Anti -hypertensive Agents Wanda Lovitz, APRN

Objectives Objectives: Anti-Hypertensives Agents For the antihypertensive agents presented: Identify the: Classification MOA Indications Common and serious adverse reactions Nursing implications

Hypertension Facts Hypertension affects 1 in 3 Americans Hypertension is the #1 reason for office visits RCT show that treating HTN can reduce: Stroke by 40% Cardiovascular death by 20% Heart failure by 50% American College of Cardiology 1996

MI (Myocardial infarction) Stroke HYPERTENSION is a major risk factor for cardiovascular disease The Problem? Cardiovascular Disease can be Deadly! MI (Myocardial infarction) Stroke Vascular Diseases DEATH!

Blood Pressure = Cardiac Output X PVR Cardiac Factors Heart Rate Contractibility Circulating Volume Salt (sodium) Aldosterone Beta-blockers Calcium channel blockers Centrally acting adrenergics/sympatholytics Can alter cardiac factors such as HR or contraction of heart – “chilling agents” Can alter the amount of fluid circulating in pipes – less volume is less pressure in the pipes! Many of the same drugs that are used for hypertension are also used for treatment of angina! We will be discussing many of them with our discussion of angina ACE inhibitors Diuretics Drugs that reduce HR, improve cardiac contractility or reduce blood volume, will lower BP

*Centrally acting adrenergics/ Blood Pressure = CO x Peripheral Vascular Resistance Hormones Peripheral sympathetic receptors CNS Local Drugs ACE inhibitors* Calcium channel blockers* Angiotensin II blockers Drugs *Centrally acting adrenergics/ sympatholytics Drugs Peripherally acting adrenergics/ sympatholytics Receptors Alpha Beta Drug Group Beta-blockers* SVR is all about constriction and dilation of arteries!! Assuming that your volume stays the same – smaller pipes increase the pressure required to push the volume through them and larger pipes decrease the amount of pressure required to push the same volume. SVR is altered by a variety of factors seen in the white boxes. Note that the drug groups in red are double dippers – they alter both CO and SV. This gives them an advantage over the more specific drugs. Drug Group Alpha 1-blockers Peripheral Vascular Resistance (PVR) is increased by arteriolar constriction. So, drugs that promote VASODILATION will decrease PVR and thus decrease BP *Red = Drugs that alter BOTH CO and PVR

Classification of BP in Adults Cardiovascular Problems - Part 1 Classification of BP in Adults 4/28/2017 Category SBP (mmHg) DBP (mmHg) Normal < 120 and < 80 Prehypertension 120-139 or 80-89 HTN, stage 1 140-159 or 90-99 HTN, stage 2 > 160 or > 100 Important facts: have lowered what is normal. Now have prehypertension designation and note that can be either SBP or DBP Diagnosis of true hypertension starts at the 140/90 settings – stage 1 NUR 870: Pathopharmacology

JNC 8 Recommendations (cont)

Regulators of Blood Pressure 1. Sympathetic Nervous System When the B/P is LOW baroreceptors in the brain are stimulated which then: 1. activate beta receptors (B1) in the heart and 2. activate vascular alpha 1 receptors in the vasculature, resulting in VASOCONSTRICTION 2. Renin-angiotensin-aldosterone system (RAAS) Can elevate BP when it is too low 3. Kidney With low B/P, the GFR falls too, promoting retention of NA,CL and water to raise the blood volume

Diuretics ARBs Aldomet Lopressor doxasin/ Cardura Capoten Losartan Vasodilator/ CENTRALLY acting sympatho- lytics Vasodilator/Peripherally acting Sympatho- lytic Beta-Blockers “olol” Vasodilator/Peripherally acting Symphatholytic/Alpha Adrenergic Blocker RAAS suppressor ACEI “prils” RAAS suppressor ARBs CCBs “pines” Thiazide hydrochlorothiazide/ HCTZ triamterene/ Dyrenium methyldopa/ Aldomet indirect alpha 2 agonist (converted in the brainstem) metoprolol/ Lopressor doxasin/ Cardura captropril/ Capoten cozaar/ Losartan Cardizem/ Diltiazem Loop furosemide/ Lasix alpha2 agonist clonidine/ Catapress amlodipine/ Norvasc Potassium- Sparing spironalactone Aldactone triameterene/ Dryenium

Indications for the various anti-hypertensive agents from JNC 8 Guidelines

Antihypertensives: Diuretics Diuretic Agents – Increase urinary output decreasing CO Decrease Circulating Volume 3. Decrease arterial resistance decreasing PVR

Classes of Diuretics Diuresis = “to urinate thoroughly” Potassium-sparing = Mild diuresis Thiazide and thiazide-like diuretics = Mild diuresis Loop = Moderate to PROFOUND diuresis 14 14

Diuretics All of the diuretics lower BP by decreasing CARDIAC OUTPUT Can ENHANCE the effect of other anti-hypertensive SOME diuretics also decrease PVR by DILATING arterioles This class (diuretics) is the LEAST expensive of all the anti-hypertensives

Thiazides Diuretics Prototype Drug MOA Indications/Therapeutic Use hydrochlorothiazide (HydroDiuril, HCTZ) MOA ↑ both Na & H2O excretion by the kidneys (less volume = less CO) WATER FOLLOWS SODIUM Dilation of arterioles (the only diuretic to widen the arteries = VASODILATION EFFECT) Indications/Therapeutic Use 1st line management of mild HTN unrelated to RAAS problems ENHANCES the effect of other antihypertensive agents Recommended as 1st line agent

Thiazide Diuretics: Side Effects SE: related to the interference with the nephron’s normal regulatory mechanisms Most common: HYPOKALEMIA (low K+) Nursing action: monitor serum potassium levels Potassium supplements may be given Nursing action: encourage foods rich in potassium 17 17

Loop Diuretics MOA Causes a decrease in fluid in the blood vessels Inhibits the kidneys ability to REABSORB SODIUM Blocks the reabsorption of sodium in the ascending loop of Henle Makes the kidneys put more sodium in the urine water follows sodium and more urine is excreted Causes a decrease in fluid in the blood vessels so …. (CO) Can cause PROFOUND DIURESIS! 18 18

Therapeutic uses for Loop Diuretics Indications Acute CHF and pulmonary edema Edema associated with renal or liver disease HYPERTENSION

Loop Diuretics Prototype: furosemide (Lasix): - Most commonly used - More diuretic effect than the thiazides PO and Parenteral (IV/IM) 20 20

Side Effects: Loop Diuretics Common SE: LOW K+ (hypokalemia) Dehydration & hypotension Important Nursing Assessment Monitor K levels closely Most patients will be receiving supplements of K WITH their Lasix dose Usually po KCL used to PREVENT hypokalemia May see IV to TREAT hypokalemia 21 21

Potassium Sparing Diuretic spironolactone Aldactone & triamterene /Dyrenium MOA: Potassium-sparing diuretics are used to reduce the amount of water in the body BLOCKS the action of ALDOSTERONE – so, increases sodium excretion while decreasing potassium excretion Unlike the other diuretic medicines, these medicines DO NOT cause the body to lose potassium – Used with thiazides and loop diuretics in the therapy of hypertension Helps to counteract potassium loss by thiazide and loop diuretics

spironlactone/Aldactone a Potassium-sparing diuretic Aldactone provides only SMALL degree of diuresis Only MODEST hypotensive effect Most significant SE = HYPERKALEMIA

Sympatholytics Sympathetic DEPRESSANTS/SNS Blockers/Anti-adrenergic Agents *These drugs decrease BP by decreasing PVR Important Principle Sympathetic NS VASOCONSTRICTS! Vasoconstriction = ↑ PVR   BP! So it you DEPRESS or BLOCK the SNS ....you BP

Therefore… Key Terms to KNOW Adrenergic – SNS stimulated; “Fight or Flight” Response predominates =VASOCONSTRICTION Cholinergic – PSNS stimulated; “Rest and Digest” Response predominates =VASODILATION Therefore…

Therefore……. Anti-adrenergic or Adrengeric Blocking agents (symphatolytics or SNS blockers) inhibit or work against SNS activity  decrease in BP and HR (GOOD!)  Anti-cholinergic agents inhibit or work against PSNS anti-cholinergic activity  increase in BP and HR NOT GOOD if you have hypertension! Many drugs for cold/flu (OTC) have anti-cholinergic Should be AVOIDED by patients with HTN

Sympatholytic Drug Classes Beta-adrenergic blockers aka “beta blockers” 2. Centrally acting alpha2 agonists 3. Alpha-adrenergic blockers

Beta Adrenergic Blockers Prototype metoprolol (Lopressor) beta blockers are all drugs that end in ‘olol’ MOST COMMON SIDE EFFECTS depression & sedation bronchoconstriction can exacerbate resp problems in pts with COPD (bronchoconstriction) MOA Blocks stimulation of beta1 (myocardial) receptors Reduces HR and contractility Indications/Therapeutic Uses Anti-hypertensive Anti-anginal

Nursing Implications with the beta blockers Important to remember that ALL of the beta-blockers REDUCE HEART RATE as well as blood pressure! The beta-blockers have a wide variety of indications/therapeutic uses: Anti-hypertensive, anti-anginal Anti-dysrhythmic

NURSING ALERT With ALL beta-blockers (drugs that end in ‘olol’) Recognize that these drugs will decrease HR and B/P- no matter WHY the patient is receiving them NURSE JUDGEMNT – HOLD med if HR is less than 60 or B/P is less than 100 systolic Know WHY your patient is on a beta-blocker for his HTN? for his Heart - antiarrhythmic, antianginal?

Centrally Acting Alpha 2 Agonists Cardiovascular Problems - Part 1 4/28/2017 Prototype methyldopa (Aldomet) MOA: Stimulates CNS by ACTIVATING inhibitory alpha-adrenergic receptors within the brain activation of these central alpha receptors produces:  sympathetic outflow and cause VASODILATION  PVR DRUG EFFECTS  BP & peripheral resistance Mild  in HR Dry mouth MOA - Produces  sympathetic outflow to heart, kidneys, & blood vessels Decreasing outflow has following effects: mild decrease in heart rate; renal vasodilation, & blood vessel vasodilation Impotence problem in men – a major reason why adherence to therapy may be a problem. Interactions – many - – particularly w/ drugs that manipulate BP or HR As a group – antihypertensives have additive effect on BP when given in combination with other antihypertensive agents or vasoactive agents. NUR 870: Pathopharmacology

Centrally Acting Alpha 2 Agonists Methyldopa/ Aldomet Side Effects Most frequent: SEDATION & Sexual dysfunction Serious: hepatic necrosis & hemolytic anemia Interactions: many drug/drug interactions Contraindications: active liver disease

Nursing Implications: Centrally Acting Alpha 2 Agonists methyldopa/Aldomet INITIALLY : Montior BP and HR frequently Monitor temp “Drug fever” possibly accompanied by encephalopathy and hepatic function changes Teaching Do not stop taking suddenly! REBOUND HYPERTENSION/HYPERTENSIVE CRISIS

Centrally Acting Alpha 2 Agonist Clonidine/Catapress CENTRALLY acting alpha 2 agonist agent INDICATION: Hypertension SE: : Essentially safe Drowsiness Bradycardia and decrease in Xerostomia (dry mouth) Rare instances of rebound hypertension if this drug is abruptly stopped MOA: alpha-adrenergic agonist Causes SELECTIVE ACTIVATION alpha2 receptors in the CNS Decreases sympathetic outflow to the blood vessels and heart resulting in VASODILATION thus decreasing PVR and B/P Route: oral or transdermal patch

Alpha Adrenergic Blockers doxazosin/Cardura MOA: Block CATECHOLAMINES to decrease heart rate and relax blood vessels Decreases CO and PVR Indication: Hypertension BPH (benign prostate hypertrophy) – these drugs relax blood vessels throughout the body Side Effects: Dizziness, Postural hypotension

Calcium Channel Blockers These drugs prevent CALCIUM ions from entering muscle cells Affect the muscle cells in the heart and around the blood vessels Also known as calcium antagonists IN THE VASCULAR SMOOTH MUSCLE, CALCIUM CHANNELS REGULATE CONTRACTION If calcium channels are blocked , contraction is prevented, thus decreasing the force and rate of myocardial contraction relaxes the muscles around the arteries resulting in VASODILATION CCBs act selectively on peripheral arterioles and arteries and arterioles of the heart

Calcium Channel Blockers = “pines” amlodoPINE/Norvasc nifedipine/Procardia nicardipine/Cardene Plus: diltaziem/ Cardizem

VaVasodilator: CCBs Major Nursing Considerations: Know WHY your patient is receiving a CCB Antihypertensive effect? Anti-anginal? Anti-dysrhythmic? Major Nursing Considerations: Take BP & HR prior to administration Monitor weights and I & O  CCBs can cause FLUID RETENTION Note: Serum calcium levels are NOT affected by the CCBs

Blood Pressure = CO x Peripheral Vascular Resistance Hormones Peripheral sympathetic receptors CNS Local Drug Groups ACE inhibitors* Calcium channel blockers* Angiotensin II blockers Drugs Peripherally acting adrenergics Receptors Drugs Centrally acting adrenergics* Beta Alpha Drug Group Beta-blockers* SVR is all about constriction and dilation of arteries!! Assuming that your volume stays the same – smaller pipes increase the pressure required to push the volume through them and larger pipes decrease the amount of pressure required to push the same volume. SVR is altered by a variety of factors seen in the white boxes. Note that the drug groups in red are double dippers – they alter both CO and SV. This gives them an advantage over the more specific drugs. Drug Group Alpha 1-blockers * Drugs that alter both CO and PVR

Cardiovascular Problems - Part 1 4/28/2017 Quick review of normal Major point = Decreased blood volume & drop in BP trigger system ACE found primarily in lung capillaries. What happens -- Decreased renal perfusion   conversion of angiotensinogen to angiotensin I release of renin converted to angiotensin II by angiotensin-converting enzyme (ACE) RAAS activated when: Loss of blood volume Drop in BP Decreased renal perfusion  release of renin  conversion of angiotensinogen to angiotensin I  converted to angiotensin II by angiotensin-converting enzyme (ACE) NUR 870: Pathopharmacology

ACEI & ARBs RAAS Suppressants ACEI (angiotension converting enzymes INHIBITORS) ARBs (angiotension RECEPTOR BLOCKERS) MOA: These drugs basically lower BP by →DECREASING peripheral vascular RESISTANCE (PVR) less pressure in the pipes or vessels less “stiff” Also DECREASES circulating VOLUME (CO) by inhibiting aldosterone reabsorption

Review of Angiotension actions Vasoconstriction Release of ALDOSTERONE Alteration of cardiac and vascular structure HYPERTROPHY REMODELING

ACEIs: VASODILATE to decrease CO MOA: BLOCKS angiotension converting enzyme (ACE) from converting angiotensin I to angiotensin II Angiotensin I is a weak vasoconstrictor Antiotensin II is a very powerful vasoconstrictor Also, angiotension stimulates release of aldosterone and ADH resulting in increase blood volume (CO) So...if we block angiotenisin II = CO ACE “inhibitors” decrease BP by BOTH vasodilating and decreasing volume

Angiotensin-Converting Enzyme Inhibitor (ACEI) RAAS Suppressant Prototype captopril (Capoten) One of the most widely prescribed classes of anti-hypertensives MOA Blocks conversion of angiotensin I to vasoconstricting angiotensin II Directly decreases the amount of antiotension II result is a decrease in systemic vasoconstriction and Result is VASODILATION → Causing decreased BP by decreasing PVR

Nursing Implications: ACEI/RASS Suppresssant: captopril/Capoten Cardiovascular Problems - Part 1 4/28/2017 Initial dosing Monitor for significant BP drop 1-3 hours following first dose! First dose hypotension  VASODILATION EFFECT May require volume expansion Stop diuretic therapy 1 week prior to initiating therapy Monitor BP & HR closely during initial dose adjustment period! Long term Periodic monitoring of: BUN/creatinine, serum K+ levels Teaching Similar to beta blockers Stopping diuretics before initiating drug may reduce BP drop with initial dosing. Emphasize importance of need to closely monitor w/ initial dosing due to big drop in vital signs as a possibility. NUR 870: Pathopharmacology 45

SE: Related to the effects of vasodilation & alterations in blood flow SE: ACE Inhibitors SE: Related to the effects of vasodilation & alterations in blood flow headache; GI irritation; RENAL INSUFFICIENCY (transient increases in creatinine & BUN levels); dry, nonproductive, PERSISTENT COUGH; angioedema; & fatigue Commonly Rx ACEI: captopril/Capoten; Lisinopril, Zesteril , & enalapril (Vasotec)

RAAS Suppressant/Angiotensin RECEPTOR BLOCKER (ARBs) MOA Blocks the action of angiotension II from the RECEPTOR SITES on the blood vessels Effectively decreases the action of angiotensin II Result is vasodilation Also blocks aldosterone and ADH release Examples: cozaar/Losartan

ACTION OF ARBS

SE: Angiotensin Receptor Blocking (ARBs) Adverse effects – Angioedema is less common than with ACE inhibitors – however, if it occurs, continued use could result in severe hypersensitivity reaction – drug is stopped permanently if occurs. Renal failure – in patients with preexisting renal stenosis Fetal harm – during 2 & 3rd trimesters – there is contraindication for use. Too new to have good data regarding its effectiveness – therefore, controversial as to where it belongs in therapy unless pt cannot tolerate ACE inhibitors which are well proven drugs. Cardiovascular Problems - Part 1 4/28/2017 Side/Adverse Effects Well tolerated Possible Angioedema Renal failure Fetal harm Nursing Implications See ACE Inhibitor (captopril) DOES NOT ACTIVATE IN LUNGS THEREFORE NO COUGH! Not 1st line therapy Often replaces ACEI Rx NUR 870: Pathopharmacology 49

Cultural Considerations for Drug Therapy – African Americans Most responsive to single-drug therapy (as opposed to combination drug regimens) More responsive to diuretics, calcium channel blockers & alpha-adrenergic blockers Less responsive to ACE inhibitors & beta-blockers Screening very important because of increased incidence & to detect early in order to prevent end-target-organ damage

Cardiovascular Problems - Part 1 4/28/2017 The End Pharmacotherapy will be handled at the end! NUR 870: Pathopharmacology