Term
| Major classes of antihypertensive agents |
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Definition
Diuretics
Sympatholytics
Vasodilators
Rein-Angiotensin System Blockers |
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Term
| beta-Adrenoceptor antagonists |
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Definition
| inhibit sympathetic stimulation of renin secretion |
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Term
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Definition
| block the formation of angiotensin II and inhibit the breakdown of bradykinin, a vasodilator |
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Term
| Angiotensin receptor antagonists |
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Definition
| (e.g., losartan) block AT1 receptors in smooth muscle and adrenal cortex. ACE = angiotensin-converting enzyme. |
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Term
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Definition
| inhibits the sodium pump (ATPase) in the sarcolemma and increases the concentration of intracellular sodium. The high sodium concentration increases the activity of the sodium-calcium exchanger (Ex), thereby causing more calcium to enter the cardiac myocyte. Calcium activates muscle fiber shortening and increases cardiac contractility, which, in turn, increases stroke volume at any given fiber length (preload). |
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Term
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Definition
| inhibits the absorption of dietary and biliary cholesterol from the intestines |
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Term
| HMG-CoA reductase inhibitors |
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Definition
| block the rate-limiting step in cholesterol biosynthesis |
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Term
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Definition
| inhibit the reabsorption of bile acids from the gut |
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Term
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Definition
| inhibits the secretion of VLDLs from the liver |
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Term
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Definition
| Fibrates such as gemfibrozil stimulate lipoprotein lipase to increase the hydrolysis of VLDL triglycerides and the delivery of fatty acids to adipose and other tissues. |
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Term
| What does nitroglycerine do |
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Definition
Agent that decreases vascular tone
Decreases the O2 supply and demand |
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Term
| NO Donors ( Organic nitrates, sodium nitroprusside) |
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Definition
| MOA: activating guanylyl cyclase and increasing deposhorylation of myosin light chain |
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Term
| cGMP phosphodiesterase type V (PDE5) inhibitors |
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Definition
| MOA: prevent cGMP hydrolysis and promote dephosphorylation of MLC |
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Term
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Definition
| MOA: reducing intracellular calcium levels |
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Term
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Definition
| MOA: opening ATP sensitive potassium channels |
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Term
| Endothelial receptor antagonists |
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Definition
| MOA: Block endothelin mediated vasoconstriction |
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Term
| α1 adrenergic antagonists |
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Definition
| MOA: inhibits vasoconstrictive action of epi and norepinephrine |
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Term
| Hydralazine and β-adrenergic antagonists |
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Definition
| MOA: modulate vascular tone |
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Term
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Definition
| A. Sodium nitroprusside is a complex of iron, cyanide (CN), and a nitroso (NO) group. B. Sodium nitroprusside spontaneously decomposes to release NO and cyanide. NO effects vasodilation; cyanide is metabolized in the liver to thiocyanate, which undergoes renal excretion. Cyanide toxicity can result from prolonged administration of the drug or in the presence of renal insufficiency. |
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Term
| Oral isosorbide 5-mononitrate |
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Definition
Advantages:
The pharmacokinetic properties make this preparation attractive for
nitrate tolerance and angina rebound
2) High bioavailability and high half life periods produce high therapeutic plasma
concentrations of plasma
3) High periods of plasma concentration is followed by low levels rather than “Zero” levels
4) Transdermal NTG or oral isosorbide 5-mononitrate illustrate how pharmacokinetic
properties of similar acting drugs can have different therapeutic utility
Mechanism of tolerance:
Sulfhydryl hypothesis
Formation of peroxynitrite
Contraindications:
Contraindicated in patients with hypotension
In patients with elevated intracranial pressure
(because can further dilate vessels and increase pressure)
Used with caution in diastolic heart failure patients
Recent discovery: Use of nitrates with sildenafil (PDE5 inhibitors) |
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Term
| Concomitant use of NO donors with PDE5 inhibitors |
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Definition
NO donors increase levels of nitric oxide
PDE5 inhibitors restrict degradation of cGMP which is effector
if NO induced vasodilation
Therefore the NO response is amplified |
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Term
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Definition
Mechanism:
Act both on vasculature and myocardium
Ca2+ channel blockers are arteriolar dilators
Treatment of hypertension, arrhythmias, some forms of angina
Main MOA: Ca2+ blockers act by blocking the entry of Ca2+ by L-type
calcium channels
In cardiomyocytes: decrease Ca2+ influx decreases contractility,
SA node pacemaker rate,
AV node conduction velocity
Chemical classes:
Dihydropyridines: nifedipine, amlidipine, felodipine
Benzothiazipines: diltiazem
Phenylalkylamines: verapamil
Toxicity and Contraindications:
Patients taking β-blockers are advised not to take Ca2+ blockers
Because they are both negative inotropes (cardiac depression)
Major indication based secondary to mechanism: smooth muscle relaxation, constipation
Increase the risk of mortality in heart failure patients |
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Term
| K+ channel openers (Modulators of K+ ATP channel) |
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Definition
Opening of K+ATP channels hyperpolarizes the membrane
As sufficient number of K+ channels remain open then the normal
excitatory stimuli would not be able to cause depolarization
Examples and mode of action
Minoxidil:
Cromakalim
Pinacidil
Nicorandil |
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Term
| Endothelial Receptor antagonists |
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Definition
Bosentan: Competitive antagonists of ETA and ETB receptors
Used in treatment of pulmonary hypertension
Major adverse effects: Elevation in serum transaminase levels
(Therefore monitor liver function tests every month)
Ambrisentan: Relative specificity for ETA receptor
Less hepatotoxicity than bosentan |
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Term
| Renin Angiotensin system blockers |
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Definition
Used for vasorelaxation effect
ACE inhibitor: Hypotensive effect by decreased catabolism of
bradykinin (vasorelaxant released in response to inflammation)
ACE inhibitors and AT1 receptor blockers are considered
“balanced” vasodilators because they effect both arteriolar and
venous tone
Used for hypertension and heart failure |
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Term
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Definition
(Na+ channel blockers) alter SA-node automaticity by two aspects :
the threshold is shifted to more positive potentials
the slope of phase 4 depolarization is decreased.
Class I antiarrhythmics (Na+ channel blockers) act on ventricular myocytes to decrease re-entry. |
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Term
| Acetylcholine and adenosine |
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Definition
slow the SA nodal firing rate by opening K+ channels that hyperpolarize the cell and
decrease the slope of phase 4 depolarization |
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Term
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Definition
exhibit moderate Na+ channel block
Procainamide |
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Term
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Definition
rapidly bind to (block) and dissociate from (unblock) Na+ channels
Lidocaine |
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Term
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Definition
produce marked Na+ channel block
Flecainide |
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Term
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Definition
| (β-antagonists) reverse the tonic sympathetic stimulation of cardiac β1-adrenergic receptors. By blocking the adrenergic effects on the SA and AV nodal action potentials, these agents decrease the slope of phase 4 depolarization (especially important at the SA node) and prolong repolarization (especially important at the AV node). These agents are useful in the treatment of supraventricular and ventricular arrhythmias that are precipitated by sympathetic stimulation. |
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Term
| Class III antiarrhythmics |
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Definition
| (K+ channel blockers) decrease the magnitude of the repolarizing K+ currents during phase 2 of the action potential and thereby prolong action potential duration. This prolongation of the plateau phase decreases re-entry, but it can also predispose to early after depolarizations. |
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Term
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Definition
Block INa
Some block IK channels
Slows conduction velocity
Pacemaker activity
APD prolongation and Refractory period
Atrial and ventricular arrhythmias
Mostly after MI
Oral and parenteral 2-3 hours
Increased arrhythmias Hypotension |
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Term
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Definition
State dependent Ina block
No effect on IK
Ventricular arrhythmias post- MI
IV and IM
1-2 hour
CNS sedation or excitation |
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Term
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Definition
State dependent block of Ina
Slowed conduction velocity
Pacemaker activity
Refractory Arrhythmias
20 hours
Increased arrhythmias
CNS excitation |
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Term
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Definition
Like ibutilide
Treatment and prophylaxis of atrial fibrallation
Oral: 7 hours
Torsades |
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Term
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Definition
| (Ca2+ channel blockers) decrease excitability of SA nodal cells and prolong AV nodal conduction, primarily by slowing the action potential upstroke in nodal tissue. Class IV antiarrhythmics are useful in the treatment of arrhythmias that involve re-entry through the AV node, but high doses of Ca2+ channel blockers can prolong AV nodal conduction to such an extent that heart block results. |
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Term
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Definition
Blocker of β receptors slowed pacemaker activity
Refractory arrhythmias
Oral duration 4-6 hours
Cardiac depression, AV block, hypotension |
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Term
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Definition
Strong IK block
Prolongation of AP and refractory period
Refractory arrhythmias (Broad spectrum therapeutic action)
Oral, parenteral half life (1-10 weeks)
Thyroid abnormalities, deposits in skin, pulmonary fibrosis, optic neuritis |
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Term
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Definition
IK block and β-adrenergic block
Vent arrhythmias and atrial fibrillation
Oral 7 hours
Dose related torsade de pointes
Cardiac depression |
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Term
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Definition
Selective IK block, prolonged AP and QT interval
Treatment of acute fibrillation
IV only 6 hours
Torsades |
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Term
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Definition
State and use dependent ICa block
AV nodal arrhythmias especially in prophylaxis
Oral, parenteral, duration 7 hours
Cardiac depression, constipation, hypotension |
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Term
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Definition
Like verapamil
Rate control in atrial fibrillation
Oral, parenteral Duration 6 hours
Cardiac depression, constipation, hypotension |
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Term
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Definition
Increase in Diastolic IK of AV node causes marked hyperpolarization and conduction block
Acute nodal tachycardias
IV only 10-15 s
Flushing, bronchospasm, pain, headache |
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Term
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Definition
Increase in all K currents
Decreased automaticity
Decreased digitalis toxicity
Digitalis toxicity
Other arrhythmias if serum K is low
Oral or IV
Severe hyperkalamia causes cardiac arrest |
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Term
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Definition
Poorly understood
Increase in Na+/K ATPase activity
Digitalis arrythmias
IV
Muscle weakness, respiratory paralysis |
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Term
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Definition
inhibit steps in ADP-mediated platelet activation.
antagonists of the P2Y(ADP) receptor. |
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Term
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Definition
inhibit steps in ADP-mediated platelet activation.
antagonists of the P2Y(ADP) receptor. |
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Term
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Definition
inhibit steps in ADP-mediated platelet activation.
antagonists of the P2Y(ADP) receptor. |
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Term
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Definition
inhibit steps in ADP-mediated platelet activation
Dipyridamole inhibits phosphodiesterase (PDE), thereby preventing the breakdown of cAMP and increasing cytoplasmic cAMP concentration. |
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Term
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Definition
| such as the monoclonal antibody abciximab and the small-molecule antagonists eptifibatide and tirofiban, inhibit platelet aggregation by preventing activation of GpIIb–IIIa (dashed line), leading to decreased platelet cross-linking by fibrinogen. |
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Term
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Definition
Aspirin inhibits cyclooxygenase by covalent acetylation of the enzyme near its active site, leading to decreased TxA2 production.
The effect is profound because platelets lack the ability to synthesize new enzyme molecules. |
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Term
| NSAIDs and GPIIb–IIIa antagonists |
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Definition
| inhibit steps in thromboxane A2 (TxA2)-mediated platelet activation. |
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