Med Chem Exam 3

Acetylcholine

Non-Selective (N+M)

non-selective, poorly absorbed across biological membranes due to being QAS; chemically unstable; cannot be administered orally

miosis; used in ocular surgeries

non-selective; poorly absorbed, not orally active

Carbachol

Non-Selective (N+M)

both m + n agonists; less hydrolyzed in GIT or by ACHE

glaucoma; induction of miosis in ocular surgery

Methacholine

Muscarinic Agonist

S + enantiomer is active isomer (hydrolyzed slower than Ach); longer duration of action than Ach

asthma

Bethanechol

Muscarinic Agonist

the S + enantiomer exhibits greater binding activity to the muscarinic receptors than R - enantiomer

treats post-surgical and postpartum urinary retention and abdominal distention

Pilocarpine HCl

Muscarinic Agonist

salt; non-traditional SAR; undergoes hydrolytic degradation

opthalmic solution, gel tablet; penetrates eye wall and is miotic of choice for glaucoma

Drug of choice for glaucoma

Nicotine

Nicotinic Agonist (cross BBB)

used as nicotine replacement therapy (patches, lozenges, and gums); pesticide for crops

nicotine replacement therapy; pesticide for crops

Varenicline

Nicotinic Agonist (cross BBB)

leads to release of dopamine in brain, reduces feelings of craving and withdrawal caused by smoking cessation

used for treatment of tobacco dependence/smoking cessation

Galantamine

Nicotinic Agonist + AChEI (cross BBB)

increases release of acetylcholine; side effects: GI, vertigo, UTI

treatment of vascular dementia and Alzheimer's Disease

Physostigmine

Reversible Anticholine Esterases

high binding affinity; not quaternary ion, so lipophilic, BBB

glaucoma; Alzheimers; antidote for overdoes of anticholinergic compounds

Neostigime

Reversible Anticholine Esterases

longer duration of action; orally active

treats: myasthenia gravis, reverses effects of neuromuscular blockers

Pyridostimine

Reversible Anticholine Esterases

longer duration of action; orally active

treats: myasthenia gravis, reverses effects of neuromuscular blockers

Rivastigimine

Reversible Anticholine Esterases

selective aryl carbamate; inhibits AChE for up to 10hrs; pseudo-irreversible AChEI; BBB

Alzheimer's

Donepizil

Non-Classical AChEI

non-competitive AChEI; BBB; undergoes CYP-catalyzed metabolism to active and inactive metabolites

Alzheimer's

Adverse effects: Elevated cholinergic activity

Isoflurophate

Irreversible AChEI

used as eye ointment and often used when other agents fail; decrease in intraocular pressure; cannot be used systemically due to toxicity

treatment of open-angle glaucoma; Alzheimer's

Echothiophate Iodide

Irreversible AChEI

decrease in intraocular pressure; cannot be used systemically due to toxicity

opthalmic solution, glaucoma; Alzheimers

Parathione

Irreversible AChEI

beneficial to agricultural productions; rapidly bioactivated by microsomal oxidation

glaucoma; Alzheimers

Malathione

Irreversible AChEI

beneficial to agricultural productions; rapidly bioactivated by microsomal oxidation

glaucoma; Alzheimers

Pralidoxime Obidoxime

Irreversible AChEI

hydrolyzes phophohorylated AChE

treats ogranophosphate poisoning; glaucoma; Alzheimers

Asoxime

Irreversible AChEI

hydrolyzes phophohorylated AChE

treats ogranophosphate poisoning; glaucoma; Alzheimers

Atropine

Anticholinergic

used in treatment of poisoning or over-dose of cholinergic muscarinic agonists; (decrease contraction of GIT, dilation of pupid, reduced salivation; inhibit excessive salivation and respiratory secretions during surgery; common in cold and flu remedies

counterindicated in glaucoma

Decamethonium Bromide

Neuromuscular Blocker

Depolarizing

short duration of action

endoscopic procedures and endotracheal intubation

Succinylcholine (Suxamethonium)

Neuromuscular Blocker

Depolarizing

rapidly hydrolyzed in aqueous and by plasma esterases and rendered inactive; short duration of action

endoscopic procedures and endotracheal intubation

D-Tubocurarine

Neuromuscular Blocker

Non-Depolarizing

excreted unchanged renally

Metocurine

Neuromuscular Blocker

Non-Depolarizing

4 times more potent and has longer duration of action than tubocurarine; excreted unchanged renally

Atracurium

Neuromuscular Blocker

Non-Depolarizing

short duration of action; undergoes hydrolysis of ester functional group that connects two quaternary nitrogen atoms; Hofmann elimination

Colterol; R1

Adrenergic Drugs

selective B2-agonist

Isoproterenol; R1

Adrenergic Drugs

non-selective B-agonist

can cause undesirable caridac stimulation due to B1-activity

a-Methyldopa; R2

Adrenergic Drugs

more selective for a2 adrenoreceptors than a1

antihypertensive drug (treats ábp)

metaproterenol; R3

Adrenergic Drugs

bronchodilators with little cardiac stimulatory activity

terbutaline; R3

Adrenergic Drugs

bronchodilators with little cardiac stimulatory activity

albuterol; R3

Adrenergic Drugs

bronchodilators with little cardiac stimulatory activity

ritodrine; R3

Adrenergic Drugs

enhanced B2-selectivity

phenylephrine; R3

Adrenergic Drugs

a-agonist

metaraminol; R3

Adrenergic Drugs

a-agonist

Epinephrine

Nonselective (a + B) adrenergic agonist

much more widely used than NE; lacks orally activity for same reasons as norepinephrine

hypotensive crises and cardiac arrest; bronchoconstrction in asthma, inhibit uterine contractions, nasal congestion, enhances activity of local anesthetics, enhances glaucoma

Norepinephrine

Nonselective (a + B) adrenergic agonist

limited clinical application, it is non-selective and causes both vasoconstriction and cardiac stimulation; no oral actiivty due to rapid metabolism by intestinal and liver COMT and MAO that limits duration of action

hypotensive crises and cardiac arrest

Methyl Norepinephrine

Adrenergic Drugs

topical nasal decongestant and vasoconstrictor

phenylephrine

a1-Adrenergic Agonist

phenylethanolamine

selective for a1-receptors with little cardiac stimulation; not substrate for COMT = longer duration of action than NE

treats hypotension during surgery, anesthesia, and shock; nasal decongestant

metaraminol

a1-Adrenergic Agonist

phenylethanolamine

selective for a1-receptors with little cardiac stimulation; not substrate for COMT = longer duration of action than NE

treats hypotension during surgery, anesthesia, and shock

naphazoline

a1-Adrenergic Agonist

2-arylimidazoline

used for short-term treatment of nasal congestion w/ non- and seasonal rhinitis, hay fever, Upper RTI, and ocular decongestant

nasal decongestants and eye drops

tetrahydrozoline

a1-Adrenergic Agonist

2-arylimidazoline

used for short-term treatment of nasal congestion w/ non- and seasonal rhinitis, hay fever, Upper RTI, and ocular decongestant

nasal decongestants and eye drops

xylometazoline

a1-Adrenergic Agonist

2-arylimidazoline

used for short-term treatment of nasal congestion w/ non- and seasonal rhinitis, hay fever, Upper RTI, and ocular decongestant

nasal decongestants and eye drops

oxymetazoline

a1-Adrenergic Agonist

2-arylimidazoline

used for short-term treatment of nasal congestion w/ non- and seasonal rhinitis, hay fever, Upper RTI, and ocular decongestant

nasal decongestants and eye drops

clonidine

a2-Adrenergic Agonist

2-amino-imidazoline

a1-agonist in periphery, but also powerful a2 agonist activity in CNS; BBB

starts as: vasoconstriction and increase BP, then overcome by vasodilation as penetrates BBB (a2); antihypertensive agent; antihypertensive agent; drowsiness, dizziness, headache, dry mouth

guanfacine

a2-Adrenergic Agonist

2-amino-imidazoline

considered analog of clonidine

antihypertensive agent; drowsiness, dizziness, headache, dry mouth

guanabenz

a2-Adrenergic Agonist

2-amino imidazoline

considered analog of clonidine

antihypertensive agent; drowsiness, dizziness, headache, dry mouth

a-Methyldopa

a2-Adrenergic Agonist

centrally active a2-agonist; prodrug; orally administered (first-pass metabolism), excreted urine

lowers BP, antihypertensive agent; drowsiness

Metaproterenol

B2-Adrenergic Agonist

oral dosage and inhalers; resistant to COMT metabolism and are slowly metabolized by MAO

bronchodilator in asthma

Terbutaline

B2-Adrenergic Agonist

oral dosage and inhalers; resistant to COMT metabolism and are slowly metabolized by MAO

bronchodilator in asthma

Albuterol

B2-Adrenergic Agonist

oral dosage and inhalers; resistant to COMT metabolism and are slowly metabolized by MAO

bronchodilator in asthma

Pirbuterol

B2-Adrenergic Agonist

oral dosage and inhalers; resistant to COMT metabolism and are slowly metabolized by MAO

bronchodilator in asthma

Bitolterol (prodrug)

B2-Adrenergic Agonist

increased lipophilicity and subject to metabolism by COMT; longer duration of action than colterol (8hr)

used as rescue drug

Salmeterol

LABA (long-acting)

selective B2-agonist, extended duration of action; metabolically stable, increased lipophilicity; resistant to COMT and MAO metabolism, metabolized by CYP3A4

Vilanterol

LABA

undergoes extensive first-pass metabolism by CYP3A4; used in combination with corticosteroid fluticasone and umeclinium bromide

COPD

Formoterol

LABA (long-acting)

racemate, used as inhaler; combination with glucocorticoids budesonide or mometasone

asthma and COPD

Arformoterol

LABA

available as solution twice daily for COPD

COPD

Bambuterol

LABA (long-acting)

prodrug of terbutaline; not to be used as rescue medication for relief of asthma

asthma

Ritodrine

Uterine Relaxant (B2)

B2-receptor agonist; (withdrawn)

uterine relaxant to delay and prevent premature labor

Dobutamine

B1-Adrenergic Agonist

selective B1-agonist; resistant to MAO, metabolized by COMT, shorter duration of action no oral activity

cardiac stimulant after surgery or in congestive heart failure

Ephedrine

Mixed/Indirect Acting Sympathomimetics

good oral activity, not substrate for COMT; more lipohpilic, BBB, has CNS stimulant activity

bronchodilator, vasopressor, cardiac stimulant, nasal decongestant

Pseudoephredrine

Mixed/Indirect Acting Sympathomimetics

ONLY INDIRECT; no direct activity and fewer CNS side effects than ephedrine

widely used as nasal decongestant

Phenylpropanolamine

Mixed/Indirect Acting Sympathomimetics

less lipophilic, no bbb; mixed, but moslty indirect activity

nasal decongestant and appetite suppressant (withdrawn)

Mephetermine

Mixed/Indirect Acting Sympathomimetics

stimultaes both a and b directly and indirectly

cardiac stimulant, hypotension (increased BP)

Propylhexedrine

Mixed/Indirect Acting Sympathomimetics

nasal decongestants + appetite suppressant

Amphetamine

BBB; CNS stimulation activity; serious abuse problems

suppress appetite, control weight, treat disorders including narcolepsy and ADHD; anti-fatigue (armed forces)

Side effects: nervousness, insomnia, irritability, anorexia, physical dependence, cardiac irregularities