Medchem I Exam 3

Normal Blood Pressure






“Silent killer”

Can lead to stroke, aneurysms, etc.


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


Propranolol (Inderal)

Nonselective Beta Blocker


Pindolol (Visken)

Nonselective Beta Blocker


Nadolol (Corgard)

Nonselective Beta Blocker


Timolol (Blocadren, Timoptic)

Nonselective Beta Blocker


Alpha-1, Beta-1, Beta-2 Blockers

Phenethylamine (phenyl, ethyl, amine)

Alpha-1, Beta-1, Beta-2 Blocker Backbone


Labetalol (Normodyne)

Alpha-1, Beta-1, Beta-2 Blockers

Beta-1 Blockers

Less lipophilic

Goes to kidney more quickly

Beta-1 Antagonist Backbone

Metoprolol (Lopressor)

Beta-1 Blocker


Acebutolol (Sectral)

Beta-1 Blocker


Atenolol (Tenormin)

Beta-1 Blocker

Alpha-1 Blockers
Peripherally acting
Alpha-1 Antagonist Backbone

Prazosin (Minipress)

Alpha-1 Blocker


Terazosin (Hytrin)

Alpha-1 Blocker


Doxazosin (Cardura)

Alpha-1 Blocker

Alpha-2 Agonists

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)


a-methyldopate HCL

Alpha-2 agonist

Ester derivative of a-methyldopa

Acidic salt given IV


Guanidino Group

In alpha-2 agonists

Decreases BP but initially causes vasoconstriction

Only given PO

Very polar and very basic

Very low bioavailability



Clonidine (Catpress)

Alpha-2 Agonist

Contains guanidino group

Only given PO

Also given epidurally to reduce pain during labor


Guanabenz (Wytensin)

Alpha-2 agonist

Contains Guanido group

Only given PO, like clonidine


Guanfacine (Tenex)

Alpha-2 agonist

Contains Guanido Group

Only given PO, like clonidine


Reserpine (Resa)

Rauwolfia (plant) alkaloid

Displaces NE from the vesicles which causes an initial increase in NE until it is metabolized away


Guanethidine (Ismelin)

Peripheral sympatholytic: Guanidine derivative

Very low bioavaiability ~16%


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


Antagonist for NE at post-synapse = octopamine theory

MAO Inhibitor mechanism


Pargyline (Eutonyl)

Peripheral smpatholytics: MAOI

Tyrosine Hydroxylase Inhibitor
Inhibits Tyrosine being convertered to DOPA

Alpha-methyltyrosine (Metirosine)

Tyrosine hydroxylase inhibitor

Given PO

Used to treat pheochromocytoma

Inducing vasodilation of blood vessels

Hydrazine group

Direct dilator


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


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


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



Treated with Minoxidil (Rogaine)

Causes hypertrichosis (increase hair growth) – induces vasodilation on scalp to allow for more blood and nutrients to flow


Sodium Nitroprusside (Nipride)

Direct dilator

Given IV for emergency

At pH 7.4>decomposes to Fe,NO,CN

NO causes vasodilation


Diazoxide (Hyperstat)

Direct Dilator

IV injection as sodium salt for HTN crisis

Acts like Minoxidil (induces hyperpolarization)

Calcium channel blockers

1,4-DHP nucleus backbone

Calcium channel blocker

More selective for blood vessels


Nifedipine (Procardia)

CCB – 1,4-DHP nucleus backbone


Amlodipine (Norvasc)

CCB – 1,4-DHP backbone

Longer acting


Nicardipine (Cardene)

CCB – 1,4-DHP backbone


Verapamil (Calan, Isopten)

CCB – arylalkyl amine


Diltiazem (Cardizem)

CCB – Benzothiazepine nucleus


Endogenous signaling molecule

Produced in Endothelium

Prostaglandin derivative

Useful in pulmonary HTN

Dilates blood vessels and prevents platelet aggregation


Epoprostenol (Flolan)


Given IV as sodium salt

Naturally occuring

Stiumulates vasodilation of pulmonary and systemic arterial vasculature


Iloprost (Ventavis)


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


Bosentan (Tracleer)

Endothelin antagonist

Given PO

Treats pulmonary HTN

May cause allergic reaction

Diuretic Uses

  • HTN
  • Edema
  • Glaucoma
  • Reducing CSF to reduce pressure usually after accidents
  • Increases the excretion of H2O and Na
  • Increases urine output


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


Urea (Carmal)

Osmotic diuretic

Given IV

Very polar


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


Sulfonamide diuretic backbone

Acidic; SO2 is a strong e- withdrawing group

Sulfonamide Diuretic Types
Carbonic anyhydrase inhibitors
Quinazolinone derivatives
Phthalimidine derivatives
Indoline derivatives

Carbonic anhydrase inhibitors


Inhibits carbonic anhydrase

No protons are exchanged with NA in the proximal tubule


Acetazolamide (Diamox)

Carbonic anhydrase inhibitor (Sulfonamide)

Need high dose to see effect to inhibit 100% of the enzyme

Thiazides (Benzothiadiazines)


Fused ring system; Benzene fused with 1,2,4-thiadiazine

 IV dosing as Na salt

Acts at the distal tubule



Thiazide (Benzothiadiazine) backbone

C6 – should have e- withdrawing group (usually Cl)

C7 – should have another sulfonamine group (SO2NH2)


Chlorothiazide (Diuril)

Thiazide (Sulfonamide)

Treats edema, HTN

Duration: short, requires multiple doses/day



Thiazide (Sulfonamide)

Oral adjunct therapy for HTN

10x more potent than chlorothiazide

Duration: short, requires multiples doses/day (same as chlorothiazide)


Bendroflumethiazide (Naturetin)

Thiazide (Sulfonamide)

Treats edema, HTN

Add benzyl group; 100x more potent than chlorothiazide

Cl replaced with CF3


Polythiazide (Renese)

Thiazide (Sulfonamide)

Treats edema, HTN

Has CF3 and Cl

1000x more potent than chlorothiazide

Very long acting; not commonly used

Quiazolinone Derivative


Replaces S in thiazide ring with C = non-classical bio-isoteric replacement

Quinazolinone derivative backbone


Replaces S in thiazide ring with C


Quinethazone (Hydromox)

Quinazolinone derivative


100x more potent than chlorothiazide

Longer acting than chlorothiazide (24h)


Metolazone (Zaroxylon)

Quinazolinone derivative

Treats HTN, CHF, edema

Methyl on C2

More potent than quinethazone 

Phthalimidine Derivative


Much longer acting (some last upto 3 days)

Indole with hydroxyl group

Everything that applied to thiazides applies to this group


Phthalimidine derivative backbone


Indole with hydroxyl group


Chlorthalidone (Hygroton)

Phthalimidine derivative


Very long acting

10x more potent than chlorothiazide (similar to HCTZ)

Indoline Derivatives


Indole nucleus

Single substituted aromatic ring with very lipophilic tail

Everything that applies to thiazides applies to this group


Indoline Derivative backbone


Indole nucleus

Single substituted aromatic ring with very lipophilic tail


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


Carboxylic group

Found in Loop Diuretics

Makes diuretic very short acting; more easily conjugated in phase 2

Given 3-4 times/day


Furosemide (Lasix)

Loop diuretic

Still has sulfonamino group = will cause allergic reaction


Ethacrynic Acid (Edecrin)

Loop diuretic

No sulfonamine group = no allergic reaction

Toxic; not commonly used

Short acting


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)


Spironolactone (Aldactone)

Endocrine (Aldosterone) Antagonist

(K-Sparing diuretic)

Competes with aldosterone at the receptor sites in collecting duct


Triamterene (Dyrenium)

Pteridine and Pyrazinoylguanidine derivative

(K-sparking diuretic)

Charged in acidic solution

Dispaces Na at its channel = Na channel blocker


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)


Enzyme that exists in kidney

Activated and released when BP is LOW

Acts on angiotensinogen

Renin-Angiotensinogen Pathway

  1. Renin cleaves off 4 AA residues from carboxyl terminal on Angiotensinogen > Decapeptide (10 AA; Angiotensin I)
  2. Angiotensins I loses 2 additional AA residues by angiotensinogen-converting-enzyme (ACE) > Angiotensin II (8 AA residue)

Angiotensin II

Causes systemic vasoconstriction

Binds to specific receptors on the blood vessels (Angiotensin II binding sites)

After acting, it is degraded by 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


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

Cough – bradykinin build-up

Captopril (Capoten)


First in class to be developed

Contains proline (-pril)

SH binds Zn – causes bad taste in mouth

-CH3 – very lipophilic


Lisinopril (Prinivil, Zestril)


Derived from Lysine

Given PO

CAN take with food (doesn’t lower bioavailability)


Enalapril Maleate (Vasotec, Vaseretic, Renitec)


DON’T take with food (low bioavailability)

Derived from Alanine

Given PO

Ester – easily hydrolyzed

Pro-drug – must be hydrolyzed to be active


Enalaprilat (Vasotec injection)


DON’T take with food

Given PO or injection

NOT a pro-drug


Benazepril (Lotensin)



Fosinopril (Monopril)


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


s – specific

a – angiotensin

r – receptor

an – antagonist



Acidic group usually found in ARBs


Irbesartan (Avapro, Aprovel)

Angiotensin II Antagonist


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


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

  1. Organic nitrates converted into NO
  2. NO activates GC >> converts GTP to cGMP
  3. cGMP activates MLCP
  4. MLCP dephosphorylates MLC
  5. Induces relaxation of smooth muscle (blood vessels)


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


Isosorbide Dinitrate (Isordil, Sorbitrate)

Organic Nitrate

Delayed onset

Longer duration

Coated to avoid hydrolysis in the stomach


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






Class of lipids



Class of Lipid



Class of lipid

Lipid Cycle

  1. Fat is emulsified in stomach, moves into intestine (Lipases continue to breakdown the emulsified fat to free fatty acids and monoglycerides)
  2. FAs combine with bile salts and cholesterol to form micelles, then moves across the intestinal epithelium
  3. FAs then leaves the micelle to recombine with one another > forms triglyceride
  4. TGs combine with phospholipids, cholesterol, and cholesterol ester to form chylomicrons


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


Comprised mostly of TG

Goes away from the liver to adipose tissue to deposit TG

Results in IDL


More CE than TG

Once lost all TGs, results in 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

Returns to the liver
Total Cholesterol

;200mg/dL = ok


;240mg/dL = DANGEROUS

Total/HDL = 4.5 or lower is better

LDL/HDL = 3 or lower is better


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)


Gemfibrozil (Lopid)

Absorbable Agent

Lowers both cholesterol and TGs

Given PO


High PPB

Metabolized by aliphalic hydroxylation, then conjugated


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

  1. Forms HMG CoA by combining 3 acetyl CoA molecules
  2. 6-C HMG CoA is then converted to 6-C mevalonic acid by HMG CoA reductase (Control point)

HMG-CoA Reductase Inhibitor


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


Lovastatin (Mevacor)

HMG-CoA Reductase Inhibitor



Pravastatin (Pravachol)

HMG-CoA Reductase inhibitor

More hydrophilic than others


Atorvastatin (lipitor)

HMG-CoA Reductase Inhibitor

Very large lipophilic area; offsets hydroxyl groups


Fluvastatin (Lescol)

HMG-CoA Reductase Inhibitor


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)


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)


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)


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

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