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1
PHARMACOLOGY FOR THE
RENAL & CARDIOVASCULAR
SYSTEMS
N402
Lipids are essential…
and can be problematic
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Triglycerides—fat storage and energy source
Phospholipids—plasma membrane component
Steroids—plasma membrane component
Excessive levels contribute to cardiovascular disease
Triglycerides
Phospholipids
Steroids
Desirable lipid levels
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Lipid
Desirable
High Risk
Total
< 200 mg/dl
Cholesterol
LDL Cholesterol < 100 mg/dl
> 240 mg/dl
HDL
Cholesterol
Triglycerides
> 60 mg/dl
< 35 mg/dl
< 149 mg/dl
> 200 mg/dl
> 160 mg/dl
Lifestyle modifications
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Monitor
No
smoking
Weight
Lipid control
Increase
fiber
Exercise
↓
Saturated
fats
Major lipid lowering agents
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Statins
Cholesterol
absorbing
Fibric acid
agents
Bile acid
sequestrants
Niacin
Statins—Mechanism of action
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HMG-CoA reductase
Regulates cholesterol biosynthesis
Statins inhibit HMG-CoA
Liver makes less cholesterol,
more LDL receptors
Increased removal of LDL→lower LDL and cholesterol
Statins—Precautions
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
Minor side effects
 Headache
 Fatigue
 Muscle,
joint pain
 heartburn

Serious adverse effects
 Severe
myopathy
 Rhabdomyolysis
Bile acid sequestrants—Mechanism of
action
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Sequestrant binds with bile acid
Bile acid contains large amounts cholesterol
Acids and cholesterol eliminated in feces
Liver makes less cholesterol, more
LDL receptors
Increased removal of LDL→lower LDL and cholesterol
Bile acid sequestrants—Precautions
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Bloating
 Constipation
 Can bind with other drugs (e.g., digoxin, warfarin)
 Bind with some vitamins
and minerals

Niacin—Mechanism of action
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Inhibits the peripheral mobilization of free fatty acids
 Less FFA available for
hepatic synthesis of
triglycerides and very
low-density lipoprotein
(VLDL) particles
 Reduces hepatic conversion of VLDL particles to LDL
particles
 Interferes with conversion of VLDL-C to LDL-C

Niacin—Precautions
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Flushing and hot flashes almost always
Nausea, gas, diarrhea
Hepatotoxicity
Gout
Can raise BG levels
Fibric acid agents—
Mechanism of action
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Activate
lipase
Lipase
increases TG
breakdown
TG
eliminated
from plasma
Fibric acid agents—Precautions
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Does not reduce mortality from CV disease
May increase mortality
Reduces triglycerides only
May be useful in combination with statins
Cholesterol absorption inhibitors—
Mechanism of action
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
Cholesterol absorbed by small intestine
⇩
Ezetimibe (Zetia) blocks absorption
⇩
Less cholesterol enters bloodstream
⇩
Body responds by producing more cholesterol

Therefore requires use of statin at same time!
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Cholesterol absorption inhibitors—
Precautions
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Nasopharyngitis
Myalgia
URI
Arthralgia
Diarrhea
Anatomy of the nephron
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Classification of renal failure
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What diuretics do….
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Remember…“water follows salt!”
Osmotic—pulls water into nephron
Thiazide—blocks reabsorption of Na+, Cl-, H20 in
distal tubule
Loop—blocks reabsorption of Na+, Cl-, H20 in loop
of Henle
Potassium-sparing—blocks reabsorption of Na+,
reduce secretion of potassium
Mechanism of action of various
diuretics
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Loop diuretics
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Work directly on loop of Henle
Rapid acting when given IV
Reduce edema from multiple causes
Increases urine output even when renal blood flow is
diminished
Can produce:
 Dehydration
 Electrolyte
 Otoxicity
imbalance
Thiazide diuretics
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Most frequently prescribed
Mild-moderate hypertension
Moderate heart, liver, renal failure
Similar adverse effects to loop diuretics
Can raise BG levels
Potassium-sparing diuretics
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Do not affect potassium levels
Produces a weaker diuresis
Reduces mortality in patients with heart failure
Should not be encouraged in increase potassium in
diet!
Examples of major groups of diuretics
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Loop
•???
Thiazide
•???
+
K
•???
Sparing
Single-tablet combination diuretics
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Can reduce adverse effects
Desired effects may be enhanced
Enhanced patient convenience
Promotes compliance
Monitoring the patient on diuretic therapy (Quality &
Safety Education for Nurses—QSEN)
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Parameter
Intake/output
Daily weight
Laboratory values
Vital signs: Pulse, BP
Level of consciousness
Hypersensitivity
Hearing and vision
Sensitivity to light exposure
Inadequate?
Excessive?
Roles of major electrolytes
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Electrolyte
Primary roles
Sodium
Muscle contraction
Nerve transmission
Chloride
Peak muscle function
Potassium
Muscle contraction
Nerve transmission
Glycogen formation
Magnesium
Muscle relaxation
ATP (energy production
Calcium
Bone health
Nerve transmission
Muscle contraction
Symptoms of deficiency or
excess???
Causes of electrolyte imbalance
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Principles of the movement of body
fluids
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Osmolality—measure of the number of dissolved
particles in 1 L of water
 Osmosis—movement of water from areas of low
concentration (low osmolality) to higher
concentration (high osmolality)
 Tonicity—ability of a
solution to cause a
change in water movement across a membrane
due to osmotic forces

Tonicity
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Potential results
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Hypotonic solution—water moves from plasma to
interstitial fluid and cells, i.e., out of vascular
system…may result in hypotension
Hypertonic solution—water moves from cells and
interstitial fluid to plasma, i.e, into the vascular
system…more water than sodium is lost from the
body…causes cell shrinkage and possible brain
shrinkage
Isotonic solution—water moves freely between
plasma and interstitial fluid and cells
Types of fluid replacement agents
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Crystalloids
Colloids
∙Contain electrolytes and other substances
that are similar to body’s ECF
∙Replace depleted fluids
∙Promote urine output
∙Sodium is most common
crystalloid added to solutions
∙Dextrose can be added
∙Increases total fluid volume in
the body
∙May be isotonic, hypertonic, or
hypotonic
∙Proteins, starches, etc.
∙Remain in blood for long time
∙Molecules are too large to cross
capillary membranes
∙Same effect as hypertonic
solution
∙AKA plasma volume expanders
∙Used in hypovolemic shock
∙Burns, hemorrhage, surgery
When imbalances occur…
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Patient can present with:
 Irregular heartbeat
 Fatigue, lethargy
 Convulsions or seizures
 Nausea and/or vomiting
 Diarrhea, constipation, abdominal cramping
 Muscle weakness or pain
 Cognitive changes (mood, confusion)
 Headache
Sodium imbalance
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Hypernatremia
Most common cause is renal disease
 Mild
cases—low sodium diet
 Severe cases—hypotonic fluids if hypovolemic, diuretics
if hypervolemic
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Hyponatremia
Caused by ↑ ADH or other disorders
 Treated
with NaCl, IV NS, or IV LR
Potassium imbalance
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Hyperkalemia
Due to diet, renal disease
Mild cases—restrict potassium
intake
 Severe cases—Glucose & insulin
(1 amp D50 and 10 U insulin)
 Kayexalate
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Hypokalemia
Can be due to excessive use of laxatives
Mild—increase potassium containing foods, oral preps
 Severe—parenteral KCl

pH: acidosis and alkalosis
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Acidosis = ↓pH
Too much acid
Too little base
Alkalosis = ↑pH
Too little acid
Too much base
Maintaining body pH
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Lungs
• Release CO2
• pH increases, acidity decreases
Kidneys
• Excrete excess acid or base
• Make changes slower than lungs
Buffer
system
• Body’s natural weak acids & bases
• Work chemically to minimize pH
changes
Treatment of pH imbalance
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
Acidosis (pH < 7.35)
 Is
cause respiratory, metabolic (renal) or both?
 Rapid infusion of NaHCo3 must be done carefully!
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Alkalosis (pH > 7.45)
 Correct
underlying condition
 Infuse NaCl and KCl to
promote excretion of NaHCO3
Treatment of hypertension based on its
classification
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Classification
Blood pressure
Without
Compelling
Indication
With
Compelling
indication
Normal
119/79 or less
No medication
Healthy lifestyle
promotion
No medication
Healthy lifestyle
promotion
Prehypertension
120-139/80-89
Lifestyle
modification
Lifestyle
modification
Stage I
140-159/90-99
Thiazide diuretic
Other
antihypertensives as
needed
Stage 2
≥160/≥100
Two drug
combination
Other
antihypertensives as
needed
Incidence of hypertension
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African Americans have higher incidence of stroke and ESRD
Caucasians and Asians have higher incidence of CAD
ACEI works best as 1st medication for Caucasians, CCB more
effective for African Americans
Hypertension rates vary
Race of
by race and ethnicity:
Women
Ethnic
Group
(CDC 07/07/2014)
Men (%)
(%)
African
Americans
43.0
45.7
Mexican
Americans
27.8
28.9
Whites
33.9
31.3
All
34.1
32.7
Lifestyle modifications for hypertension
management
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Treatment with CCBs
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Helpful in patients who are not as responsive to
other medications: African Americans, elderly
Can be either selective (blood vessels), e.g.,
Nifedipine, or nonselective (affect both blood
vessels and heart), e.g., Diltiazem (add)
Adverse effects are related to vasodilation
Immediate-acting preparations can cause reflex
tachycardia
Treatment with β-adrenergic
antagonists (β-blockers)
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First-line drugs for treatment of HTN
Reduce heart rate and contractility
Can reduce angina because CO decreased
Can treat certain dysrhythmias:
Also useful in treating heart failure, MI, and
migraines
Treatment with β-adrenergic
antagonists (β-blockers)
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First-line drugs for treatment of HTN
 Reduce heart rate and contractility
 Can reduce angina because CO decreased
 Also useful in treating heart failure, MI, and migraines
 Adverse effects due
to mechanism of action:
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Fatigue, activity intolerance
 Heart less responsive to
exertion
 Male sexual dysfunction

Treatment with Alpha1-Adrenergic
Blockers
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Block sympathetic receptors in arterioles causing
vasodilation
 Used in conjunction with other medications, not firstline
 Also used in treatment
of BPH, so be sure to
ask patient why he is
taking the drug!

Summary of heart failure
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Heart’s ability to pump becomes weaker
Can be right-sided or both right- and left-sided
Right-sided failure—heart cannot pump enough
blood to lungs for oxygenation
 Causes
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fluid build up in LEs, abdomen and liver, NVD
Left-sided failure—heart unable to pump enough
blood to systemic circulation
 Fluid
build up plus SOB and fatigue
Symptoms of heart failure
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Treatment with ACE-inhibitors
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Angiotensin II increases blood pressure by
stimulating smooth muscle cells:
ACE-inhibitors lower peripheral resistance, inhibit
aldosterone secretion, and dilate veins
Treatment with diuretics
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Produce few side effects
Increase urine flow:
 Reduce
blood volume
 Less peripheral edema
 Less pulmonary congestion
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Cardiac workload
reduced, output
increased
Treatment with cardiac glycosides
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Digoxin is only cardiac glycoside available in US
Oldest of cardiac medications
Can cause bradycardia
Monitor potassium
Check serum dig levels
Digoxin toxicity
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Can progress to…
Treatment with vasodilators
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Act directly on blood vessels
 Hydralazine (Apresoline) works on arterioles
 Isosorbide dinitrate (Isordil) works on veins
 Combination form
available (BiDil)
 BiDil highly effective
in African Americans
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Labs to monitor for CV disease
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Renal
function
Drug
levels
Liver
function
K+
EKG
Cholesterol
Na