Medchem I Exam 3 – Flashcards
Unlock all answers in this set
Unlock answersNormal Blood Pressure |
120/80 Systolic/Diastolic Contraction/Relaxation |
Hypertension |
140/90 "Silent killer" Can lead to stroke, aneurysms, etc. |
Norepinephrine |
Induces vasoconstriction, leads to reflex bradycardia Innervated by sympathetic NS Acts on alpha-1, alpha-2, beta-1 Stronger affinity for alpha-1 |
Nonselective Beta Blockers |
Contraindicated for asthma, liver damage, DM Very lipophilic |
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Propranolol (Inderal) Nonselective Beta Blocker |
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Pindolol (Visken) Nonselective Beta Blocker |
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Nadolol (Corgard) Nonselective Beta Blocker |
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Timolol (Blocadren, Timoptic) Nonselective Beta Blocker
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Alpha-1, Beta-1, Beta-2 Blockers |
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Phenethylamine (phenyl, ethyl, amine) Alpha-1, Beta-1, Beta-2 Blocker Backbone |
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Labetalol (Normodyne) Alpha-1, Beta-1, Beta-2 Blockers |
Beta-1 Blockers |
Less lipophilic Goes to kidney more quickly |
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Beta-1 Antagonist Backbone |
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Metoprolol (Lopressor) Beta-1 Blocker |
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Acebutolol (Sectral) Beta-1 Blocker |
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Atenolol (Tenormin) Beta-1 Blocker |
Alpha-1 Blockers |
Peripherally acting |
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Alpha-1 Antagonist Backbone |
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Prazosin (Minipress) Alpha-1 Blocker |
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Terazosin (Hytrin) Alpha-1 Blocker |
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Doxazosin (Cardura) Alpha-1 Blocker |
Alpha-2 Agonists |
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a-methyldopa (Aldomet) Alpha-2 agonist Dopa with methyl group Inhibits synthesis of NE, less vasoconstriction Leads to production of alpha-methyl NE (Pro-drug) Crosses BBB through active transport Given PO (to produce a-methyl NE) |
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a-methyldopate HCL Alpha-2 agonist Ester derivative of a-methyldopa Acidic salt given IV |
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Guanidino Group In alpha-2 agonists Decreases BP but initially causes vasoconstriction Only given PO Very polar and very basic Very low bioavailability
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Clonidine (Catpress) Alpha-2 Agonist Contains guanidino group Only given PO Also given epidurally to reduce pain during labor |
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Guanabenz (Wytensin) Alpha-2 agonist Contains Guanido group Only given PO, like clonidine |
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Guanfacine (Tenex) Alpha-2 agonist Contains Guanido Group Only given PO, like clonidine |
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Reserpine (Resa) Rauwolfia (plant) alkaloid Displaces NE from the vesicles which causes an initial increase in NE until it is metabolized away |
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Guanethidine (Ismelin) Peripheral sympatholytic: Guanidine derivative Very low bioavaiability ~16% |
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Guanadrel (Hylorel) Peripheral sympatholytic: Guanidine derivative "Spiro" linked rings = fused at one atom Higher bioavailablility than guanethidine |
Monoamine oxidase inhibitors (MAOI) |
Inhibits metabolism by MAO Causes tyrosine to be converted into octopamine Initial increase in NE, then NE levels decrease |
Octopamine |
Antagonist for NE at post-synapse = octopamine theory MAO Inhibitor mechanism |
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Pargyline (Eutonyl) Peripheral smpatholytics: MAOI |
Tyrosine Hydroxylase Inhibitor |
Inhibits Tyrosine being convertered to DOPA |
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Alpha-methyltyrosine (Metirosine) Tyrosine hydroxylase inhibitor Given PO Used to treat pheochromocytoma |
Inducing vasodilation of blood vessels |
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Hydrazine group Direct dilator |
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Hydralazine (Apresoline) Direct (arteriolar) dilator Binds to epithelium and releases NO to induce relaxation via GTP>cGMP Metabolized in liver by CYP450 or n-acetyltransferase |
N-acetyltransferase |
Direct dilator Metabolizes Hydralazine Inserts an acetyl (COCH3) between the Hydrazine group |
Acetylation Rates |
Slow ~35% Fast ~16% Everyone has to be classified with enzyme levels test Reason why Hydrazaline effects are hard to predict and not used much |
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Minoxidil (Loniten; Rogaine) Arteriolar dilator Pyrimidine derviative Given PO because drug is inactive Pro-drug - active form must be sulfurated (sulfo-transferase in liver) Induces hyperpolarization>inhibits depolarization>muscle relaxation |
Alopecia |
Baldness Treated with Minoxidil (Rogaine) Causes hypertrichosis (increase hair growth) - induces vasodilation on scalp to allow for more blood and nutrients to flow |
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Sodium Nitroprusside (Nipride) Direct dilator Given IV for emergency At pH 7.4>decomposes to Fe,NO,CN NO causes vasodilation |
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Diazoxide (Hyperstat) Direct Dilator IV injection as sodium salt for HTN crisis Acts like Minoxidil (induces hyperpolarization) |
Calcium channel blockers |
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1,4-DHP nucleus backbone Calcium channel blocker More selective for blood vessels |
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Nifedipine (Procardia) CCB - 1,4-DHP nucleus backbone |
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Amlodipine (Norvasc) CCB - 1,4-DHP backbone Longer acting |
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Nicardipine (Cardene) CCB - 1,4-DHP backbone |
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Verapamil (Calan, Isopten) CCB - arylalkyl amine |
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Diltiazem (Cardizem) CCB - Benzothiazepine nucleus |
PGI2 |
Endogenous signaling molecule Produced in Endothelium Prostaglandin derivative Useful in pulmonary HTN Dilates blood vessels and prevents platelet aggregation |
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Epoprostenol (Flolan) PGI2 Given IV as sodium salt Naturally occuring Stiumulates vasodilation of pulmonary and systemic arterial vasculature |
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Iloprost (Ventavis) PGI2 Given as inhalation Synthetic analogue to PGI2 Dilates pulmonary and systemic arteries |
Endothelin antagonists |
Endothelin is endogenously released and causes vasoconstriction (especially in bronchus and lungs) Type-B causes vasoconstriction Drugs are type-b endothelin ANTAGONISTS |
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Bosentan (Tracleer) Endothelin antagonist Given PO Treats pulmonary HTN May cause allergic reaction |
Diuretic Uses |
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Saluretic |
A drug that increases the excretion of H2O and Na i.e. Diuretics |
Osmotic Diuretics |
Water move according to osmotic gradient Increases the osmolality of the urine; water is drawn out of the filtrate (Na follows) Drugs are very polar Given IV to decrease blood volume |
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Urea (Carmal) Osmotic diuretic Given IV Very polar |
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Mannitol (Osmitrol) Osmotic diuretic Given IV to decrease blood volume Very polar |
Sulfonamide Diuretics |
Acidic (SO2 is a strong electron withdrawing group) Initiates the formation of antibodies; may lead to allergic reactions (rash) Metabolized by KIDNEYS; in the nephron/urine Lipophilic; high plasma protein binding (PPB); risk of DI with other high PPBs |
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Sulfonamide diuretic backbone Acidic; SO2 is a strong e- withdrawing group |
Sulfonamide Diuretic Types |
Carbonic anyhydrase inhibitors Thiazides Quinazolinone derivatives Phthalimidine derivatives Indoline derivatives |
Carbonic anhydrase inhibitors (Sulfonamide) |
Inhibits carbonic anhydrase No protons are exchanged with NA in the proximal tubule |
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Acetazolamide (Diamox) Carbonic anhydrase inhibitor (Sulfonamide) Need high dose to see effect to inhibit 100% of the enzyme |
Thiazides (Benzothiadiazines) (Sulfonamide) |
Fused ring system; Benzene fused with 1,2,4-thiadiazine IV dosing as Na salt Acts at the distal tubule Causes HYPOKALEMIA |
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Thiazide (Benzothiadiazine) backbone C6 - should have e- withdrawing group (usually Cl) C7 - should have another sulfonamine group (SO2NH2) |
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Chlorothiazide (Diuril) Thiazide (Sulfonamide) Treats edema, HTN Duration: short, requires multiple doses/day |
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HCTZ (HydroDIURIL) Thiazide (Sulfonamide) Oral adjunct therapy for HTN 10x more potent than chlorothiazide Duration: short, requires multiples doses/day (same as chlorothiazide) |
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Bendroflumethiazide (Naturetin) Thiazide (Sulfonamide) Treats edema, HTN Add benzyl group; 100x more potent than chlorothiazide Cl replaced with CF3 |
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Polythiazide (Renese) Thiazide (Sulfonamide) Treats edema, HTN Has CF3 and Cl 1000x more potent than chlorothiazide Very long acting; not commonly used |
Quiazolinone Derivative (Sulfonamide) |
Replaces S in thiazide ring with C = non-classical bio-isoteric replacement |
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Quinazolinone derivative backbone (Sulfonamide) Replaces S in thiazide ring with C |
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Quinethazone (Hydromox) Quinazolinone derivative (Sulfonamide) 100x more potent than chlorothiazide Longer acting than chlorothiazide (24h) |
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Metolazone (Zaroxylon) Quinazolinone derivative Treats HTN, CHF, edema Methyl on C2 More potent than quinethazone |
Phthalimidine Derivative (Sulfonamide) |
Much longer acting (some last upto 3 days) Indole with hydroxyl group Everything that applied to thiazides applies to this group |
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Phthalimidine derivative backbone (Sulfonamide) Indole with hydroxyl group |
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Chlorthalidone (Hygroton) Phthalimidine derivative (Sulfonamide) Very long acting 10x more potent than chlorothiazide (similar to HCTZ) |
Indoline Derivatives (Sulfonamide) |
Indole nucleus Single substituted aromatic ring with very lipophilic tail Everything that applies to thiazides applies to this group |
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Indoline Derivative backbone (Sulfonamide) Indole nucleus Single substituted aromatic ring with very lipophilic tail |
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Indapamide (Lozol) Indoline derivative (Sulfonamide) More potent and longer lasting than chlorthalidone t1/2 = 36h Given twice a week |
Loop Diuretics ("High ceiling" or "peak" diuretic) |
Acts at the Loop of Henle (where 25% of Na reabsorbed) Very effective "Peak" - Na peak on HPLC (Chromatography test) Causes HYPOKALEMIA; more Na in collecting duct, more K exchange |
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Carboxylic group Found in Loop Diuretics Makes diuretic very short acting; more easily conjugated in phase 2 Given 3-4 times/day |
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Furosemide (Lasix) Loop diuretic Still has sulfonamino group = will cause allergic reaction |
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Ethacrynic Acid (Edecrin) Loop diuretic No sulfonamine group = no allergic reaction Toxic; not commonly used Short acting |
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Bumetanide (Bumex) Loop diuretic Short acting Has sulfonamide group; causes allergic reaction |
K-Sparing Diuretics |
Can cause HYPERkalemia Acts in the collecting duct Given in conjunction with hypokalemia-inducing diuretic K is not reabsorbed; not recycled in body Exchanged with Na (in the urine) in the collecting duct;K serum Exchange is controlled by Aldosterone |
Endocrine (Aldosterone) |
A mineralocorticoid Increases reabsorption of Na and H2O Increases blood volume, which increases BP (inc. HTN) |
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Spironolactone (Aldactone) Endocrine (Aldosterone) Antagonist (K-Sparing diuretic) Competes with aldosterone at the receptor sites in collecting duct |
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Triamterene (Dyrenium) Pteridine and Pyrazinoylguanidine derivative (K-sparking diuretic) Charged in acidic solution Dispaces Na at its channel = Na channel blocker |
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Amiloride (Midamore) Pteridine and Pyrazinoylguanidine derivative (K-sparing diuretic) Na channel blocker Charged in acidic solution (urine) |
Kidney - Angiotensin II and Aldosterone (Endocrine) |
Kidney releases the hormone angiotensin II (systemic vasoconstrictor) Angiotensin II also stimulates release of aldosterone from KIDNEYS Aldosterone stimulates reabsorption of Na and H2O and excretion of K |
Renin-Angiotensin System |
Produces Angiotensin II Mainly in kidneys; also in lungs (moisture-rich areas in the body) |
Renin |
Enzyme that exists in kidney Activated and released when BP is LOW Acts on angiotensinogen |
Renin-Angiotensinogen Pathway |
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Angiotensin II |
Causes systemic vasoconstriction Binds to specific receptors on the blood vessels (Angiotensin II binding sites) After acting, it is degraded by Angiotensinase |
Angiotensinase |
Cleaves off 1 AA residue off Angiotensin II to inactivate it Left with Angiotensin III (mostly inactive) |
Diuretics - Electrolytes |
Acts in the kidney Lowers blood volume > lowers HTN Also increases concentration of electrolytes and sugar (false highs) |
Renin Inhibitor |
Angiotensinogen (14 AA res) is the substrate for Renin AA-like side chain > may cause allergic reactions |
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Aliskiren (Tekturna) Renin Inhibitor Similar in structure to PG (causes abortion, severe diarrhea) Contraindicated in pregnant women Given PO Can cause allergic reaction due to protein-like side chain |
Angiotensin-Converting Enzyme (ACE) Inhibitors |
Substrate = Angio I (10 AA) Cleaves 2 AA to yield Angio II Competitive antagonist for the catalytic site Names come from derived AA (-pril = proline) |
ACE-I Limitations |
If given PO > degrades too rapidly (low bioavailability) Not taken with food - release of HCl in stomach causes hydrolysis of peptide |
ACE-I ADR |
Cough - bradykinin build-up |
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Captopril (Capoten) ACE-I First in class to be developed Contains proline (-pril) SH binds Zn - causes bad taste in mouth -CH3 - very lipophilic |
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Lisinopril (Prinivil, Zestril) ACE-I Derived from Lysine Given PO CAN take with food (doesn't lower bioavailability) |
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Enalapril Maleate (Vasotec, Vaseretic, Renitec) ACE-I DON'T take with food (low bioavailability) Derived from Alanine Given PO Ester - easily hydrolyzed Pro-drug - must be hydrolyzed to be active |
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Enalaprilat (Vasotec injection) ACE-I DON'T take with food Given PO or injection NOT a pro-drug |
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Benazepril (Lotensin) ACE-I |
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Fosinopril (Monopril) ACE-I |
Angiotensin II Antagonists (ARBs) |
Blocks the action of Angiotensin II at the blood vessels ALL given PO In combo with ACE-I NOT polypeptide Acidic group is usually tetrazole |
"sartan" |
s - specific a - angiotensin r - receptor an - antagonist |
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Tetrazole Acidic group usually found in ARBs |
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Irbesartan (Avapro, Aprovel) Angiotensin II Antagonist |
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Losartan (Cozaar, Hyzaar) Angiotensin II Antagonist |
Angina Pectoris |
Chronic disease in coronary arteries which supply oxygenated blood from left ventricle to itself and all heart tissues When lumen of coronary artery becomes restricted ; less efficient in supplying blood/oxygen to the heart ; ischemic Angina - sudden, severe pain in chest; radiating up to left shoulder and down the left arm |
Typical (Exertional) Angina |
Arteriosclerosis - vessels lost elasticity (can't dilate) Occurs in episodes Exacerbated by emotions, smoking, food, exercise Tx - prophylaxis (prevent by taking meds before exertions) |
Variant Angina |
Can occur at any time and age without warning Vasospasm (sudden constriction) in coronary artery Tx - treat within 1 min or else MI |
3 Drug Classes to Treat Angina |
Calcium channel blockers - decrease afterload Beta-blockers - decrease HR and contractility Organic nitrates - decrease preload
ALL decreases demand |
CCB - Angina Limitations |
Decreases work load, induces vasodilation NOT good to treat arteriosclersos (typical/exertional angina) because cannot induce vasodilation |
Beta-blocker - Angina Limitation |
Not useful in treating vasospastic (variant) angina > can make it worse Better as a prophylactic for exertion-induced angina Decreases morbidity and mortality post-MI Beta-1 antagonist is better because are mostly in heart |
Organic Nitrate - Angina limitation |
Very fast acting (very lipophilic > absorbed quickly) - used in emergencies Induces the release of NO > smooth muscle relaxation |
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Glyceryl Trinitrate/Nitroglycerin (Nitro-Bid, Nitro-Dur, Nitro-Stat) Organic Nitrate Produces an effect within 15-30 seconds Very short acting (metabolite is inactive) |
Organic Nitrate Pathway |
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Erthrityl Tetranitrate (Cardilate) Organic Nitrate Similar in structure to NTG Very long acting (45 mins) because metabolite is active Delayed onset Coated to avoid hydrolysis in the stomach |
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Isosorbide Dinitrate (Isordil, Sorbitrate) Organic Nitrate Delayed onset Longer duration Coated to avoid hydrolysis in the stomach |
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Ranolazine (Ranexa) Miscellaneous anti-angina agent Similar structure to Na channel blocker and Beta-blocker side chain Affects Na flow Does not affect HR or BP Increases ATP in heart by stimulating oxidation of glucose (glycolysis produces ATP) New energy used to help the heart contraction |
Cholesterol and Lipids |
Deposits on wall of coronary arteries Over time, forms plaques and narrow the artery Leads to aTHerosclerosis (buildup of fatty material) |
3 Classes of Lipids |
Prostaglandins Steroids Triglycerides |
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Prostaglandin Class of lipids |
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Steroid Class of Lipid |
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Triglyceride Class of lipid |
Lipid Cycle |
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Chylomicron |
Outside is polar, inside is nonpolar Cholesterol outside, CE inside Phosholipid outside, triglyceride inside Usually more TGs than CE After formation, coated with apolipo-protein (directs globule to specific tissue) Apo-B 100 - very bad for arteries because they're sticky Picked up by adipose tissue and skeletal muscle (extracts FAs from Tgs to use for energy) ; reminant chylomicron ; |
Reminant Chylomicron |
Still too big to move in circulation Picked up by liver - broken down and reassembled into smaller particles Then, enters circulation through thoracic duct |
VLDL |
Comprised mostly of TG Goes away from the liver to adipose tissue to deposit TG Results in IDL |
IDL |
More CE than TG Once lost all TGs, results in LDL |
LDL |
Mostly CE inside globule (dangerous Apo-B 100) Will bind to coronary arteries Also goes to other tissues where the CE is hydrolyzed to cholesterol |
HDL |
Returns to the liver |
Total Cholesterol |
;200mg/dL = ok 200-240 ;240mg/dL = DANGEROUS Total/HDL = 4.5 or lower is better LDL/HDL = 3 or lower is better |
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Nicotinic Acid (Niaspan) Absorbable Agents This is vitamin B3 (niacin) Effective in lowering LDL and raising HDL Peripheral vasodilator (SE - flushing) Metabolized in the liver May enhance lipoproteinlipase - breaks down chylomicron (increases catabolism of LDL) |
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Gemfibrozil (Lopid) Absorbable Agent Lowers both cholesterol and TGs Given PO BID High PPB Metabolized by aliphalic hydroxylation, then conjugated |
Cholesterol |
27 carbon steroid Important component of cell membranes Pre-cursor to androgens, estrogens, progesterone, and adrenocorticoids Liver make it de novo (from scratch) |
Cholesterol Synthesis |
Synthesized from Acetyl CoA
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HMG-CoA Reductase Inhibitor "Statins" |
Most common cholesterol controlling class Blocks conversion of HMG-CoA to mevalonic acid This block inhibits endogenous cholesterol bio synthesis in the liver ; LESS LDL Statins do NOT affect dietary cholesterol level (cholesterol-rich foods) |
Statin Properties |
Absorbed well from the stomach and GI (carbon-rich ; lipophilic) High PPB All have similar potency |
Statin Metabolism |
High first pass metabolism ; low bioavailability Phase 2 conjugation Further hydroxylation |
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Lovastatin (Mevacor) HMG-CoA Reductase Inhibitor PRODRUG |
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Pravastatin (Pravachol) HMG-CoA Reductase inhibitor More hydrophilic than others |
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Atorvastatin (lipitor) HMG-CoA Reductase Inhibitor Very large lipophilic area; offsets hydroxyl groups |
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Fluvastatin (Lescol) HMG-CoA Reductase Inhibitor |
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Rosuvastatin (Crestor) HMG-CoA Reductase Inhibitor Has sulfonamide ; may cause allergic reaction |
Bile Acids |
Metabolites of cholesterol Liver breaks down cholesterol to create bile acids (also recycled) If trapped (sequestered) in the GIT, liver cholesterol will be depleted |
Bile Acid Sequestrant |
Adsorption of bile acids in the GIT and preventing their reabsorption into the liver May be used alone or in combo with HMGRIs or nicotinic acid (niacin) |
Bile Acid Sequestrant - Properties |
Positively charged N (Quaternary amine will not be absorbed) DONT want the drug to be absorbed Want it to stay in GIT and work LOCALLY Polmeric liophilic area (polymers are not absorbable) |
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Cholestyramine Cl (Questran, Cuemid) Quaternary amine Very safe Absorbs bile acid and WATER which leads to severe CONSTIPATION Non-selective - sequesters anything highly lipophilic (DI risk) Interacts with oral contraceptives ; ineffective Will bind Vit K ; clotting problems Decreases absorption of non-water soluble vitamins (D,E,A,K) |
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Colestipol (Colestid) Bile Acid Sequestrant Polymer of tetraethylenepentamine Non-quaternary amine but is protonated in GIT SE - constipation, DDI |
Cholesterol transporter-inhibitor (CTI) |
Lowers plasma cholesterol levels by inhibiting the absorption of cholesterol at the brush border of SI Inhibits EXOgenous cholesterol absorption (from FOOD) Body compensates by upregulating LDL receptors and producing more HMG-reductase to make more cholesterol To block these compensatory responses, usually given as combo Vytorin (simvastatin and ezetimibe) |
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Ezetimibe (Zetia) Cholesterol transporter-inhibitor (CTI) Very lipophilic, very poor dissolution rate Conjugated in phase 2 with glucuronic acid and goes back to GIT and interacts with transporter |