1. Anti -hypertensive Agents
Wanda Lovitz, APRN

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

3. 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

4. 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!

5. 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

6. *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

7. 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
or 80-89
HTN, stage 1
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

9. JNC 8 Recommendations (cont)

10. 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

11. 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

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

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

14. 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

15. 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

16. 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

17. 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

18. 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

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

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

21. 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

22. 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

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

24. 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

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

26. 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

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

28. 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

29. 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

30. 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?

31. 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

32. 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

33. 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

34. 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

35. 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

36. 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

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

38. 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

39. 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

40. 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

41. 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

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

43. 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

44. 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

45. 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

46. 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)

47. 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

48. ACTION OF ARBS

49. 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

50. 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

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