drug actions exam 1 drugs

Isoproterenol

Non-selective beta1&beta2 agonist Same structure as NE but with N-isopropyl Isopropyl pulls nitrogen away from alpha and causes more affinity to beta

Dobutamine

Selective beta1 agonist Removal of a hydroxyl group from beta carbon Lipophilic substitution  Used in injection to increase heart force of contractions to treat CHF

Metaproterenol

Selective beta2 agonist Same structure as isoproterenol, but a hydroxyl group at 3, 5 instead of 3, 4

Terbutaline

Selective beta2 agonist Same as metaproterenol, but tert-butyl instead of isopropyl

Fenoterol

Selective beta2 agonist Same as terbutaline but different N-substitution

Albuterol

Selective beta2 agonist Same as terbutaline, but aliphatic carbon

Salmeterol

Selective beta2 agonist Same as albuterol, but lipophilic N-substitution

Mirabegron (Myrbetriq)

Selective beta3 agonist Treats overactive bladder Similar to antimuscarinic medication (anticholinergic drug)

Vibegron (Solabegron)

Selective beta3 agonist Treats OAB

Labetalol (Normodine)

Nonselective adrenergic antagonist Carbon outside phenyl ring = antagonist Blocks alpha1 = vasodilation Blocks beta1 = decreases cardiac output Blocks beta2 = bronchoconstriction

Carvedilol

Nonselective adrenergic antagonist Blocks alpha1 = vasodilation Blocks beta1 = decreases cardiac output Blocks beta2 = bronchoconstriction Predicts ADME properties  …OCH2 connected to COH = antagonist

Ivabradine (Procoralan)

Nonselective adrenergic antagonist Pacemaker current inhibitor  Treatment of angina pectoris

Propranolol (Inderal)

Non-selective beta antagonist Angina, HTN, arrhythmia Metabolized by aromatic hydroxylation by CYP Should not give to patient with liver failure

Pindolol (Visken)

Non-selective beta antagonist Angina, HTN, arrhythmia Indole nucleus  Lipophilic  Similar contraindication to propranolol

Nadolol (Corgard)

Non-selective beta antagonist Angina, HTN, arrhythmia Should not give to patient with kidney failure

Timolol Maleate (Timoptic/Istalol)

Non-selective beta antagonist Glaucoma eye drops = opens up canal of Schlemm hydrophilic side-chain

Atenolol (Tenormin)

Selective beta1 antagonist Angina, arrhythmia, HTN Metabolized by amidases in liver -> ammonia and carboxylic group = inactive product

Esmolol (Brevibloc)

Selective beta1 antagonist Acute MI, HTN, arrhythmia Short acting = ester is easily hydrolyzed

Metoprolol (Succinate = Toprol XL) (Tartrate = Lopressor)

Selective beta1 antagonist Angina, arrhythmia, HTN Metabolized by O-demethylation by CYP in liver

Bisoprolol Fumarate (Zebeta)

Selective beta1 antagonist HTN Less likely to undergo O-demethylation by CYP in liver = longer duration

Betaxolol (Betoptic S, Kerlone)

Selective beta1 antagonist Similar to bisoprolol

Phenylephrine

Selective alpha1 agonist Same as epinephrine, but missing 4-phenolic OH Not deactivated by MAO or COMT, since it is no longer a catechol

Methoxamine

Selective alpha1 agonist Missing 4-hydroxyl Amino group has a methyl group  No longer a substrate for MAO Ether -> more lipophilic and easier to penetrate into tissues, but decreases activity compared to hydroxyl

Metaraminol

Selective alpha1 agonist Not deactivated by MAO or COMT, since it is no longer a catechol

Xylometazoline

Selective alpha1 agonist with imidazoline backbone Imidazoline + methylene group -> carries an aromatic ring with electron donating alkyl groups  Alkyl groups on benzene makes the aromatic ring extra negative charge Alpha1 receptors have a specific interaction with the extra negative charge, opposite to alpha2

Oxymetazoline

Selective alpha1 agonist with imidazoline backbone Same as xylometazoline

Naphazoline

Selective alpha1 agonist with imidazoline backbone Same as xylometazoline  If one of the rings were saturated -> Tetrazoline, with the same properties

Droxidopa

Nonselective adrenergic agonist (alpha leaning) Not selective, but more toward alpha like NE Also known as: L-threo-dihydroxyphenylserine (L-DOPS), Northera, and Dops Sympathomimetic medication used in the treatment of hypotension  Can cross biomembranes Prodrug of NE

Clonidine

Selective alpha2 agonist Imidazole is substituted at p-2 with benzene + 2 Cl groups -> withdraw electrons from the ring creating a partial positive charge on the ring -> alpha2 selective interaction Oral tabs for HTN and sometimes intrathecal injection to suppress pain in surgery

Guanabenz

Selective alpha2 agonist Same as clonidine, except imidazole ring is opened -> guanidine back bone system -> higher alpha2 affinity

Guanfacine

Selective alpha2 agonist Same as guanabenz

Apraclonidine

Selective alpha2 agonist Amino derivative clonidine Added polar groups -> more polar -> not suitable for BBB  Only as eye drops for glaucoma

Tolazoline (Priscoline)

Nonselective alpha antagonists For pulmonary HTN (newborns with increased BP in lungs); IV administration Only structure where antagonist is less lipophilic than agonist

Phentolamine (Regitine, OraVerse)

Nonselective alpha antagonists For pheochromocytoma diagnosis

Phenoxybenzamine (Dibenzyline, Dibenyline)

Nonselective alpha antagonists Irreversible alpha blocker, permanent covalent bond with alpha receptors For pheochromocytoma induced HTN Slower onset and longer duration

Prazosin (Minipress)

Selective alpha1 antagonists Metabolized by demethylation

Terazosin (Hytrin)

Selective alpha1 antagonists Has ester function -> used by injection only

Doxazosin (Cardura)

Selective alpha1 antagonists Same as terazosin

Trimazosin

Selective alpha1 antagonists OH group makes it shorter acting as it is metabolized directly to phase 2 = conjugation

Tamsulosin (Flomax)

Special alpha1 antagonist For BPH Phenethylamine nucleus No affinity to blood vessels More selective to alpha1A receptors “Sul” = sulfur -> goes to kidneys, concentrated in urinary tract

Alfuzosin (Uroxatral)

Special alpha1 antagonist For BPH Quinazoline nucleus No piperazine ring -> less affinity to circulatory alpha1 -> more selective to alpha1A

Yohimbine HCl (Yocon)

Selective alpha2 antagonist Sexual dysfunction (impetus)

Metyrosine

Indirect sympatholytic drug Inhibits tyrosine hydroxylase (essential for synthesis of tyrosine -> LDOPA)

Alphamethyl Dopa

Indirect sympatholytic drug Prodrug metabolized into alpha methyl NE, very powerful alpha 2 central agonist

Guamethidine Sulfate

Indirect sympatholytic drug Displaces NE from vesicles

Reserpine

Indirect sympatholytic drug Prevents reabsorption of NE into vesicles No longer used because of low therapeutic index

Syrosingopine

Indirect sympatholytic drug Modified reserpine, benzoic acid replaced acetate ester Useful in treating certain cancers

Midodrine

Indirect sympatholytic drug Prodrug, forms desglymidodrine

Desglymidodrine

Indirect sympatholytic drug Active metabolite of midodrine formed from deglycination  Alpha1-adrenergic agonist for arteriolar and venous vasculature -> increase in vascular tone and elevation of BP

Fenoldopam

Selective D1 agonist Fast-acting IV drug and synthetic benzazepine derivative Selective D1 agonist and peripheral vasodilator  For short-term, in-hospital management of severe hypertensive emergencies Mechanism: stimulates peripheral dopamine D1 receptors -> vasodilation of renal arteries -> lowers BP and increasing renal blood flow and sodium excretion  Administration: IV

Nifedipine

Calcium-channel blocker (1,4-dihydropyridines) 2 alkyl side chains at positions 2 and 6 2 esters at positions 3 and 5  Phenyl ring with an electron drawing group at position 4  Non-basic nitrogen atom -> lone pair is conjugated with double bonds and the ester carbonyl  Phenyl ring + 2 ethyl groups + lack of strong polar groups -> lipophilic -> suffers from first-pass, low bioavailability, metabolized from esterase enzymes in GIT, liver, and plasma Used only for HTN and angina

Nicardipine

Calcium-channel blocker (1,4-dihydropyridines) Basic nitrogen on ester alkyl at position 3 Given only by injection

Amlodipine

Calcium-channel blocker (1,4-dihydropyridines) Basic nitrogen in the side chain at position 2 -> allows formation of a salt with besylic acid  Commonly used in combination with ARBs

Verapamil

Calcium-channel blocker (aryl-alkyl amine) Uses: HTN, angina, arrhythmia  Affinity to both blood vessels and cardiac tissues High absorption rate due to high lipophilicity, but extensively undergoes first pass metabolism by O-demethylation or Ndemethylation -> low bioavailability

Diltiazem

Calcium-channel blocker (benzothiazepine) High lipophilicity = high absorption and high PPB Low bioavailability due to 1st pass -> esters are quickly hydrolyzed Identical properties to verapamil in how it can be formulated as HCl salt and given IV and affects both cardiac and vascular tissues

Inamrinone

PDE3 inhibitor Bi-pyridine backbone with an amide functionality Both used only in IV, in severe cases of CHF

Milrinone

PDE3 inhibitor Bi-pyridine backbone with an amide functionality 10x more potent Used only in IV, in severe cases of CHF

Cilostazol (Pletal)

PDE3 inhibitor Inhibits platelet aggregation and dilates arteries

1-Crisaborol (Eucrisa)

PDE4 inhibitor Nonsteroidal topical medication for mild-to-moderate atopic dermatitis (eczema)

2-Roflumilast

PDE4 inhibitor For severe COPD, plaque psoriasis, seborrheic dermatitis, and atopic dermatitis  Prevention of exacerbations in COPD

3-Apremilast (Otezla)

PDE4 inhibitor For certain psoriasis and psoriatic arthritis

Sildenafil (Viagra)

PDE5 inhibitor For ED

Tadalafil (Cialis)

PDE5 inhibitor For ED, BPH, and pulmonary arterial HTN

Avanafil (Stendra, Spedra) 

PDE5 inhibitor