titrating 4 wgt loss, monitor 4 signs of over diuresis (eg orthstasis,↑BUN) 

Regulation

HOMEOSTASIS: Norm adult body k= 50-55mMol/kg; >95% intracell (opp of na)* avg daily turnover 50-150 mMol (similar to na), excre 90% renal 10% GI (inverse w/amnt of na) *aldosterone ↑ its secretion; *aldosterone secretion is modulated by K lvl. **ICF/ECF distrib= na/k atpase in the cell mem*insulin ↑intracell K(w/ some1 w/ DM- k leaks out. Give insulin and uptake in K) , beta 2 adrenergic recep stimulus ↑ intracell  K (ex saba use) * exΔ w/ h+(varaiable FX of pH on K)*Serum K+ norm: 3.5-4.8mMol/L

Cause

poor diet (not sole cause unless prolonged ↓- almost everything has K unless weird diet). Intracell shift (transient but symp determined by the ratio of the extracell and the intracell lvls, (you not Δing your whole body k and you drive the k into cells- still some FX)= insulin, b2 agonist use, endog. sympathetic tone (ep, alkalemia, xanthines) Gi/sweat loss, laxative/ enema abuse(2 main places lose the most amnt of k= gut&urine, diarrhea=common way 4 hypokal, esp in kid). Unrinary loss(mineralcort XS ie aldosterone steroid RX),(think about prednisone burst, if used prolonged  could get k Δ)↑ in Na secretion- ↑ na intake, diuretic Rx, osmostic diuresis, salt wasting nephropathies, magnesium deficiency, metabolic alkalosis, ↑ dose RX w/ penicillin class, amphotericin B RX. *K & DIURETIC THERAPY:K losses-related to the amnt of Na excreted- ↑ during Rx of edema or when na intake is ↑(1st starting a diuretic or Δing dose- monitor carefully). not com during chronic maintenance diuretic RX for htn. K sparing diuretitcs are effective to avoid hyperkal, but risk of hyperkalemia (?) if k intake↑ or ↓ renal function.(the diuretics work well, worry about hyperkal- monitor closely.)  

Presentation of Symptoms

*MANIFEST OF HYPOKAL: muscle weak/paralysis (assos with serum k<2.5 mMol/L, gut- constip or ileus, skeletal muscle(effect on the Smooth M, ie gut)-↓extremities most senstive, cramps, tetany, paresthesia, weak, tender, ischemia, rhabdomyolysis, myoglobinuria)(NOTE - k is released=vasodilator to get blood flow to active muscle, when don't have enough K, the muscle can become ischemic & starved for blood flow)=> rhabdomyolysis/lysing of blood cells) =>cardiac FX (u waves- xtra hump in k wave=heart issues, digitalis toxicity, arrthymias in unhealthy hearts, renal FX (impaired concentrating- only seen at ↓ lvls, metabolic alkalosis)- fix k would solve all- Glucose intolerance- ↓insulin secretion. 

Treatments

MANAGE OF HYPOKAL: for 3.0-3.5 range= asymptomatic (mayB muscle weak)po supplment if on digitalis, otherwise dietary K adequate (foods) . 2.5-3.0: tx with p.o suppl (40-60 mMol 3-4 times qd til serum k>3.0 (don't need>norm range, just >3) 2.0-2.5= some clinical manifestat likely, RX prompt w/ po suppl, iv suppl if po route questionable or recieving IV flds.K-<2.0= severe hypokal w/ probable tot body deficit 400-9900 mMol k; i.v- start immediat. (this is the lvl where  can have prblms with resp muscles&breathing)PO K SUPPLE: choice of salt:KCl preferred 4 most cases,Cl- deficit commonly accompanies k deficit (eg gastric losses, diuretics),K phos in pnts with phos deficits,non-CL salts- bicarb, citrate, acetate, lactate, or gluconate salts useful when bicarb deficit- this is good 4 diarhhea & kidney loss with the bicarb (EG, ↓GI losses or renal tubular acidosis)choice of dosage frmsol effective(taste like shit), inexpensive, unpalatable wax matrix tabs (8, 10 mMol), microencap caps (8.10 mMol),SR microcrystalloids(10, 20 mMol) - if som1 has troubles where lodged in the esophagus- can cause issues 2 tissues even though SR. as long as ok transport =safe to use & effective.DIET SOURCES- grms of food needed to obtain 10-12 mMol's K: lean meat or chicken=120g, Fruits (banana 150g, OJ 250 g, oranges 200 g, grapes 200 g, pears 400 g, apples 450 g) veggie (cauliflower 150 g, shrooms 100g, potatoes 100g, broccoli 150 g, carrots 250 g, lettuce 200g, spinach 100g, tomatoes 200 g)  legumes (canned beans 230 g, peas 260 g, dry Chickpeas 60 g) salt substitute (1g) - some of these salts are k salts. sometimes  txd as supple. 96 bananas to treat hypokal *IV POTASSIUM TX- in pnts recieveing IV fld via peripheral vein( small veins w/ little blood flow, k can be quite limited to the veins) may include up to 40mMol K/L(really the limit) . ↑ conc tolerated via central vein- use pump for safe(can use↑amnts of fld here)often admin as a piggyback I.V in 10 mMol increments, infused over1hr.For urgent situations: 10-20 mMol/hr infusion rate via central vein(limit here is cardiotox- needs to be monitored by EKG), use dextrose free iv fld, monitor ECG for ≥ 20 mMol/hour, 40 mMol/hour in Xtreme emergenC 

Toxicity 

CAUTIONS FOR K RX- K lvls may rise ↑ than expective if compromised ability to excrete k or shift K into ICF norm (ksparing diuretic - spironolactone, amioride, triamterene)- don't want k supple w/ k sparing diuretic for long tm tx.  RX trimethoprim RX, heparin RX. Beta 2 block rx, ↓renal func(GFR<30), ACEI or AII antag RX

Regulation

REG OF na+ balance= diet intake, kidney filtration reabsorp, and excre. (fitration rate, gfr, depends on renal blood flow and renal func. Absorp is norm adjusted by aldosterone (↑reabs) & by atriopeptin (↓ reabs), excretion is the net filtration and reabsorp. *excretion- inake in order to maintain balance of tot body na and ECF fld vol

Assessment

Monitor Na and wtr balance: body na balance status determined from clin assess of ECF vol (each L of ECF reps 140 mMol of Na, serum na conc and osmolality=indicators of wtr balance relative 2 Na, serum na=NOT indicator for Na balance- if interested in na balance, look vol and vice versa for wtr. 

TX

PT=ace or AII inhib GET NOTES

Therapeutic Considertions

na stays in ecf-wtr accompanies na+, if w/ na+ will stay, if separate you retain water w/osmolality. Ie ECF vol Δing. The tx target for ECF vol is Na+ balance* XS na & ECF VOL= ↑intravasc vol, venous vol/venous return, ↓CVP (CVP normally <5mmhg)  jugular venous distension (JVD) , hepato-jugular reflux (HJR), left ventric filling pressure (S-3 heart snd=↑pressure in hrt chambers) 

What is going on in the body

Na balance reg ECF vol

Resorption

%reabsorped: pt=70%,LH=20%,distal tubul= 5%,CT= 4%-hay drugs can work @ each 1

Distribution

Na+= plasma(142 mMol/L) vs intracell=12 mMol/l. K= 4.4 plas, 140 intracell, cl=104 plasma, 4 intracel- regulate solute content by channels/pumps

Cause

untx hbp=↑ hrt dz. BP= COX PR. CO frm preload, fld vol, renal na renten,↑contract, ↑HR. PR due to SNS, RAS. *causes= OSA, drug-induced or related, CKD, 1° aldosteronism, renovas dz, chron steroid tx, cushings synd- fld renten, pheochromocytoma- tumor in adrenal glnds- this ΔNE and E, coarctation of aorta, thyroid/ parathyroid dz. ↑ w/ age, AAs, ↓educated, ↓SES, men (yng adult-mid, women (mid- eld), the SE USA (stroke belt)

Presentation of symptoms

Varies throughout day- circadian, ↓@ night, ↑@morn &pm. The temp, meals, time, act, posture, emotions, stress (ex white coat htn) 

Assessment of Disorder

JNC- outdated. 120/80"norm", prehtn (120-139/80-89), HTN: stge 1=sys 140-159 OR dias 90-99, stg 2 = >160 OR  >100 (when the SBP and DBP fall into diff cat, use the ↑cat) . Take bp for office- 2 read 5 min 1 arm and confirm in another arm(sit). Serial in office-one q 5 for 30min in office to detect "white coat"htn. ambul BP monitor-indicated for eval of "white coat" HTN. Absenece of 10-20%↓Bp during sleep:mayB ↑CVD risk.  (no Δin sleep) self measure- promote!more adherent,can eval HTN provides info on response and adhere to tx. May help to ↑adhere to tx & eval "white coat" HTN** benefit of home measure- office measure sometimes poor w/ norm BP, might misclassify pt as htn, may fail dx with variation in BP. Supple w/ self measure w/ validated devices @ home. Home read predict CV events, identify white coat HTN. Home read ↑# of BP taken to rep true avg.  * ambul BP monitor can provide: read thrughout dy during daily act. read during sleep to assess nocturnal Δs, SBP and DBP load, correlation w/TOD. ABPM read usually ↓ than clinic. indications:office/white coat htn,borderline or episoid HTN, drug resist, drus SE or duration of FX, nocturn HTN.  Follow-up: 1st bp: norm-2 yrs, prehtn- 1 yr, stge1 htn- 2 mo, stge2- eval source of care w/in 1mo >180/110 mmhg eval/tx immed!. med hx (duration/class, pnt history of CVD, fam hx, symp suggest causes of htn, lifestyle factors, current and previous meds) PE (bp readings- two or more, verify in contralateral arm, ht/wgt/waist circumference, eye exam, exam in neck/hrt/lungs/abs/extremeties, neuro assess)labs- to deteremineTOD/otherRF,specific causes(recommemd: urinalysis, CBC, blood chem-k,na,ca,creatinine, hemocrit and fast glucose, FLP(TC/HDL, 12-lead ECG), opt*(microalbuminiuria, 24hr urinary protein, serum ca,uric acid, fasting TG, LDL, glycosylated hemoglob, TSH, plasa rening activity/ urinar determine 1 or 2 htn, 1 about 90%, assess presence/absence of na, limited echocardiography, ulstrasonography, measurement of ankle/arm)  target-organ disease (TOD)- cardiac(CAD, LVH, CHF)  cerebrovascular (TIA, stoke) peripheral (claudication, aneurysm) renal (serum Cr>1.5 mg/dl, proteinuria 1+ or greater) retinal (exudates, papilledema) , assess for presence/absence of CV factors. FEATURES/ KEY MESSAGE OF JNC-7- age >50, SBP more important as CVD RF(if SBP ↑= worse)start @115/75mmhg- CVD risk 2X w/ each incre of 20/10mmhg thrughout BP range. persons who are normotensive @ 55 have a 90% lifetime risk for develope HTN, most pnts require 2+  antihtn drugs 4 goal. Normal BP have↑risk compared to BP.*special considerations 4 tx: demopgraphics, coexist diz and tx, QOL, phys and biochem measure, drug interactions, economic 

Treatments

* benefit of home manage- office measure correlates poor w/ BP. May misclassify pt as htn,. Norm- lifestyle mode, prehtn- lifestyle mod instruct, no med unless compelling indication (HF), stg1- tx, lifestyle med, stg2- lifestyle, 2 drugs. * lifestyle mod: weight reduc is HUGE≈20mmhhg, DASH ≈ 14, diet na, pe, down alcoholism, flavonol- rich choc. that shows that reduces bp by 2-3 mmhg/day. *goals JNC7= <140/90, w/ CKD(scr>1.5 mg/dl or presence of albuminuria >300 mg/day or 200 mg/g creatinine) = <130/80. American DM association guidelines-<140/80 mmhg, the <30mmhg may be target in yngr patients if easy achieved overall benefit of tx - can still see ↓ in population%- a lot ↓changes in mortality, stroke, and CV morbid. Drug tx: 2 schools= 1 drug + slow titrate. Not controlled and need to do it in all pnts. 2= other drug, 2 drugs can go faster & sustain. two↓doses- ↓SE(look @ accelerate study) . *Followup-1-2 mo after initiate tx is ideal, certain meds may require ealier montor, recognize that ↑-risk patients often require ↑dose combo and shorter intervals btwn changes in meds, consider reasons for lack of response if BP is uncontrolled after full dose* Stg 1: thiazide type diuretics, Stg 2= two-drug combo. (usually thiazide diuretic, βB, ACE-I, ARB, CCB) * ace inhib or arb= hrt fail*compelling indications=trump: most things to consider when choosing med**DM: (1- ACE-I or ARB, 2-Ca channel blocker, 3 Diuretic, 4 β blocker) **HRT FAIL (1-ACEI or ARB, 2- βBlocker, 3- aldosterone blocker, diuretics (loop) used for symps) ANGINA-β blockers, ca2+ antagonist. ATRIAL TACHYCARDIA AND FILBRILLATION (β blockers, non dihydroppyridine ca2+ antagonists, ACE I and ARBS)**CYCLOSPORINE-INDUCED HTN- ca2+ antagonists, thiazide diuretics **DYSLIPIDEMA- α blockers *PROSTATISM (BPH)- α blockers, ESSENTIAL TREMOR- non cardioselective beta blockers, HYPERTHYROIDISM: β blockers, MIGRAINE- non cardioselevtive beta blockers, non-dihydropyridine ca2+ antagonists.*OSTEROPOROSIS- thiazides**PRE-OP HTN- β blockers. *GOAL of HTN prevent & manage: to ↓morbidity&mortality (by least intrusive way), achieve/maintain bp to recommend goals, control other CRF, QOL ($, least intrusive) * pharm tx- protects against stroke, coronary events, hrt failure, progression of renal dz, progression to more severe htn, and all cause mortality. (↓Δs= ↑FX) **TX PRINCIPLES- require 2 or 3 drugs 4 goal. Get familiar w/ couple drugs frm each class & use them , initiate tx w/ diuretic unless CI or co-exist dz, no response/ intol SE, sub another agent.partial response w/mod-high dose and still not @ goal=+ 2nd agent. **SUMMARY- diuretic for uncomplicated HTN= consider other drug tx if compelling indications for tx exist, consider other drug txs based on comorbid cond. 

Therapeutic Considerations

Framingham study- longitudinal study, follow ppl over 60 yrs then look @offspring & CV risk. Bp is continuum- ↑BP, ↑cardiac risk. *NHANES study: % of adults that have treated htn. and % that is controlled.

Prevalence

 txd people for bp and 1/2 @ goal. continuing to get them better but a lot of work still. *about 65 mill americans= ↑w/ age, AA, ↓educated, ↓SES, men (yng adult-mid age, women (mid age- eld), SE USA "stroke belt"*40% of the world pop.

Other

There are diff guide for HTN in UK (ref) *CAUSES FOR INADEQUATE RESPONSE TO TX- improper techn, ↑dose corticoster(stim)amphetamines, PSE, lots of things. doses of drugs for htn adequate?; smoking, OSA, insulin resist, chronic PA, ethanol; 2dary causes. BARRIERS TO HTN CNTRL: whether physcian attitude, followed with stg 2- clinicians would only ↑the meds for systolic and only Δ for diastolic. There was some lingering attitude. 

Cause

SEE TRIALS

Assessment of Disorder

JNC-8 "CRITCAL ?"= how do you get there?  Very specific. Ex diuretics for people that are volume expanded. There is specific evidence. 

Therapeutic Considerations

*evaluating HTN studies:looking @ clinical trials-look @pop.studied (↑risk, Dm,etc) so can apply 2 in real life. Outcome measures- surrogate measure? left ventric hypertroph vs looking @ mortality,etc. if CV or mortality are endpoints- did they acieve similar BP reduction in comparison groups?for true comparison- look at the BP that actually Δ. this can explain the mortality. if don't do that do it in statistical endpnt. Are diff clinically sig? How do diff in components influence edpnt?dont get frequently enough of the componenet- it was all determined by differences in stroke- such a ↑diff that it affected. Short term or long term? ADRs? - ya u get bp goal but what about the SE. what BP assess did they use? office? home?the gold standard is 24hr tx. 

Presentation of symptoms

CNS, EYES (retinal hem, HRT, KIDNEYS (blood/protein in urine, inflam in kidneys) - the 4 main areas looking at. 

Assessment of Disorder

*urgency (hrt dz, post/pre op htn, and severe kidney transplant) vs emergenC (aorta disecting and the heart is going to split?) (drug induced- cocaine) , this one is life threating

Treatments

emergenc- right away IV, urgency over several dys. GOALS OF TX- not > 25% drop in Bp w/in minute-2 hrs- then to 160/100- don’t want to limit perfusion to vital organs since  baroreceptors will kick in and we don't want a compensatory rxn=organ damage. 5-10 every 5-10min. be careful 4 ppl @ risk for hypotensive responses (elderly). those with chronic BP- might have hard time to respond. Urgency- treat pnt and not #'s ORAL AGENTS- nifedipine: AVOID USING!!- stoke Mi and death happen- ↓ BP well but it ↓ perfusion too much causing CV events.  *ORAL CLONIDINE- MAP, CO, SV HR. 25% bp in the1st hr- safe&effective *CAPTOPRIL-works quickly - good for CKD. can induce acute renal fail. great for ppl with kidney dz but it causes acute renal fail(↓perfusion to kidney) *LABETOLOL- blocks βrecep in hrt, SE orthostatic htn. bradycardia. *PRAZOSIN- causes sev hypotension- not used much. *PARENTERAL AGENTS- nitroprusside- protect from lght(compound) - direct act arterial. kinda like NO meds but better, doesnt affect CO. cause some reflex sympathetic act- agent of choice for min 2 min. this is good for cont. infusion. has a t1/2 of 2 min= rapid reversal. the prob w/this- cyanide accum. this is a prob with pnts with renal dysfunc- particular aware in these pnts. fast on & off. very fine tuning and causes ↓sedation. some ↓of appetite. * nitroglyc- ↓afterload- useful in pnts with MI, and chest pain- improves oxygenation, people w/ chest pain. the one thing is not for is HTN encephalopathy (↑intracranial pressure- KNOW THIS), works fast and can be titrated. use>dy or 2- tachyphylaxis. hydrazaline- ↑intracranial pressure- not this. also ↑pressure wave so avoid in aortic dissection.↑oxygen demand.use eclampsia or preeclampsia. or renal insufficiency. *labetalol- MI oxy demand- the oxy outake. can cause orthostatic hypoten- usual concerns. Esmolol- variety of issues= arrhythmias.can titrate very quickly=if U have target issues in kidneys. if using nitroprusside- good choices- sweating dizziness and na, used in aortic disections. *fenoldopam*Clevidipine. 

Prevalence

2-5% in htn pnts, if <30=suspect 2ndary cause.

Other

 consider the entire pnt/comorbities. 

What is going on in the Body

NO organ damage in hypertensive urgency!!!!!!! 

Triggers

pheochromocytoma, poor controlled htn, renal vasc dz. Noncomplie with drug tx. Important-take your medications- the bp will start to swing ↑ and ↓: one of them is βblock- doesn't always happen but it can happen.

 Treatments 

Ace-I or ARB, Ca2+ blocker, diuretic, βblock (this order) 

 Treatments 

ACE-I or ARB, βBlocker, aldosterone blocker, diuertics (looP) for symtoms (this order) 

 Treatments

Beta blockers, Ca2+ antagonists

 Treatments

βblockers, non dihydropyridine, ca2+ antagonists, ACE I and ARBS. 

 Treatments

Ca+ antag, thiazide diuretics?

Treatments

Alpha blockers

 Treatments 

non cardioselective βblock

 Treatments

βBlockers

 Treatments

non cardio seletive βblockers, non dihydropyridine Ca2+ antagonists

CI

Can ↑ blood level&masks some symp of ↓BS- βblockers

Triggers

Diuretics

Presentation of symptoms

muscle cramps, muscle weakness, malaise, arrhythmias

Therapeutic Considerations

hyperkalemia can have the same symptoms

Triggers

Beta blockers, cept carvedilol, metoprolol, bisprolol, CCB cept amlodipine and felodipine

Cause

↑HTN w/ age. ↑prevalence w/ isolated sys HTN. ↓mortality w/drugs. SBP ↑w/ advancing age, DBP ↓w/advancing age. ↑prevalence of isolated systolic hypertension (ISH)

Treatments

↓mortality w/ antihtn tx(stoke, MI, CHF).BP=↓slowly &  cautiously. Promote lifestyle mod. Target BP: <140/90 if possible. Sometimes just trying to get to 160 if they can because sometimes that ↑ (bit by bit) as long as 180 mmhg. try a nondrug tx, Anti-HTN agents:↓est dose and tritrated gradually.ADR FX more com. HCTZ 12.5mg-25mg. Loops-furosemide 20mg *good in sys. Diuretics good 4 edema. Ca Block- very effect, avoid in CHF.  α1 block- ↑ hypoten in elderly.  improves BPH. ACEI- well as  combo, ↓ effective monotx.Synergy w/ diuretic. β block- good post MI, ↓morbidity and mortality-lot ↓ tolerated.more metabolic effects- pick an agent -appropriate. hay lipids, and affects the renal/liver metabolism.  VERY ELDERLY-very beneficial to ↓BP in elderly hypertn>80 yrs. 

Therapeutic Considerations

↑ADR,not very plastic. Importance of SBP-NHBEP emphasized.↓& go slow!*advntg: ↓morbid and mortal, produces grter ↓in SBP. Remember ADR on electrolytes, lipids, glucose. (monitor electrolytes/creatinine. orthostatics. 

Prevalence Other What is going on in the Body Triggers

Cause

95th or ↑in stg 1 above the 99th %-ile in stg 2- ↑CO & normal plasma vol & cardiac resist

 Treatments

we start tx in stg 2 & look 4 cause. Stg1=lifestyle Δ.  don't see a lot. β block preferred. Valsartan now FDA approved

Therapeutic Considerations

try 2 determine other causes of HBP & other CV risk factors. Usually associated with ↑CO and normal plasma vol and total PVR. Pnts w/ stg 1 htn who are symptomatic when left ventric hypertrophy is present. Stg 1 htn when blood pressure is unresponsive to lifestyle Δs 

Cause

chronic htn(before preg or before hoop of gestation), preclampsia- edema, don't use ace and ArBs. Drug of choice- methyldopa in preclampsia.  and transient HTN and preclampsia. Some women on OC- on the whole is not a pressor prohtn agent. 

Treatments

methyldopa=recomend 4 women dxd during preg

Therapeutic Considerations

must differentiate btwn chnc & transient htn of preg & preclampsia. Chronic htn is hbp present b4 preg or dxd b4 20th wk of gestation. Preeclampsia= ↑bp (↑of 30 mmhg systolic or 15 mmgh distolic),occurs in preg (gen after the 20th week),w/ edema, proteinura, or both. 

 Triggers

ACEI and ARBs are CI for preg women. 

 Treatments

may be used w/chrnc(DBP>100mgHG) or acute (DBP>105):central α agonists-methyldopa=rx of choice. βblock:metoprolol & labetolol=safe/effective in late preg. Diuretics=OK 4 chrnc HTN if prescribed b4 gestation and if vol depletion avoided-not recommend 4 preeclamp. Direct vasodilators: hydrazaline=parenteral rx of choice cuz of hx of safe & efficacy. 

Therapeutic Considerations

Clin trials-not demonstrated sig diff btwn men and women in tx response outcomes. Some women using OC may have sig↑BP but OC tx does not appear to ↑ mortal.

Therapeutic Considerations

BP response similar to white. ↑response to salt restrict

Prevalence

↑prevalence of HTN, stg 2 HTN. 80% of ↑stoke risk, 50% ↑ cardiac mort, 320% greater end-stage renal fail rate. ↑prevalence of CV RF.

MOA

4 class-CAH(acetazolamide),Thiazides (HCTZ, chlorthalidone),loop(not best, furosemide/bumetanide),k sparing (careful with hyperkal, triamterene);↓BP, fluid vol, PVR. Prevent strokes from occur?, synergistic FX w/ other meds. 

Dosing/TX

**KEEP AT OR <W/ HCTZ &CHLOROTHALIDONE- <25mg, NOT MORE

ADR

Electrolyte disturbances- ↓k+, MG.↑ Ca, uric acid.

CI

*Cholestyramine (↓HCTZ absorp), *Li- (↑Li serum conc)* NSAIDS- ↓diuresis, *digoxin-↑risk of digox tox-Thiazide+ACE+NSAID-↑risk of acute renal injury. Sulfonylureas (↓sulfonylurea efficacy). Cyclophos/fluorouracil/methotrex= myelosuppress 

Therapeutic Considerations

synergistic FX w/ other meds. Thiazides=1st line tx per JNC 7. Thiazides most effective, loops&k+ sparing weakly when alone. High diet na+ can reverse benefits. NSAIDS can antag FX. ↓effective in lean patients(mayB?). Diuretic FX on electrolytes, chl, glucose (monitor K+, creatinine: baseline, approx 2 wks later then periodically thereafter)-> since diuretics take other electrolytes out w/ na, be careful.cheap meds. *better w/ eld & AA? MayB. 20%↓in hip fracture with long term use. *√ 4 orthostasis, esp in eld!! **DIURETIC TX in ISH- SHEP STUDY- sys HTN in elderly program- used chlorthalidone- goal BP reached by 65-72% of placebo., ↓cumulative stroke rate in Shep trial. *HCTZ vs Chlorthalidone- meta analysis-chlorthalidone was grtr ↓ in SBP & K than HCTZ. ↓not=btwn 2 RXs

PK

thiazides not effective <30ml/min CL. Loop diuretics are effective here.

PROS

Cheap, can be dosed 1qd, 30 yrs of data to support ↓ in mortal & morbid(SHEP, SYST-EUR/CHINA, ALLHAT), better for AA &eld, 20% ↓in hip fract 

CONS

 Electrolyte disturb (↓K&Mg, ↑Ca&uric acid) diabetics-↓ dose, gout-↓dose, hyperlipid- ↓dose. ↓efficacy as kidney func↓(not effective when GFR<30ml/min) , √orothostasis!! Thiazides are ?d as the other meds cheaper. 

MOA

Multifact, ↓co by -chronotrop & inotrop FX, ↓renin release, ↓PVR

 
Indication

2nd line tx per JNC. They are post MI. ↓mortal&morbid in CHF (meto, bisprolol, carvedilol) for kid's stg 2 htn

Dosing/TX

can get by w/ 1qd

ADR

glucose intol. May ↑lipids, asthma copd, caution in CHF, angina w/ ISA agents. Sex dysfunction. ↓exercise capacity(cant get right response in hrt rate,dont enjoy their exercise) yng people really dislike-  trough level but idk if help, *withdraw syndr(reboundhtn) talk to them @ start the med- taper med! BP gets worse if not. Tpr 1/2 dose q2-3 days over 2 wk. * bradycardia, tiredness, cold extremeties, CNS(lipophillic propranolol)

CI

cimetidine(↓metab of meto, labet, propran), amiodarone (hypoten, bradycard), ritonavir (↑meto c), digoxin(AV nod block), SSRI- cyp 2D6-(↑meto c), st johns wort(↓β block effect), diltia/verap-(↑bradycard, hypoten,& AV conduct abnorm)

Therapeutic Considerations

Differentiated by:cardioselect (dose depend),ISA, metab. pretty affordable, but so are others. More effective 4 white &yngr pnts. No lab, utility?d- partic in ↓stoke (↓effective than other htn in ↓stroke,↓effective @ ↓central SBP, mayB explained by 1qd dosing of atenolol- better results w/ bid, others argue- βblock should not be 1st line anti-htn or 2drug + diuretic. 

PROS

modest $, 1qd dosing, ↓CAD mortal and progression, ↓mortal post-MI (avoid agents w/ ISA) ↑FX in whites/young, dec M&M in CHF (metoprolol, bisoprolol, carvedilol), no routine lab 

CONS

*diabetes: glucose intol, can mask hypogly(carvedilol vs metoprolol)- WONT MASK SWEATING, may ↑lipids, asthma/COPD, caution in CHF, ?atenolol, aginia with ISA agents, sex dysfunction, ↓exercise capacity, withdraw syndr (rebound htn) - taper 1/2 dose q 2-3 days over 2 wks. *↓effective than other Anti-HTN in ↓stroke, ↓effectively ↓central SBP 

Indication

↓mortal in CHF (sympto and asympto), ↓progression of DM nephropathy, ↓progression of CKD, ↓mortality frm CV causes, MI, stroke 4 ↑risk pnts. 

Dosing/TX

no salt sub- they might get hyperkal. Use Mrs. Dash/herbs. Careful with K supple- not good. 

ADR

chronic cg. Rash, angioedema, hyperkal,renal fail (if bilat RAS present) 

CI

DON'T use these in preg. Or RAS bilateral renal artery stenosis (RAS), NO salt sub w/ ACE-I (they contain K), instruct pnts to use Mrs. Dash/herbs. Careful w/ K+ supple,K+ sparing diuretics, spironolactone. 

Therapeutic Considerations

helps w/AA w/combo of diuretic. Monitr- serum creatinine, K+, @ baseline, 2 wks, then periodic. 

PROS

good in white & young pnts, ↑response in AA w/ diuretic, neutral on lipids, DM nephropathy- renal protective, improve survival in heart fail, ↓mortal in HTN- similar to conventional tx (CAPP, ALLHAT, STOP-2) 

CONS

↑hypoten rxn- in renovas HTN, CHF, hypocolemia, +of diuretic….CG (10%- consider switch to ARB) 

MOA

lostartan, valsartan, candesarten, AII affects brain, hrt, all in a -manner, causes organ damage.  Competitively inihb ANG II at AT1 receptor 

ADR

dizzy, cg (<ace) angioedemia, get notes.

Therapeutic Considerations

AII plays a central role in organ damage

PROS

similar ben FX as ACEI, CV, renal outcomes, DM, no lipid, glucose Δs. Useful in combo w/ other antihtn.

CONS

more $, concerns about CA&CV events, not free frm ACEi-type SE (dizzy, cg- <ACEI, angioedema, hyperkal) 

MOA

SM relax in arteries.(vasodil) -iontropic & chronotropic FX. Reflex neurohormonal or sympath act. hay 3 class:dihydropy/nondihydropy( nifedipine, amlodipine), benzothiaz(diltiazem), phenylalky(verapamil)**Benzothiaz & phenyalky(diltiazem and verapamil)- these are coronary and systemic vasodilat, ↓myocardial contract, HR, AV node conduct. The dihidropy (amlodipine, felodipine, nifedipine)- coronary & systemic vasodilation, or ↓myocardial contract, 0-little ↑HR, no FX on AV node.

Indication

amlod felo- only ones to use in heart fail

ADR

verapamil-↑issue with constipat. Periph edema for all. Constipat, bradycardia, AV block, CHF (VERAP AND DILTIA) …..Edema, dizzy, HA, tachycard(esp diydropy), gingival hyperplasia (nifedipine) 

Therapeutic Considerations

have smiliar antihtn FX

PROS

Studies show ↓mortal in HTN similar to conventional RXs (INSIGHT and NORDL studies) . More response in elderly for sys htn, effective in CAD, ↓angina SX, 1qd dose, additive BP-↓effects w/ ACE-I, BB. Neutral on lipids/glucose, ↓CV mortality similar to conventional tx

CONS

↑mortal(?)= possible risk of MI w/ SA CCB (nifedipine esp). ↑MI w/ SA agents-FDA warn! More $(general), caution in HRT Fail (only use amlodipine, felodipine) 

MOA

inhib efferent sympath act. Selective α1 avoids reflex tachycardia associated with non-selective α blocks. (doxasosin, prazosin) 

Indication

monotx or alternative tx.

ADR

HA, fatigue, drowsy, weak, vivid dreams. 

Therapeutic Considerations

ALLHAT STUDY!!Antihtn-42,418 particip

♥superior of thiazide-type diuretics in prevent one or + major frms of CVD & their ↓$,Rxs of choice for 1st-step antihtn tx

♥cant take diuretic(unus), consider CCB’s/ ACEI’s 

♥ Most htn pnts need 1+ rx. Diuretics=part of  regimen. Lifestyle advice=>provide!

Lipid Trial – 10,355 participants

♥ ALLHAT pravastatin &usual care grps both attained substan chl ↓, =modest chl diff btwn them.

♥ ALLHAT found smll ↓ CVD events(nonsig) for pravastat compared w/ usual care & no diff in mortal

♥study results dont alter current chl tx guidelines, = based on clinical trials with ↑chl reduc than observed in ALLHAT. Thus, chl ↓ing by lifestyle Δs & RX tx is recommended to ↓CVD morbid/mortal

PROS

↓TC, LDL, TG, ↑HDL, improve BPH symp

CONS

hypotn w/1st dose (1st dose phenomen), transient dizzy or faint, syncope, take 1st dose @ HS. Not recommend as 1º monotx 4 HTN (ALLHAT study) 

MOA

stim central α2 receptors. Inhib sympath outflow (↓NE,HR,CO, &PVR), clonidine and methyldopa

ADR

withdraw symp- CNS sedate, ↓alert, depress. Dry mouth, bradycard, na and fluid reten(methyldopa)

PROS

cheap, neutral FX on lipids, clonidine patch, methydopa safe in preg. 

CONS

withdraw syndr, rebound htn due to ↑NE 

MOA

block act of renin =>no conversion of atn to atnI- no reflex ↑ in AII- renin blockade inhib entire RAS at its point of act. (PUT IN FLOW CHART)

Dosing/TX

aliskiren 150 to 300 mg qd

ADR

same as ACE inhib, seeing more now. more of Gi (diarrhea &cg) 

CI

careful w/ DM & renal impair

PROS

well tolerated. No dose ↓ in eld, hepatic impair or mild mod renal impair. Safe in combo w/ ARB, CCB & thiazide. Little hyperkal in monotx. ↓incidence of: rash, cg, angioedema compared to ace-I and ARB.

CONS

$, avoid w/ACE-I/ARB in DM and renal impair. ↑fat meals ↓absorp.t1/2= 23.7 +/- 7.6 hours, ok4 1 qd dose. Alkskiren is metab via CYP3A4 (rx interactions) 

 MOA

 direct arteriolar smooth muscle relax=afterload ↓ing agents. ↓systemic pressure in arterial sys. ↓ impedance of myocard contract. - hydrazaline &minoxidil. 

ADR

Hypertrichosis(minoxidil), lupus-like syndr (hydrazaline), dermatitis, rx fever, periph neuropathy, hepatitis, HA. 

PROS

cheap, hydralyzine+isosorbide useful in CHF.

CONS

reflex sympathetic act- leads to ↑HR, ↑CO, & renin release. Effect ↓ over time unless pnt taking sympath inhib on diuretic. ↑angina in pnts w/ CAD. 

MOA

deplete NE frm postgang nerve term. Inhib release of NE in response to sympath stimulat. ↓CO and PVR. Usu reserved for refrac HTN. - guanthidine and guanadrel 

Indication

 very very refractory HTn

ADR

orthostat hypoten syncope, impotence, diarrhea, wgt gain 

Therapeutic Considerations

usually last choice

PROS

Cheap, ↑effective 

CONS

orthostatic hypoten, syncope

Classification

Diuretic

Therapeutic Considerations

?d-weaker vs other agents.shift 2 chlorothalidone. 

Brand

Bystolic

MOA

selective β1 antag-vasodil via NO release. 

Therapeutic Considerations

newest βblocker, similar tol to carvedilolol

Pros

don't ↑BS as well- not really demonstrat, Better SE profile? - not fully demonstrat, may have better FX on glucose in DM compared to other βblock 

MOA

deplete NE from sympath nerve end. Block transport of NE into storage granules. ↓sympathetic tone, depletes catechol. 

ADR

depression, sedation

Therapeutic Considerations

cheap, highly efficacious

Cons

sedation, depression, Na/fluid retnetion, diarrhea, depression 

 MOA

Inhib sympathetic outflow

Classification

central acting alpha 2 agonist

Indication    

htn crisis/urgency               

ADR

↑IOP-don't use 4 ppl w/ glaucoma or simliar  

MOA

tyramine crisis, w/ cocaine or lots catecholamine

Indication

IV of amolodopine?

Indication

FDA 4 children's stg 2 htn

Presentation of Symptoms

↑risk of: HTN, TII DM, CHD, gallbaldder dz, certain CA, dislipid, stroke, osteoarthritis,OSA. 

Assessment of disorder

BMI- wgt(KG)/ht (m^2), wgt (lb)/ht (in^2) X703, table. *waist circum: ↑risk= men >102 cm(40in), women >88cm (35in) *WAIST CIRCUM MEASURE: locate upper hip bone and top right of illiac crest, measuring tape in the horizonatal plane round the ab @ level w/ iliac crest- tape snug but doesn't compress skin,// to floor. Measure @ end of exp. Underwgt=<18.5, norm=18.5- 24.9, overwgt=>25, obese=>30, 40+ damn!*ABSOLUTE RISK STATUS: evaluate: dz cond (ie CHD,TIIDM, OSA)+ = a very high risk!, other obesity assoc DZ (↑LDL, ↓HDL, IGT, fam HX (≥3= ↑risk), other RF (Phys act, ↑serum TG (>200mg/dL) *Goals: prevent further wgt gain,↓BW, maintain ↓body wgt 4 LT.

Treatments

 balancing act of cal in & cal out- walk leisurely for 1 hr and 10 min-burn≈400 calories.clean for 2 hr and 35 min-burn≈525 cals *target wgt: realistic, sub healthier wgt for ideal.slow incremntl progress to goal- short term: 5-10% loss, 1-2 lbs/wk (4lbs/4 wks), interm goal: maintain. LT- more wgt↓, if desired+LT maintain. *strategies- dietary tx, phys act, behavior tx, combined tx, pharmacotx, wgt↓surgery. * never use rx alone, combo w/diet/exercise/behavior * rx tx-AFTER 6 mo diet/exercise/behavior have fail wgt↓. 

Therapeutic Considerations

↓body weight 10%. If achieved, further weight↓if indicated. 6mo tx reasonable. Mod cal↓, wgt↓1-2 lbs/week. maintain after 6mo. Combo diet/act/behavior.may need continued indef.can't ↓wgt, prevent wgt+. *BMI,waist circum=assess tot body fat than wgt alone-independent of predictors of obseity related dz risk. weight↓of 5% can sig improve BP, lipid lvls, and glucose control. 

Prevalence

≈108 mill American-overwght/obese.↑ing, ↑prevalence=south.  

Other

Def: BMI- relative wgt for height: wgt (KG)/Ht(m^2)- overwgt=25-29.9 BMI, obesity≥39 BMI 

Presentation of Symptoms

overwgt child= overwgt adult. prevent/treat child=↓risk of adult overwgt. May ↓hrt dz+ other dz 

Assessment of disorder

consider both wgt and body comp

Prevalence

males: whites-31.9% mexicans- 40.8%, blacks- 30.8% Females: whites- 29.5%, 39.2%, 35.0%

Treatments

all=regardless of wgt should quit smoke. Implement wgt +prevent, tx efforts as necessary. 

Treatments

evaluate risk-benefit ratio

Treatments

tx +obesity=>OSA- med tx& surgical tx.

Other 

benefits of tx- 10% wgt↓ associate w/ 50%↓severity of OSA. ↓specific cv RF. 

MOA
methamphetamine HCL (desoxyephedrine HCL), amphetamine sulfate, dextroamphetamine sulfate (dexedrine) , amphetamine/dextro (adderall), benzphetamine (didrex), ephedrine

Therapeutic Considerations

pharmacotx agents not for wgt↓

Combined TX for Wgt Loss

MOA

cal↓ diet, ↑phys act, behavior tx 

Therapeutic Considerations

most successful for wgt↓/maintain. *cat A recommend-Nonrx-attempted 4 6mo b4 Rx. *+FX of behavior/diet w/ pharmtx for obesity. 

Indication

limited# of pnts w/severe obesity(cat B), BMI ≥40 or ≥35 comorbid cond. 4pnts in whom medical tx fail

Dosing/TX

gastric↓/gastric bypass.

Therapeutic Considerations

integrated program must be in place before+after surgery. 

PK

PROS

CONS

Brand

xenical

MOA

 GI lipases (gastric pancr carboxylester)=need for LCT absorp. Lipase inhib=↓FFA form frm diet TG. induces wgt↓by ↓diet fat absorp. Up to 30%↓in fat absorp occurs daily w/doses of 360mg. 

Classification

GI lipase inhib

Indication    

FDA-weight↓    

Dosing/Treatment

Hyperlipid/obesity: 120tidcf, OTC- 60mg tid during or w/in 1 hr of eat fat meal. Peds= 12-16 ys, 120tidcf 

ADR

soft stools, ab PA, flatulence, fecal urg, incont (1in occurs in 80% of individ)- usu 1st 1-2mo of tx. oily spotting/evacuation. Na, flu, URI, backPA, HA, menstual irregularity, or cholethiasis. 

CI

only sig interact w/ cyclosporine,↓cyclosporine w/concurrent use.

Therapeutic Considerations

cf w/ fat for FX. OTC= approved by FDA.  eat nutrition balance diet w/ 30% calories frm fat, as taken w/ rx w/ a ↑fat or meals that ↑GI effects.MVT w/fat-sol vit@ least 2 hrs b4 or 2 hrs after rx, absorp of some fat sol vit and βcarotine may be ↓

Cons

malabsorbof fat sol vit- consid vit suppl *safety and efficacy beyond 4 yrs=unkown.

Brand

qsymia

Indication 

adjunct to ↓cal diet and ↑phys act for chronic wgt manage in adults with 1º BMI of ≥30, ≥27 in presence of at least 1 wgt-related comorbid such as htn, TII DM, or dyslipid  

Dosing/Treatment

14 dy regimen, then ↑dose. DC or ↑dose after 12 wks if loss not achieved.Dc if 5% not lost on mx in 12 wks

ADR

tingling sensa of hands/ft, dizzy, alt taste, is, constipat and dry mouth

CI

OC- alt expose, irreg bleed- not ↑ risk of preg. no DC OC if spotting. CNS depress/alcohol: potential CNS depress FX, avoid alcohol. non-K sparing diuretics- hypokal, measure k before/after tx. 

Therapeutic Considerations

qam, avoid eve (is) Safe and effect in <18= unknown. Dc slow-prevent seizure. DNE min dose w/ mod/sev renal impair/pnts w/mod hepatic impairment. 

Pros

Cons

Brand

Belviq

MOA

↑satiety/↓food intake by activating 5-HT (2C), recep on anorexigenicopiomelanocortin neurons in hypothal

Classification

selective serotonin 2c (5-ht 2C) recep agonist

Indication

tx of obesity-adults w/BMI >30, adults w/ BMI of 27 or > w/ 1+ wgt related health condition such as htn, type II DM, or high chl.  

Dosing/Treatment

obesity- 10mgbid, dc @ 12w if not 5% achieved- max 20qd. 

ADR

new/worsening depress, suicidal thoughts/behave, or unus Δ in mood/behave. *may cause dizzy, confusion, and somnolence. *long erections >4 hours. 

CI

concurrent use= serotonin syndr (htn, tachycardia, hyperthermia, myoclonus, mental status changes)- dextromethorphan, desipramine, serotonergic agents, amitrptyline, imipramine, clomipramine, paroxetine.* atomoxetine (↑), metoprolol (↑), propafenone (↑)  

Therapeutic Considerations

safety/efficacy=not estab in peds pnts=not recommend. Weight↓=efficacy. MONITOR: bld gluc, CBC periodically, prolactin lvls. Response-12wks. *avoid act w/metal alertness/coordination until drug FX realized. *report signs/symp of serotonin syndr (agitation, confusion, diaphoreis, halluc, hyperrelexia) *dc rx,report erection that >4 hours, dc if 5% not in 12w, report worsen behavior, depress, suicidal thoughts 

Cause

prob frm single or combo of 4systems of erection: vasc, neurologic, hormonal- organic ED (80% of pnts), psychogenic for 20% of pnts. Metabolic syndr, BPH symp (↓NO in urogen tract), CV dz (liningin BP cant produce NO), smoking, central probs in brain, spinal cord, stressors (psychogenic), endocrine, DM (impaired bp control,neuropathy) *RX CAUSES: diuretics, antihtn, CV or chl RX, hormones, chemotx, recreational rxs, antichol, anti-androgens, antipsychotics

Assessment of disorder

*Hx: sex, med (comorbid, CV dz, dm), psych (depress, stress, social relation), Med hx *Phys exam- neurologic, genitourinary, periph puslses, prostate *LABS: serum prostate PSA for men> 50, testost (certain pnts), fast BS* OThER : ultrasnd or arteriograp=>vascular func& arterial insufficiency * patient montor: outcomes= ↑quant/qual erections. avoid ADR andrx interactions. assess after 1-3 weeks for efficacy/tox. each pnt=diff, pnt satisfaction=key. if not effect with adequate trial- ensure max dose, switch PDE-inhib for trial, surgical tx or ptns who fail drug tx. 

Treatments

Oral, surgical, inj, mechanical, lifestyle mods. *ORAL; non-invas, easily admin, effective/ well tol *PDE-5 inhib=1st line

Therapeutic Considerations

patient pref for selecting tx.  3 major studies pnts-tadalafil>sildenafil. 

What is going on in the Body 

PATHOPHYS: 4 things need= vascular (if have heart dz, risk @ ED) , neurologic (nerve degne, spinal injury) , hormonal (↓testosterone, hypogonadism) , 3= most cases. 20%=psychogenic *NO diffuse to cells- ↑ GTP=> CGMP- ↓ca2+, decre?? sm relax- tumesence. PDE-5 norm breaks↓CGMP, but prob- ppl have a hard time making NO 

Other 

risk 4 ED: surgery4 prostate CA (post radical postatectomy), post CA tx (radiation), spinal cord inj (↓ injury, ↑risk), ↓testost , certain Med; *types of male sexual dysf: ↓libido, ↑libido, ED, delayed ejac, retrograde ejac, infertility

MOA

inhib PDE-5- norm Breaks ↓CGMP. CGMP to accumulate. 

Dosing/TX

*daily admin= steady state and ↑CGMP, lack of spontaineity may lead to drug DC, daily dosing may modify dz (vascular) *prn use of PDE-5 inhibitors=not as effective in some (diabetes, neurological damage, severe vasc dz, w/prostate CA undergoing radical prostatectomy) anx from plan sex activity may ↓ efficacy.

ADR

*inhib PD-1: vasodil, tachycard,& flush. PDE-6: visual disturb( see blue) , PDE-11: back PA, myalgia *not ↑freq w/daily doses * most ADR= inhib of PDE-1/PDE6, /PDE 11* for daily most com-dyspepsia, back PA, flu-like. 1study reported ha ↓common w/daily dose vs PRN dose

CI

CYP 3A4: cimet, erythro, clarithro, ketoco, itracon, ritonavir, saquin. *NITRATES (nitrogly, isosorb dinitrate) ,- NOT USE IN CLOSE PROXMITY *α-block(doxazosin, terazosin), nicorandil.not in pnts w/ high or intermed risk of CAD, retinitis pigmentosa, nonarteritic anterior ischemia optic neuropathy. 

 MOA

Alprostadil

Indication

2ndry tx options if PDE-5 inhib unsuccess

 MOA

testost

Indication

for testosterone deficiency 

Dosing/TX

Goal- correct symp of hypogonad(malaise,↓libido,↓muscle strength, depress) restore testosterone conc to 300-1100 ng/dl. 

Therapeutic Considerations

measure serum testost in AM with LH conc. Distinguish from 1° to 2°. 1°is ↑LH, 2°=↓LH. Variety- transdermal, IM, buccal, SQ implants. 

 Brand

viagra

MOA

PDE-5 inhibitor

Indication

ED, pulmonary htn

Dosing/Treatment

25-100mg 60 min b4 desired FX.  Use a dose of 35mg in severe 

ADR

more like inhibit 1A *HA, flush, dizzy, dyspepsia, nasal conges, altered vision. 

CI

*NITRATES- don't use in 24 hours

Therapeutic Considerations

 want to work FAST,  look for ↓est tmax. Take on ES.  Use the 25mg in pnts w/severe renal dys/hepatic impair(daily dosing) . Sep frm food by 2 hrs. 

PK

F= 41, 29% ↓cf, tmax= 0.83, t1/2=3.7, CYP 3A4, 4-5 h duration

 Brand

levitra

MOA

PDE-5 inhibitor

Indication

ED

Dosing/Treatment

2.5-20mg qd, usual dose 10mg 1 h prior to sex. Duration: 4-5 hours 

ADR

more likely to inhibit 1A, flush, ha, dyspepsia, na, dizziness, rhinitis. 

CI

*NITRATES- don't use in 24 hours

Therapeutic Considerations

Works 2nd fast. Take on ES. ↓dose w/cyp3A4 inhib or pnts w/ mod-severe liver dys. Sep frm food by 2 hours. 

PK

F= 15, 20% ↓cf, tmax= 1, t1/2=3.3-39, CYP 3A4, 4-5 h duration

 Brand

Cialis 

MOA

PDE-5 inhibitor

Indication

ED

Dosing/Treatment

2.5-20mgqd, 10mg prior to sex. *only rx approved for qd 

ADR

cause PDE-11 ADR, HA, dyspepsia, dizzy, flush, nasal conges, back PA, myalgia. 

CI

*reduce dose with cyp3A4/ mod-sev liver NITRATES- don't use in 48 hours

Therapeutic Considerations

36 hour duration, ↓likely to cause PDE-1 inhb, PDE-6 *study tadalfil over sildefil (kinda) * ↑t1/2allows pnt to take med hours-days before sex.. May take longer to be effective.  ↓dose with comcomitant cyp3A4 inhibitors or pnts with mod-severe liver dysfunc. can be taken w/o regard to food. daily use more effective than PRN- pnt satisfaction↑. daily- ↓ ADR if↓dose can be used. 

PK

unchange cf, tmax= 2, t1/2=17.5, CYP 3A4, up to 36 h duration *favorable Pk profile allows constant steady state conc. (20mg biw) 

 Brand

stendra

MOA

PDE-5 inhibitor

Indication

ED

Dosing/Treatment

50-200mg, usual dose 100mg, up to 6 hr duration, take w/o regard to food. 

ADR

HA, flush, nasal conges, back pA, dizzy. 

CI

erythromycin, diltiazem, fluconazole, verpamil. 

Therapeutic Considerations

Works fastest, ↓PDE-6 (not as much as tadalafil) . Not w/ strong CYP3A4 inhibitors. ↓dose to 50mg when using mod cyp3A4 inhib . Take w/o regard to food (↓Cmax are called "not sig".

PK

unΔ cf, tmax= 0.5-0.75, t1/2=5, CYP 3A4, up to 6 h duration 

Cause

*HTN and coronary hrt dz(MI, angina) = CVD

Presentation of Symptoms

*COM SYMTP OF CV DISORDERS: chest PA(location/duration/intensity, associated symp, relation to act, tx attempted), Heart fail(pulmonary vascular congest: dyspnea/ orthpnea/paroxymal nocturnal dypnea/ nocturia, peripheral venous congestion: ab swell/N&V/↓ extremity edema/fatigue/dyspnea) Others(hemoptysis, cg/wz, palpitations, confusion/dizzy) 

Assessment of disorder

*CARDIAC ASSESS: 1) gather patient hx(employ- PE demands/stress, tobacco hx, nutritional stat- diet, wgt, lipid panel, alch use, act lvl-exercise, fam hx( import 4 CVD), rx. *üfor hx of leg cramps/cold exremeties, swell or edema/fluid retention/personality Δs/syncopy/faint or dizzy and rx use. , 2) Assess potential CV RF 3)phys Assess *CV PHYS ASSESS: examination of the CV system- 4 stgs: Gen appearance, phys signs w/ arterial circ, phys signsw/ venous circ, phys signs w/ heart *arteries- pulse: best palpated over arteries that are close to surface of body and lie over bones. Palpate to assess hrt rate/rhythm. *evaluate pulse: present or absent, rate (pulse rate= hrt rate, reported in bpm, normal hrt rate is 60-110 BPM, rhythm= reg or irreg) *measure of arterial pressure. * the new BP recommend for dM=140/80* look for breuis?ABI's-severity of dz in periph of legs. taken at arms- systolic BP. use an ultrasound. As the number↓= ↑ obstruct/dz. Venous circ- jugular should be normal. Norm= < 9.if it is above this- this is ↑fluid reflux. sustained elevation- sign for heart fail. Edema- do + test. 

Prevalence

CVD STATISTICS: ≈83.6 mill American adults (>1 in 3) have 1+ types of CVD. 42.2 mill-60+ yrs. CVD= 32.3% deaths in US 2009 - always yrs behind. (≈ 1 in 3 deaths- CVD, >2150 Americans die of CVD/day, an average of 1 deathq40 sec)  direct/indirect cost of CVD for 2009=$312.6 billion