PathPharm unit 3 COMBO set

Largest area of pharmacology

cardiovascular meds

Cardiovascular meds often have multiple

indications

Diuretics act on

kidneys to increase sodium and water excretion

diuretics act on the kidneys to

decrease reabsorption of sodium, chloride, water, and other substances

diuretics

increase sodium and water excretion

Diuretics decrease

fluid in vascular system

diuretics indications

HTN, CHF, CHF assoc edema, pulmonary edema, glaucoma

Diuretics examples

-thiazides

-loop diuretics

-potassium-sparing agents

loop diuretics

Loop of Henle

Thiazides

chlorothiazide (Diuril)

loop diuretics

Furosemide (Lasix)

potassium sparing agents

Spironolactone (Aldactone)

Diuretics: adverse effects

Possible fluid depletion; electrolyte imbalance (Na+ , K+ )

Diuretics rehab concerns

Watch for...

---> Orthostatic hypotension

---> Weakness, fatigue

---> Confusion, mood changes

Sympatholytics

beta blockers

Sympatholytics bind to

heart, block effects of epinephrine and norepinephrine

sympatholytic drugs

try to lyse activity in the SNS

Sympatholytics decrease

HR and contraction force

Sympatholytics Can also produce a more general

↓ in sympathetic responses

sympatholytic effect

decrease in sympatholytic responses

Beta blockers cardiovascular indications

- hypertension

- angina

- arrhythmias

- heart failure

- recovery from MI

Beta blockers others: indications

● Migraine

● Raynaud's

● Situational anxiety

raynauds disease

a peripheral arterial occlusive disease in which intermittent attacks are triggered by cold or stress

common beta blockers

end with "olol"

metoprolol (lopressor)

atenolol (tenormin)

propranolol (inderal)

nadolol (corgard)

carvedilol (corge)

esmolol (brevibloc)

cardioselective beta blockers

metoprolol, atenolol

nonselective beta blockers

propranolol, timolol, nadolol, pindolol

cardioselective vs non selective is dependent on

the affinity of the drug for the B-1 receptor

beta-1 subtype predominates

on the heart

cardioselective drugs have a higher affinity to the

B-1 receptor

Nonselective drugs bind to

both B1- and B-2

Beta-2 receptors are found

primarily on the lungs

non-selective beta blockers block

Block both beta-1 and beta-2 receptors.

beta-blockers adverse effects, rehab concerns

● Bronchoconstriction

● Orthostatic hypotension

● Psychotropic effects (depression, lethargy, ↓ libido), esp. older men

● Decreased maximal exercise capacity

beta blockers reduce Max HR by

20-30 BPM

beta blockers can cause bronchoconstriction especially if used by

someone using a non selective drug and likely has a bronchocnsrtictive disease

common affect in any drug that lowers BP

OH

Your patient with hypertension was recently prescribed a beta blocker to help improve cardiac function. During an aerobic exercise session, she begins to wheeze and have difficult, labored breathing (dyspnea). Which of the following factors is TRUE?

it is likely she has some form of bronchoconstrictive disease, and she is taking a nonselective beta blocker that affects her lungs as well as her heart

sympatholytic drug

drug that interrupts, or "lyses," the function of the sympathetic system

Other sympatholytic antihypertensives

-alpha blockers: doxazosin (Cardura), prazosin (Minipress)

-presynaptic adrenergic inhibitors: reserpine

-centrally-acting agents: clonidine (Catapres), methyldopa (Aldomet)

-ganglionic blockers: mecamylamine (Inversine), trimethaphan (Arfonad)

Alpha blocker

blocks the alpha-1 receptor on the arteriole and causes vasodilation

presynaptic adrenergic inhibitors

inhibit the release of norepinephrine to the arteriolesc

centrally-acting agents

Act on the central nervous system to reduce sympathetic drive at the medulla and pons

Ganglionic blockers

Block transmission at autonomic ganglia.

ganglionic blockers are only used

during emergencies

● You are designing an aerobic exercise program for a patient who is taking a cardioselective beta blocker to control hypertension

● This drug is designed to suppress heart rate (HR) and ↓ sympathetic nervous system activity

● So... will the patient experience a "training effect" and undergo beneficial changes in cardiovascular function, or will the beta blocker prevent the heart and vasculature from adapting to the exercise program?

● Yes... cardiovascular function will still improve even when taking the beta blocker

● As indicated... this drug will decrease maximal HR, and training HR will need to be reduced proportionally

● But, beneficial effects such as lower resting HR, improved vascular endothelial function, and reduced hypertension should still occur as a result of aerobic training

Diuretics are useful in HTN and HF because they

decrease excess fluid in the CV system, thus reducing stress on the heart & vasculature

Beta blockers directly ↓

SNS stimulation of the heart, and also have a general "quieting" effect on SNS activity throughout the body

Several other drug strategies can be used to treat resistant or severe HTN by inhibiting SNS activity at

peripheral arterioles, the CNS, or sympathetic ganglia

Vasodilators Act directly on

vascular smooth muscle to inhibit contraction

Vasodilators indications

hypertension, heart failure

Vasodilator examples

Hydralazine

Minoxidil

minoxidil aka

Rogaine (it causes hair growth)

Vasodilators: adverse effects

● Reflex tachycardia

● Orthostatic hypotension

● Dizziness, headaches

● Edema, fluid retention

reflex tachycardia

Increased heart rate due to blood pressure drop. Caused by baroreceptor reflex

how to prevent reflex tachycardia

Vasodilator+ Beta blocker

Avoid what on drugs that cause vasodilation

systemic heat (large whirlpool, Hubbard tank, etc)...

Renin-angiotensin system (RAS)

neuroendocrine response that helps control BP and other physiological reactions in various tissues

Some people have excessive or inappropriate RAS responses

causes ↑'d BP, damage to CV system & kidneys

angiotensinogen

Protein converted to angiotensin I by renin.

renin

Secreted by kidney converts angiotensinogen to angiotensin I

Angiotensin I

Converted to angiotensin II by ACE.

Most powerful vasoconstrictor

Angiotensin II

Angiotensin II acute effct

powerful vasoconstriction

Angiotensin II chronic effect

Vascular remodeling/occlusio

We now have 3 options to prevent harmful effects of Ang II

1.ACE inhibitors 2.Angiotensin II receptor blockers 3.Direct renin inhibitors

Angiotensin converting enzyme (ACE) inhibitors

Inhibit ACE

Angiotensin converting enzyme (ACE) inhibitors decreases formation of

Angiotensin II

Ace inhibitors prevent

acute vasoconstriction from Ang II... decrease BP

Ace inhibitors also prevent vascular

hypertrophy from Ang II... decrease long-term detrimental effects on heart, vasculature

Ace inhibitor indications

hypertension, heart failure

Common ACE inhibitors

captopril, enalapril, fosinopril, lisinopril

ACE inhibitors adverse effects

Effects may include fatigue; dizziness; mood changes; headache; dry, nonproductive cough;

first-dose hypotension; loss of taste; proteinuria; hyperkalemia; rash; pruritus; anemia;

neutropenia; thrombocytosis; and agranulocytosis.

ACE Inhibitor cough

Typically resolves 1-4 days after discontinuation of therapy but may linger up to 4 weeks.

Ang-II receptor blockers

Block angiotensin II receptors.

Ang-II receptor blockers prevent

detrimental effects of Ang II on heart, vasculature

Ang-II receptor blockers may be

as effective as ACE inhibitors, but fewer side effects

-sartan drugs

Angiotensin II Receptor Blockers

Direct Renin Inhibiotrs

inhibits renin's ability to convert angiotensinogen to Ang I

Aliskiren (Tekturna)

renin inhibitor

direct renin inhibitors prevent

production of precursor to Ang II

RAS drugs: adverse effects, rehab concerns

● Generally well-tolerated... some nausea, dizziness

● Possible allergic reaction (rash, angioedema)

● ACE inhibitors: dry cough (due to ↑'d bradykinin)

allergic reactions to RAS Drugs

rash, angioedema

Ace inhibitor effects

dry cough due to increased bradykinin

Excessive renin-angiotensin activity should be controlled because increased production of _____ causes _____.

angiotensin II; vasoconstriction and vascular smooth muscle hypertrophy

Calcium channel blockers Limit

calcium entry into vascular smooth muscle and cardiac muscle

Calcium channel blockers promote

vasodilation and stabilize HR

Calcium channel blockers indications

HTN, angina pectoris, arrhythmia, CHF

Calcium channel blockers examples

- Diltiazem (Cardizem)

- Amlodipine (Norvasc)

- Verapamil (Calan)

- Nifedipine (Procardia/Adalat)

CCBs adverse effects

● Swelling in feet, ankles

● Orthostatic hypotension

● Altered heart rate

● Avoid systemic heat

● Increased risk of heart attack?

CCB can create

arrhythmias

Nephedipine

short acting form may cause a heart attack

anti-anginals

organic nitrates,

Anti-anginal drugs

1. Nitrates (Nitroglycerin, Isosorbide Dinitrate)

2. Beta blockers

3. Calcium Channel Blockers

anti-anginals traditional route

sublingual

sublingual

under the tongue

Why is sublingual better for anti-anginals

because they get metabolized extensively in the liver by the first pass effect. It will reach the heart before this happens

Anti-anginal transdermal administration

creams and patches

anti-anginal primary indication

angina pectoris

Nitrates: primary effects

• Dilate peripheral vasculature...

venous dilation causes ↓'d

cardiac preload