MedChem Final Drugs

Botulinum Toxin

MOA - Prevents pre-synaptic release of Ach at NMJ

Effect - Paralysis of voluntary muscles

Use - Wrinkles

Varenicline

MOA - Partial agonist of Nicotinic_N Receptor a4b2

Effect - partial effect of nicotine, prevents nicotine from binding

Use

• smoking cessation

• Nasal spray for dry eyes

d-Tubocurarine

MOA - non-depolarizing NMJ blocker

Effect - paralysis without fasciculation

Atracurium

MOA - non-depolarizing NMJ blocker

Effect - paralysis without fasciculation

Use - RSI

Succinylcholine

MOA - Depolarizing NMJ blocker

Effect - paralysis with fasciculation, fast

Use - RSI

Side Effects - Hyperkalemia

Broken down by pseudocholinesterase

Carbachol

MOA - Muscarinic Agonist

Use - Glaucoma and miosis for eye surgery

Has carbamate that slows down metabolism as not as recognized by AchE

Bethanechol

MOA - Muscarinic Agonist

Use - urinary retention post-op

Pilocarpine

MOA - Muscarinic Agonist

Effect - increases humor outflow via conventional route

Use - Glaucoma, Miosis for eye surgery, Xerostomia in Sjorgen’s syndrome (may be with cevimiline)

Xanomeline

MOA - Muscarinic Agonist for M1 and M4

Use - Schizophrenia

Usually taken with Trospium Chloride

Edrophonium Chloride

MOA - Reversible AchEI

Use - diagnosing myasthenia gravis, reversing non-depolarizing NMJ block

Tacrine

MOA - Reversible AchEI

Not used due to toxic imidoquinone metabolite and hepatotoxicity

Donepezil

MOA - Reversible AchEI

Use - Alzheimers

Neostigmine

MOA - Reversible AchEI

Use - reversing non-depolarizing NMJ block

Pyridostigmine

MOA - Pseudo-Irreversible AchEI

SAR - has carbamate

Use - Sarin Prophylaxis, Myasthenia Gravis treatment

Rivastigmine

MOA - Pseudo-Irreversible AchEI

SAR - has carbamate

Use - Alzheimer’s and Dementia

Malathion

MOA - Irreversible AchEI, forms organophosphate

Use - Nerve toxin, insecticide

Pralidoxime

MOA - Stronger nucleophile that can reactive AchE by breaking organophosphate

Use - treatment of nerve gas

Atropine

MOA - Muscarinic Antagonist

Use - bradycardia, induce mydriasis, muscarinic agonist poisoning, nerve gas poisoning

BEERS med, Contra Glaucoma

Scopolamine

MOA - Muscarinic Antagonist

Use - N/V, motion sickness

BEERS med, Contra Glaucoma

Tiotropium

MOA - Muscarinic Antagonist

Use - COPD and Asthma

Effects - bronchodilation and reduce secretions

Longer acting that ipratropium, QD

Ipratropium

MOA - Muscarinic Agonist

Use - COPD and Asthma

Effects - bronchodilation and reduce secretions

Shorter acting than Tiotropium, QID

Trospium Chloride

MOA - Muscarinic Antagonist

Use - with Xanemoline for Schizophrenia

BEERS med, Contra Glaucoma

Oxybutynin

MOA - Muscarinic Antagonist

Use - overactive bladder

BEERS med, Contra Glaucoma

Tolterodine

MOA - Muscarinic Antagonist

Use - overactive bladder

BEERS med, Contra Glaucoma

Benztropine

MOA - Muscarinic Antagonist

Use - Parkinson’s

BEERS med, Contra Glaucoma

Dicyclomine

MOA - Muscarinic Antagonist

Use - IBS

Contra - breastfeeding, glaucoma, ulcerative colitis

BEERS med, Contra Glaucoma

Norepinephrine

MOA - Adrenergic Agonis a>B1>B2

Effects

• Peripheral Vasoconstriction

• Heart stimulation

• Coronary dilation due to B2

Use

• Heart failure

• Life threatening hypotension

Contraindications

• MAOIs

• Hypertension

Epinephrine

MOA - Adrenergic Agonist B>a (= at high [epi])

Effects

• Cardiac Stimulation

• Vasodilation at low, Vasoconstriction at high (Coding)

• Bronchodilation (inhaled)

Uses

• Cardiac Arrest

• Anaphylaxis

• Bronchospams

• Hypotension

Phenylephrine

MOA - Adrenergic Agonist (mostly a1)

Effects

• Vasoconstriction

• Lower secretions

Use

• Vasoconstriction

• Nasal decongestion

• pupillary dilation and glaucoma

Midodrine

MOA - Adrenergic Agonist (a1)

SAR - Phenylethanolamine prodrug

Use - Orthostatic hypotension

Tetrahydrozoline/Xylometazoline

MOA - Adrenergic Agonist (a1)

SAR - Imidazoline

Effect - Vasoconstriction

Use - Nasal decongestant

Clonidine

MOA - Adrenergic Agonist (a2)

SAR - Imidazoline

Use

• hypertension

• ADHD/Anxiety

Side effects

• sedation

• xerostomia

BEERs med

Tizanidine

MOA - Adrenergic Agonist (a2)

SAR - Imidazoline

Use

• Muscle spasticity with MS and spinal cord injuries

Avoid with CYP1A2 inhibitors

a-Methyldopa

MOA - Adrenergic Agonist (a2)

SAR - Phenylethanolamine

Use - hypertension in pregnancy

Dopamine

MOA - Adrenergic Agonist

• low dose - dopaminergic - parkinson’s

• mid dose - B1 - cardiac stim

• High dose - a1 - vasoconstriction

SAR - phenylethanolamines

Effects

• Cardiac stimulation

• Vasoconstriction

• Increase kidney perfusion

Use

• hypotension

• Cardiac shock

• Parkinson’s

Dobutamine

MOA - Adrenergic Agonist (B1)

SAR - phenylethanolamines

Effects

• Inotropic cardiac stim

• Vasodilation

Isoproterenol

MOA - Adrenergic Agonist (B)

SAR - Phenylethanolamines

Effect

• Vasodilation

• Cardiac Stim

Use

• bronchospasm

• hypotension

• heart block

Albuterol

MOA - Adrenergic Agonist (B2) (SABA)

Sar - Phenylethanolamine

Effect

• bronchodilation

Salmeterol

MOA - Adrenergic Agonist (B2) (LABA)

Sar - Phenylethanolamine

Effect

• bronchodilation

BBW of monotherapy, must use with ICS

Mirabegron

MOA - Adrenergic Agonist (B3)

Effect - relaxes bladder

Use - Overactive bladder

Ephedrine

MOA - Stimulates NE release, prohibits reuptake, weakly activates adrenergic receptors

Use

• hypotension and hypothermia

• Asthma

Pseudoephedrine

MOA - Stimulates NE release, prohibits reuptake, weakly activates adrenergic receptors

Use - Nasal decongestant

Amphetamine

MOA - Inhibits NET and VMAT → more NE in synapse

Use - ADHD, Narcolepsy

Lisdexamphetamine

MOA - Inhibits NET and VMAT → more NE in synapse

• prodrug to amphetamine

Phentermine

MOA - Inhibits NET and VMAT → more NE in synapse

Use - weight loss

Me-Tyrosine

MOA - inhibits tyrosine hydroxylase

Use - pheochromocytoma

Effect - lower NE production

Phenoxybenzamine

MOA - non-selective irreversible adrenergic antagonist via Aziridium covalent bond

Use

• hypertensive episode in pheochromocytoma

• Raynaud’s disease

Side effects

• inhibition of ejaculation

• hypotension

• arrythmia

Tamsulosin

MOA - a1 adrenergic antagonist

SAR - Phenylethanolamine

Effects - relaxes smooth muscles of prostate

Use - BPH

Side effects

• orthostatic hypotension

• Allergic from sulfa

Terazosin/Doxazosin/Prazosin

MOA - a1 adrenergic antagonist

SAR - Quinazoline ring

Effects

• lowers peripheral vascular resistance

• Relaxes smooth muscle in bladder

Use

• hypertension

• BPH

Side effects

• first dose orthostatic hypotension

• syncope

BEERs med if for hypertension

Propranolol

MOA - non-specific Beta Antagonist/blocker

Effects - lower cardiac output

Side Effects - rebound hypertension (taper off)

Contraindicated

• diabetes

• asthma

• peripheral vascular disease

• thyroid disease

Use

• Angina

• afib

• MI

• Anxiety

• migraines

Nadolol

MOA - non-selective Beta antagonist/blocker

• Doesn’t cross BBB, no CNS

Effects - lower cardiac output

Use

• angina

• afib

• MI

Contraindicated

• diabetes

• asthma

• peripheral vascular disease

• thyroid disease

Side Effects - rebound hypertension (taper off)

Metoprolol/Atenolol

MOA - B1 adrenergic blocker (cardioselective)

Effect - Lower Cardiac output

Use

• hypertension

• angina

• afib

• MI

• Pediatric Hypertension

• Used in diabetic or asthmatic

Nebivolol

MOA - B1>B2 antagonist and release NO for vasodilation

Effect

• reduce cardiac output

• vasodilation

• [low] - B1, [high] - B2 and B1

Metabolism - CYP2D6 ^

Labetolol

MOA - Blocks Beta and alpha adrenergic receptors

Effects

• reduce cardiac output (B)

• vasodilation (a)

Use

• hypertension in pregnancy

Side effects - orthostatic hypotension (a)

Contra - same as non-selective B

Carvedilol

MOA - Blocks Beta and alpha adrenergic receptors

Effects

• reduce cardiac output (B)

• vasodilation (a)

Use

• hypertension

• heart failure

• MI

• afib

Side effects - orthostatic hypotension (a)

Contra - same as non-selective B

Perfluorohexyloctane

MOA - prevents evaporation of tears

Use - dry eyes

Bevacizumab

MOA - Mab that binds to VEGF

Use - wet form of Macular degenration

Aflibercept

MOA - Soluble VEGF receptor

Use - wet form of macular degenration

Faricimab

MOA - Bi-specific antibody for VEGF and Angiopoietin 2

Use - wet form of macular degeneration

Latanoprost

MOA - Bind to Prostaglandin F receptors, activate Gq, prodrug by esterases

Effect - increase drainage via the uveoscleral route

Use - First line for open-angle glaucoma

Latanoprostene Bunod

Latanoprost but also releases nitric oxide - vasodilator which increases outflow through trabecular meshwork (conventional) while latanoprost increases outflow via uveoscleral route

Bimatoprost

MOA - Bind to Prostaglandin F receptors, activate Gq, prodrug by N-delkylation

Effect - increase aq humor outflow via uveoscleral route

Use - open-angle glaucoma, or eyelashes

Side effects - eyelash growth and darkening

Netarsudil

MOA - RHO Kinase inhibitor

Effect - lower IOP via conventional route

Use - open-angle glaucoma

Timolol

MOA - B2 adrenergic antagonist

Effect - lowers humor production

Acetazolamide

MOA - inhibits carbonic anhydrase

Effect - lowers humor production

Contraindicated in sulfonamide allergy

Brimonidine

MOA - a2 adrenergic agonist

Effect - lowers humor production and increases outflow

Mannitol

MOA - forms a hyperosmotic solution that draws water out and into the mucus, loosening it

Use - Cystic Fibrosis

Use with bronchodilator prior to inhalation

Dornase Alpha

MOA - DNAse that breaks up DNA in mucus, thinning mucus

Use - Cystic Fibrosis

Ivacaftor

MOA - CFTR Potentiator, potentiates CFTRs to work and transport Chloride

Use - Cystic Fibrosis

SAR - Needs tautomer form, Amide linker, aryl ring, quinoline ring

• Phenolic group on aryl important for H-bond

• R4 T-but important for hydrophobic int

• R6 T-but important for PK

CYP3A4 metabolized

Lumacaftor

MOA - CFTR chaperone, promotes CFTRs making it to surface

Use - cystic fibrosis with potentiator

CYP3A4 inducer - must adjust ivacaftor dose up

Cromolyn Sodium

MOA - Mast Cell Stabilizer, prevents increase of Ca

Use - prevention of asthma

Diphenhydramine

MOA - 1st gen H1R inverse agonist

SAR - ethanolamine

Use - Allergies, Cold, Pruritus, sleep aid, hypersensitivity, local anesthetic
Metabolism - CYP

Side Effects

• sedation/CNS depression

• paradoxical excitation in kids

• dry mouth

• Can enter breast milk

BEERs criteria

Contra - glaucoma, BPH, infantile febrile seizures

Meclizine

MOA - 1st H1R inverse agonist

SAR - Piperazine

Uses - N/V, motion sickness

Side Effects

• sedation/CNS depression

• paradoxical excitation in kids

• dry mouth

• Can enter breast milk

BEERs criteria

Contra - glaucoma, BPH, infantile febrile seizures

Promethazine

MOA - 1st gen H1R inverse agonist

SAR - tricyclic antihistamine

Use

• allergic conjunctivitis

• allergic rhinitis

• N/V, motion sickness

Side effects

• Anticholinergic/sedation

• QT prolongation

• BBW if <2 fetal respiratory syndrome

Terfenadine/Fexofenadine

MOA - 2nd gen H1R inverse agonist

terfenadine → fexofenadine

• terfenadine removed due to QT prolongation

Use - urticaria, allergic rhinitis

Avoid with antacids and fruit juice

Loratadine/Desloratadine

MOA - 2nd gen H1R Inverse Agonist

SAR - tricyclic antihistamine

Loratadine → desloratadine

Loratadine use - allergic rhinitis, urticaria

Desloratadine use - acne with tretinoin/abx

Metabolism - CYP3A4

Cetirizine

MOA - 2nd gen H1R inverse agonist

SAR - piperazine metabolite of hydroxyzine

Use - allergic rhinitis, urticaria

• Most drowsy

Pitolisant

MOA - H3R Antagonist, lower negative feedback, more histamine, wakefulness

Use - Narcolepsy

Metabolism - CYP2D6 metabolism

Side Effects - QT prolongation

Cimetidine/Famotidine

MOA - H2R Inverse Agonist on parietal cells

Time - Onset 1 hour, 24 hour DOA

SAR

• 4 methyl increase N tau

• Electron withdrawing good - less ionized, more N tau

• Polar tail needed for antagonism

Use - Decreasing gastric acid

• Use before antacid, needs acid to activate

Adverse - GI upset, confusion, hallucinations, Long-term pernicious anemia

• Tachyphylaxis from repeated use

Cimetidine - is strong CYP inhibitor due to imidazole binding heme

BEERs

Omeprazole/Esomperazole

MOA - Irreversibly inhibits active proton pump via covalent disulfide bond

SAR - benzimidazole + Sulfinyl + 2-pyrdily methyl, sulfinyl needed for bonding

• prodrug that must be enteric coated, activated by acid, and absorbed in duodenum

Use - frequent heartburn, GERD

Metabolism

• omeprazole - 2C19

• Esomeprazole - less 2C19

Adverse

• bond fractures

• Increased risk of C diff

DDIs

• Warfarin

• cyclosporine

• diazepam

BEERs

Vonoprazan

MOA - Blocks active or inactive proton pump reversibly

• luminal side due to high ionization

Benefits

• rapid effect

• good for long-term

• less adverse than PPIs

Bismuth subsalicylate/subcitrate

Use - symptomatic relief of heartburn

Avoid with fluoroquinolones and tetracyclines, chelation

Sucralfate

MOA - coats stomach in protective coating

Avoid in renal failure

Misoprostol

MOA - prostaglandin analogue

Use - Chronic NSAID ulcers

Acetylsalicylic Acid (NSAIDS)

MOA - irreversibly inhibits COX-1 and COX-2

• slight selectivity for COX-1 at [low]

Use

• low dose for cardioprotection

• high dose for anti-inflammatory

• Ischemic attacks

Adverse

• Induced asthma

• GI effects

• Hyperuricemia at low dose

• Reye’s syndrome can occur in kids

DDIs

• loop diuretics

• ACEI

• Warfarin, increases effect

• Ibuprofen

Toxicity

• tinnitus

• respiratory alkalosis

Indomethacin

MOA - non-selective COX inhibitor (potent)

Uses

• arthritis

• Bursitis

• Corneal Abrasion

• Gout

Adverse

• B and T cell depletion

• pancreatitis

• psychosis

• fluid retention

DDIs

• Probenecid

Ibuprofen (NSAIDS)

MOA - Non-selective COX inhibitor

Adverse

• GI effects

• Nephrotoxicity

• increased risk of CV effects

Active form - S isomer

CYP2C9 metabolized

Vitamin B1

Active Form - Thiamine pyrophosphate

Reaction - Oxidative decarboxylation via a carbanion

Deficiency - due to alcoholism

• Wet Beri Beri - CV

• Dry Beri Beri - CNS effects

• Wernicke-Korsakoff, severe CNS effects

Vitamin B2

Active Form - FMN or FAD

Eaten as FMN or FAD, absorbed as riboflavin, back to FMN or FAD in body

Reaction - Electron transfer

Deficiency - Ariboflavinosis

• Alcoholism, medication, Celiac

Use - bulging cornea after Lasik

Vitamin B3

Active form - NAD or NADP

Reaction - hydride acceptor or donor

Deficiency - Pellagra (dermatitis, dementia, diarrhea)

• Alcoholism

• Weight Loss Surgery

• Isoniazid or barbiturates

Use - Hyperlipidemia

• Nicotinamide has no flushing, or take with aspirin

Vitamine B5

Active - Coenzyme A

Absorption - SMVT

Reaction - acetylation

Rare deficiencies

Vitamin B6

Active - phosphorylated form, mostly PLP

Reaction - Transamination or decarboxylation using a Schiff base with AAs

Toxicity - sensory neuropathy

Deficiency

• alcoholism

• isoniazid, hydralazine, contraceptives

• Can cause peripheral neuropathy, cognitive defects, or cause Pellagra like disease

• sideroblastic anemia

Use - morning sickness in pregnancy

Vitamin B7

Active - Covalently bonded to Lysine of BCCP

Absorption - SMVT

Reaction - Carboxylation

Deficiency - lots of avidin, raw egg whites

• Can interfere with troponin tests

Vitamin B9

Active - THF (polyglut is trapped)

Absorption - SLC transporter

Reaction - 1 carbon transfer

Toxicity - no toxicity but may mask B12 deficiency

Deficiency - Alcoholism, weight loss

• Megaloblastic anemia

• Neural tube defects

Use - Leucovorin is used to prevents methotrexate side effects by lowering THF levels

Vitamin B12

Active - planar ring with Cobalt

Absorption - Endocytosis with IF

Reaction - many: tranferase/isomerase

Deficiency - malabsorption/NO/H2RA/PPI

• Pernicious anemia, lack of B12 absorption

• Causes neurological damage

Vitamin C

Active - L-isomer

Reaction - Electron donation for metal cofactors (redox)

Excretion - can form kidney stones

Deficiency - Scurvy (lack of collagen synth)

• lack of fruits, alcoholism

Use - enhance absorption on non-heme iron

Vitamin D

Active - calcitriol, double hydroxylated, one in kidney and one in liver

Role - modulates gene expression for absorption of Ca and Phosphorous in small intestine

Deficiency - rickets, hypocalcemia

Toxicity - anorexia, hypercalcemia, arrythmia

Vitamin E

Active form - tocopherol

Use - antioxidant

Deficiency

• neurological symptoms

Use

• hemolytic anemia in premature infants

• macrocytic megaloblastic anemia in children

• lowering effectiveness of anticancer agents

Vitamin A

Form - all kinds of retinols

Transported by RBP as insoluble in blood

can’t OD on beta-carotene

Use - vision and acne and psoriasis and kaposi

acitretin - psoriasis

Kaposi’s - 9-cis-retinoic acid

• 11-cis-retinal to 11-trans-retinal

• Couples via Schiff base

Deficiency - night blindness, overgrowth of teeth

Toxicity - increase in CSF pressure, blurred vision

Vitamin K

DDIs - orlistat, warfarin, cephalosporin,

Important in bleeding

Used for warfarin reversal