Lecture 17: Cardiac Glycosides & Antianginal Drugs

red dot slides only

What are 5 compensatory mechanisms in CHF (congestive heart failure?

1. increased ventricular volume (Frank-starling compensation)

2. tachycardia (reflex adrenergic activity)

3. salt and water retention: renin-angiotensin mech

4. increased systemic vascular resistance

5. cardiac hypertrophy

• congestive heart failure: heart muscle weakened and can’t pump blood effectively

  • compensatory mechanisms try to increase cardiac output

In heart failure, the contractility of the heart is __, and the cardiac function curve is __.

reduced; suppressed

In the Frank-Sterling compensation, for any given state of the heart, if end diastolic volume increases, then force of contraction __.

increases

The Frank Sterling compensation increases the __ to increase cardiac output and overcome __ symptoms, but this can lead to __ symptoms.

EDV/preload; hypotensive; pulmonary congestion

• hypotensive = reduced blood flow

• pulmonary congestion bc during heart failure (when heart can’t efficiently pump the excess blood), blood gets backed up in pulmonary circulation and causes fluid to leak out of blood vessels into lung tissues

__ can be used to treat CHF.

cardiac glycosides

What are 5 characteristics of digoxin?

(therapeutic range, half life, bioavailability, excretion method, plasma protein binding)

1. therapeutic range: 0.5-2 ng/mL

2. half life: 1.5 days

3. variable bioavailability

4. excreted by kidney

5. 25% plasma protein binding

What are 5 characteristics of digitoxin?

(therapeutic range, half life, bioavailability, excretion method, plasma protein binding)

1. therapeutic range: 10-35 ng/mL

2. half life: 7 days (very long)

3. consistent bioavailability

4. relies on hepatic metabolism for excretion

5. 95% plasma protein binding

Cardiac glycosides __ increase isometric and isotonic indices (= plural index) of myocardial contractility, which result in: (4). This mode of action is a __ inotropic effect.

directly

1. decreased duration of systole

2. increased ventricular filling time

3. shortened ventricular ejection with more complete emptying

4. increased cardiac output

positive

• explanation:

• cardiac glycosides block Na/K pump, which increases Na concentration inside cell. this causes decreased Na/Ca exchanger function bc no concentration gradient for Na to come into cell —> increases Ca concentration in cell

• increased cardiac output —> more complete emptying —> less preload

In normal hearts, __ cancel out the positive effects of digitalis (digitoxin and digoxin) on cardiac contractility.

reflex mechanisms

Cardiac glycosides have a __ effect on __ of vascular smooth muscle. In normal subjects, this results in increased __.

direct; constriction; systemic vascular resistance

Cardiac glycosides have a __ effect on electrical activity changes in the heart. This results in: (4)

direct

1. decreased resting potential or maximal diastolic potential

2. decreased action potential amplitude and conduction velocity

3. increased rate of phase-4 depolarization (faster depolarization)

4. appearance of delayed afterdeloparizations

Cardiac glycosides can __ enhance vagal impulse activity, which leads to: (2)

indirectly

1. reduction of SA node automaticity

2. increased refractoriness and decreased conduction at the AV node

Cardiac glycosides can __ sensitize baroreceptors, which leads to: (1)

indirectly; decreased blood pressure

The combination of direct and indirect effects in cardiac glycosides accounts for the __ effect of digitalis in CHF patients.

diuretic

What are 3 untoward effects of cardiac glycosides in terms of cardiac toxicity?

1. sinus bradycardia or block

2. AV block

3. ventricular extrasystoles (aka premature ventricular contractions: irregular heartbeats that originate in ventricles)

untoward = bad

What are 4 untoward GI effects as a result of cardiac glycosides?

1. anorexia

2. nausea

3. vomiting

4. diarrhea

What are 6 untoward neurological effects as a result of cardiac glycosides?

1. headache

2. fatigue

3. drowsiness

4. visual disturbances

5. neuralgic pain (usually involving lower third of face)

6. paresthesias (tingling, prickling, burning, numbness)

__ drugs are used to treat digitalis toxicity. In severe cases, a digoxin __ may be administered.

antiarrhythmic; antibody

What are 5 drug interactions with cardiac glycosides?

1. quinidine —> decreased renal clearance of digitalis (quinidine= antiarrhythmic drug)

2. sympathomimetic amines

3. anticholinergics

4. antibiotics —> decreased metabolism of ingested digoxin

5. corticosteroids, thiazides —> decreased serum [K+]

If a patient is on cardiac glycosides indicating they have CHF, what precautions should be taken in a dental setting? (4)

1. check vital signs

2. be sure pt is under adequate medical control

3. minimize stress and pain

4. determine if prophylactic antibiotics are needed

If a patient has low BP, HR and labored breathing while in a supine position, there may need to be __ of a dental procedure.

postponement

How does stable angina pectoris develop?

1. exercise, emotional stress, cold, meals, posture, smoking, drugs

2. catecholamine release —> inc venous return, inc ventricular size, inc ventricular pressure

3. increased myocardial oxygen demand

4. autoregulation: coronary artery dilatation

5. fixed blood flow from coronary sclerosis

   1. VS coronary vasodilatation in a NORMAL response ›

6. inadequate oxygen supply

7. angina

angina pectoris = chest pain/discomfort bc of reduced blood flow to heart muscle

Hypoxia of coronary vasculature results in decreased __. Acid-sensing nociceptive sensory fibers in coronary vasculature convey this signal to spinal cord and brain, where it is perceived as __.

pH; pain

How do nitrates affect stable angina?

dec O2 demand by dilating veins, which decreases preload

How do nitrates affect variant angina?

inc O2 supply by relaxing coronary vasospasm

• variant angina = caused by spasms in coronary arteries

An injected nitrate has __ effect, while a sublingual tablet provides __.

no; relief

How do beta blockers affect stable angina?

dec O2 demand by decreasing HR and contractility

How do beta blockers affect variant angina?

not used for variant angina bc they don’t affect vasospasm and bc unopposed alpha-adrenoceptor mediated vasoconstriction is detrimental, esp when nonselective beta blockers are used

How do Ca2+ channel blockers affect stable angina? (2)

1. Dec O2 demand by dilating arterioles, which decreases afterload (all calcium channel blockers do this)

2. dec HR and contractility (only in verapamil and diltiazem)

How do Ca2+ channel blockers affect variant angina?

inc O2 supply by relaxing coronary vasospasm

What are 4 untoward effects of organic nitrates?

1. headache (migraines for those migraine-prone)

2. orthostatic hypotension (w/ dizziness, flushing, and syncope)

3. tolerance

4. dependence

can also have alcohol/drug interactions

How do diltiazem, nifedipine, and verapamil (Ca channel blockers) affect coronary vasodilation?

• diltiazem: +++

• nifedipine: +++

• verapamil: ++

How do diltiazem, nifedipine, and verapamil affect peripheral vasodilation?

• diltiazem: +

• nifedipine: +++

• verapamil: ++

How do diltiazem, nifedipine, and verapamil affect contractility?

• diltiazem: ←→ = no change

• nifedipine: reflex tachycardia

• verapamil: decreases a lot

How do diltiazem, nifedipine, and verapamil affect heart rate?

• diltiazem: dec or ←→

• nifedipine: reflex tachycardia

• verapamil: dec

How do diltiazem, nifedipine, and verapamil affect AV nodal CV?

• diltiazem: dec

• nifedipine: ← →

• verampil: dec a lot

Combination therapy allows delivery of lower __ of individual drugs with different mechanisms of action. In combination therapy for angina, some of these drugs preferentially affect __ at low concentrations, which allow for greater therapeutic effect and __ side effects.

dosages; vascular beds; minimized

In combination therapy, DHP (dihydropyridine) is often combined with __ or __.

beta blockers or organic nitrate

In combination therapy, beta blockers can be combined with (2)

DHP or organic nitrate

In combination therapy, organic nitrate can be combined with (2)

DHPs or beta blockers

If a patient on antianginal drugs is in a dental setting, what should the dentist take precaution of? (7)

1. medical history

2. stress

3. emergency meds

4. orthostatic hypotension

5. preop sedation

6. sympathomimetics

7. gingival hyperplasia