Drugs

Affecting
Blood Pressure
Chapter 43
Review of Blood Pressure Control
Blood pressure is determined by three elements:

● Heart Rate (HR)

● Stroke Volume (SV)

● Peripheral Resistance (PR)

Two compensatory systems regulating blood pressure:

● Baroreceptors

● Renin-Angiotensin-Aldosterone System
Baroreceptors
Sufficient pressure in the vessel stimulates
baroreceptors sending information to the brain -
medulla (cardiovascular center)

● High pressure vasodilation and

decreased HR and output decreased BP

● Low pressure vasoconstriction and

increased HR and output increased BP

Baroreceptor reflex maintains BP within normal

range.

Retrieved image from http://pharmacology-online.blogspot.com/2011/03/

Renin-Angiotensin-Aldosterone System
Low BP or poor oxygenation of kidneys causes release of RENIN into the bloodstream to the liver

Renin converts angiotensinogen to ANGIOTENSIN I which travels to the bloodstream to the lungs

Where angiotensin-converting enzyme (ACE) converts angiotensin I to ANGIOTENSIN II

Angiotensin II reacts with specific angiotensin II receptor sites on blood vessels to vasoconstrict

Increase total PR = Increased BP = Kidney

Angiotensin II also stimulates adrenal cortex to release ALDOSTERONE acts on nephrons to cause retention
of Na+ and water

Increased blood volume = Increased BP

Image retrieved from: https://i.pinimg.com/736x/be/fd/3c/befd3c90277746fa66a96bdb17b3ba6a.jpg
ANGIOTENSIN-
CONVERTING
ENZYME (ACE)
INHIBITORS
Angiotensin-Converting Enzyme Inhibitors
Indications: 1st line therapy to treat HTN. Used alone or with other agents.

Pharmacotherapeutics:

● Lowers BP

● Treats CHF (in combination with diuretics)

Pharmacokinetics: Oral; food decreases absorption

Pharmacodynamics: Block conversion of angiotensin I to angiotensin II

Prototype: Captopril (Capoten)

Captopril (Capoten)
Contraindications:

● Black Box warning: injury or death to fetus in second or third trimester

● Angioedema

ADRs: Resp: chronic dry cough. CV: hypotension (1st dose hypotension). Derm:
rash. F&E: hyperkalemia.

● Life threatening: angioedema or neutropenia

Captopril (Capoten)
Nursing Considerations:

● Always take the BP prior to administration

● Monitor I&O and daily weight

● Monitor for signs of angioedema

Maximizing Therapeutic Effects: Administer 1 hour before meals

Minimizing Adverse Effects: Take before bed (1st dose hypotension) and determine
baseline BP
Captopril (Capoten)
Patient Education:

● This medication may cause drowsiness - change positions slowly

● Monitor WBC count, Na+, K+ levels

○ Avoid K+ supplements

● Report chest pain, palpitations, or swelling of the lips, face or tongue

ANGIOTENSIN II
RECEPTOR
BLOCKERS
Angiotensin II Receptor Blockers
Pharmacotherapeutics: Management of HTN. For patients who cannot tolerate
ACE inhibitors.

Pharmacokinetics:

● Oral

● First pass metabolism (converted to active metabolite and highly protein

bound)

Pharmacodynamics: block receptors for angiotensin II

Prototype: Losartan
Losartan
Contraindications:

● Black Box Warning: injury or death to fetus in second or third trimester

ADR: CNS: dizziness, HA. CV: hypotension. Resp: upper respiratory infection. GI:
diarrhea. F&E: hyperkalemia.

Drug Interactions:

● Lithium, grapefruit juice, drugs that produce hyperkalemia.

Losartan
Nursing Considerations:

● Always take BP prior to administration

● Monitor patient for dizziness

● Monitor I&O and daily weight

● Monitor for K+ level

Losartan
Patient Education:

● This medication may cause dizziness - change positions slowly

● DO NOT USE K+ supplements or SALT SUBSTITUTES containing K+.

● Women of childbearing age should use contraception

BETA BLOCKERS
Beta-Blockers
Pharmacotherapeutics:

● Treatment of HTN

● Prevention of MI and decrease mortality in patients with recent MI

● Management of CHF

Pharmacokinetics:

● PO (1st pass metabolism)

● IV

Pharmacodynamics: Blocks stimulation of beta 1-adrenergic receptors

Metoprolol (Lopressor, Toprol XL)
Contraindications: CV abnormalities (CHF, unstable HR)

ADR: CNS: depression, dizziness, drowsiness. CV: bradycardia, hypotension,

peripheral vasoconstriction.

Nursing Considerations:

● Assess the pulse and BP prior to administering

Patient Education:

● Take medications as prescribed

● Monitor BP and HR - Notify HCP if slow pulse or dyspnea occurs

CALCIUM
CHANNEL
BLOCKERS
Calcium Channel Blockers
Pharmacodynamics
● Prevent movement of calcium ions into myocardial and arterial muscle cells →
● Reduced myocardial contractility; slowed cardiac impulse formation; arteriole relaxation →
● Reduced BP and decreased venous return

Prototype = diltiazem
(Others: clevidipine, diltiazem, felodipine, isradipine, nicardipine, nifedipine, nisoldipine, verapamil)
diltiazem
Pharmacotherapeutics:
● HTN
● Angina: will be discussed in a later lecture
Pharmacokinetics:
● PO
CIs and Cautions:
● Hypersensitivity + Heart block or Sick Sinus syndrome
● Pregnancy category C
● Lactation: pt’s should use another method of feeding while
on this medication
● Caution: renal/hepatic dysfunction ^^Looks nice, huh? But you
CV ADRs: Ca+N’T have it! You should
● Hypotension
increase fluids to prevent
● Bradycardia
● Peripheral edema
constipation, which is a unique
● Heart block ADR of CCBs
DIs:
● Grapefruit Juice
● Diltiazem + cyclosporine = toxic cyclosporine levels
VASODILATORS
Vasodilators
Pharmacodynamics: act directly on vascular smooth muscle → muscle relaxation →
vasodilation → decreased BP

Prototype = nitroprusside (Nitropress)

(Others: hydralazine, minoxidil)

nitroprusside (Nitropress)
Pharmacotherapeutics:
● Hypertensive Crisis: severe HTN that is not relieved by other therapy
○ Systolic > 210 mm Hg
○ Diastolic > 120 mm Hg

Pharmacokinetics:
● nitroprusside:
○ Titrate IV to reduce risk of cyanide toxicity
○ Reconstitute in D5W
○ Protect from light
● hydralazine: PO, IV, IM
● minoxidil: PO only
CIs and Cautions:
● Hypersensitivity + conditions that are worsened by a decrease in BP
○ Cerebral insufficiency
● Pregnancy: Category C
● Caution: PVD, CAD, HF, tachycardia
nitroprusside (Nitropress)
ADRs:
● Hypotension
● Reflex tachycardia
● Heart failure
● Chest pain
● Edema
● GI/Skin reactions
● Cyanide Toxicity
○ S/S= dyspnea, confusion, bright red venous blood, metabolic acidosis, air hunger, death
● Methemoglobinemia
○ Chocolate brown color blood
DIs:
● PDE5 inhibitors (Sildenafil, Vardenafil, Tadalafil)
○ Potent vasodilators
RENIN INHIBITORS
Brief Review of the Renin-angiotensin
system
● Release of Renin = angiotensinogen → Angiotensin I

● Angiotensin I → Angiotensin II by ACE enzyme

● Angiotensin II → vasoconstriction and increased BP

● Angiotensin II → secretion of aldosterone from adrenal cortex

● Aldosterone → increased reabsorption of sodium (and thus water) into the blood; increased excretion of
potassium into the urine

A Renin Inhibitor will prevent this cascade from occurring, through its direct inhibition of
Renin
aliskiren (Tekturna)
● Pharmacotherapeutics

○ Approved for the treatment of HTN in 2007

● Pharmacodynamics: directly inhibits renin, thereby inhibiting conversion of

angiotensinogen to angiotensin I →

○ Decreased BP

○ Decreased aldosterone release

○ Decreased sodium reabsorption

● Pharmacokinetics:

○ PO: slowly absorbed from the GI tract

aliskiren (Tekturna)
CIs and Cautions:
● Pregnancy category D: should be avoided during pregnancy and breastfeeding
● Women of childbearing age should use contraception while using this medication
ADRs:
● Hyperkalemia
● Angioedema
○ Difficulty breathing or swelling of the face, lips, or tongue
DIs:
● + furosemide = decreased diuretic effect
● + ACE inhibitors = severe combined ADRs
SELECTIVE
ALDOSTERONE
BLOCKERS
Selective Aldosterone Blockers
● Pharmacodynamics: binds selectively to the mineralocorticoid receptors

● Mineralocorticoids help maintain salt and water balance

● The main mineralocorticoid = aldosterone

○ By blocking aldosterone, these agents reduce sodium and water retention

○ Considered a potassium-sparing diuretic: kidneys excrete water and body

keeps potassium

● Selective aldosterone blockers are selective in that they do not interfere with
glucocorticoid, progesterone, or androgen receptors
Eplerenone
Pharmacotherapeutics:
● Used as 2nd line tx for HTN
● Used alone or with other HTN medications
● Reduce end-organ damage r/t HTN
Pharmacokinetics:
● PO
● Absorption not affected by food
● Metabolized in liver, eliminated by urine and stool
Eplerenone
CIs and Cautions:
● K+ > 5.5
● Any condition that can increase the risk of hyperkalemia
○ Type 2 diabetes with microalbuminuria; serum creatinine >2mg/dL in men or >1.8 mg.dL in
women; creatinine clearance <50 mL/min
○ Renal failure
ADRs: usually well tolerated, ADRs are typically mild
● Serious: Hyperkalemia r/t to potassium-sparing effects
DIs:
● ACE inhibitors
● ARBs
● CYP3A4 potent inhibitors
● Drugs that elevate K+
● + St. John’s Wort → decreased bioavailability
● + Grapefruit juice → increased bioavailability
Eplerenone
Nursing assessment and Pt. Edu:
● Monitor serum potassium levels periodically during therapy
● Monitor renal function
● Avoid potassium-based salt substitutes
● Avoid potassium supplements
● Avoid foods high in potassium, such as bananas
● Avoid grapefruit juice and St. John’s Wort
● If pt. experiences dizziness, use precautions and assistance to avoid falls
Eplerenone vs. Spironolactone (Aldactone)
● Both

○ Block mineralcorticoid receptors for aldosterone → decreased sodium and fluid retention →
decreased HTN

○ Risk for hyperkalemia

● Eplerenone = selective for aldosterone receptor

○ ADRs are not very common

● Spironolactone (Aldactone) = nonselective

○ Equally stimulates androgen and progesterone receptors → frequent endocrine ADRs

■ Inability to achieve an erection

Antihypotensive Agents:
VASOPRESSORS
Overview of
Vasopressors
Vasopressors = Adrenergic Agonist = Sympathomimetic
● Affects both alpha and beta receptors

● Action of sympathomimetic drugs:

○ Increase heart rate with increased myocardial contractility

○ Dilate bronchi and respirations increase in rate and depth

○ Vessel constriction = increased blood pressure

○ Decrease intraocular pressure

○ Glycogenolysis

○ Dilate pupils
Vasopressors: Indications

Dobutamine: Heart Failure

Dopamine: Shock

Epinephrine: Shock

● When increased BP and heart contractility are essential

● To prolong effects of regional anesthetic

● Primary treatment for bronchospasm

Norepinephrine: Shock

● During cardiac arrest to get sympathetic activity

Dobutamine
Indication: Heart Failure
Pharmacodynamics: Acts on both
receptor sites, but has slight
preference for B1-receptor sites. It
can increase myocardial contractility
without significant change in rate and
does not increase the O2 demand of
the heart
Pharmacokinetics: IV
Contraindications: Pheochromocytoma,
tachyarrhythmias/VFib, hypovolemia
Caution: Peripheral vascular disease (e.g.
Atherosclerosis, Raynaud's disease)
Adverse Effects: Arrhythmias, HTN, palpitations,
angina, dyspnea, nausea, vomiting, constipation,
headache, sweating, hypokalemia, muscle cramps
Drug Interactions: TCAs, MAOIs, caffeine
Dopamine
Indication: Shock
Pharmacodynamics: Stimulates heart
and blood pressure, dilates renal and
splanchnic arteriole dilation, and
increases blood flow to kidneys (to
prevent renal failure secondary to
epi/norepi)
Pharmacokinetics: IV
Contraindications: Pheochromocytoma,
VFib, hypovolemia
Adverse Effects: Ectopic beats,
tachycardia, angina, palpitations,
headache, hypotension, vasoconstriction,
ventricular arrhythmias
Pregnancy Category: C
Epinephrine (Adrenalin, Adrenaclick)
Indications: Anaphylactic Shock, Cardiac
Emergencies, VFib, Asthma, Glaucoma
Pharmacodynamics: Many responses in different
organs/tissues (CV: Positive Inotropic and
Chronotropic Effects). Nonselective adrenergic
agonist.
Pharmacokinetics: IV, subQ, IM, inhaled
Contraindications: Sulfite sensitivity, closed
angle glaucoma, active labor
Adverse Effects: Hypertensive crisis, angina,
cerebral hemorrhage, cardiac arrhythmias,
extravasation (necrosis)
Many drug interactions because it stimulates
many receptors
Pregnancy Category: C
Norepinephrine (Levophed)
Indications: Shock, and used during cardiac
arrest to get sympathetic activity
Pharmacodynamics: Peripheral vasoconstrictor,
dilates coronary arteries, increase BP, increase
strength of muscle contraction
Pharmacokinetics: IV
Contraindications: Pheochromocytoma,
tachyarrhythmias/VFib, hypovolemia
Caution: Peripheral vascular disease (e.g.
Atherosclerosis, Raynaud's disease)
Adverse Effects: Arrhythmias, HTN, palpitations,
angina, dyspnea, nausea, vomiting, constipation,
headache, sweating, hypokalemia, muscle cramps
Drug Interactions: TCAs, MAOIs, caffeine
 Diuretic
Agents
Chapter 51
Depaul University
Nursing 426
Diuretics (hydrochlorothiazide, furosemide, spironolactone)

Use: HTN and Edema Contraindications: Renal

Insufficiency/Anuria, Preexisting F/E
Pharmacokinetics: PO, IV, or both imbalances

Pharmacodynamics: Work in specific Adverse Reactions: F/E imbalances

areas of the kidneys to alter the F/E (Potassium Imbalances), Hypotension
balance
Lifespan: Older individuals are at an
Min/Max: Take in the morning,
increased risk for adverse effects
Monitor I/O’s, Monitor
Electrolytes, Monitor Body
Weight
Thiazide Diuretics
Pharmacokinetics Interactions

● PO Sulfa Drugs

Location of Action Dofetalide (antiarrhythmic)

● Distal Tubule

Electrolytes Affected

● Na+, Cl-, H2O, K+, HCO3, Mg

● Ca2+

Prototype = hydrochlorozide
Loop Diuretics
Pharmacokinetics Interactions

● PO ● Sulfa Drugs

● IV ● Aminoglycoside Antibiotics

Location of Action Adverse Effects

● Ascending Loop of Henle ● Ototoxicity

Electrolytes Affected:

● Na+, Cl-, H2O

Prototype = furosemide
Potassium-Sparing Diuretics
Pharmacokinetics

● PO

Location of Action

● Distal Tubule

Electrolytes Affected:

● Na+, H2O

● K+

Prototype = spironolactone
S/S of K+ Imbalances
Carbonic Anhydrase Inhibitors
Use: Edema from CHF, Open Angle Glaucoma, Aspirin OD

Pharmacokinetics

● PO

● IV

Pharmacodynamics

● Decrease Aqueous Humor Decrease Intraocular Pressure

● Blocks carbonic anhydrase Decreased H+ excretion and increased excretion of Na+, H2O, K+,
HCO3
Prototype = acetazolamide
acetazolamide
Contraindications Adverse Reactions

● Same as other diuretics ● Hypercholeremic Acidosis

Interactions ● Most Serious = Bone Marrow

Suppression
● Sulfa drugs
Min/Max
● Thiazide diuretics
● Same as other diuretics

● CBC d/t bone marrow suppression

Osmotic Diuretics
Use: Acute renal failure and cerebral edema/increased ICP

Pharmacokinetics

● IV

Pharmacodynamics

● Increases osmotic pressure, leading to decreased sodium and water reabsorption and
increased/forced urine production

● Pulls fluid from tissue into the vascular space

Prototype = mannitol
mannitol
Contraindications Min/Max

● Pulmonary edema Warm vial to eliminate crystals and use in-line filter

● Intracranial Hemorrhage Monitor vitals and F/E

● Severe Dehydration Signs of H2O Toxicity

Adverse Effects ● SOB

● Acute Pulmonary Edema/CHF ● Chest Pain

● Dehydration ● Edema

● H2O Toxicity

● F/E imbalances