WK7: Drugs-Acting-on-Cardiovascular-System

• systimetic = peripheral circulation, outside the heart circulation,

• left side = pulmonary and cardiac problem

• right side = edema, hepatomegaly

• cholesterol is much riskier, more waxy,

Drugs affecting blood pressure

• Blood pressure = CO × SVR

  • CO = cardiac output

  • SVR = systemic vascular resistance (left, away, palabas ng puso)

Elements determining blood pressure

• Heart rate

  • Stroke volume - amount of blood that is pumped out of the ventricle with eachheartbeat

  • Total peripheral resistance – resistance ofthe muscular arteries to the blood being pumped through

Categories rating the severity of hypertension

• stages, based on BP measurements (adults) | dalawang beses na mataas(different days tinake), there could be high blood pressure, need doctor’s check up to make sure

  • Normal: < 130/85

  • High normal: 130-139/ 85-89

  • Stage 1: 140-159/90-99

  • Stage 2: 160-179/100-109

  • Stage 3: 180-209/110-119

  • Stage 4: 210 or greater/120 or greater

Classification of BP

• Hypertension can also be defined by its cause

  • Unknown cause

    • – Essential, idiopathic, or primary hypertension

    • – 90% of the cases

  • Known cause (may dahilan)

    • – Secondary hypertension

    • – 10% of the cases

    • Ex. diabetes, tumor in brain

• High diastolic BP (DBP) is no longer considered to be more dangerous than high systolic BP (SBP)

• Studies have shown that elevated SBP is strongly associated with heart failure, stroke, and renal failure

Steeped care approach to treat hypertension

1. Step 1 lifestyle modification

2. Step 2 drug therapy is added (one type of drug)

3. Step 3 drug dose or class may be changed or another drug added

4. Step 4 includes all of the above measure with the addition of more antihypertensive agents until BP is controlled

• Thiazide-type diuretics should be the initial drug therapy for most patients with hypertension (alone or with other drug classes)

• The previous labels of “mild,” “moderate,”and “severe” have been dropped

• smoking = vasocontriction

Anti-Hypertension Drugs

Diuretics

• Diuretics are drugs that increase renal excretion of water, sodium & other electrolytes, thereby increasing urine formation & output

• Used in the management of heart failure, renal & hepatic disease, hypertension

• lythics = vasodilation

• water + sodium = high blood volume/pressure

Thiazide diuretics

• Decrease reabsorption of Na, water, Cl & bicarbonate in the distal convoluted tubule

• Hydrocholorothiazide

• Indapamide

• Contraindicated in severe renal and hepatic impairment, hypokalemia, hyponatremia

• Side effects are postural hypotension, hyperglycemia

Loop Diuretics

• Inhibit Na & Cl reabsorption in the ascending loop of Henle

• Frusemide

• Bumetanide

• CI : renal failure with anuria

• SE: hyponatraemia

Potassium-Sparing Diuretics

• Act directly on the distal tubule to decrease the exchange of Na for K

  • – Amiloride

  • – Triamterene

• Spironolactone

  • – Block the Na-retaining effects of aldosterone in the distal tubule

• CI: hyperkalaemia, renal failure

• SE: dry mouth, rashes, with spironolactone gynaecomastiya can occur

ACE Inhibitors

ACE inhibitors and Angiotensin II receptor antagonists may cause first dose hypotension

Angiotensin-converting enzyme (ACE) inhibitors (activates angiotensin))

• Block the enzyme (ACE) that normally converts angiotensin I to angiotensin II

• Decrease vasoconstriction & decrease aldosterone production, reducing retention of Na and water Calcium Channel Blockers

• Used to treat hypertension, heart failure, myocardial infarction, and diabetic nephropathy

  • – Enalapril

  • – Captopril (Capoten)

  • – Lisinopril

• Side Effects:

  • – Can produce serious first-dose hypotension

  • – Cough, due to accumulation of bradykinin

  • – Hyperkalaemia, due to inhibition of aldosterone release

• CI: In hypersensitivity to drug

Angiotensin II receptor blockers (ARBs) (inactivates angiotensin)

• Compete with angiotensin II for tissue binding sites & prevent angiotensin II from combining with its receptors in body tissues

• Used for hypertension, may be used as an alternative to ACE inhibitors in the management of heart failure and diabetic nephropathy.

  • » Irbesartan

  • » Losartan

  • » Valsartan

• Side-effects

  • – Hypotension

  • – Less likely to cause cough and hyperkalaemia than ACE inhibitors

Calcium Channel Blockers

• Drugs the prevent calcium ions from entering cells

• positive inotropic effect = pinapalakas ung puwersa

• no vasoconstriction

• Vascular Smooth Muscle:

  • – Calcium channels regulate contraction

  • – If channels are blocked, contraction will be prevented and vasodilation will result

  • – Act selectively on peripheral arterioles and arteries and arterioles of the heart (no effect on veins)

• Heart:

  • – Regulate function of myocardium, SA & AV nodes.

  • – Myocardium

    • Positive inotropic effect (increases force of contraction)

    • Calcium is blocked, contractile force will diminish

  • – SA Node

    • Pacemaker activity regulated by calcium influx

    • Calcium is blocked, heart rate is reduced

  • – AV Node:

    • Excitability of AV nodal cells is regulated by calcium entry

    • Calcium is blocked, discharge of Av nodal cells is suppressed (decreases the velocity of conduction through the AV node).

• Three chemical families in CCB’s

• Verapamil:

  • – Blocks calcium channels in blood vessels and in the heart

  • – Used for:

    • Angina Pectoris (vasodilation) = chest pain (5mins) | myocardial (MI) = chest pain (15-20 mins)

    • Hypertension

    • Cardiac dysrhythmias

  • – Careful administration/contraindications:

    • Cardiac failure, AV block, sick sinus syndrome

  • CVA = cardiovascular accident (heart failure), cerebrovascular accident (stroke)

• Diltiazem(Cardizem): similar to Verapamil

• Nifedipine

  • Relaxes vascular smooth muscle and dilates coronary and peripheral arteries

  • More effect on vessels less on myocardium

    • – Used for:

      • Prophylaxis of Angina Pectoris (vasodilation)

      • Hypertension

    • – Careful administration/contraindications:

      • Cardiac shock, advanced aortic stenosis, within one month of MI, acute attack of angina

Sympatholytics (Adrenergic Antagonists)

• Suppress the influence of the sympathetic nervous system on the heart, blood vessels, and other structures

• Beta 1 = heart | Beta 2 = lungs | Beta 1 and Beta 2 (good for heart, bad for heart) Blocker = both for heart

• Five Subcategories:

– Beta-blockers

• Most widely used antihypertensive drugs

• Four useful actions in hypertension:

  • – Blockade of cardiac beta1 receptors

    1. Decreases heart rate and contractility(decreases cardiac output)

    2. Suppress reflex tachycardia caused by vasodilators in the regimen

    3. Blockade of beta1 receptors on juxtaglomerular cells of kidney reduce release of renin

       • – Reduces Angiotensin II vasoconstriction, aldosterone mediated volume expansion

    4. Long term use reduces peripheral vascular resistance

  • – Adverse effects:

    • Bradycardia, decreased AV conduction, reduced contractility

  • – Contraindicated:

    • Sick sinus syndrome / AV blocks / asthma (bronchoconstrictive effects)

• Two subgroups:

• – Nonselective Beta Blockers (Propanolol Beta1& Beta2)

  • Reduce heart rate, decrease force of ventricular contraction, suppress impulse conduction through the AV node, suppress secretion of renin, bronchoconstriction, inhibition of glycogenolysis.

    • Propranolol hydrochloride (not for lung problem)

    • Sotalol

    • Timolol

    • Pindolol

    • Levobunolol

    • Nadolol

    • Metipranolol

• – Cardioselective Agents (Metoprolol-Beta1only)

  • Same as nonselective except it does not block bronchial beta2 receptors so does not increase airway resistance.

    • Atenolol

    • Acebutolol

    • Metoprolol

    • Bisoprolol

    • Esmolol

    • Betaxolol

    • Nebivolol

– Alpha1 Blockers

• Prevent stimulation of alpha1 receptors on arterioles and veins, thereby preventing sympathetically mediated vasoconstriction.

• Resultant vasodilation results in lowered blood pressure

• nit given as first drug therapy

• Blockade of Alpha1 receptors can cause orthostatic hypotension, reflex tachycardia.

  • – 1% of patients lose consciousness 30-60minutes after receiving their first dose

  • – NOT be used as first line therapy for hypertension.

    • Prazocin

    • Doxazosin

    • Indoramin

    • Terazosin

– Alpha/Beta Blocker

• Block Alpha1 and Beta receptors

• Blood pressure drops:

  • – Alpha1 blockade promotes dilation of arterioles/veins

  • – Blockade of cardiac beta1 receptors reduced heart rate and contractility

  • – Blockage of beta1 receptors on juxtaglomerular cells suppresses release of renin

  • – Reduce peripheral vascular resistance

• Watch for:

  • – Bradycardia, AV heart block, asthma, postural hypotension

• Prototypes: Carvedilol, Labetalol

– Centrally Acting antihypertensive

• Methyldopa

• Use for management of hypertension in pregnancy

• Block sympathetic activity within the brain

– Adrenergic Neuron Blockers

• Decrease blood pressure through actions in the terminals of the post ganglionic sympathetic neurons.

• Inhibit/deplete norepinephrine release

  • – Resulting in decreased sympathetic stimulation of the heart and blood vessels

• Watch for:

  • – Severe orthostatic hypotension

• Guanethidine monosulphate

• Derisoquine

• Contraindicated in heart failure, phaeochromocytoma

Vasodilators

• Vasodilators differ in respect to the types of blood vessels they affect.

  • – Dilation of arterioles

  • – Dilation of veins

  • – Uses:

    • • Hypertension, Angina, heart failure, myocardial infarction.

  • – Adverse Effects:

    • Orthostatic hypotension caused by relaxation of smooth muscle in veins.(dizziness, lightheadedness)

    • Reflex tachycardia places unacceptable burden on heart, tachycardia rises blood pressure

    • Expansion of blood volume-secretion of aldosterone—(diuretic may need to be added)

• ANTIHYPOTENSIVE AGENT (sobrang bagsak ng BP) = MIDODRINE(pataas ng BP)

Hydralazine (sublingual, oral)

• – Causes selective dilation of arterioles, has little or not effect on veins

• – Peripheral resistance and arterial blood pressure fall

• – Heart rate and myocardial contractility increase

• inotropic, monotropic

• – Uses:

  • Hypertension, heart failure

• – Adverse Effects:

  • Reflex tachycardia, increased blood volume (sodium/water retention), Systemic Lupus Erythematosus-like syndrome (muscle pain, joint pain, fever, nephritis, pericarditis).

Sodium Nitroprusside

• – Potent and efficacious vasodilator

• – Fastest acting antihypertensive agent available

• – Causes venous and arteriolar dilation

• – IV infusion, onset is immediate

• – Uses:

  • Hypertensive emergencies

• – Potent and efficacious vasodilator

• – Adverse Effects:

  • Excessive hypotension

  • Thiocyanate Toxicity (patients on med> 3 days)

• – Administration:

  • Degraded by light--cover

ACE Inhibitors

Calcium Channel Blockers

Sympatholytics

Nitroglycerin

Antianginal drugs

• Angina Pectoris

  • It is a coronary artery disease

  • Types:

    • Stable angina - no damage to heat muscle ; basic reflexes surrounding the pain store blood pressure (activity then rest)

    • Unstable angina - episodes of ischemia occur even when at rest

    • Prinzmetal’s angina - caused by spasm of the blood vessel, not just by vessel narrowing (bigla bigla nalang, whether rested or not)

• Nitrates - Nitroglycerin (sublingual, patch dermal)

  • Nitrates are converted to NO in vascular smooth muscle

  • NO activates guanylate cyclase

  • Increase formation of cGMP so that the intracellular calcium levels decrease

  • Vasodilation

  • Used to treat or prevent angina

    • – Relieves anginal pain by relaxing smooth muscles in the blood vessels(vasodilation) by several mechanisms

      • Dilate veins

      • Dilate coronary arteries

      • Dilate arterioles

    • – Adverse Effects

      • Headache

      • Orthostatic hypotension

    • – Symptoms include lightheadedness and dizziness

      • Reflex tachycardia

  • Examples:

    • Glyceryl Trinitrate

    • Isosorbide Mononitrate(Ismo, Imdur)

    • Isosorbide Dinitrate (Isordil)

    • Nitroglycerin (Nitro.Bid,Nitrostat)

    • Nitrate of choice before chest pain begins

• Calcium channel blockers - Diltiazem

• Beta-adrenergic blockers - Metoprolol

Cardiac Glycosides

• – Profound effects on the mechanical/electrical properties of the heart

• inotropic

• energy drinks = pampalakas ng puwersa

• – Most widely used prescription drugs, they are the most dangerous (toxic—dysrhythmias)

• – Prototype (Digoxin—only cardiac glycoside available in most countries)

• – Uses:

  • • Heart failure, dysrhythmias

• Cardiotonic Agents

  • Cardiac Glycoside - Digoxin

  • Phosphodiesterase Inhibitors - Inamrinone

  • Digoxin Antidote - Digoxin immune Fab

Digoxin

• Exerts a positive inotropic action on the heart(increases the force of ventricular contraction,enhancing cardiac output)

• Digoxin Uses:

  • – Heart failure:

    • Increased cardiac output by increasing myocardial contractility

      • –Sympathetic tone declines

        • Because Digoxin increases arterial pressure.

        • Heart rate is reduced, allowing more complete ventricular filling

      • –Increased urine production

        • Increased cardiac output increases renal blood flow

        • Loss of water (urine) decreases blood volume which reduces cardiac distension, pulmonary congestion, and peripheral edema.

      • –Decreased Renin Release

        • In response to increased arterial pressure, decrease in Angiotensin Decreased aldosterone decreases retention of sodium/water, reducing blood volume

• Digoxin overall effects on CHF:

  • – Cardiac output improves, heart rate decreases, heart size declines, constriction of arterioles and veins decrease, water retention reverses, blood volume declines, peripheral and pulmonary edema decrease, weight is lost, exercise tolerance improves, fatigue is reduced.

• Digoxin treats dysrhythmias:

  • – Through a combination of actions, digoxin can alter the electrical activity in non contractile tissue (SA & AV nodes, Purkinje fibers), as well as the ventricular muscle.

• Toxicity:

  • – Dysrhythmias: AV block, ventricular flutter, ventricular fibrillation

  • – Predisposing factors:

    • Hypokalemia (usually secondary to the use of diuretics)

    • Elevated digoxin levels–Narrow therapeutic range

    • Heart disease

  • – Side Effects: anorexia, nausea, vomiting, fatigue, visual disturbances

  • – Administration: Count heart rate—less than60 or change in rhythm detected HOLD THEDOSE AND CALL THE PHYSICIAN!

Antidysrhythmic Medications (Antiarrhythmic Agents)

• Class IA – Disopyramide (Norpace)

• Class IB- Lidocaine (Xylocaine)

• Class IC – Fleicanide(Tambucor)

• Class II- Propanolol (Inderal)

• Class III- Sotalol (Betapace)

• Class IV- Diltiazem (Cardizem)

• Dysrhythmia (Arrhythmia):

  • – Defined as abnormality in the rhythm of the heartbeat.

  • – Associated with high degree of morbidity/mortality

• Types:

  • – Tachydysrhythmias

  • – Bradydysrhythmias

• Vaughan Williams Classification:

  • – Class I: Sodium Channel Blockers

  • – Class II: Beta Blockers

  • – Class III: Potassium Channel Blockers

  • – Class IV: Calcium Channel Blockers

  • – Class V: Other Antidysrhythmic Drugs ( Adenosine, Digoxin)

– Class I: Sodium Channel Blockers

• Sodium Channel Blockers:

  • – Block cardiac sodium channels

  • – Decrease conduction velocity in the atria, ventricles, and Purkinje system

  • – Class IA agents for atrial fibrillation, flutter; supraventricular & ventricular tachyarrhythmias

    • Eg: Quinidine, procainamide

    • SE: tachycardia, dry mouth, urinary retention, blurred vision

  • – Class IB agents for ventricular tachyarrhythmias (VT)

    • Eg: Lidocaine

  • – Class IC for life-threatening supraventricular tachyarrhythmias (SVT) and ventricular tachyarrhythmias (VT)

    • Eg: Flecainide

• These drugs will be contraindicated in atrioventricular block

– Class III: Potassium Channel Blockers

• Potassium Channel Blockers:

  • – bind to and block the potassium channels that are responsible for repolarization

• Bretylium

  • – For life-threatening ventricular tachycardia and fibrillation

  • – can lead to hypotension

• Amiodarone

  • – Effective against both atrial and ventricular dysrhythmias (only for life-threatening because of toxicity—lung damage/visual impairment

Other Antidysrhythmic Drugs

• Adenosine:

  • – Slows conduction through the AV node

  • – Treats SVT

  • – Short plasma half life (less than 10 seconds)

    • Given IVP—closest IV site to the heart,followed by push of saline

• Digoxin

Principles of Antidysrhythmic Drugs

• Treat only if there is a clear benefit and then only if the benefit outweighs the risks

• Treatment reduces:

  • – Symptoms (palpitations, angina, dyspnea, and faintness)

  • – Mortality

Antidysrhythmics : Bradydysrhythmias

• Atropine:

  • – Muscarinic Antagonist

    • Competitively block the actions of acetylcholine

    • Stimulation of muscarinic receptors decreases heart rate

      • –Blocking these receptors will INCREASE heart rate

• Isoproterenol:

  • – Acts on Beta-adrenergic receptors

  • – Activates Beta1 receptors on the heart-overcomes AV block, restarts the heart following cardiac arrest, increases cardiac output during shock

Anticoagulants

• Prevent formation of new clots and extension of clots already present

• Heparin and warfarin (Coumadin) are commonly used

• Used to prevent or manage thrombophlebitis, DVT, and PE

• Main adverse effect is bleeding

• Drugs Affecting Blood Coagulation

  • Antiplatelet Drugs – Aspirin (generic)

  • Anticoagulants – Heparin (generic)

  • Low-Molecular Weight Heparins

  • Anticoagulant Adjunctive Therapy

  • Hemorrheologic Agent

  • Thrombolytic Agents – Streptokinase (Streptase)

• Actions of anticoagulants

  • Anticoagulants

  • Antiplatelets

  • Thrombolytic drugs

• Drugs Used To Control Bleeding

  • Antihemophilic Agents - Antihemophilicfactor (Bioclate)

  • Systemic Hemostatic Agents – Aminocaproic acid (Amicar)

  • Topical Hemostatic Agents

Heparin (unfractionated)

• Intrinsic pathway is affected

• Its major anticoagulant effect by inactivating thrombin and activated factor X (factor Xa) through an antithrombin (AT)-dependent mechanism.

• Intravenous therapy

• Require a PTT monitoring (Activated partial thromboplastin time)

• Uses: Inhibit additional clotting, allowing body tolyse

  • current clot – Treatment and Preventative uses(hospital)

  • Pulmonary embolism (PE)

  • Stroke evolving

• Massive deep venous thrombosis (DVT)

• Adverse effects

  • Hemorrhage

  • Heparin-induced thrombocytopenia

  • Hypersensitivity reactions

• Contraindications: GI ulcers, blood dyscrasias

• Protamine (reversal agent)

Low-Molecular-Weight Heparin

• Fixed dose schedule, don’t require aPTT monitoring• Can be used at home (unlike Heparin)

• Much less likely to cause thrombocytopenia (than Heparin)Therapeutic use• 1st line therapy to prevent and treat DVT

• Prevention of DVT following surgery

• Treatment of established DVT

• Prevention of ischemic complications

• Adverse effects and interactions

  • Bleeding

• Example

  • Enoxaparin

Warfarin

• Oral anticoagulant

• Antagonist vitamin K

• Blocks the biosynthesis of factors VII, IX,X, II

• Anticoagulant effects occur 3-5 days afteroral use

• No effect on circulating clotting factors or platelets

• Therapeutic uses

  • Long-term prophylaxis of thrombosis

  • Prevention of venous thrombosis and associated pulmonary embolism

  • Prevention of thromboembolism (inpatients with prosthetic heart valves)

  • Prevention of thrombosis during atrial fibrillation

• Adverse effects

  • Hemorrhage

  • Fetal hemorrhage and teratogenesis from use during pregnancy

  • Do not use during lactation

Antiplatelet

Aspirin

• Suppress the production of prostaglandins and thromboxanes due to its irreversible inactivation of the cyclooxygenase (COX)enzyme

• Normally COX produces prostaglandins, most of which are pro-inflammatory, and thromboxanes, which promote clotting

• Low-dose, long-term aspirin use irreversibly blocks the formation of thromboxane A2 in platelets, producing an inhibitory effect on platelet aggregation

• This anticoagulant property makes aspirin useful for reducing the incidence of heart attacks

• Adverse effect

  • Increase risk of GI bleeding

Clopidogrel

• Irreversibly inhibits ADP receptor on platelet cell membranes, which is important in aggregation of platelets and cross-linking by the protein fibrin.

• Used to inhibit blood clots in coronary artery disease, peripheral vascular disease, and cerebrovascular disease

• Adverse effects include hemorrhage, Severe neutropenia, and Thrombotic thrombocytopenic purpura (TTP)

• Aspirin and clopidogrel given orally

Fibrinolytic drugs

• First Generation – Streptokinase

• Second Generation – Altepase (tPA)

• Third Generation – reteplase recombinant (retavase)

Streptokinase

• A protein (secreted by several species of streptococci) can bind and activate humanplasminogen

• Uses

  • Acute coronary thrombosis (acute MI)

  • Deep venous thrombosis (DVT)

  • Massive pulmonary emboli

  • Plugged AV shunt, central lines

• Adverse effects

  • Bleeding

  • Antibody production

  • Hypotension

  • Fever

• Contraindications Absolute

  • Previous intracranial bleeding at any time, stroke in less than a year, active bleeding, uncontrolled high blood pressure (>180 systolic or >100 diastolic).

  • Streptokinase is contraindicated in patients who have been previously treated with streptokinase, as there is a risk of anaphylaxis, a life-threatening allergic reaction, due to the production of antibodies against the enzyme.

  • Current anticoagulant use, invasive orsurgical procedure in the last 2 weeks,prolonged cardiopulmonary resuscitation(CPR) defined as more than 10 minutes,known bleeding diathesis, pregnancy,hemorrhagic or diabetic retinopathies,active peptic ulcer, controlled severehypertension

Recombinant tissue plasminogenactivator (t-PA, alteplase)

• t-PA is produced by endothelial cells

• It is nonantigenic and causes a more selective thrombolysis than streptokinase.

• Alteplase, the recombinant t-PA, is produced by recombinant DNA technology.

• Uses:

  • Acute myocardial infarction.

  • Acute cerebrovascular thrombosis.

  • Pulmonary embolism.

  • Central venous catheter occlusion

• Adverse effects:

  • Major bleeding.

  • Cardiac arrhythmias.

  • Anaphylactoid reaction.

  • Cerebrovascular accident.

  • Intracraneal hemorrhage.

Reteplase

• It has an increased half life than t-PA andincreased specificity for fibrin.

• Its efficacy and adverse effect profile aresimilar to those of streptokinase and t-PA

Antifibrinolytic drugs

• Interfere with the formation of the fibrinolytic enzyme plasmin from its precursor plasminogen by plasminogen activators

• Block the binding sites of the enzymes or plasminogen respectively and thus stop plasmin formation

• Aminocaproic acid and tranexamic acid

• Use in bleeding tendencies

Lipid-lowering agents

• HMG-CoA Reductase Inhibitors –Atorvastatin (Lipitor)

• Fibric acid derivatives (Fibrates)

• Bile Acid Sequestrants – Cholestyramine (Questran)

• Nicotinic acid (niacin)

• Cholesterol absorption inhibitors –Ezetimibe

HMG CoA reductase inhibitors(Statins)

• Inhibits HMG CoA reductase, the rate-limiting enzyme in cholesterol synthesis

• Increase LDL receptors in hepatocytes

  • This enables hepatocytes to remove more LDLs from the blood

• Also decrease VLDL levels and increase HDL levels

• Atorvastatin

• Fluvastatin

• Pravastatin

• Simvastatin

• Adverse Effects

  • Headache, GI side effects (e.g.abdominal pain, flatulence, diarrhoea,nausea andvomiting)

  • Hepatoxicity

  • Myopathy

Fibric acid derivatives (Fibrates)

• Increase oxidation of fatty acids in liver and muscle tissue, decrease hepatic production of triglycerides, decrease VLDL cholesterol and increase HDL cholesterol

• Main indication is hypertriglceridemia (high plasma triglycerides)

• Adverse Effects

  • Nausea, vomiting and GI upset

  • Cholelithiasis (stones in the gallbladder) and cholecystitis (inflammation of the gallbladder)

  • Myopathy

• Clofibrate

• Fenofibrate

• Gemfibrozil

Bile acid sequestrants

• Bind bile acids in the intestinal lumen. This causes the bile acids to be excreted in feces and prevents them being re-circulated to the liver

• Mainly used as an adjunct to Statins to decrease LDL cholesterol levels

• Cholestyramine

  • Adverse effects

    • Constipation, diarrhea, nausea, vomiting, gastro-intestinal discomfort

    • Decreased absorption of fat-soluble vitamins

• Nicotinic acid

  • Inhibits mobilization of free fatty acids from peripheral tissues, there by reducing hepatic synthesis of triglycerides and secretion of VLDL, which leads to decreased production of LDL cholesterol

  • Besides reducing LDL and VLDL levels, also effective in increasing HDL levels

  • Adverse effects

    • Flushing, itching, nausea, vomiting, diarrhea

    • Hepatotoxic

    • Hyperglycemia and hyperuricemia