Pharm Vasodilators (Block 1)

Front 1

Prazosin

Back 1

Vasodilator - A1 Blocker

Half Life = 3 hours, active orally

DOXAZOSIN - Much longer half life of 20 hours. Also, beneficial effects on BLOOD LIPIDS.

TERAZOSIN - Another long acting A1 Blocker

Effects both Arterial and Venous Systems (Arterial more so)

Uses:
1) Antihypertensive Therapy
2) Reduction in Afterload (and some reduction in Preload)
3) BPH (TAMSULOSIN preferred because of affinity to A1AR)

Side Effects:
1) Little Postural Hypotension
2) Syncope common upon initiation of therapy

TOLERANCE with Chronic Use!

Front 2

Enalapril, Captopril

Back 2

ACE Inhibitors

Effects Arteries (Resistance Vessels) MORE than Veins (More AgII Receptors on Arteries)

Uses:
1) Antihypertensive
2) Reduction in Afterload
3) Beneficial with Angina and Cardiac Ischemia

Relatively "KIDNEY-SPARING" compared to other Anti-Hypertensive Agents!

Front 3

Losartan

Back 3

Angiotensin II (AT-1) Receptor ANTagonist (Others include VALSARTAN and IRBESARTAIN)

20,000-Fold Higher Affinity for AT-1 vs AT-2 Receptors

Approx same Anti-hypertensive activity as ACE Inhibitors

Side Effects:
1) Do NOT Use in PREGNANCY!!!

Front 4

Aliskiren

Back 4

Renin Inhibitor (Inhibits Peptidase Activity of Renin)

Limited Clinical Experience - About the same efficacy as ACE Inhibitors or ARBs

Front 5

Nifedipine
Felodipine
Diltiazem
Verapamil

Back 5

Specific L-Type Calcium-Channel Blockers

Orally active, used for LONG-TERM therapy

Nifedipine - "Cardiosparing" in that it has LITTLE effect on heart while having potent peripheral vasodilatory activity. Sustained and short-acting preparations.

Felodipine - Virtually NO Cardiac Effects

Diltiazem and Verapamil - Much Greater Cardiac Effects

Cardiac Effects OFFSET due to Increased Catecholamine Secretion (Baroreceptor Reflex)

Uses:
1) Mild Hypertension and Severe Malignant Hypertension
2) Angina due to Coronary Artery Spasm)

Side Effects:
1) Headache and Facial Flushing
2) Decreased Activity in Other Smooth Muscles
-GI Tract: Constipation
-Premature Labor
3) Peripheral Edema

Front 6

Nitroglycerine

Back 6

Organic Nitrate (Nitrogenous Esters of Glycerol)

VERY Lipid Soluble

Effects predominantly the VENOUS Circulation (higher doses can affect arterial)

Labile, NOT effective if given orally. Acid DECREASES activity. Large first-pass effect.

Effects within 1-2 min and last 15-30 mins.

Uses:
1) Coronary Insufficiency
2) Acute Anginal Episodes

Side Effects:
1) Headache
2) Hypotension
3) Flushing and Burning Sensation (= Drug is ACTIVE)
4) Unstable in Storage

Front 7

Amyl Nitrate

Back 7

Organic Nitrate

Volatile Liquid administered by Inhalation

Very Rapid Onset: <30 Sec. Short acting: 5 mins.

Diagnostic Uses:
1) Murmur
2) Angina

Front 8

Isosorbide Dinitrate/Mononitrate

Back 8

Organic Nitrates (Sugar Nitrates)

Stable, Orally Active. Last 2-4 Hours.

Uses:
1) Angina Prophylaxis
2) Congestive Heart Failure (Decreases Preload and Afterload)

Mononitrate has LONGER Half Life

Front 9

Sodium Nitroprusside

Back 9

Unusual Structure, must be intact for activity.

Very selective in Actions on Vascular SMooth Muscle, Extremely Potent Vasodilator

Half-Life: 30 Seconds. Immediate Onset. Administered by constant IV Infusion.

Uses:
1) Hypertensive Emergencies (Balanced Decrease in Afterload and Preload)
2) Malignant Hypertension
3) Acute Heart Failure

Toxicity:
1) Hypotensive Crisis
2) Accumulation of Thiocyanate --> CNS Abnormalities (limits use to 48-72 hours)
3) B12 REDUCES Toxicity

Front 10

Diazoxide

Back 10

Arterial Relaxant

Chemically related to Thiazides, but NO Diuretic Activity

Opens K+ Channels

IV - Arterial Vasodilator and Increases CO

Orally - Interferes with K-Coupled Insulin Secretion --> HYPERGLYCEMIC EFFECT

Uses:
1) Emergency Settings

Side Effects:
1) Profound Hypotension

Front 11

Hydralazine

Back 11

Arterial Relaxant

Orally Active with Controllable Side Effects

Often used with B-Blocker and Diuretic and Captopril

Metabolism via Acetylation in Liver and Kidney (More Side Effects with Slow Acetylators)

Uses:
1) Hypertension
2) CHF

Side Effects:
1) Headache
2) Flush
3) LUPUS-LIKE SYNDROME**

Front 12

Minoxidil

Back 12

Arterial Relaxant similar to Hydralazine

May be useful in patients refractory to Hydralazine

Side Effects similar to Hydralazine, with two differences:
1) NO Lupus-Like Syndrome
2) Hypertrichosis

Front 13

Pinacil

Back 13

Arterial Relaxant

At least as effective as Prazosin

Requires FEWER additional drugs (Diuretics) to reduce BP to desired levels

Front 14

Sildenafil (Viagra)

Back 14

Phosphodiesterase Type 5 Inhibitor

Onset = 40 Mins
Duration = 3-4 Hours

Restricted tissue distribution: 1) Corpus Callosum
2) Corpus Spongiosum
3) Lungs
4) Esophagus

Causes Increase cGMP --> Vasorelaxation of Corpus --> Erection

Side Effects:
1) Headache
2) Flushing
3) Nasal Congestion
4) Visual Disturbances
More Serious:
1) MI
2) Ventricular Arrhythmias
3) Priapism (Penis Stays Erect)

Drug Interaction:
Nitrates and A1 Antagonists --> Fatal Hypotension!

Also approved for treatment of Pulmonary Hypertension

Alternatives:
1) Vardenafil (Levitra): More rapid onset of about 20 mins.

2) Tadalafil (Cialis): Same onset as Sildenafil, but lasts for 36 hours! More specific PDE Type V Inhibitor!