Mechanism of Action:
Inhibits enzymatic activity of renin
Direct renin inhibitor, decreasing plasma renin activity and inhibiting conversion of angiotensinogen to angiotensin I.
EFFECTS:
Reduces angiotensin I and II and aldosterone
Indications:
Hypertension
Reflex: inhibits RAAS reflex
Mechanism of Action:
Blocks enzyme (ACE)that cleaves
Angiotensin I  Angiotensin II
Diminish rate of bradykinin inactivation
(   bradykinin   vasodilation)
EFFECTS:
 in vascular resistance, venous tone, BP

Blunts usual angiotensin II-mediated  in epinephrine and aldosterone seen in
CHF.
Pharmacokinetics:
Given orally
Metabolized by CYP3A4 in liver
25% excreted in urine
Indications:
Single-agent therapy: patients with mild dyspnea on exertion, no signs and symptoms of volume overload. (HEART
FAILURE)
 CHF in asymptomatic patients w/ ejection fraction < 35%
Early use indicated in patients with ALL stages of LV failure, + or – symptoms, and therapy should be initiated
IMMEDIATELY after an MI.
-Hypertension
-Diabetes
Reflex:
Inhibits RAAS reflex
No reflex sympathetic activation
(can be used safely in Ischemic
Heart Disease)
Absence of reflex tachycardia due to downward resetting of the baroreceptors/enhanced parasympathetic activity.
Pharmacokinetics:
Adequate but incomplete absorption
orally.
Take on empty stomach to  absorption.
Pro-drugs (except Captopril) that require hydrolysis by hepatic
enzymes.
Mostly renal elimination (except fosinopril)
Mechanism of Action:
Nonpeptide, orally active, extremely potent competitive antagonists of angiotensin type 1 (AT
1
) receptor.
EFFECTS:
MORE complete blockade of angiotensin action than ACE Inhibs.
DO NOT affect bradykinin levels.
Indications:
Use as a substitute for ACE Inhibs in patients with severe cough/angioedema.
Hypertension – lowers BP, reduces
M&M.
Reflex: (see ACEI) Pharmacokinetics:
Orally active
Require only once-daily dosing.
Losartan – extensive first-pass
metabolism (unlike others)
Highly plasma protein bound
(>90%), high volumes of distribution.
Adverse Effects
Hyperkalemia, renal impairment, angioedema hypotension, gout, renal stones, allergy, diarrhea, NO cough
Contraindications:
Pregnancy (Teratogenic)
Antidotes: None
Adverse Effects:
Postural hypertension, renal insufficiency, hyperkalemia,
angioedema, persistent dry cough,
Severe hypotenstion.
(Bradykinin/Substance P responsible for cough and angioedema)
Contraindications:
Pregnancy (Teratogenic)
(fetal hypotension, anuria,
malformations, death)
Renal artery bilateral stenosis
Ang II effects on EA predominate so
GFR ↓ with ACEIs b/c EA dilates
Antidotes: none
Adverse Effects:
Similar to ACE Inhibs (Postural hypertension, renal insufficiency, hyperkalemia, angioedema), but NO
COUGH
Contraindications:
Pregnancy (teratogenic see ACEI)
Renal artery bilateral stenosis
Ang II effects on EA predominate so
GFR ↓ with ACEIs b/c EA dilates
Antidotes: none

(Technically diuretics)
Mechanism of Action:
Blocks cytoplasmic aldosterone receptors in the collecting tubules of nephron. (pharmacological competitive antagonist of aldo)
EFFECTS:
Has a possible membrane effect
-Leads to  salt and water excretion
(reduces Na retention and K wasting in kidney)
-Reduces remodeling (poorly understood antagonism in heart and vessels)
-Reduces mortality
**Can be classified as a K+ sparing diuretic
** Has weak antoagonism of androgen receptors
Indications:
Chronic Heart Failure
Post-MI
Aldosteronism, (cirrhosis, adrenal tumor, or any cause)
Hypertensiion- lowers BP, reduces fluid volume
Hypokalemia due to other diuretics
Reflex: none Pharmacokinetics:
Slow onset and offset of effect (several days)
Duration 24-48 hours
Substantial inactivation occurs in the liver
Mechanism of Action:
Competitively blocks 
1
receptors
EFFECTS:
Improved systolic functioning
Reverse cardiac remodeling
Ability to prevent chances that occur because of chronic activation of
SympNS (  HR, Inhibit renin release).
Prevent direct deleterious effects of NE on cardiac muscle fibers,  remodeling, hypertrophy, cell death.
Overall:  HR,  BP, poorly understood effect  reduces HF mortality
Carvedilol – nonselective β-receptor antagonist, α-receptor antagonist/blocker.
Indications:
-Hypertensive patients.
(  BP b/c of  CO)
β-blockade recommended for all patients with heart disease
EXCEPT those who are at high risk but have no symptoms or those who are in acute HF.
-Chronic heart failure NOT acute:
1.
Slows progression
2.
Reduces mortality in moderate and sever heart failure
-Angina Pectoris
-Arrhythmias
-Pheochromocytoma
(carvedilol/labetolol)
Reflexes:
Baroreceptor reflex blocked (see notes for exam 2)  postural hypotension
Pharmacokinetics:
Oral
Duration of action is 10-12 hours
Metoprolol – β-1 selective antagonist
Propanolol - 
1
= 
2
Adverse Effects:
Hyperkalemia, gynecomastia (spiro
NOT epeleronone), Acute Renal Failure,
Kidney stones, Hyperchloremic
Metabolic Acidosis
Contraindication:
Additive interaction with other Kretaining drugs (oral K+ retaining diuretics)
Use of other RAAS system drugs
Liver disease
Antidotes: None
Adverse Effects:
Bronchospasm, bradycardia, atrioventricular block, acute cardiac
decompensation, postural hypotension, Withdrawl syndrome, MI, fatigue, vivid dreams, cold hands, sedation, impotence
Contraindications:
Antidotes: none

EFFECTS:
 plasma volume   venous return
(preload)   cardiac workload (pre- and after-) & O
2
demand. Reduces pulmonary and peripheral edema
**Metolazoneis popular for use with loop agents for synergistic effects
**Chlorothiazide: only IV
Mild-Moderate Hypertension – lowers
BP, reduces M&M.
Mild Chronic Heart failure
Nephrolithiasis
Nephrogenic diabetes insipidus
Mechanism of Action:
Blocks Na/Cl transporter in renal distal convoluted tubule (inhibits reabsorp.)
Indications:
Use as a substitute for ACE Inhibs in patients with severe cough/angioedema.
Reflex:
Stimulation of sympathetic activity
Activation of RAAS
Mechanism of Action:
Decreases NaCl and KCl reabsorption in thick ascending limb of the loop of
Henle in the nephron (blocks Na/K/2Cl transporter)
EFFECTS:
Increased excretion of Salt and water  plasma volume   venous return (preload)   cardiac workload
(pre- and after-) & O
2
demand. Reduces pulmonary and peripheral
Some K wasting,, hypokalemic metabolic alkalosis, increased urine Ca and Mg
**ethancrynic acid is not a sulfonamide
Indications:
Acute and chronic heart failure
Severe Hypertension
Edematous conditions
Pulmonary edema
Peripheral edema
Acute hypercalcemia or hyperkalemia
Acute renal failure
Anion overdose
Reflex:
Stimulation of sympathetic activity
Activation of RAAS
Pharmacokinetics:
Orally active
Duration of action 8-12 h
Pharmacokinetics:
Orally and parentral preparations
Duration of action 2-4 h
Adverse Effects:
Hypokalemic, metabolic alkalosis,
 Increases digitalis, quinidine toxicity
(torsades de points) and V-fib hyperuicemia (gut, hyperglycemia, hyponatremia, hyperlipidemia, sulfonamide allergy, weakness, lassitude, impotence
Contraindications:
Pregnancy
Adverse Effects:
Ototoxicity, hypovolemia,
Hypokalemia (K wasting)  Increases digitalis, quinidine toxicity (torsades de points) and V-fib, hyperuricemia (gout), hypomagnesemia
Contraindications:
Pregnancy

Verpamil/Dilatazem
Mechanism of Action:
Nonselective block of L-type calcium
Indications:
Stable and prinzmetal angina
Hypertension
Reflex:
Increase End diastolic pressure and ejection time, while channels in vessels(SMC) and heart
(cardiac muscle)
Decrease calcium influx during action potentials thus decreasing contractility.
EFFECTS:
Reduced vascular resistance, cardiac rate and cardiac force results in decreased oxygen demand
Dihydropyridines
Mechanism of Action:
Blocks vascular L-type calcium cannels
> cardiac channels
EFFECTS:
Like verapamil and dilitazem; less cardiac effects
Supraventrical tachycardia
(arrhythmias)
Migrane
Preterm labor
Stroke
Raynaud’s phenomenon
Indications:
Prophylaxis of angina and hypertension decreasing heart rate, contractility and arterial pressures
Reflex:
Same as above
Mechanism of Action:
Causes nitric oxide release from endothelial clls
EFFECT:
Vasodilation
Reduces vascular resistance
Arteriorles amore sensitive than veins
Reflex tachycardia
Mechanism of action:
Opening of K channels in smooth muscle membranes by minoxidil sulfate causes increased K permeability which stabilizes the membrane at its resting potential and makes contraction less likely
EFFECTS:
Dilates arterioles but NOT veins.
Promotes hair growth
Indications:
Hypertension
Indications:
Severe Hypertension (b/c extremely efficacious)
Hair growth (when applied topically)
Reflex:
Marked Tachycardia
Salt and water retention (RAAS)
Reflex:
Marked salt and water retention
(RAAS)
Marked tachycardia
**Must be used in combo w/  blocker and a loop diuretic b/c of reflex
Pharmacokinetics;
Oral/IV preparations
Duration of action 4-8 hrs
½ life is 3-6 hrs
Pharmacokinetics:
Oral, duration of 4-6 h
Pharmacokinetics:
Oral, rapidly metabolized by liver
Bioavailability low (25%)
-
Rapid acetylators have greater first pass (16% in fast acetylators
35% in slow acetylators)
T ½ = 1.5-3h
Pharmacokinetics:
40% bioavailability
Oral preparation
16% in fast acetylators
35% in slow acetylators
Adverse Efffects:
Atrioventricular block, acute heart failure, constipation, edema, nausea flushing and dizziness.
Contraindications:
Additive with other cardiac depressants and hypotensive drugs
Antidotes:
Adverse Effects:
Excessive hypotension
Contraindications
Additive with other vasodilators.
Antidotes:
Adverse effects:
Angina, Tachycardia, Lupus-like
Syndrome, headache, nausea, anorexia, sweating and flushing.
Contraindications:
Monotherapy
Antidotes:
Adverse effects:
Severe compensatory responses
(tachycardia, palpitations, angina, and edema), hirsutism(hypertrichosis), and pericardial abnormalities
Contraindications:
Monotherapy
Antidotes:

Mechanism of action:
Releases nitric oxide (from the drug molecule itself), which stimulated guanylyl cyclase and increases cGMP in
SMC.
EFFECTS:
Powerful vasodilation
Indications:
Hypertensive Emergencies
Severe heart failure
Reflex:
Salt and water retention (RAAS)
Pharmacokinetics:
Parentral (IV)
Short duration (minutes)
Rapidly metabolized by uptake into
RBC and liberation of cyanide (which is metabolized by mitochondria into thiocyanate)
Adverse Effects:
Accumulation of CN, metabolic acidosis, arrhythmias, excessive hypotension, shock, and death. Hypothyroidism is rarely reported.
Contraindicatons:
Renal insufficiency
Antidotes:
Sodium thiosulfates is administered as a sulfur donor to facilitate the metabolism of cyanide.
Hydroxycoobalmin combines with CN to form nontoxic cyanocobalmin
Mechanism of Action:
It prevents vascular SMC contraction by opening K channels and stabilizing membrane resting potential
(hyperpolarization  relaxation)
Releases insulin from pancreas
EFFECTS:
Vasodilation
Reduces insulin release
Mechanism of action:
An agonist of dopamine D
1
receptors
EFFECTS:
Dilation of peripheral arteries
Natriuresis
Indications:
Hypertensive Emergencies
Treatment of hypoglycemia caused by insulin-producing tumors (insulinoma)
Indications:
Hypertensive emergencies
Postoperative hypertension
Reflex;
Sympathetic response
Tachycardia
Renal salt and water retention
(but rarely problem b/c short acting)
Reflex:
Tachycardia
Pharmacokinetics:
Bound extensively to albumin and vascularttissue
T ½ = 24 hrs.
BP lowering w/in 5 minutes of administration
Pharmacokinetics:
Rapidly metabolized by conjugation
T ½ =10 min
Adverse Effects:
Excessive hypotension can lead to stroke and MI. Angina and arrhythmias from reflex response
Contrainidcations:
Renal failure (b/c lose serum protein)
Ischemic heart disease
Antidotes:
Adverse Effects:
Headache, flushing, increased intraocular pressure
Contraindications
Glaucoma
Antidotes:

Mechanism of Action:
Inhibits Na + -K + ATPase pump on the cell membrane of the cardiac myocyte. 
INC intracellular Na +  DEC activity of
Na + /Ca 2+ exchanger (usually takes Na + into cell in exchange for pumping Ca 2+ out)  INC intracellular Ca 2+  INC contractility.
EFFECTS:
Increased contractility
INC parasympathetic outflow at SA and
AV nodes  DEC heart rates via slowed sinus rhythm and AV conduction
Indications:
Congestive Heart failure:
INC contractility in patients suffering L-
SIDED heart failure. (Chronic symptomatic heart failure)
Atrial arrhythmias  Rapid ventricular rate in atrial fibrillation
Reflex:
Parasympathetic flow increased
Pharmacokinetics:
Steroid nucleus and a lactone ring
Oral/parentral formulations
Duration of action is 36-40hrs
Bioavailability 50-85%
Eliminated in kidney (60%) and liver
(40%)
20-40% bound to plasma protein
Mechanism of Action Indications: Reflex: Pharmacokinetics:
DEnitration of nitrates w/in SMC releases nitric oxide , which activates gaunylyl cyclase and increases cGMP, which causes relaxation via dephosphorylation of myosin light chain phosphate
EFFECTS:
Smooth muscle relaxation especially in vessels
Other smooth muscle I relaxed but not as markedly

Vasodilation decreases venous return and heart size
May increase coronary flow in some areas and in variant angina
**Isosorbide dinitrate is very similar to nitroglycerin but with longer duration of action
Angina: sublingual form for acute epsodes
Oral and trandermal forms for prophylaxis
IV form for acute coronary syndrome
Cyanide poisoning
Increased heart rate, contractility, ejection time
Can be prevent with combined beta blocker/calcium channel blocker
Very high first pass effect (90%)in liver
(rapidly denitrated), so sublingual dose is much smaller than oral
High lipid solubility ensures rapid absorption
Sublingual 10-20 min
Oral 4-6 h
Transdermal formulation can maintain up to 24h
Adverse Effects:
Arrhythmia characterized by slowing of
AV conduction associated with atrial arrhythmias.
(DEC in intracellular K + is primary predisposing factor)
EKG changes (prolonged PR inverval,
DEC QT interval, ST segment scooping,
T-wave inversion);
GI: Anorexia, nausea, vomiting
CNS: headache, fatigue, confusion, blurred vision, alterations of color perceptions, halos on dark objects.
Contraindications:
Quinidine, amiodarone, verapamil, increased K and Mg, Loop diuretics may reduce serum K and precipitate toxicity
Antidotes: Digoxin antibody (Digibind)
Correction of K or Mg deficiencies
Anti-arrhythmic agents
Adverse Effects
Orthostatic hypotension, tachycardia, headache, Tolerance develops after 8-
10 hours
Contraindications
Synergistic hypotension with PDE-5 inhibitors (i.e Viagra)
Antidotes:
Antidote for cyanide poisoning b/c will for methemoglobin which will absorb cyanide better.


See previous Indications:
Only for prophylactic therapy of angina, no value in acute attack
See previous See previous
Verpamil/Dilatazem
Mechanism of Action:
Nonselective block of L-type calcium channels in vessels(SMC) and heart
(cardiac muscle)
Decrease calcium influx during action potentials thus decreasing contractility.
EFFECTS:
Reduced vascular resistance, cardiac rate and cardiac force results in decreased oxygen demand
Dihydropyridines
Mechanism of Action:
Blocks vascular L-type calcium cannels
> cardiac channels
EFFECTS:
Like verapamil and dilitazem; less cardiac effects
Mechanism of Action
Inhibits late sodium current in the heart
Also may modify fatty acid oxidation
EFFECTS:
Reduces cardiac oxygen demand
Fatty acid oxidation modification may improve efficiency of cardiac oxygen utilization
Indications:
Stable and prinzmetal angina
Hypertension
Supraventrical tachycardia
(arrhythmias)
Migrane
Preterm labor
Stroke
Raynaud’s phenomenon
Indications:
Prophylaxis of angina and hypertension
Indications:
Prophylaxis of angina
Reflex:
Increase End diastolic pressure and ejection time, while decreasing heart rate, contractility and arterial pressures
Reflex:
Same as above
Reflex not applicable
Pharmacokinetics;
Oral/IV preparations
Duration of action 4-8 hrs
½ life is 3-6 hrs
Pharmacokinetics:
Oral, duration of 4-6 h
Pharmacokinetics:
Oral
Duration 6-8hrs
See previous
Adverse Efffects:
Atrioventricular block, acute heart failure, constipation, edema, nausea flushing and dizziness.
Contraindications:
Additive with other cardiac depressants and hypotensive drugs
Antidotes:
Adverse Effects:
Excessive hypotension
Contraindications
Additive with other vasodilators.
Antidotes:
Adverse effects:
QT interval prolongation, nausea, constipation, dizziness
Contraindications:
Inhibitors of CYP3A increae ranolazine concentration and durationof action