Flashcards in Pharmacology Deck (38)
6 Types of Drugs for Acid Neutralization; which is the most potent drug that we use today?
- anatacids, muscurinic receptor antagonists (anti-cholinergics), gastrin receptor antagonists, H2-receptor antagonists, prostaglandin analogs, proton pump inhibitors
- PPIs are the most potent
2 Types of Mucosa Protective Agents
- bismuth chelate and sucralfate
- a mixture of Mg and Al salts to neutralize stomach acid
- provides symptomatic relief only (but can promote the healing of DUODENAL ulcers if used long enough)
- side effects: bloating, hypokalemia, constipation (aluminum), diarrhea (magnesium)
Muscurinic Receptor Antagonists (anti-cholinergics)
- block muscurinic receptors from binding to ACh = less stimulation for HCl secretion
- M3 antagonists decrease direct ACh stimulation of parietal cells
- M1 antagonists decrease ACh stimulation of ECL cells to inhibit histamine secretion, thus decreasing HCl production
- (G cells do not use ACh; they respond to the more specific muscarinic transmitter, GRP)
- "-pine" (Atropine, Pirenzepine, Telenzipine)
- a muscurinic receptor antagonist
- non-specific, so has a bunch of side effects associated with its anti-cholinergic action
- muscurinic receptor antagonists
- M1-specific (ECL cell activation via ACh), so they have less side-effects compared to Atropine
Gastrin Receptor Antagonists
- blocks the gastrin receptors (CCK-B) of parietal and ECL cells, preventing HCl secretion
- Proglumide; a general antagonist that blocks both CCK-B and CCK-A (blocking the latter results in CNS side effects)
- blocks the histamine H2-receptors of parietal cells, preventing HCl secretion
- "-tidine" (Cimetidine, Ranitidine, Famotidine, Nizatidine)
Cimetidine was the 1st H2-receptor antagonist used; what side effect lead to it being no longer used?
- it resulted in increased estrogen levels
- PGE1 analogs that act as agonists to the prostaglanin receptors, resulting in decreased HCl secretion and increased mucus and bicarb secretion
- prevents NSAID-induced peptic ulcers (NSAIDs block PGE1)
- side effects: diarrhea, cramping, uterine contraction (so avoid using during pregnancy!)
- (also used to maintain a PDA!)
Proton Pump Inhibitors (PPIs)
- bind to and IRREVERSIBLEY inhibit the H+-K+-ATPase of the parietal cells, preventing HCl secretion
- they are initially inactive pro-drugs that are activated in the acidic environment of the stomach
- they are the most potent inhibitors of acid secretion
- "-prazole" (Omeprazole, Esomeprazole, Pantoprazole)
What's the mechanism of action for mucosa protective agents?
- they create a barrier over the stomach to provide physical protection against the acid
Bismuth Chelate (4 actions)
- a chemical that coats any ulcers, absorbs pepsin, increases prostaglandin synthesis, and increases bicarb secretion
- side effects: nausea, blackening of tongue and feces
- forms gel complexes with mucus to coat any ulcers
- side effects are more limited than bismuth chelate's (about 15% of patients have mild constipation)
- these agents increase the emptying of the stomach and increase the lower esophageal sphincter pressure to inhibit reflux
- these help treat GERD, but do NOT treat P.U.D.
Triple Therapy for H. pylori Infection
- Amoxicillin + Clarithromycin + PPI (Omeprazole)
- (if patient has Penicillin allergy, replace Amoxicillin with Metronidazole)
Quadruple Therapy for H. pylori Infection
- triple therapy + a mucosa protective agent (bismuth chelate)
There are approximately only ___ antivirals available for use. Most are for which two viruses?
- only about 30; most are against HIV and herpes
What are the 7 basic steps involved in viral replication (and hence the 7 targets for antivirals)?
- attachment (Maraviroc; HIV) --> penetration --> uncoating (Amantadine) --> replication/transcription (interferon, nuceloside analogs, RT inhibitors) --> translation (interferon) --> assembly (protease inhibitors) --> release (Relenza, Tamiflu)
- (HIV has an additional step: gag cleavage via HIV aspartic protease; inhibited by Saquinavir and Indinavir)
- HIV antiviral
- target: the CCR5 chemokine receptor that HIV binds to
- mechanism: binds to CCR5, altering its conformation without inhibiting it = prevents HIV binding, but allows normal function
- target: the viral-encoded M2 ion channel, which is necessary to trigger the uncoating phase
- mechanism: blocks the M2 ion channel, preventing the H+ uptake needed to trigger uncoating
When using nucleotide analogs as antiviral therapy, why are the doses given very frequently?
- because viral replication is very rapid!
- a reverse transcriptase inhibitor
- a very efficient drug that only gets activated in the presence of the herpes virus, so it only works on infected cells = very few side effects
How are nucleotide analogs and reverse transcriptase inhibitors activated?
- they require 3 consecutive phosphorylations
- (in the case of Acyclovir, the 1st phosphorylation is from the herpes virus itself, which is why the drug only works in the presence of the virus)
T or F: HIV actually leaves the host cell in an immature form.
- HIV requires a unique cleavage event once it buds off from the host cell in order to be activated; this "gag cleavage" is mediated by HIV aspartic protease
- HIV antivirals that target the virus's unique cleavage event
- they inhibit the HIV aspartic protease needed to mediate the gag cleavage
What 4 drug treatments are available for Inflammatory Bowel Disease? Which is the most effective?
- 5-aminosalicylates: designed to reach the colon (so most used for UC); topical action - requires massive amounts to work; Sulfasalazine
- coritcosteroids: interfere with NF-KB signaling, turning off inflammation; don't use chronically
- thiopurines: originally developed to treat leukemia; analogs of guanine that interfere with 2nd messenger signaling involved in inflammation; very slow onset (about 16 weeks); 6-Mercaptopurine, Azathiopurine
- anti-TNFalpha monoclonal antibodies/ biologicals: quite effective for both UC and CD, but more effective for CD; Infliximab, Adalimumab
- most effective: combo of a thiopurine (AZA) + anti-TNF antibodies
- can also use methotrexate (mainly works for CD)
- (corticosteroids for initial, 5-ASA for UC, 6-MP for CD, methotrexate if 6-MP no good, anti-TNFs for both types)
The vomiting center has ________ receptors; a major component of the vomiting center is the ______________, which has _______ receptors.
- vomiting center: mACh (muscarinic receptors)
- major component: chemoreceptor trigger zone (CTZ), uses dopamine D2-receptors + serotonin 5HT3-receptors
- (the CTZ lies outside the BBB)
Note the vomiting pathway due to pain, repulsive sights/sounds, emotions; due to motion sickness; due to toxins/drugs; and due to stimuli from the pharynx/gut
- pain/sights/sounds/emotion: sensory --> CNS --> higher brain centers --> vomiting center
- motion sickness: labyrinth --> vestibular nuclei (H1 + mACh receptors) --> CTZ --> vomiting center
- toxins/drugs: multiple pathways --> CTZ --> vomiting center
- stimuli from gut option 1: visceral afferents (5-HT3 receptors) --> CTZ --> vomiting center
- stimuli from gut option 2: visceral afferents --> nucleus of solitary tract (H1 and mACh receptors) --> vomiting center