Fitz-antiulcerdrugs Flashcards
What are these drugs used for?
- Peptic Acid Disease
a. H. Pylori (95%)
b. NSAID-Induced
c. Other - GERD/NERD Treatment (non-erosive reflux disease)
- Hypersecretory states
a. Hyperacidity → dyspepsia
b. Stress ulcers
c. Gastrinoma (Zollinger-Ellison Syndrome)
d. Systemic Mastocytosis
What are the management objectives
- Heal Lesion
- Relieve Pain
- Removing reoccurance possibilities
- Avoid Complications→ avoid drug interactions
- Eliminate need to take maintenance
- H. pylori→ prevent development of resistance
Treatment strageties?
- Eliminate H. pyloric
- Reduce Pain (↓H+ secretion)
a. ↓ Stimulation (anticholin, H2 blockers)
b. ↓ Secretion (PPIs)
c. Buffer Acid (Antiacids)
d. Protect Surfaces
e. Replace Prostaglandins (unique to NSAID-Induced)
What antimicrobials are most effective for H. pylori and preventing peptic ulcer disease?
AMOXICILLIN, CLARITHROMYCIN, METRON-IDAZOLE, RIFABUTIN and TETRACYCLINE
What factors influence the choice of specific antimicrobial agents for treatment of H. pylori infection:
- Susceptability to drug: measured by MIC 50/90
- Pharmacokinetics: Esp. distribution→ where it is in the stomach- through the stomach cells or needs to be acid stable
- Drug Resistence
Why use amoxocillin the choice?
Needs to be effective against gram neg (3), orally available (3), acid stable (3)
What kind of drugs are penicillin?
- Cidal
- Cell Wall Inhibitors
- Major toxicity of penicillins are hypersensitivities
How do you end up with clarithroymycin?
has the lowest MIC50 and is more acid stabile.,
Why not azithryomcyin?
decrease dosing, decrease Gi effectsm
Macrolydes side effects (clartthydromycin)
bacteriostatic drugs
Inhibit protein synthesis via 50s RNA
-GI Irritation
-Drug interactions-CYP 3A4
Why does tetracycline good?
- It is incompletely absorbed which is good when it’s isolated to stomach
- Give with Food (opposite of normal)
- Don’t give with anything that has metal ions (antiacids) since chelation will occur
Tetracyline MOA and toxicity
- Static
- Protein Synthesis inhibitors on 30S
- GI Irritation
- Photosensitiity
- Teeth Discoloration (in pregnant women and children)
When all else fails what drug do you use?
Rifabutin (rifamycin)
Why do we use Rifabutin
- It’s more effective than other Rifamycins
- It is CIDAL
- MOA: Inhibits bacterial DNA dependent RNA polymerase
Toxicity of rifabutin
o HS
o Liver problems
o CYP450 inhibitor*
o Orange pee/secretions *
What s tinidazole?
• newer drug which requires less administration, less dosing
• MOA is unknow but:
o May cause DNA Damage
• 35-65% of H. pylori infections are resistant, so use is decreasing
Side effects of tinidzole
CNS Toxicitity*
Produce Disulfarum rxn*
GI
Teratogenic
Inhibit CYP2C9*
↑Warfarin’s Actions..shit if someone has a bleeding ulcer*
↓ Clearance of H2 Blockers (that’s actually good though)*
↑Effectiveness, ↑ Side Effects of H2 Blockers*
MOA of Bismuth?
Antimicrobial action via cell wall disruption or preventing adhesion or my inhibiting urease
It protects the surface
o Coats the Surface (think bandaid)
o Stimulates secretion of mucous prostaglandins and HCO3-
What is the active ingrideint?
bismuth in stomach, not the lower GI
Sx of bismuth?
Caused by the subsalicylate
o Turns tongue black (not harmful, hideous)
o Turns stool black which makes it hard to visualize blood
o Vomiting
o Tinnitus*
o Confusion/CNS*
o Hyperthermia
o Respiratory Alkalosis→ can cause metabolic acidosis via correction
Tx failure of H pylori reasons?
- Resistance to the drugs given
(35-65% occurs) Metronidazole, 5-10% (may now be 35-50%) for clarithromycin, rarely H. pylori is resistent to tetracycline, amoxiciliin, and rifabutin - Treatment Compliance
Too many pills for too long. Damn.
Why dont we use muscarinc receptors anatgonstis anymore?
• Very rarely (not used) because they slow emptying and prolong exposure of ulcer to acid
How do muscarinic receptors work again?
M1 and M3 are G-proetein linked
Activate phospholiapse C: ↑ IP3: ↑ Ca2+ release
What are the Muscarinic Receptor Antagonists
- Atropine
* Pirenzipine
Muscarinic Receptor Antagonists MOA?
• comp. inhibitors of ACh
Which muscarininc receptor agonist is more selective?
pirenzipine
Side Effects of Anticholinergics?
“ABCD’S” o Anorexia o Blurry Vision o Constipation o Dry Mouth o Sedation o Stasis (urine)
OVerdose of anticholiergic- higher doses?
o CNS→ hallunications/confusion
o Tachycardia
o Hot dry skin
Are anticholingerics used to tx uclers
NO!
Wha are the H2 Receptor Anatgonists:
CIMETIDINE, FAMOTIDINE, NIZATIDINE, RANITIDINE
What is the MOA for H2-Receptor Antagonists?
- Highly selective with no H1 activity
* Competititve antagonists of H2 receptors
What are H2 receprots secondary effects?
o ↑ IC cAMP→ impact basal and nocturnal secretion due to other agents
o Known to ↓ meal-time stimulation
What are the pharmacokinetics of H2-Receptor Antagonists
- OTC→ 6 hours
- Prescription→ 10 hours
- Undergo extensive hepatic metabolism
- Renal excretion
Side effects of H-2 RA?
• None when given orally to healthy patients except…
o Rapid IV infusion may result in bradycardia and hypotension*
o H2-receptors in heart→ give slow infusion*
• Unknown pregnancy effects so not recommended
What are the H2-RA drug-drug interactions?
• ↓ Ethanol metabolism ( in women)*
• Compete for tubular secretion with weak basics*
o metronidazole is a weak base*
What’s special about cimetidine?
has side effects at high doses-
o Decreased binding of dihydrotestosterone (DHT) to androgen receptors
o ↓ estrogen metabolism
o ↑ prolactin excretion
o Results in gynecomastia and impotence in males*
o galactorrhea in females*
Cimetidine is an inhibitor of CYP450
↑effects of other drugs (boosts concentrations),
It is an isozyme of a lot of drugs
Proton Pump Inhibitors (Block Acid Secretion) are?
ESOMEPRAZOLE/OMEPRAZOLE,LANSOPRAZOLE, PANTOPRAZOLE, RABEPRAZOLE
OMEPRAZOLE-racemic mix and esomeprazole-slowly metabolized
What is the MOA of PPIs?
• IRREVERSIBLY block the final common pathway in acid secretion — the H+/K+ ATPase
When do we prefer to use PPIs?
- ZE syndrome and GERD*
* Very Effective for many purposes
Pharmacokinetics of PPIs?
• They are prodrugs and acid-labile*
o they must pass through stomach to be absorbed (they have a special coating on them)
• Absorbed into the small intestine→circulate throughout body
• They are attracted to acidic compartments
o they are protonated and converted to activated form
o require and acidic environment to function*
What’s critical about Ppis?
o Give in a fasting state so that motility is low, preventing the pills getting crushed
o The drug only inhibits active pumps (in fasting state only 10% of PP are active)
o SO! Take the drug ½ hour before the meal allowing the drug concentration to be highest (when pump activity is highest)
How many doses of PPI do you need to take a day?
1! They have a short ½ life, but they’re irreversible inhibitors, it takes 18 hours to make new pumps
Full inhibition of all pumps takes how long?
3-4 days, and recovery takes 3-4 days as well., So take high initial dose and then taper as symptoms are controlled.
How are PPIs broken down?
• Broken down by 1st pass metabolism
Which PPI is not available via IV
omeprazole
What are the PPI SE?
- None, that’s why they’re OTC
- 1-5% of patients report headache/diarrhea/nausea
- When the patient stops taking drug, there is significant hypersecretion-rebound effect*
What if taking PPI long term?
↓ B12, Fe, Ca2+, Zinc absorption→↑Hip fractures*
↑Respiratory and Enteric Infections (d/t ↑ pH which normally is low in order to kill bugs)
Why do you get ECL Hyperplasia (hypergastrinemia) with PPI?
Normally ↓ gastric pH: ↑Somatostatin release: ↓gastrin
but with Long-term PPI use, ↑↑ gastrin
What are some weak bases to buffer acid?
ALUMINUM HYDROXIDE, CALCIUM CARBONATE, MAGNESIUM HYDROXIDE and SODIUM BICARBONATE)
What are the factors affecting usefulness of base agents?
- Systemic Absorption
- Rate of dissociation (fast→faster effect→ shorter duration
- Cation/Product effects
What are the drug interactions of Buffer drugs?
↑ gastric pH: ↑/↓ absorption of other drugs
bind drugs: ↓ absoprtion
Bulky: ↑ Gastric Emptying: ↓Absorption
Systemically absorbed will alkalinize urine: ↓ elimination
o You need to be extremely careful with tetracycline *
Side effect of ALUMINUM HYDROXIDE
constipation
What is simethicone?
- antifoaming agent: ↓gas pain
- We add it to Sodium bicarbonate
- also affects absorptions
Why use antacids?
rapid onset but short duration of action; no prevention of ulcer recurrence → useful for intermittent dyspepsia
why use H2 blocks?
relatively rapid onset, intermediate duration, some prevention → many uses
Why use PPIs
slow onset of action, very long duration of action, excellent prevention → drugs of choice for Zollinger-Ellison syndrome and GERD, as well as ulcer treatment
What is sucralfate?
- Al(OH)3 and sulphated sucrose
- Not an antacid
- basically a band-aid, stress induced ulcers in the ICU
MOA of sucralfate:
- attaches to ulcer surface
* stress-induced gastritis (ICU)
Pharmacokinetics of sucralfate
• Requires acidic environement
o cannot be given with PPI, H2 Blocker
SE of sucralfate?
- constipation
* binds other drugs
Whewn is misoprostol used?
- accounts for 5% of ulcer treatment (NSAID induced only)
* 15-25% of arthritis patients develop this though, so # maybe ↑
Misoprostol MOA:
- You’re replacing PGE1 to reactivate PG→ GI pathway to inhibit cAMP, and reduce H+
- Works because PGE1 is not that involved in inflammation compared to other prostaglandins
- Misoprostol has a short ½ life compared to NSAIDS (around 2 hours)
Pharmacokineteics of misoprostol?
- rapid absorption and metabolism
* excreted in urine
Misoprostol SE?
• diarrhea, nausea, cramping, abdominal pain
o 10-20% of patients which → ↓ compliance
• In preggers stimualtes uterine contractions→ abortifactant
What do all combo therapy have?
pain and eradication!
What form crosses more easily?
• Unionized, Increase in pH shifts right
“net thing to worry about”
o anything like PPI, H2 Blockers, Antiacids→ affect absorption
o systemically absorbed antiacids will affect excretion of other drugs
