BP Goals for HTN treatment

< 140/90 mmHg

< 130/80 mmHg if DM or kidney disease

Number of drugs required by most patients

to reach BP goals

> 2 drugs

Initial treatment choice for Hypertension

Thiazide diuretics

Initial therapy in most patients

(monotherapy or in combination)

Use unless compelling indications for other antiHTN

Compelling indication for use of BB

(Alternative: CCB)

HTN + stable angina pectoris

Drug types to use Post MI with HTN

ACEI

BBs

Aldosterone Antagonists

Along with Lipid Management & Aspirin

Drugs to use with Heart Failure & HTN

Asymptomatic ventricular dysfunction

ACEI or BB

Symptomatic Ventricular Dysfunction or

End-stage heart disease

ACEI, BB, ARBs, Aldosterone blockers

Loop Diuretic

Drugs to use with Diabetes & HTN

ACEI or ARBs

Slow progression of diabetic neuropathy

& reduce albuminuria

Thiazides, BB, ACEI, ARBs, & CCBs

Reduce CVD & CVA

Definition of Chronic Kidney Disease

Based on GFR & Albuminuria

GFR < 60 mL/min

Albuminuria (> 300 mg/day)

Treatment of HTN with Chronic Kidney Disease

Aggressive BP management

ACEI & ARBs show benefit in renal disease

ACEI & ARBs may cause ↑ in Cr

(up to 35% above baseline)

Monitor for increases > 35% or Hyperkalemia

Treatment of HTN with Cerebrovascular Disease

↓ Recurrent stroke rates with ACEI + Thiazide

Special Considerations for African Americans with HTN

↓ response to monotherapy: BB, ACEI, ARBs

compared to diuretic or CCBs

ACEI - angioedema is more common

Special Considerations for Elderly patients with HTN

Initiate at lower doses & titrate slowly

Special considerations in treating

pregnant women with HTN

AVOID ACEI & ARBs

Methyldopa, Labetolol, & Vasodilators

should generally be used

Special Considerations for Patient with Eclampsia/HTN

ONLY curative treatment is delivery

Manage with IV antihypertensives & magnesium sulfate

Additional Considerations for Thiazide therapy for HTN

May slow progression of osteoporosis

May precipitate acute gout attacks

Additional considerations for Beta Blocker therapy for HTN

Beneficial in the treatment/prophylaxis of migraine, tachyarrhythmias, essential tremor

Caution in reactive airway disease

Avoid in 2^nd or 3^rd degree heart block

Additional considerations for HTN treatment

with alpha blockers

Beneficial in prostatic hyperplasia

Additional considerations for treatment of HTN

using CCBs

Beneficial in Raynaud's syndrome

Thiazide Diuretics Action Site & Characteristics

Action at DISTAL TUBULE

Mainly used for essential HTN

Caution in sulfa allergy

Ex: Hydrochlorothiazide (HCTZ)

Loop Diuretics Action Site & Characteristics

Action: LOOP OF HENLE

MOST EFFECTIVE diuresis

Mainly used for edematous conditions (HF, cirrhosis with ascites, renal failure w/ volume overload)

Caution in sulfa allergy

Ex: Furosemide (Lasix®)

K-sparing diuretics Action Site & Characteristics

Action: DISTAL TUBULE, COLLECTING TUBULE

Mainly used in combo with other diuretics for HTN or ascites

Ex: Spironolactone (Aldactone®)

Triameterene

Most frequent problem with use of Thiazide Diuretics

Hypokalemia

May predispose to digoxin toxicity & arrhythmias

K supplementation - dietary, K salts, K-sparing diuretics: typically useful in countering the effects of aldosterone

Adverse Effects of Thiazide Diuretics

Hypokalemia

Hyponatremia

Hyperuricemia

Hyperlipidemia

Volume depletion

Hypercalcemia

Skin - photosynsitivity, SJS

Hyperglycemic

Hypersensitivity - potential of sulfa-allergic 

patientsto react to thiazides

Rare - Bone marrow supressior vasculitis, dermatitis

How Hyperuricemia occurs with Thiazide Diuretics

Serum uric acid is increased by decreasing

the amount of uric acid lost in the urine

May precipitate acute gout attacks

Use/Action of Loop Diuretics

High Ceiling: highest efficacy in mobilizing Na & Cl from the body & most efficacious of all diuretics

Results in large amounts of urine

Some are sulfonamide derivatives

Adverse Effects of Loop Diuretics

Ototoxicity

Hyperuricemia

Hypocalcemia

Hypomagnesemia

Acute Hypovolemia/CV

Substantial rapid ↓ blood volume may cause

hypovolemia, tachycardia arrhythmias

MoA of Spironolactone

(Aldosterone Antagonist K-Sparing diuretic)

• Synthetic diuretic with hormone effects that antagonize aldosterone
• Prevention of Na reabsorption (leading to ↓ K secretion)

Actions of Spironolactone

(K-sparing diuretic/Aldosterone Antagonist)

↓ aldosterone - diuretic of choice in cirrhosis

Causes retention of K & excretion of Na

Renal function for diuretic effects

Use of Non-aldosterone antagonist K-sparing diuretics

Typically used only for k-sparing properties

Frequently used in combination with other diuretics (Triametrene/HCTZ)

Non-aldosterone antagonist K-sparing Diuretics

Triamterene

Amiloride

Adverse Effects of K Sparing Diuretics

GI: GI upset, peptic ulcers

Hormonal (spironolactone) - Gynecomastia,

menstrual irregularities

Hyperkalemia

Drug interactions with K Sparing Diuretics

Other medications that may cause hyperkalemia - ACEI, ARBs, NSAIDs

Medications with hormonal effects

Therapeutic Uses of K-Sparing Diuretics

Diuretic: low efficacy in mobilizing NaCl (compared to other diuretics)

Secondary hyperaldosteronism

Heart failure: prevention of remodeling

Actions of Beta Blockers for HTN Treatment

Reduction of BP occurs primarily through reduction of cardiac output

Secondary effects - inhibition of renin release

Therapeutic Uses of Beta Blockers in Treatment of HTN

Population subsets - More effective in Caucasians 

and in young to middle-age patients

Hypertension with comorbid disease -

Previous MI, CHF, Migraines, Angina, SVT

Common Adverse Effects of Beta Blockers

in HTN treatment

Cardiovascular: Bradycardia, hypotension

CNS: fatigue, insomnia

Other: sexual dysfunction

Uncommon Adverse Effects of Beta Blockers

in HTN treatment

May adversely effect cholesterol

Cautions with use of Beta Blockers

Asthma/COPD: bronchoconstriction (esp. non-selective)

Unstable HF: may cause decompensation

PVD: potential to cause some vasoconstriction

Withdrawal: abrupt cessation of BBs may cause angina, MI, or sudden death (patients w/ ischemic heart disease)

Nonselective Beta Blockers

Propranolol (Inderal®)

Nadolol (Corgard®)

Cardioselective Beta Blockers

Atenolol (Tenormin®)

Metoprolol (Toporol XL, Lopressor)

Actions of ACE Inhibitors for HTN treatment

↓ BP by reduction of peripheral vascular resistance

Prevents conversion of Angiotensin I to Angiotensin II

(it is a potent vasoconstrictor)

↓ Aldosterone

Slows progression of diabetic nephropathy, ↓ proteinuria

Prevents cardiac remodeling after MI

Relationship of ACE & Bradykinin

Responsible for the breakdown of bradykinin

With use of inhibitor, bradykinin levels increase, which causes vasodilation & may be involved in the cough associated with ACEI treatment

Therapeutic uses of ACE Inhibitors

HTN

Population subsets: most effective in young, Caucasian patients - Gains effectiveness in African Americans when combined with a diuretic

Heart failure (helps prevent remodeling)

Diabetic nephropathy

Especially useful in patients with diabetes & HTN

Adverse Effects of ACE Inhibitors

Dry cough

Hypotension

Hyperkalemia

Angioedema

Renal Failure

Other: fever, rash

TERATOGENIC:

Black Box Warning

Renal Failure with ACE Inhibitor Use

Caused in patients with bilateral renal stenosis

Usually reversible upon discontinuation

ACE Inhibitors for HTN

Lisinopril (Prinivil, Zestril®)

Benzapril (Lotensin®)

Captopril (Capoten®)

(Most end with "-pril")

Actions of Angiotensin Receptor Blockers

Effects similar to ACE inhibitors - ↓ BP - Vasodilation

↓ aldosterone secretion but doesn't increase bradykinin l

Therapeutic Uses of Angiotensin Receptor Blockers

Alternative to ACE inhibitors -

HTN, HF, diabetic nephropathy

Adverse effects of Angiotensin Receptor Blockers

Similar to ACEI:

↓ risk of cough & angioedema

TERATOGENIC

Angiotensin Receptor Blockers for HTN treatment

Valsartan (Diovan®)

Losartan (Cozaar®)

(typically end with "-sartan")

Actions of Renin Inhibitors for HTN Treatment

Direct inhibitors of renin

Adverse Effects of Renin Inhibitors

Hypotension

Diarrhea

Cough

Angioedema

TERATOGENIC

Hyperkalemia

Renin Inhibitors for HTN treatment

Aliskiren (Tekturna®)

(Ending of -iren is helpful - i = inhibit, ren = renin)

Actions of Calcium Channel Blockers for HTN treatment

Block the entrance of Ca into the cells, causing vascular smooth muscles to relax and dilation of arterioles

Therapeutic uses of Calcium Channel Blockers

HTN

Angina

SVT

Adverse Effects of Calcium Channel Blockers

Constipation (esp. with verapamil)

Dizziness

Headache

Fatigue

Adverse effects of Verapamil, CCB for HTN

(-) inotropic

Avoid in CHF or AV block

Non-Dihydropyridine Calcium Channel Blockers

for HTN Treatment

Examples

Block Ca channels of myocardial & vascular smooth muscle

Slow automaticity/AV nodal conduction

Verapamil

Diltiazem

Dihydropyridine Calcium Channel Blockers

for HTN treatment

Examples

↓ vascular resistance: most useful for HTN

Less drug interactions

Amlodipine (Norvasc®)

Nifedipine (Adalat, Procardia®)

(Most end with "-pine")

Actions of Alpha Blockers for HTN treatment

Competitive blockade of α1-receptors

Relaxation of arterial & venous smooth muscle

Therapeutic Uses of Alpha-Blockers

HTN

BPH

Adverse effects of Alpha-Blockers for HTN Treatment

Postural hypotension

Tachycardia (reflex)

Edema

Syncope (esp. w/ 1st dose)

Tolerance to antiHTN effects

Alpha-Blockers for HTN Treatment

Doxazosin (Cardura®)

Terazosin (Hytrin®)

(most end with "-zosin")

Centrally acting adrenergics for HTN treatment

α2-agonist (↓ central adrenergic outflow)

Do not typically ↓ blood flow to the kidneys

(useful with renal disease)

Centrally Acting Adrenergics for HTN Treatment

Clonidine (Catapress®)

Methyldopa (Aldomet®)

Clonidine (Catapress®)

Centrally Acting Adrenergic

Urgent: 0.1mg QH with max of 0.6mg PO

Used for HTN (2nd line)

Adverse effects of Clonidine (Catapress®)

Dry mouth/nasal mucosa

Sedation

Rebound HTN with abrupt withdrawal

Methyldopa (Aldomet®)

Used in:

HTN in pregnancy

Hypertensive emergency

Hypertensive urgency

Action of Vasodilators for HTN treatment

Direct-acting smooth muscle relaxants

Reflex stimulation of the heart

(Some reflexive actions can be

blocked with the β-blockers)

Action & Uses of Hydralazine (Apresoline®)

Vasodilator - Arterial & venous dilation

Predominant dilation of arterioles & arteries

Used in HTN & HTN in Pregnancy

Adverse effects of Hydralazine (Apresoline®)

Headache

Tachycardia

Nausea

Sweating

Arrythmia

Lupus-like syndrome

Action & Uses of Minoxidil

Vasodilator - Dilation of arterioles

Severe/refractory HTN

Topically to treat male-pattern baldness

Adverse Effects of Minoxidil

Reflex tachycardia

Fluid retention

Hypertrichosis

Definition of Hypertensive Emergency

Usually BP > 210/150

Lower if there is evidence of end-organ damage or patients with other cardiovascular risk factors

Treatment of Hypertensive Emergency

Sodium Nitroprusside

Labetolol

Nicardipine (CCB)

Fenoldopam

Sodium Nitroprusside in Treatment of HTN Emergency

IV: causes prompt vasodilation (arterial & venous)

Rapid metabolism (requires continuous infusion to maintain actions)

AE (mostly associated with very high doses or prolonged administration) - Cyanide ion production, Hypotension

Labetolol in treatment of HTN emergency

α & β non-selective β blockade

Given as IV bolus or IV infusion in HTN emergencies,

no reflex tachycardia

Fenoldopam in treatment of HTN emergency

Parenteral antiHTN with different MoA

Dopamine-1 agonist

Lowers BP but maintains or ↑ renal perfusion

Treatment of Ischemic Heart Disease

Antiplatelet Agents

ACE Inhibitors

Statins

Beta Blockers

Calcium Channel Blockers

Antiplatelet Agents used in Treatment of

Ischemic Heart Disease

Aspirin

Inhibition of cyclooxygenase

Reduces risk of acute CV events

Doses of 75-235 mg/day are CV protective

Contraindicated with aspirin allergy or active PUD

Clopidogrel (Plavix®)

Alternative antiplatelet for patients who can't take aspirin

ACE Inhibitors in Treatment of Ischemic Heart Disease

↓ risk of CV events in patients with chronic,

stable angina, or significant IHD risk factors

ARBs can be used as substitutes

Statins for Treatment of Ischemic Heart Disease

↓ mortality/morbidity associated with IHD

Primary & secondary prevention of CV events

Beta Blockers in Treatment of Ischemic Heart Disease

Use/Actions

Part of 1st line treatment for ↓ symptoms in IHD

↓ myocardial oxygen demand

ISA activity: less reduction of HR but less effective for angina

Beta Blockers in Treatment of Ischemic Heart Disease

Contraindications/Cautions

Contraindicated in patients with severe bradycardia, AV conduction defects (without a pacemaker)

Caution with other agents that ↓ AV nodal conduction

Relative contraindications: bronchospastic disease, severe depression, PVD

Calcium Channel Blockers in treatment of

Ischemic Heart Disease

Indicated in IHD when BB cannot be used or in combination with BB for refractory symptoms

Use of Short-Acting Nitrates

1st line treatment for termination of acute episodes of angina

Convert to nitric oxide and cause venodilation

↓ myocardial O₂ demand & ↑ myocardial O₂

Supply, resolution of vasospasm

Angina treatment: 0.3-0.4 mg SL, repeat x 5 min until resolution of sx; unimproved after 1-2 doses, call EMS

Prophylaxis: use 5 min prior to activity (effective for ~30 min)

Distinction of Isosorbide dinitrate (Isordil®)

Longer half life of the short-acting nitrates

Short-acting nitrates as monotherapy

Useful for patients with angina symptoms every few days

If more frequent attacks -

Use long-acting anti-anginal therapy

Long-acting anti-anginal therapies

BB, CCB, long-acting nitrates

Drug interactions with short acting nitrates

Phosphodiesterase 5 inhibitors: serious HYPOTENSION due to combined vasodilatory effects (avoid taking PD5 inhibitors for 24-48 hours after taking nitrates)

Adverse effects with Short-Acting Nitrates

Dizziness

Headache

Hypotension

Use of Long-acting Nitrates

PO & transdermal dosage forms

Nitroglycerin ER

Isosorbide mononitrate or dinitrate SR formulations

Development of tolerance is common

Nitrate-free interval each day for 8-12 hours

Caution with Use of Long-acting Nitrates

Avoid monotherapy due to reflex tachycardia

Adverse effects: same as short-acting nitrates

(dizziness, headache, hypotension)

Often resolve with continued treatment

Treatment summary for IHD

Lifestyle modifications

ACEI or ARB

BB or CCB for prevention of ischemic events

Nitrates (Short or long acting)

Statins for CV protection

Antiplatelets for CV event prophylaxis

Interventional treatments for severe or refractory disease

Compensatory Physiology of HF

3 major responses

↑ SNS activity

Activation of RAAS

Myocardial hypertrophy

Classes of drugs used for Heart Failure Treatment

ACE Inhibitors

β-blockers

Diuretics

Vasodilators

(+) inotrope

ACE Inhibitors & ARBs used for HF treatment

Prevent activation of RAAS & remodeling

β-blockers for HF treatment

↓ workload of heart

Caution with initiation due to possible exacerbation

from ↓ CO (initiate when pt is stable)

Secondary action of inhibiting renin

Inhibits myocardial remodeling

Use of diuretics for HF treatment

↓ plasma volume (↓ cardiac workload & oxygen demand) & reduction of symptoms of volume overload

Use of vasodilators for HF treatment

↓ preload & afterload

Use of (+) inotropic drugs for HF treatment

Enhancement of cardiac muscle contractility leading to better ejection fraction & ↑ cardiac output

Digitalis/Digoxin

Use of Digitalis/Digoxin for HF treatment

Indicated in severe left ventricular systolic dysfunction after initiation of a ACE & diuretic

HF with atrial fibrillation

Adverse Effects of Digitalis/Digoxin

Narrow TI - requires labs

Cardiac effects - Slowing of AV conduction (arrhythmias)

GI effects - anorexia, N/V

CNS effects - HA, fatigue, confusion, blurred vision, alteration of color perception & halos on dark objects

Toxicity with enhanced hypokalemia

Drug interactions with Digitalis/Digoxin

Protein Binding

Renal elimination

Class I Antiarrhythmics

Blockade of fast Na channels: 

↓ conduction velocity in non-nodal tissue

Class IA Antiarrhythmics

Direct effect on AP is modified by anticholinergic actions

Anticholinergic - ↑ in SA & AV conduction

(may cancel other effects).

Procainamide - Used for ventricular & supraventricular tachycardias; weak anticholinergic actions; short half life, lupus-like syndrome

Quinidine - used for atrial & ventricular tachycardia, anticholinergic actions; Toxicity - Cinchonism (blurred vision, tinnitus, HA, psychosis); enhanced Digitalis toxicity

Class IB Antiarrhythmics

Class IC Antiarrhythmics

Class II Antiarrhythmics - Beta Blockers

Class III Antiarrhythmics:

K-channel blockers

Class III Antiarrhythmics:

Amiodarone

Class III Antiarrhythmics:

Ibutilide

Used for A.fib; helps convert to normal sinus rhythm

Class IV Ca Channel Blockers

(Non-dihydropyridines)

Antiarrhythmic Properties of CCBs

↓ conduction velocity & prolong repolarization (especially at the AV node

Help block re-entry mechanisms, ↓ the firing rate of aberrant pacemaker

Cautions - excessive bradycardia, impaired conduction or contractility

Drugs in Class IV CCB Antiarrhythmics

AEs

Verapamil & Diltiazem

Used for re-entrant SVT, ↓ ventricular rate in

a.flutter & fibrillation

AEs: inotropic effects, hypotension, avoid use with Class II (could lead to complete heart block)

Digoxin as antiarrhythmic

Shortens ERP in atrial & ventricular cells, while prolonging the refractory period in the AV node

Therapeutic uses: to control the ventricular response rate in a. fib or flutter

Adenosine as antiarrhythmic

Marked, immediate ↓ in AV node conduction

In IV form, the drug of choice for aborting acute SVT

When given IV in large doses: slows or completely blockss conduction in the AV node

Extremely short DoA

AEs: flushing, CP, hypotension

Potassium as antiarrhythmics

Depresses ectopic pacemakers

(too much can cause re-entry arrhythmias)

Magnesium as antiarrhythmic

Shortens QT duration

Sometimes effective in arrhythmias caused by digoxin toxicity or Torsades