Drugs Affecting Blood Pressure

Hypertenstion

• excessive high blood pressure

• Is recognized as a major risk factor for several potentially lethal cardiac conditions, including myocardial infarction and heart failure.

• This can damage the fragile inner lining of blood vessels and cause a disruption of blood flow to the tissues.

• It also puts a tremendous strain on the heart muscle, increasing myocardial oxygen consumption and putting the heart muscle at risk

Blood Pressure = CO x SVR
- CO = Cardiac Output
- SVR = Systemic Vascular Resistance

Elements Determining Blood Pressure

1. Heart Rate

2. Stroke Volume

   • amount of blood that is pumped out of the ventricle with each heartbeat

3. Total Peripheral Resistance

   • resistance of the muscular arteries to the blood being pumped through

Categories Rating Severity of Hypertension

• Normal: < 130/85

• High Normal (Elderly): 13-=139/85-89

• Stage 1: 140-159/90-99

• Stage 2: 160-179/100-119

• Stage 3: 180-209:110-119

• Stage 4: 210 or greater/120 or greater

Classification of Blood Pressure

• Hypertension can also be defined by its cause

• Primary Hypertension

  • Essential, Idiopathic

  • UNKNOWN cause

  • 90% of the cases

• Secondary Hypertension

  • KNOWN CAUSE (Pheochromocytoma)

  • 10% of the cases

• 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

• 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

Renin Angiotensin Aldosterone System

Anti-Hypertensive Drugs

Diuretics

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

• Used in:

  • management of heart failure

  • renal & hepatic disease

  • hypertension

• Problems is Alteration of RAAS

Thiazide Diuretics

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

  • Hydrochlorothiazide

  • Indapamide

• Contraindicated: severe renal and hepatic impairment, hypokalaemia, hyponatraemia

• Side effects: postural hypotension, hyperglycemia

Loop Diuretics

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

  • Furosemide

  • Bumetanide

• ContraIndications: renal failure with anuria

• Side Effects: 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

• ContraIndications: hyperkalaemia, renal failure

• Side Effects: dry mouth, rashes, with spironolactone gynaecomastia can occur

ACE Inhibitors

• 2 Families of Drugs

• The Problem is Altered RAAS (Renin Angiotensin Aldosterone System)

Angiotensin-Converting Enzyme (ACE) Inhibitors

• (…pril)

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

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

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

  • Captopril (Capoten)

  • Enalapril

  • Lisinopril

• Indications

  • hypertension

  • heart failure

  • diabetic nephropathy

  • left ventricular dysfunction after a myocardial infarction (MI).

• Side Effects

  • Can produce serious first-dose hypotension

  • Cough, due to accumulation of bradykinin

  • Hyperkalaemia, due to inhibition of aldosterone release

• Contraindications

  • In hypersensitivity to drug

Angiotensin II Receptor Blockers (ARBs)

• (…sartan)

• 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

• Indications

  • hypertension

  • diabetic nephropathy (elevated serum creatinin and proteinuria)

• Side Effects

  • Hypotension

  • Less likely to cause cough and hyperkalaemia than ACE inhibitors

• ACE inhbitors and Angiotensin II receptor antagonists may cause first dose hypotension

Calcium Channel Blockers

• Drugs the prevent calcium ions from entering cells

• 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).

Chemical Families in CCB’s

1. Verapamil

   • Blocks calcium channels in blood vessels and in the heart

   • Used for:

     • Angina Pectoris (vasodilation)

     • Hypertension

     • Cardiac dysrhythmias

   • Careful administration/contraindications:

     • Cardiac failure, AV block, sick sinus syndrome

2. Diltiazem

   • Similar to Verapamil

3. 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

• Increased activity in the SNS causes the hypertension

• Five Subcategories:

  • Beta blockers

  • Alpha1 blockers

  • Alpha/beta blockers

  • Centrally acting antihypertensives

  • Adrenergic neuron blockers

Beta-Adrenergic Blockers

• (…olol)

• Most widely used antihypertensive drugs

• Four useful actions in hypertension:

  • Blockade of cardiac beta1 receptors

    • Decreases heart rate and contractility (decreases cardiac output)

    • Suppress reflex tachycardia caused by vasodilators in the regimen

    • Blockade of beta1 receptors on juxtaglomerular cells of kidney reduce release of renin

      • Reduces Angiotensin II vasoconstriction, aldosterone mediated volume expansion

    • 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

  1. 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

       • Sotalol

       • Timolol

       • Pindolol

       • Levobunolol

       • Nadolol

       • Metipranolol

  2. Cardioselective Agents (Metoprolol-Beta1 only)

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

       • Atenolol

       • Acebutolol

       • Metoprolol

       • Bisoprolol

       • Esmolol

       • Betaxolol

       • Nebivolol

Alpha 1 Blockers

• (…zosin)

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

• Resultant vasodilation results in lowered blood pressure

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

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

  • NOT be used as first line therapy for hypertension.

  • Prazosin

  • Doxazosin

  • Indoramin

  • Terazosin

Alpha/beta blockers

• 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 Antihypertensives/ Alpha 2 Adrenergic Agonist

• Methyldopa

  • Clonicine

  • Guanfacine

• 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 postganglionic 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, pheochromocytoma

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)

Hydralazine

• 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

• DIRECT acting vasodilator

• 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

• DIRECT acting vasodilator

• Uses:

  • Hypertensive emergencies

• Adverse Effects:

  • Excessive hypotension

  • Thiocyanate Toxicity (patients on med > 3 days)

• Administration:

  • Degraded by light--cover

• MIDODRINE - Reversal agent

ACE Inhibitors

Calcium Channel Blockers

• INDIRECT acting vasodilator

  • NIFEDIPINE

  • AMLODIPINE

  • FELODIPINE

  • VERAPAMIL

  • DILTIAZEM

Sympatholytics

Nitroglycerin

Angina Pectoris

• It is a coronary artery disease

• Imbalance between decreased oxygen and increased cardiac workload

• Types: Stable angina- no damage to heat muscle ; basic reflexes surrounding the pain rstore blood pressure: fixed at rest or with medicine

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

• Prinzmetal’s angina- caused byspasm of the blood vessel, not just by vessel narrowing

Antianginal Drugs

• To increase oxygen

• to decrease cardiac workload

Nitrates

• Nitroglycerin

• Nitrates are converted to NO (nitric oxide) 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 light headedness 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

• inhibits the movement of calcium ions across the membranes of myocardial and arterial muscle cells

  • altering the action potential and blocking muscle cell contraction o

  • depresses myocardial contractility

  • slows cardiac impulse formation in the conductive tissues, and relaxes and dilates arteries

  • fall in BP and a decrease in venous return

  • decreases the workload of the heart and myocardial oxygen consumption

• relieves the vasospasm of the coronary artery

• increasing blood flow to the muscle cells (Prinzmetal angina).

• Diltiazem

Beta-Adenergic Blockers

• competitively blocks beta-adrenergic receptors in the heart and kidneys, decreasing the influence of the sympathetic nervous system on these tissues and the excitability of the heart;

• decreases cardiac output, which results in a lowered blood pressure and decreased cardiac workload.

  • Metoprolol

  • Nadolol

Cardiotonic Agents

Cardiac Glycoside

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

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

• Uses:

  • Heart failure, dysrhythmias

Digoxin

• (Prototype - available in most counties)

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

• 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 noncontractile 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 than 60 or change in rhythm detected HOLD THE DOSE AND CALL THE PHYSICIAN!

• Phosphodiesterase Inhibitors

  • Inamrinone

• Digoxin Antidote

  • Digoxin Immune Fab

Antidysrhythmics

• Dysrhythmia (Arrhythmia):

  • Defined as abnormality in the rhythm of the heartbeat.

  • Associated with high degree of morbidity/mortality

• Types:

  • Tachydysrhythmias: > 100bpm

  • Bradydysrhythmias:: <60 bpm

• Vaughan Williams Classification:

  • Class I: Sodium Channel Blockers (Disopyramide, Lidocaine, Fleicanide)

  • Class II: Beta Blockers (Propranolol)

  • Class III: Potassium Channel Blockers (Sotalol)

  • Class IV: Calcium Channel Blockers (Diltiazem)

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

• Cardiac myocyte Conduction Cycles

  • Phase 0: Depolarization, when voltage-gated fast sodium channels open, causing sodium to flow into the cell

  • Phase 1: Overshoot, when sodium channels close and potassium leaves the cell

  • Phase 2: Plateau, when calcium influx stabilizes the cell against potassium efflux

  • Phase 3: Repolarization, when calcium influx stops and potassium efflux increases

  • Phase 4: Resting, when sodium, potassium, and calcium are actively transported against electrochemical gradients

Class I: Sodium Channel Blockers

• Sodium Channel Blockers:

  • Block cardiac sodium channels

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

  • Inhibits depolarization of Abnormal Rhythm

  • Acts on Phase 0

• Class IA agents

  • prolonging repolarization

  • for atrial fibrillation, flutter; supraventricular & ventricular tachyarrhythmias

  • Eg: Quinidine, procainamide

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

• Class IB agents

  • shorten repolarization

  • for ventricular tachyarrhythmias (VT)

  • Eg: Lidocaine, Mexiletine

• Class IC

  • minimal effect on repolarization

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

  • Eg: Flecainide, Propafenone

• These drugs will be contraindicated in atrioventricular block

Class II: Beta Blockers

• competitively blocks beta-adrenergic receptors in the heart and kidney, has a membrane-stabilizing effect, and decreases the influence of the sympathetic nervous system

• Prolonged resting to slow down impulses and remove abnormal rhythm

• acts on phase 4

• Propranolol

• Acebutolol

• Esmolol

Class III: Potassium Channel Blockers

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

• Prolong cardiac repolarization

• Acts on Phase 3

• 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)

  • Dofelitide

Class IV: Calcium Channel Blockers

• blocks the movement of calcium ions across the cell membrane, depressing the generation of action potentials, delaying phases 1 and 2 of repolarization, and slowing conduction through the AV node.

• Acts on phase 2

• Diltiazem

• Verapamil

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

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 heartovercomes AV block, restarts the heart following cardiac arrest, increases cardiac output during shock

Drugs Affecting Blood Coagulation

Drugs Used to Control Bleeding

• Antihemophilic Agents- Antihemophilic factor (Bioclate)

• Systemic Hemostatic Agents – Aminocaproic acid (Amicar)

• Topical Hemostatic Agents

• Antiplatelet Drugs – Aspirin (generic)

• Anticoagulants – Heparin (generic)

• Low-Molecular Weight Heparins

• Anticoagulant Adjunctive Therapy

• Hemorrheologic Agent

• Thrombolytic Agents – Streptokinase(Streptase)

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

Heparin

• 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 aPTT monitoring (Activated partial thromboplastin time)

• Uses: Inhibit additional clotting, allowing body to lyse

  • 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 SULFATE - 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

  • Bleeding

• ENOXAPARIN

Warfarin

• Oral anticoagulant

• Antagonist vitamin K

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

• Anticoagulant effects occur 3-5 days after oral 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 (in patients 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

Antiplatelets

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

  • hemorrhage

  • Severe neutropenia

  • Thrombotic thrombocytopenic purpura (TTP).

• Aspirin and clopidogrel given orally

Fibrinolytic/Thrombolytic 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 human plasminogen

• 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

Recombinant tissue plasminogen activator (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 and increased specificity for fibrin.

• Its efficacy and adverse effect profile are similar 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

  • Tranexamic Acid

  • Aminocaproic Acid

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 ratelimiting 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

• Examples

  • Atorvastatin

  • Fluvastatin

  • Pravastatin

  • Simvastatin

• Adverse Effects

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

  • 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)

• Examples

  • Clofibrate

  • Fenofibrate

  • Gemfibrozil

• Adverse Effects

  • Nausea, vomiting and GI upset

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

  • Myopathy

Bile Acid Sequestrants

• Bind bile acids in the intestinal lumen. This causes the bile acids to be excreted in faeces 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, diarrhoea, nausea, vomiting, gastro-intestinal discomfort

  • Decreased absorption of fat-soluble vitamins

Nicotinic Acid

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