Medchem-Test 3- Cardiac Agents

Front 1

What three major disorders are associated iwth heat disorders?

Back 1

cardiac failure

ischemia

cardiac arrythmia

Front 2

Describe what happens in all of the phases of the heart beat.

Back 2

Phase 0 : Rapid depolarization by Na+ influx
Phase 1 : (i) Rate of Na+ influx decreased
(ii) Influx of Cl-
(iii) Efflux of K+
Phase 2 : (i) Slow influx of Ca 2+ . (Ca 2+ -ion channel)
(ii) Continued efflux of K+
Phase 3 : (i) Decreased influx of Ca 2+
(ii) Continued efflux of K+
Phase 4 : Resting potential
Na+/K+-exchange by Na+, K+-ATPase pump
restores the initial negative potential.

Front 3

What is CHF?

Back 3

Cardiac Failure [Congestive Heart Failure (CHF)] :
• Inability of the heart to pump blood effectively.
• Generally caused by reduced contractility of the cardiac muscles.
• Decreased cardiac output increases blood volume of the heart (congested).
• Systemic blood pressure and renal blood flow are both reduced.
• Can cause edema in the lower extremities and the lung, and renal failure.

Front 4

What are generally the drugs of choice for treatment of CHF and associated edema?

Back 4

cardiac glycosides

Front 5

whats the MOA of cardiac glycosides?

Back 5

Mechanism of action :
Inhibits the membrane bound Na+, K+-ATPase and prevents active transport of Na+ and K+
ions across cell membranes. The positive inotropic effect and electrophysiologic changes
(increased intracellular Na+ and Ca2+ ions) results in greater force of heart contraction.

Front 6

what are the major structural fragments of cardiac glycosides?

Back 6

steroid - aglycone

sugar

Front 7

what are the most commonly used cardiac glycosides?

Back 7

digitoxin and digoxin

Front 8

what are the differences between digitoxin and digoxin?

Back 8

Pharmacokinetics of Digitoxin and Digoxin
Digitoxin Digoxin
GI absorption > 90% 70 – 85%
Protein binding 90-95% 25 – 30%
T1/2 5-7 days 1-2 days
Excretion Liver; Metabolism Kidney; Largely unchanged
Formulation Oral; IV Oral; IV

Front 9

How does Eubacterium Lentum affect digoxin?

Back 9

E. Lentum can convert digoxin into inactive metabolites; thus causing apparent resistance to standard doses of oral digoxin

Front 10

What are some symptoms of cardiac glycoside toxicity?

Back 10

Blurred visions; Disorientation; Delirium; Fatigue; Anorexia; Nausea; Vomiting; Muscular Weakness;
Abdominal Pain; Bradycardia; Tachycardia etc.

Front 11

What is the antidote for digoxin or digitoxin toxicity?

Back 11

Administration of K+- salts to stimulate Na+, K+-ATPase pump (decreases intracellular Na+ and Ca2+
ions)
• Antidigoxin immunotherapy with Fab (ovine) antidigoxin antisera (Digibind ®).

Front 12

Whats the mechanism of nonglycosidic iontropic agents?

Back 12

Positive inotropic effect via inhibition of a phosphodiesterase in the
myocardium.

Short term therapy (iv) in patients with severe heart failure refractory to other
measures.

Front 13

what are some nonglycosicic iontropic agents?

Back 13

inamirnone milrinone dobutamine

Front 14

compared to inamrinone how strong is milrinone?

Back 14

milrinone is more potent than amrinone

Better tolerated with no apparent thrombocytopenia or GI disturbances

Front 15

what is dobutamine an anolog of?

MOA?

route of administration?

Back 15

• A dopamine analog
• Potent β1-adrenergic agonist
• Potent positive inotropic effect
• Active only by iv route (extensive first pass metabolism)

Front 16

what is angina pectoris?

Back 16

• Disease of the coronary artery, caused mainly by atheroma deposits in arteries serving the heart.
• Inefficiency in supply of blood and oxygen to heart causes ischemic heart.
• Angina is characterized by sudden, severe pain originating in the heart, often moving towards left
shoulder and down the arm.
• Therapy involves alleviating and preventing anginal attacks by dilating the coronary artery.

Front 17

what are the three classes of drugs for anti-anginal agents?

Back 17

Three classes of drugs;
 Organic Nitrates
 Calcium Channel Blockers
 β-Adrenergic Blockers

Front 18

what are the pharmacologic actions of organic nitrates?

Back 18

Pharmacologic Actions :
Decreases generalized myocardial workload (preload and postload) via vasodilation of veins
(decreased venous return to the heart) and arteries (decreased peripheral resistance), causing reduced
oxygen demand by myocardium.

Front 19

What is the MOA of organic nitrates?

Back 19

Biochemical Mechanism of Action ;
Organic nitrates causes their pharmacological effects by generating / releasing nitric oxide (NO) insitu.
The NO released activates guanylate cyclase, causing increased formation of c-GMP, which in
turn reduces the Ca2+ mediated vascular contraction.

Front 20

what is an antidote for cyanide poisoning?

Back 20

amyl nitrate

its also volatile and flammable liquid,

available in inhalant form

Front 21

What drug uses sublingual adminstration the best?

Back 21

glyceryl trinitrate (nitroglycerin)

Front 22

What has the longest duration of action for antianginal drugs?

Back 22

Isosorbide 4-6 hrs

nitroglycerin < 1 hr

Amyl nitrate ~1 min

Front 23

What antianginal drug has a slower onset and longer duration of action, it is used prophylacticly against angina pectoris

Back 23

erithrityl tetranitrate

Front 24

What are adverse effects of organic nitrates?

Back 24

• Headache is common and can be severe
• Postural hypotension and related effects (dizziness, nausea, vomiting etc).
• Can cause drug rash occasionally.
• Tolerance can develop (shortened duration of action).

Front 25

drug interactions of organic nitrates?

Back 25

Drug Interactions :
• Can cause significant interactions with other vasodilators, alcohol etc.
• Concurrent administration with sympathomimetic agents may lead to decreased antianginal efficacy.
• Individuals taking organic nitrates should not be prescribed Sildenafil (Viagra), as the combination
can cause dramatic fall in blood pressure.

Front 26

whats the MOA of calcium channel blockers and what is the result of this?

Back 26

Through a cascade process, Ca2+ ions are responsible for myocardium contraction, while vascular smooth
muscles depend on Ca2+ ion influx for contraction. Calcium channel blockers inhibit calcium ion influx into
myocardial cells, causing a negative inotropic effect on the heart and also leads to vasodilation, particularly
in the arterial smooth muscles.

The sum effect is decreased heart workload and afterload.

Front 27

what are the three classes of calcium channel blockers?

Back 27

• Dihydropyridine
• Benzothiazepine
• Aralkylamine

Front 28

what are the therapeutic uses of calcium channel blockers?

Back 28

Calcium channel blockers are used clinically as antianginal, antiarrhythmic, and antihypertensive agents.
While the dihydropyridine drugs are used mainly as antianginal and antihypertensive agents, drugs
belonging to the remaining two classes are frequently used in the management of angina, hypertension and
cardiac arrhythmia.

Front 29

What are two examples of dihydropyridines?

Back 29

nifedipine, amlodipine,

Front 30

Is nifedipine highly protein bound?


where does nifedipine generally work?

Back 30

• Potent peripheral vasodilatory properties
• Orally active drug. Highly protein bound (~ 90%). T1/2 = 2 – 5 hrs
• Uses : Vasospastic angina; Angina pectoris.

Front 31

Does amlodipine have a greater affinity for vascular smooth muscle or myocardial tissue?

Does it have a long duration of action?

Back 31

• Greater selectivity for vascular smooth muscle (vs. myocardial tissue)
• Long duration of action. T1/2 = 34 hrs
• Uses : treatment of chronic stable angina

Front 32

what is an exampel of a benzothiazepine?

Back 32

diltiazem

• Calcium channel blocker with vasodilating activity.
• Orally active. Rapidly absorbed from the GI tract.
• Undergoes extensive first pass metabolism involving deacetylation (retains ~
50% activity), and, O- and N-demethylation (inactive metabolites).
• Uses : Angina; Hypertension; Cardiac arrythmia.

Front 33

what is an example of a aralkylamine?

Back 33

verapamil

• Prototypical Ca2+ antagonist. Coronary vasodilator. Introduced in 1962.
• Selectively blocks Ca2+ entry into myocardial cell.
• Racemic drug. S-Enantiomer more active.
• Orally active. T1/2 = 3 - 7 hrs. Liver metabolized (N- and O-Dealkylation).
• Uses : Angina; Hypertension; Cardiac arrythmia.

Front 34

what is cardiac arrythmia?

Back 34

Cardiac Arrythmia : Abnormalities of cardiac rhythm. Caused by perturbation of the normal sequence of
impulse initiation and propagation.

Front 35

what do class 1 cardiac antiarrythmic agents do?

Back 35

Class I : Membrane Depressant Drugs [Shifts membrane to more negative potentials]
• Acts on the fast Na+ ion channels by binding and blocking its function (prevents Na+ conductance).
• Further classified into three subgroups (IA, IB, IC), based on the relative ease of dissociation of the
agents from the Na+ ion channel.
Sub-Classes :
IA (intermediate rate of dissociation) : Quinidine; Procainamide; Disopyramide. Lengthens the refractory
period of cardiac tissue to cause cessation of arrthymia.
IB (fast dissociation from Na+ ion channels) : Lidocaine; Phenytoin; Tocainide. Shortens duration of action
Potential.
IC (most potent Na+ ion channels blockers) : Flecainide; Encainide etc. Slows conduction.

Front 36

What do class 2 antiarrythmic agents do?

Back 36

Class II : β-Adrenergic Blockers [Supresses sympathetic activity].
Propranolol is the prototype drug;

Front 37

What do class 3 antiarrythmic agents do?

Back 37

Class III : Repolarization Prolongators [Prolonging of action potential].
Bretylium; Amiodarone are the typical drugs.

Front 38

What do class 4 agents do?

Back 38

Class IV : Calcium Channel Blockers [Blocking of inward slow Ca2+ ion current].
Prototypical drug is Verapamil.

Front 39

What class is quinidine?

Back 39

class 1A

Alkaloid found in cinchona bark. Two basic nitrogen atoms.
• Orally available as the corresponding salt.
• T1/2 = 6 hrs. Liver metabolized.
• Use : Long term oral antiarrythmic therapy.
• Side effects : GI disturbances (nausea, vomiting, diarrhea etc.)

Front 40

What class is procainamide?

What is its side effect?

Back 40

Class 1 A

• Synthetic compound. Structurally related to local anesthetic
procaine.
• Major drug in the treatment of cardiac arrythmias.
• Oral drug. Liver metabolized (~ 50%) into p-aminobenzoic acid
and N-acetyl procainamide (active metabolite).
• Use : Various cardiac arrythmias.
• Side Effects : Drug induced lupus syndrome.

Front 41

What class is lidocaine?

Back 41

class 1B

• Original use as a local anesthetic.
• Drug of choice for emergency treatment of ventricular arrythmia
(parenteral). Also, used parenterally for suppression of arrythmias
associated with acute myocardial infraction and cardiac surgery.
• T1/2 = < 30 min. Liver metabolized (N-Deethylation and amidase hydrolysis)
Adverse Effects : Dizziness, paresthesis and seizure in severe cases.

Front 42

What class is phenytoin?

Back 42

class 1B

• Structurally analogous to barbiturates but does not possess sedative properties.
• Long history of use for the treatment of seizures.
• Useful antiarrythmic agent for the treatment of digitalis induced arrythmias.
• Orally active. High plasma protein binding (~ 90%).
• T1/2 = 15 -30 hrs. Metabolized in the liver.

Front 43

What class is flecainide?

Back 43

class 1C

Class IC antiarrythmic drug with local anesthetic activity.
• Orally administered for the treatment of ventricular tachycardia.
• Well absorbed. T1/2 = 14 hrs. Metabolized in the liver.
• Side effects : Occasional incidences of aggravating existing
arrythmias or induce new ones.

Front 44

What class is propranolol?

Back 44

class 2

• Prototypical adrenergic β-blocker, is also a Class II antiarrythmic.
• Used in the treatment of ventricular arrythmias, tachycardia and atrial
fibrillation.

Front 45

What class is bretylium tosylate?

Back 45

class 3

• Originally developed as an antihypertensive.
• Currently used for emergency life threatening ventricular arrythmias that are
resistant to other therapy.
• Usually administered iv or im.
• Adverse Effect : Hypotension

Front 46

What class is verapamil?

Back 46

class 4

• Blocks slow inward Ca2+ currents in cardiac fibres.
• Initially developed as a coronary vasodilator for angina.
• Also used widely for the treatment of supraventricular arrythmias.
• Extensive first pass metabolism. Excreted in urine.