Histamine, H1 Antagonists, H2, Antagonists

Phillip Exam 2

Alkylamines

Gen I, H1 Antagonists, Antihistamines, Chlorpheniramine and brompheniramine

Piperazines

Gen 1 Antihistamines. Chemical structure of this group increases lipophilicity, increases CNS concentration, gives prolonged DOA, and is CENTRAL ANTINAUSEA ACTIVITY. Really good antinausea activity and prolonged DOA bc ring system binds to the particular receptor better.

Hydroxyzine

Piperazine, Gen 1 antihistamine. Causes cardiotoxicity due to ethoxyethanol tail. As the drug gets metabolized, you generate a hydroxy free radical.

Piperazines

Gen 1 Antihistamines. Moderate sedation and LOW anticholinergic effects. Due to 6 membered ring system with 2 nitrogens. This unique ring increases lipophilicity, increases CNS concentration and prolongs DOA. Because it is able to cross into CNS, gives wonderful anti-nausea activity.

Piperazines

Gen 1 antihistamines, 3 of them. Contain 6 membered ring with 2 Nitrogens. Typically used as antinausea. the great ring system binds to receptor for antinausea much better than other antihistamines.

Alkylamines

Gen 1 antihistamines, 2 of them. Contain 2 pyridine ring systems with halogens in the para position. Pyridine is 6-membered aromatic ring with a Nitrogen.

Piperidines

Gen 1 antihistamines. Fused, 3 ring system (tricyclic with each having an attached non-aromatic 6 membered ring with a nitrogen.). VERY POTENT ANTIHISTAMINES. Includes Cyproheptadine HCL and ketotifen.

Cyproheptadine HCL

Gen 1 antihistamine. Potent antihistamine activity. Anti-sertonergic and anti-cholinergic activity. Pronouncced Sedation. SUPER DRY MOUTH.

KETOTIFEN

gEN 1 ANTIHISTAMINE. Potent antihistamine. Inhibits histamine release by stabilizing mast cells. Has a very localized ability to inhibit histamine release which is why it is a good opthalmic product.

Ethanolamines

Gen 1 antihistamine. Strong sedative effects, potent antihistamines, fast to take action, short DOA. Includes Diphenhydramine HCL, Dimenhydrinate, Doxylamine succinate, and clemastine.

Dramamine

1st gen antihistamine, ethanolamine. Used for motion sickness, is a sedative but includes a stimulant of theophylline or caffeine.

Promethazine

1st gen antihistamine. potent sedative effects, long DOA, potent anti-cholinergic, moderate anti-histamine, treats nausea and vomiting associated with motion sickness. Much better anti-emetic/ anti-nausea than anti-histamine. It’s phenyl rings make a v-structure, not flat planar structure so it doesn’t have high binding affinity with Histamine receptors. All of this shit is due to it’s UNIQUE structure. Also, if you can’t tell by now this is a phenothiazine.

Doxepin

Potent H1, antagonist, Gen 1 antihistamine. Zonalon cream for pruritis. Anti cholinergic and sedation SEs. 7 membered ring system, topical admin. only bc if taken orally = extreme sedation.

loratidine

Gen 2. tricyclic antihistamine. non-sedative property due to its ethoxycarbonyl group. Carbamate N (Nitrogen + carbonyl ester) is a neutral N which gives it rapid absorption and fast acting.

Loratidine

Gen2, tricyclic antihistamine metabolized by CYP3A4/ 2D6

CYP3A4/ 2D6

Loratidine is metabolized by what enzymes

Desloratidine

Gen 2. Metabolite formed by CYP3A4/2D6. Does not cross BBB due to Nitrogen having a + positive charge. tricyclic antihistamine.

Olopatadine

Gen 2, Doxepin + CH2COH. Rapid onset, long DOA because slow receptor dissociation, strong binding to H1 receptor, Dr. Phillip’s favorite drug.

Olopatidine

Gen 2. Inhibits histamine release and other inflammatory mediators (PGD2/ tryptase) from mast cells. Less Sedating! Has a (-COOH) group so does Not cross BBB.

Levocetirizine

Preferred drug for anti wheal and flare. R-isomer of cetirizine.

Hydroxyzine

Gen 1 . Can get converted to a free radical and cause cardiotoxicity, Oxidizes to Cetirizine.

Cetirizine

Gen 2. (-COOH) group = Higher H1 selectivity = less anticholinergic effects. (-COOH) group = no cardiac toxicity. (-COOH) group = zwitterionic, so if both charges, means it is neutral, can’t effectively cross BBB and makes less permeability and less sedating. Has many enantiomers because it has a chiral carbon. Much better anti-histamine than hydroxyzine.

fexofenadine

Gen2. (-COOH) group so higher H1 selectivity= less anti-cholinergic FX. Zwitterion so no cross BBB and less sedating. (-COOH) means less cardiotoxicity because not creating free radical round hyah. STRONG PGP SUBSTRATE = HI DRUG DRUG INTERACTIONS, SEVERE DISADVANTAGE.

Benadryl

Diphenhydramine

dramamine

dimenhydrinate

Unisom

Doxylamine

Phenergan

promethazine

Silenor, Zonalon

Doxepin

Zaditor

ketotifen

Periactin

cyproheptadine

Atarax, vistaril

Hydroxyzine

Bromfed

Brompheniramine

Zyrtec

cetirizine

Allegra

fexofenadine

Claritin

Loratidine

Clarinex

desloratidine

Pataday

olopatadine

Tagamet

cimetidine

Zantac

ranitidine

Axid

nizatidine

Pepcid

famotidine

H2 Antagonists

Not very lipophilic, do not cross BBB. No sedation. Therapeutic uses: duodenal ulcers, gastric ulcers, pathologic hpersecretory conditions (Zollinger-Ellison syndrome, multiple endocrine adenomas), reflux esophagitis.

Cimetidine (Tagamet)

potent CYP3A4 inhibitor, competitive antgonist H2 receptor, contains imidazole ring. Antacids only before or after this drug. This drug extremely basic and needs extremely acidic environment for solubility/ absorption. Gen 1 agent. EXTREME DANGER DRUG DRUG INTERACTIONS BC STRONG CYP ENZYME INHIBITION.

Ranitidine (Zantac)

Gen 2 agent. Competitive H2 receptor antagonist. WEAK CYP INHIBITOR. Do not take with antacids. Recalled bc containe carcinogenic NDMA contaminant. 

Famotidine (Pepcid)

Good H2 antagonist, much more potent with strongest binding affinity. DOES NOT INHIBIT CYP ENZYMES. DRUG DRUG INTERXNS less of an issue so SAFER. Good balance of acidity and alkalinity, doesn’t need acidic enviro. so much bc water soluble on its own.