PHARM

Cardiovascular meds

-largest area of pharmacology

-meds often "wear several hats, have multiple indications"

Diuretics

● Act on kidneys: ↑ sodium and water excretion

● Decrease fluid in vascular system

● Indications: Hypertension, Congestive heart failure

Diuretics examples

-thiazides

-loop diuretics

-potassium sparing agents

Diuretics: adverse effects, rehab concerns

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

● Watch for.......

● orthostatic hypotension

● weakness, fatigue

● confusion, mood changes

Sympatholytics Beta Blockers

-bind to heart, block effects of epinephrine and norepinephrine

-decrease HR and contraction force

-can also produce a more general decrease in sympathetic responses (sympatholytic effect)

Beta Blockers Indications

Cardiovascular: hypertension, angina, arrhythmia, heart failure, recovery from MI

Others: migraine, raynaud's, situational anxiety

Common beta blockers suffix

-olol

Which areas do the different beta blockers predominate over?

Beta 1 receptor: heart

Beta 2 receptor: lungs

-cadioselective drugs have a higher affinity for the beta 1 receptors

-nonselective drugs bind more equally to both

beta blockers adverse effects

-bronchoconstriction

-orthostatic hypotension

-psychotropic effects (depression, lethargy, decreased libido in older men)

-decreases maximal exercise capacity

Other sympatholytic antihypertensives

-alpha blockers,

-presynaptic adrenergic inhibitors

-centrally acting agents

-ganglionic blockers

Segment Recap: Diuretics and Sympatholytics

● 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

-as directly on vascular smooth muscle..inhibit contraction

-indication: hypertension, heart failure

Vasodilators adverse effects

- reflex tachycardia

- orthostatic hypotension

- dizziness, headaches

- edema, fluid retention

- AVOID SYSTEMIC HEAT..true for all drugs that cause vasodilation

Drugs that control the renin-angiotensin system

-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 increased BP, damage to CV system and kidneys

What are the inert portions of the renin angiotensin system?

angiotensinogen and angiotensin 1

What are the effects of the Angiotensin 2 in the Renin-Angiotensin System?

-powerful vasoconstriction (acute effect)- more powerful than adrenaline helpful is shock

-vascular modeling/ occlusion (chronic effect)- puts tremendous workload on the heart

What are the 3 options to prevent harmful effects of Ang 2?

1. ACE inhibitors

2. Angiotensin II receptor blockers

3. Direct renin inhibitors

1. Angiotensin converting enzyme (ACE) inhibitors

-inhibit angiotensin converting enzyme (ACE)

-decrease formation of angiotensin II, from the presence of the angiotensin 1

-prevent acute vasoconstriction from ang 2..decrease BP

-also prevent vascular hypertrophy from Ang II, decrease long-term detrimental effects on heart, vasculature

Common ACE inhibitors endings

-pril

Newer option: Ang-II receptor blockers

● Block angiotensin II receptors

● Prevent detrimental effects of Ang II on heart, vasculature

● May be as effective as ACE inhibitors, but fewer side effects

● Examples: losartan (Cozaar), eprosartan (Teveten), other

Common endings for newer option:ang-2 receptor blockers

-sartan

Direct renin inhibitors

● Aliskiren (Tekturna): inhibits renin's ability to convert angiotensinogen to Ang I

● Prevents production of precursor to Ang II

● Other direct renin inhibitors currently in development

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)

Calcium Channel Blockers

● Limit calcium entry into vascular smooth muscle and cardiac muscle

● Promote vasodilation, stabilize HR

● Indications: Hypertension, Angina pectoris , Arrhythmias

Calcium channel blockers endings

-ipine

Calcium Channel blockers: adverse effects, concerns

● Swelling in feet, ankles

● Orthostatic hypotension

● Altered heart rate

● Avoid systemic heat

● Increased risk of heart attack?

Segment Recap: Vasodilators, RAS Drugs, Calcium Channel Blockers

● "Vasodilators" are so-named because they have a direct

inhibitory effect on smooth muscle in peripheral arterioles

● Excessive activity in the renin-angiotensin system must be reduced to prevent detrimental effects of Ang II on the heart and vasculature

● Calcium channel blockers selectively limit Ca++ entry into heart cells and peripheral vascular smooth muscle, thus

↓ing BP by reducing cardiac contraction force and promoting peripheral vasodilation, and... treating certain cardiac dysrhythmias

Ant-Anginals: Organic Nitrates

● Anti-anginals: Organic

Nitrates

-Nitroglycerin, isosorbide dinitrate, others

-Traditional route: sublingual

-Transdermal administration: creams,

patches

-Primary indication: angina pectoris

Nitrates: primary effects

Dilate peripheral vasculature...

● venous dilation causes ↓'d cardiac preload(blood returning to heart)

● arterial dilation causes ↓'d afterload (pressure heart pumps against)

● Result: ↓'d cardiac workload, ↓'d O2 demand

Nitrate tolerance

● Continuous administration (e.g. patches) reduce drug effects

● Reasons unclear

● Effectiveness restored quickly when nitrates

are discontinued

● Prevention: daily nitrate-free intervals (e.g. patch 12 hr on, 12 hr off)

Nitrates: adverse effects, rehab concerns

● Headache, dizziness

● Orthostatic hypotension

● ↑'d vasodilation... exaggerated response to systemic heat

● Sublingual doses:

● check drug viability