Module 4.docx

Module 4: Cardio vascular I 15 - - - - **Sites of Diuretic action** - **PCT:** The PCT has a high resorptive capacity. A large fraction (about 65%) of filtered sodium and chloride is reabsorbed at the PCT. In addition, essentially all of the bicarbonate and potassium in...

Module 4: Cardio vascular I 15 - - - - **Sites of Diuretic action** - **PCT:** The PCT has a high resorptive capacity. A large fraction (about 65%) of filtered sodium and chloride is reabsorbed at the PCT. In addition, essentially all of the bicarbonate and potassium in the filtrate is reabsorbed here. Solutes and water are reabsorbed at equal rations, so this urine remains isotonic. - **Loop of Henle:** The descending limb of the loop of Henle is freely permeable to water. Hence, as tubular urine moves down the loop and passes through the hypertonic environment of the renal medulla, water is drawn from the loop into the interstitial space. This process decreases the volume of the tubular urine and causes the urine to become concentrated (tonicity increases to about 1200 mOsm/L). - **Early segment of distal convoluted tubule:** About 10% of filtered sodium and chloride is reabsorbed in the early segment of the distal convoluted tubule. Water follows passively. - **Distal Nephron:** The distal nephron is the site of two important processes. The first involves exchange of sodium for potassium and is under the influence of aldosterone. The second determines the final concentration of the urine and is regulated by antidiuretic hormone (ADH). - **Sodium-Potassium Exchange:** Aldosterone, the principal mineralocorticoid of the adrenal cortex, stimulates reabsorption of sodium from the distal nephron. At the same time aldosterone causes potassium to be secreted. Although not directly coupled, these two processes---sodium retention and potassium excretion---can be viewed as an exchange mechanism. Aldosterone promotes sodium-- potassium exchange by stimulating cells of the distal nephron to synthesize more of the pumps responsible for sodium and potassium transport Compare and contrast the diuretics presented in the module. - - **Furosemide (LOOP diuretic) MOA**: acts in the thick segment of the ascending limb of the loop of Henle, blocks reabsorption of Na and Cl, preventing reabsorption of water which = profound diuresis even when renal blood flow and GFR are low. If tx is insufficient with just Lasix, it can +-----------------------+-----------------------+-----------------------+ | | | be combined with a | | | | thiazide diuretic (no | | | | use in combining with | | | | any other loop | | | | diuretic). | | | | | | | | - **Hydrochlorothia | | | | zide/Microzide | | | | (Thiazide | | | | diuretic) MOA**: | | | | steroid | | | | derivative, | | | | promotes urine | | | | production by | | | | blocking | | | | reabsorption of | | | | Na and Cl in the | | | | early segment of | | | | the distal | | | | convoluted tubule | | | |  water retention | | | | in nephron and | | | | increased flow of | | | | urine | | | | | | | | - **Spironolactone/ | | | | Aldactone | | | | (Aldosterone | | | | Antagonist, | | | | potassium-sparrin | | | | g | | | | diuretic)**: | | | | blocks the action | | | | of aldosterone in | | | | the distal | | | | nephron  | | | | retention of K | | | | and excretion of | | | | Na. Diuresis is | | | | scanty because | | | | most Na has | | | | already been | | | | reabsorbed before | | | | reaching the | | | | distal tubule. | | | | | | | | - **Triamterene/ | | | | Dyrenium | | | | (non-aldosterone | | | | antagonist, | | | | potassium-sparrin | | | | g | | | | diuretic):** | | | | disrupts Na-K | | | | exchange in the | | | | distal nephron by | | | | direct inhibition | | | |  decreased Na | | | | reabsorption and | | | | reduced K | | | | secretion  Na | | | | excretion is | | | | increased K is | | | | conserved. | | | | Minimal diuresis. | | | | | | | | | | | | | | | | - - **Furosemide | | | | USE**: when | | | | rapid or | | | | massive | | | | mobilization | | | | of fluid is | | | | required such | | | | as pulmonary | | | | edema | | | | associated | | | | with CHF, | | | | edema from | | | | heart, liver, | | | | or kidney | | | | that haven't | | | | responded to | | | | other drugs, | | | | and/or HTN | | | | | | | | - - **Spirono | | | | lactone | | | | USE**: HTN, | | | | edema, CHF | | | | (blocking | | | | aldosterone | | | | creates | | | | protective | | | | effects), | | | | counteracts | | | | K-wasting | | | | diuretics, | | | | off-label: | | | | acne, hair | | | | loss, | | | | hirsutism, | | | | hormone | | | | therapy for | | | | transgender | | | | females. | | | | | | | | - **Triamterene | | | | USE**: HTN, | | | | edema, combo | | | | drug can | | | | augment Lasix | | | | and | | | | counteract K | | | | wasting | | | | effects | | | | | | | | - What factors | | | | should be | | | | considered when | | | | choosing which | | | | diuretic to | | | | prescribe a | | | | patient? Produce | | | | some example | | | | scenarios of when | | | | you would | | | | prescribe one | | | | versus the other. | | | | How does renal | | | | function come | | | | into play? | | | | | | | | - **Furosemide* | | | | *: | | | | more loss of | | | | fluid and | | | | electrolytes | | | | than any | | | | other | | | | diuretic, K | | | | wasting, do | | | | not give if K | | | | is low, beer | | | | criteria use | | | | in caution in | | | | pts over 65 | | | | who are at | | | | higher risk | | | | for | | | | hyponatremia | | | | | | | | - **Thiazide**: | | | | MUST have an | | | | adequate | | | | kidney | | | | function to | | | | work (minimum | | | | 20-30mL/min), | | | | CI with | | | | digoxin, | | | | lithium, and | | | | other HTN | | | | meds. | | | | | | | | - - - Loop & | | | | thiazide AE: | | | | hyponatremia, | | | | hypochloremia | | | | , | | | | dehydration, | | | | hypotension, | | | | hypokalemia, | | | | ototoxicity | | | | (loop), | | | | hyperglycemia | | | | , | | | | hyperuricemia | | | | , | | | | reduced HDL, | | | | increased LDL | | | | | | | | - | +-----------------------+-----------------------+-----------------------+ +-----------------------+-----------------------+-----------------------+ | | | - **Spironolactone | | | | AE:** | | | | hyperkalemia | | | | (dysrhythmias), | | | | deep voice, | | | | impotence, | | | | menstrual | | | | irregularities, | | | | hirsutism | | | | | | | | - | | | | | | | | | | | | | | | | - How would you | | | | know if your | | | | patient was | | | | experiencing AE | | | | like ototoxicity, | | | | dehydration, hypo | | | | or hyperkalemia, | | | | and hypotension. | | | | What would be | | | | subjective and | | | | objective | | | | findings? | | | | | | | | - - - - - - | | | | - - | | | | | | | | - - - - - | | | | | | | | Know about the RAAS | | | | and how this affects | | | | fluid and blood | | | | pressure changes in | | | | the body. | | | | | | | | - RAAS: Decreased | | | | perfusion | | | | pressure in the | | | | afferent | | | | arteriole | | | | stimulates | | | | secretion of | | | | renin by | | | | juxtaglomerular | | | | cells  renin | | | | reacts with | | | | Angiotensin in | | | | liver to make | | | | Angiotensin I  | | | | Angiotensin I | | | | converts to | | | | Angiotensin II in | | | | the lungs  | | | | Angiotensin II | | | | causes | | | | vasoconstriction | | | | in the blood | | | | vessels  | | | | Angiotensin II | | | | becomes III in | | | | the adrenal | | | | cortex | | | | stimulating | | | | aldosterone | | | | release  | | | | Aldosterone | | | | increases Na and | | | | water | | | | reabsorption by | | | | kidney tubules | | | | which = increased | | | | blood volume & | | | | increased BP | | | | (slide 35) | | | | | | | | - | | | | | | | | Review HTN guidelines | | | | presented in PPT and | | | | module. | | | | | | | | - Drug of choice | | | | for pregnant | | | | women with mild | | | | pre-eclampsia: | | | | labetalol and | | | | methyldopa, MgSO4 | | | | used for seizures | | | | | | | | - In older adults, | | | | avoid central | | | | acting alpha | | | | agonists and | | | | peripheral alpha | | | | 1 antagonists, | | | | start low doses, | | | | risk of | | | | orthostatic | | | | hypotension is | | | | high | +-----------------------+-----------------------+-----------------------+ +-----------------------+-----------------------+-----------------------+ | | | - In African | | | | Americans, | | | | diuretics are | | | | 1^st^ choice. | | | | CCBs and α/β | | | | blockers are also | | | | effective. | | | | HOWEVER, | | | | monotherapy with | | | | β blockers or | | | | ACEIs is less | | | | effective in | | | | African Americans | | | | than in | | | | Caucasians. BUT | | | | for example, if | | | | pt is black and | | | | has DM I and | | | | proteinuria, give | | | | ACEI | | | | | | | | - When BP cannot be | | | | adequately | | | | controlled with a | | | | single drug, one | | | | of several | | | | two-drug | | | | combinations are | | | | recommended: an | | | | ACEI plus a | | | | thiazide | | | | diuretic, an ACEI | | | | plus a CCB, or a | | | | β blocker plus a | | | | thiazide. | | | | | | | | Review what comorbid | | | | conditions influence | | | | a prescriber's choice | | | | of antihypertensive | | | | medication. | | | | | | | | - HTN & CKD: ACE | | | | inhibitor + loop | | | | diuretic (avoid | | | | thiazide and | | | | potassium | | | | sparring drugs; | | | | ineffective), if | | | | intolerant to | | | | ACE, do ARB | | | | | | | | - - - - | | | | | | | | - - - - 25% | | | | decrease in | | | | stroke in | | | | patients | | | | 55-80 using | | | | losartan vs. | | | | atenolol, 20% | | | | decrease in | | | | DM with | | | | candesartan | | | | vs placebo | | | | | | | | - Compare and | | | | contrast ACE-I | | | | and ARB. What are | | | | the differences | | | | in these drugs? | | | | What are the | | | | similarities? | | | | When would it be | | | | better to | | | | prescribe one or | | | | the other? | | | | | | | | - ACEI "Prils": | | | | blocks the | | | | conversion of | | | | angiotensin I | | | | to II  | | | | vasodilation, | | | | decreased | | | | blood vol & | | | | cardiac | | | | remodeling, | | | | potassium | | | | retention and | | | | fetal injury | | | | can occur. | | | | ACEI also | | | | increase | | | | levels of | | | | bradykinin | | | | through the | | | | inhibition of | | | | Kinase II | | | | which also | | | | | | | |  vasodilation, | | | | COUGH, and rarely | | | | angioedema | | | | | | | | - How does a direct | | | | Renin inhibitor | | | | work? What | | | | patient teaching | | | | would be included | | | | with our | | | | prototype drug in | | | | this class? | | | | | | | | - | | | | | | | |  MOA: lowers | | | | angiotensin II levels | | | |  dilation of blood | | | | vessels, decreased | | | | blood volume, reduce | | | | cardiac afterload, | | | | increase CO, venous | | | | dilation, suppresses | | | | aldosterone, reduces | | | | GFR | +-----------------------+-----------------------+-----------------------+ +-----------------------+-----------------------+-----------------------+ | | |  USE: LV | | | | dysfunction, HTN, | | | | nephropathy (DM & | | | | nonDM), HTN, CHF, | | | | acute MI, prevention | | | | of MI, stroke, and | | | | death r/t CV events | | | | (ramipril), diabetic | | | | retinopathy | | | | (enalapril) | | | | | | | |  CI: rental artery | | | | stenosis (can lead to | | | | renal failure) & | | | | pregnancy | | | | | | | |  PE: take with food, | | | | first dose | | | | hypotension (start | | | | with low dose, check | | | | BP at home if | | | | hypotension develops | | | | lay down), avoid K | | | | supplements, notify | | | | HCP for cough & | | | | facial swelling, | | | | avoid diuretics & | | | | lithium, NSAIDS can | | | | reduce effects of | | | | ACEIs | | | | | | | |  AE: first dose | | | | hypotension, | | | | hyperkalemia (due to | | | | inhibition of | | | | aldosterone & | | | | angiotensin II), | | | | cough (bradykinin | | | | accumulation), renal | | | | failure (in pts with | | | | renal problems), | | | | angioedema (serious | | | | but rare) | | | | | | | |  BBW: fetal injury | | | | | | | | - | | | | | | | |  MOA: blocks action | | | | of angiotensin II at | | | | receptor sites | | | | (similar to ACEI but | | | | blocks AII in a | | | | different way)  | | | | dilates arterioles & | | | | veins, decreases | | | | aldosterone which  | | | | increased renal | | | | excretion of Na & | | | | water | | | | | | | |  Use: HTN, CHF, | | | | diabetic nephropathy, | | | | MI, stroke prevention | | | | | | | |  Same CI as ACEI | | | | | | | |  Less AE than ACEIs; | | | | ARBs don't cause | | | | hyperkalemia, no | | | | cough side effect, | | | | | | | |  PE: notify HCP for | | | | cough & facial | | | | swelling | | | | | | | |  BBW: fetal injury | | | | | | | | - | | | | | | | |  MOA: binds tightly | | | | with renin, | | | | inhibiting the | | | | cleavage of | | | | angiotensinogen to | | | | angiotensin I, | | | | influences the entire | | | | RAAS system | | | | | | | |  USE: HTN | | | | | | | |  BBW: fetal injury | | | | | | | |  AE: usually well | | | | tolerated, rare: | | | | cough, angioedema, | | | | hyperkalemia, | | | | diarrhea | | | | | | | |  Pt ed: high fat | | | | meals decrease | | | | absorption, interacts | | | | with grapefruit juice | | | | | | | | How does Inspra work? | | | | What is it used for? | | | | What factors should | | | | be considered by the | | | | provider when adding | | | | this drug to a | | | | current regimen. | | | | | | | | - - | | | | | | | | hormones; promotes | | | | retention of | | | | potassium & increased | | | | secretion of Na and | | | | water which  | +-----------------------+-----------------------+-----------------------+ +-----------------------+-----------------------+-----------------------+ | | | reduced blood volume | | | | and BP | | | | | | | | - - - ***Curren | | | | t | | | | guidelines*** | | | | recommend adding | | | | an aldosterone | | | | antagonist to HF | | | | therapy but only | | | | in pts with | | | | symptoms despite | | | | tx with ACEIs and | | | | BBs | | | | | | | | - - | | | | | | | | CCB | | | | | | | | - MOA? Prevent | | | | calcium ions from | | | | entering cells. | | | | Biggest effect on | | | | heart, blood | | | | vessels, vascular | | | | smooth muscle | | | | (VSM).  prevents | | | | contraction  | | | | vasodilation. | | | | Similar effect on | | | | heart as Beta | | | | blockers; reduce | | | | hearts | | | | contractile | | | | force, reduce HR, | | | | suppress | | | | conduction | | | | through AV node | | | | | | | | - - CI? | | | | Hypotension, sick | | | | sinus syndrome, | | | | 2^nd^ or 3^rd^ | | | | degree HB, | | | | grapefruit juice, | | | | can intensify | | | | effects of beta | | | | blockers | | | | | | | | - - - | | | | | | | |  ***Verapamil*** can | | | | be used in infants | | | | | | | |  ***Diltiazem | | | | (Cardizem)*** | | | | | | | | - | | | | | | | | | | | | | | | | - | | | | | | | |  ***Nifedipine | | | | (Procardia)*** 10-20 | | | | mg IR and 30-60 mg ER | | | | | | | | - - | | | | | | | | **reflex effects | | | | occur primarily with | | | | the immediate-release | | | | (IR) formulation of** | +-----------------------+-----------------------+-----------------------+ Vasodilators **nifedipine, not with the slow-release (SR) formulation**. This is because the baroreceptor reflex is turned on only by a rapid fall in blood pressure; a gradual decline will not activate the reflex. - With the IR formulation, blood levels of nifedipine rise quickly; hence blood pressure drops quickly and the reflex is turned on. Conversely, with the SR formulation, blood levels of nifedipine rise slowly, so blood pressure falls slowly and the reflex is blunted. So usually the SR/ER is prescribed and coupled with beta blockers to avoid this and decrease anginal pain! - Use: Long-term use reduces the rates of overt heart failure, coronary angiography, and coronary bypass surgery but not rates of stroke, myocardial infarction, or death. Also, because nifedipine causes minimal blockade of calcium channels in the heart, the drug is not likely to exacerbate AV block, heart failure, bradycardia, or sick sinus syndrome. **Nifedipine is preferred to verapamil for patients with these disorders.** - Pt education: Record anginal episodes, BP, AE - - - - - - - - **HF** -  HF is ventricular dysfunction, reduced CO, insufficient tissue perfusion, fluid accumulation. Tx: diuretics, RAAS inhibitors, beta blockers, digoxin  Systolic HF (LV dysfunction) now known as HF w/ reduced EF (HFrEF) -- LV can't contract properly  heart cannot pump the blood out with enough force  Diastolic HF (HFpEF -- preserved) -- LV can't relax, muscle is stiff  heart can't fill properly +-----------------------+-----------------------+-----------------------+ | | |  Left -- if LV pumps | | | | inefficiently, blood | | | | backs up into the | | | | lungs -- pulmonday | | | | edema (rales, | | | | wheezes, blood-tinged | | | | sputum, low O2, S3) & | | | | leads to... | | | | | | | |  Right -- if RV | | | | pumps inefficiently, | | | | blood backs up into | | | | the venous system | | | | (back in body) -- | | | | liver congestions, | | | | ascites, edema in | | | | legs  RHF occurs | | | | because of LHF | | | | | | | | A diagram of a | | | | patient\'s heart | | | | failure Description | | | | automatically | | | | generated | | | | | | | | - | +-----------------------+-----------------------+-----------------------+ +-----------------------+-----------------------+-----------------------+ | | | of toxicity? What is | | | | the antidote? | | | | | | | |  MOA: treats CHF & | | | | dysrhythmias; (+) | | | | Inotropic action, | | | | increase myocardial | | | | contraction force  | | | | increase CO, alter | | | | eclectic activity of | | | | the heart | | | | (neurohormonal), | | | | reduces s/s of HF but | | | | does not prolong life | | | | (2^nd^ line agent), | | | | | | | |  AE/CI: | | | | digoxin-induced | | | | dysrhythmias, Narrow | | | | therapeutic window, | | | | hypokalemia | | | | (increases risk of | | | | dysrhythmia), many | | | | interactions, hold | | | | for HR \ | | | | | | | | - | | | | | | | |  MOA: delays | | | | repolarization, | | | | prolongs action | | | | potential | | | | | | | |  Use for life | | | | threatening | | | | dysrhythmias (a fib, | | | | v tach, v fib) | | | | | | | |  CI: 2^nd^ & 3^rd^ | | | | degree HB, sick sinus | | | | syndrome | | | | | | | |  AE: lung damage, | | | | visual impairment, | | | | thyroid toxicity, | | | | optic neuropathy, | | | | photosensitivity, | | | | bradycardia, | | | | hypotension | | | | | | | |  BBW: pulmonary | | | | toxicity (pneumonitis | | | | & pulmonary | | | | fibrosis), liver | | | | toxicity, arrythmia | +-----------------------+-----------------------+-----------------------+