Term
| Peptic ulcers occur in areas of the GI tract exposed to __ and __ when there is an imbalance of aggressive vs. protective factors. |
|
Definition
|
|
Term
| Aggressive factors in GI Tract: |
|
Definition
- acid
- pepsin
- Helicobacter pylori |
|
|
Term
| Protective factors in GI tract: |
|
Definition
- bicarbonate and mucus secretion
- prostaglandin formation |
|
|
Term
| Protective actions of Prostaglandins (3): |
|
Definition
- inhibit acid production
- stimulate mucus and bicarbonate secretion
- stimulate vasodilation in gastric mucosa |
|
|
Term
| __ and ___ (non-selective COX 1/2 inhibitors)inhibit prostaglandin synthesis and thus may lead to PUD/GERD. |
|
Definition
|
|
Term
| __ __ selective inhibitors, such as Celecoxib, have less incidence of causing PUD/GERD. |
|
Definition
- COX-2 selective inhibitors
This is FYI: drug name was not in red. |
|
|
Term
|
Definition
- Aspirin/NSAIDs
- Alcohol in excess
- Smoking
- Helicobacter pylori infection |
|
|
Term
Chronic GERD and episodic heartburn are extremely common (10%-50% of U.S.).
Patients often self-medicate with over-the-counter antacids. GERD is associated with __ ___ __ of the lower esophageal sphincter, ___ gastric emptying, and impaired resistance of the ___ __ to injury. |
|
Definition
- repeated transient relaxation of LES
- delayed gastric emptying
- impaired resistance of the esophageal mucosa to injury |
|
|
Term
| Therapeutic overall goals for PUD/GERD: |
|
Definition
Overall goals:
Relief of symptoms
Healing of ulcers
Prevention of recurrence
Prevention of complications (hemorrhage, perforation, and obstruction)
Reduce aggressive factors
Hyper-acid condition, maintain stomach pH>4
Eradicate H. pylori infection
Increase protective factors |
|
|
Term
| when treating PUD and GERD, the goal is to maintain a stomach pH ___ __ __. |
|
Definition
| stomach pH greater than 4 |
|
|
Term
| Life style changes to help with GERD/PUD: |
|
Definition
- raise head of bed
- stop smoking
- decrease alcohol consumption
- avoid caffeinated/acidic drinks
- three balanced meals per day
- do not lay down 2-3 hours after meals
- stop NSAID use unless absolutely necessary |
|
|
Term
| Pharmacological therapy for GERD/PUD (4): |
|
Definition
- Proton pump inhibitors
- H2 antagonists
- Antacids (good for symptoms but not long term treatment)
- Sucralfate |
|
|
Term
| Proton Pump Inhibitors inhibit the __ __ ___ pumps, name 2: |
|
Definition
- inhibit the H+K+ATPase
- Omeprazole
- Lansoprazole
these are both OTC |
|
|
Term
| Drugs that end in "-prazole" are: |
|
Definition
|
|
Term
| Proton pump inhibitors are very efficacious is inhibiting __ production and promote the healing of ulcers in the __, ___, and ___. |
|
Definition
- acid
- stomach, duodenum, and esophagus |
|
|
Term
| Proton pump inhibitors __ bind ___ groups on the proton pump which ____ inactivates ___ secretion. |
|
Definition
- covalently bind
- sulfhydryl groups
- irreversibly inactivates
- H+ secretion |
|
|
Term
| Proton pump inhibitors have __ distribution to _____ in ___ cells. The pH has to __ for these drugs to be activated, then the drug gets trapped at the site of action. Proton pump inhibitors only work on __ __ __. |
|
Definition
- selective distribution
- H+K+ATPase in parietal cells
- pH has to be acidic/low
- only work on actively secreting pumps |
|
|
Term
| Proton pump inhjibitors have short half life, but it doesn’t matter b/c once they have deactivated the pump, you have to make new pump moleculess. It takes several doses/days of proton pump inhibitor to bring down acid production. If stop proton pump inhibitor, it takes a few days to return back to normal state. |
|
Definition
this was in my notes.
So basically takes a few doses for it to start working and it takes missing a few doses to stop working. |
|
|
Term
| Proton Pump Inhibitors are actually administered as __. They are also __ coated so that the __ is not released until its in the intestines where there is a __ pH. |
|
Definition
- prodrugs
- enteric so that the prodrug
- neutral PH |
|
|
Term
| In the neutral pH of the intestine, the PPI prodrug is ___, __ __, and devoid of __ ___. |
|
Definition
- stable
- lipid soluble
- devoid of inhibitory activity |
|
|
Term
| Absorption and Action of PPIs (proton pump inhibitors): |
|
Definition
| - neutral weak base absorbed in intestines b/c of the neutral pH environment> blood stream> parietal cells in stomach> prodrug diffuses into secretory canaliculi> acid pH causes protonation and trapping of drug near proton pump |
|
|
Term
|
Definition
- nausea
- diarrhea
- abdominal colic
- headache
- dizziness
- skin rash |
|
|
Term
|
Definition
- PPI inhibit cytochrome p450
- Omeprazole reduces metabolism of phenytoin, warfarin, and diazepam |
|
|
Term
| PPIs inhibit cytochrome p450, so Omeprazole will reduce metabolism of what 3 drugs: |
|
Definition
- phenytoin
- warfarin
- diazepam |
|
|
Term
| Food inhibits PPI, so take PPI 30-45 minutes before you eat. But they really need to eat 30-45 minutes later to activate the pump so that the pumps will be killed off. |
|
Definition
|
|
Term
| A patient is on PPI, when should they eat? |
|
Definition
| - 30-45 minutes after taking medication |
|
|
Term
| H2 Histamine Receptor Antagonists: |
|
Definition
|
|
Term
| Drugs that end in "-tidine" are : |
|
Definition
| H2 antagonists (blockers) |
|
|
Term
| H2 antagonists are used for treatment of __ and __ ulcers, ___, __ __, and ___ states. These are also used as ___ medication to reduce danger of ___ __. |
|
Definition
- gastric and duodenal ulcers
- GERD
- stress ulceres
- hypersecretory states
- preanesthetic medication to reduce danger of aspiration pneumonitis |
|
|
Term
| what drug is used as a preanesthetic medication to reduce danger of of aspiration pneumonitis? |
|
Definition
H2 antagonists
(Cimetidine/Ranitidine) |
|
|
Term
| Cimetidine, a __ __, inhibits many ___ enzymes included ___, so it has a lot of drug interactions. ___ has less drug interactions. |
|
Definition
- H2 antagonist
- CYP450 enzymes
- CYP3A4
- Ranitidine has less drug interactions |
|
|
Term
| ___ and ___ stimulate histamine release from ___ __ ___. Then histamine activates the ___ ___ of receptor on __ cells and stimulates __ __ __activity and acid secretion into the lumen. |
|
Definition
- Gastrin and Ach stimulate histamine release
- from enterochromaffin-like cells (ECL)
- histamine activates H2 subtype
- on parietal cells
- stimulates H+K+ATPase |
|
|
Term
| gastrin and Ach> activate ECL cells> release histamine> H2 receptors on parietal cells> stimulates H+K+ATPase pumps> acid secretion |
|
Definition
|
|
Term
| gastrin and Ach> activate ECL cells> release histamine> H2 receptors on parietal cells> stimulates H+K+ATPase pumps> acid secretion |
|
Definition
|
|
Term
| H2 inhibitors block the __ pathway. |
|
Definition
|
|
Term
| H2 blockers __ ___ histamine-mediated acid secretion and also blunt the response to __ and __. |
|
Definition
- competitively inhibit
- blunt the response to gastrin and Ach |
|
|
Term
| Classic antihistamines are H1 blockers and do not __ __ __. |
|
Definition
| - do not inhibit acid secretion |
|
|
Term
| H2 receptors blockers are highly selective for H2 histamine receptors with minimal side effects. They inhibit __, __ __, and __ acid secretion. Thus, they reduce both the __ and __ __ of gastric secretions. |
|
Definition
- inhibit basal, food-stimulated, and nocturnal acid secretion
- reduce both the volume and H+ concentration |
|
|
Term
| Adverse effects of H2 blockers: |
|
Definition
- infrequent and mild
- All agents that inhibit gastric acid secretion may alter the bioavailability or rate of absorption of certain drugs secondary to changes in gastric pH. |
|
|
Term
| Cimetidine is a __ __ that inhibits the activity of ___. This drug also reduces testosterone action on androgen receptors and results in __ __. |
|
Definition
- H2 blocker
- CYP450 enzymes
- gynecomastia in men |
|
|
Term
| Treatment for PUD not associated with H. pylori: |
|
Definition
- PPI one hour before first and second meal for 2 months
- H2 blocker at bedtime if breakthrough symtpoms
- Reduce PPI to once daily until symptoms are gone |
|
|
Term
| H. pylori is a __ __ __ bacteria which is found in the mucus of the luminal surface of the gastric epithelium. Both normal patients and patients with ulcers have this bacterium. Eradication of H. pylori can hasten healing from ulcers. |
|
Definition
|
|
Term
| Triple therapy for H. pylori eradication: |
|
Definition
- PPI twice a day
- Clarithromycin twice a day (or metronidazole)
- Amoxicillin twice a day (or metronidazole if patient is allergic)
TAKE ALL OF THESE FOR 14 DAYS. |
|
|
Term
| Quadruple Therapy for H. pylori eradication: |
|
Definition
- PPI twice a day
- Tetracycline 4 times a day
- Metornidazole 3-4 times a day
- Peptobismol 4 times a day
Quadruple therapy is cheaper than triple therapy, but requires more compliance.
TAKE ALL OF THESE FOR 14 DAYS. |
|
|
Term
|
Definition
(not in red on slides)
- combination of PPI (Lansoprazole), Clarithromycin, and Amoxicillin
- used to eradicate H.pylori infection |
|
|
Term
| To see if a H.pylori infection has resolved, do a __ __ __ b/c this is the most sensitive test. Unresolved infections could lead to recurrence. |
|
Definition
|
|
Term
| After 14 day treatment of H.pylori, take patient off of the ___ for one week, and then do stool antigen test. The __ can cause a false positive. |
|
Definition
|
|
Term
Presence of H. pylori does not necessarily equal ulcers
On average, 30% US adults have H. pylori
Older age, greater prevalence
Higher incidence rates in lower socioeconomic classes
Oral-fecal route: personal hygiene, home environment
Genetics
Water supply? |
|
Definition
|
|
Term
| Travelers should cut their dose of ___ in half b/c stomach acid protects against traveler's diarrhea. |
|
Definition
PPI
(but don't cut tablet in half b/c they are enteric coated) |
|
|
Term
| Antacids therapeutic use (3): |
|
Definition
- simple dyspepsia
- adjuncts to primary therapy with PPI or H2 blockers
- primary therapy in uncomplicated GERD |
|
|
Term
| Antacids are weak __ that chemically neutralize acid. The goal is to raise gastric pH above __. |
|
Definition
|
|
Term
|
Definition
- ALUMINUM HYDROXIDE
- MAGNESIUM HYDROXIDE
- Calcium carbonate
- Sodium bicarbonate
- Simethicone
- Gaviscon |
|
|
Term
| Aluminum hydroxide antacid tends to cause ___. |
|
Definition
|
|
Term
| Magnesium hydroxide (antacid) tends to cause ___. |
|
Definition
|
|
Term
| Most common combination of antacids and why? |
|
Definition
- Aluminum hydroxide and Magnesium hydroxide
- this combination minimizes disturbance in bowel motility |
|
|
Term
| Antacids should be taken __ hour and __ hours after a meal, and at bedtime. |
|
Definition
|
|
Term
| Adverse effects of antacids: |
|
Definition
- changes in bowel motility
- alkalosis
- significant effects on absorption of other drugs
- DO NOT TAKE ANTACIDS WITHIN 1-2 HOURS OF OTHER DRUGS
- Rebound acidity upon discontinuation |
|
|
Term
| Examples of Cytoprotective Agents (2): |
|
Definition
- Pepto-Bismol= bismuth subsalicylate
- Misoprostol |
|
|
Term
| Cytoprotective agents (pepto-bismol, bismuth subsalicylate) mechanism of action: |
|
Definition
- enhances secretion of mucus and HCO3-
- inhibits pepsin activity
- chelates with protein at base of ulcers and forms protective barrier against acid and pepsin
- may inhibit H. pylori |
|
|
Term
| Cytoprotective agents are effective adjuncts for treatment and prophylaxis of __ and __ __, ___, and ___. |
|
Definition
- duodenal and gastric ulcers
- GERD
- diarrhea |
|
|
Term
| Pepto-bismol (bismuth subsalicylate) and Misoprostol work by ___ mucus and HCO3- production and __ pepsin activity. They chelate with proteins at the base of __ and form a protective barrier against acid and pepsin. They may also inhibit __ __. |
|
Definition
- increasing
- inhibiting
- ulcers
- H. pylori |
|
|
Term
| Side effects of Pepto-bismol: |
|
Definition
- black tarry stools- most bismuth is eliminated in feces
- black tongue with long term use |
|
|
Term
| Misoprostol is a ___ agent. |
|
Definition
|
|
Term
| Misoprostal is a __ agent that is a slowly metabolized analogue of ___. It stimulates production of __ and __. But it causes __ in 30% of patients. This is mostly used in patients who have to use ___. |
|
Definition
- cytoprotective
- PGE1 (prostaglandin E1)
- mucus and HCO3-
- diarrhea in 30% of patients
- who have to use NSAIDs |
|
|
Term
| 6 Categories of Antiemetic agents: |
|
Definition
- 5-HT3 blockers
- Neurokinin-1 blockers
- D2 blockers
- Antihistamine H1 blockers
- Antimuscarinics
- Cannabinoids |
|
|
Term
| 5-HT3 antagonist/blocker antiemetic drug: |
|
Definition
|
|
Term
| 5-HT3 receptors are located many places involved in the __ __ including the __ __ __. Antagonists of these receptors, like ___, are very effective inhibitors of emesis even with ___. These are most effective when combined with ___ therapy short term like ___. These are very safe and have few side effects. |
|
Definition
- vomiting reflex
- chemoreceptor trigger zone
- Ondansetron
- chemotherapy
- corticosteroid
- dexamethasone |
|
|
Term
| Ondansetron is what type of drug? |
|
Definition
| - Antiemetic 5HT3 blocker |
|
|
Term
| ___ is an antiemetic that is a neurokinin 1 receptor blocker. |
|
Definition
|
|
Term
| Aprepitant is what type of drug? |
|
Definition
- antiemetic
- neurokinin 1 blocker |
|
|
Term
| Aprepitant an antiemetic that blocks __ _ receptors is usually used with a ___ ___ and __ for prevention of chemotherapy induced nausea and vomiting. |
|
Definition
- Neurokinin-1
- 5HT-3 blocker
- corticosteroids |
|
|
Term
| what drug combination would you use for a patient on chemotherapy to prevent nausea and vomiting? |
|
Definition
- Ondansetron
- Aprepitant
- corticosteroids |
|
|
Term
| Side effects of Aprepitant, a Neurokinin-1 blocker antiemetic: |
|
Definition
- fatigue
- dizziness
- diarrhea |
|
|
Term
| Name the drug that is an antiemetic Dopamine D2 blocker: |
|
Definition
|
|
Term
| Metoclopramide is an ____ ___ ___ ___ that is also a weak ___ __. |
|
Definition
- antiemetic dopamine D2 blocker
- also a weak 5HT3 blocker
(aka Reglan, what Amy was on) |
|
|
Term
| Antiemetic antihistamines, which are H1 blockers (2): |
|
Definition
- Promethazine (fyi: Phenergan)
- Dimenhydrinate (fyi: Dramamine) |
|
|
Term
| Antiemetic Antimuscarinic (1): |
|
Definition
| Scopolamine- patch for motion sickness |
|
|
Term
| Antiemetic agent that is a cannabinoid: |
|
Definition
| - Dronabinol aka marinol delta 9 tetrahydrocannabinoid (THC) |
|
|
Term
| Dronabinol is what type of drug and is used for what? |
|
Definition
- cannabinoid antiemetic
- used for chemotherapy-induced nausea and vomiting
- also an appetite stimulant |
|
|
Term
|
Definition
- euphoria
- dysphoria
- sedation
- hallucinations |
|
|
Term
| Antiemetic agent indications: |
|
Definition
- motion sickness
- vertigo
- postoperative recovery
- Pregnancy (note: doxylamine/pyridoxine, discontinued)
- cancer chemotherapy
- migraine |
|
|
Term
|
Definition
- Metoclompramide (Reglan)
- Motilin
- Macrolide Antibiotics: Erythromycin |
|
|
Term
| Metoclopramide is a __ receptor blocker that ___ esophageal persistalsis, ___ lower esophageal sphincter pressure, and promotes gastric ___. It has __ effect on small intestine or colon. |
|
Definition
- D2 receptor blocker
- increases
- increases
- gastric emptying
- no effect on SI or colon |
|
|
Term
| Metoclopramide (Reglan) side effects: |
|
Definition
- hyperprolactinemia
- anxiety
- depression
- tardive dyskinesia (typically limited to 2 week course) |
|
|
Term
| Motilin hormone stimulates motility. |
|
Definition
|
|
Term
| Uses for promotility agents: |
|
Definition
- gastroparesis, but tolerance develops
- acute GI hemorrhage, promote emptying of gastric blood before endoscopy |
|
|
Term
|
Definition
- antiemetic drug
- promotility drug |
|
|
Term
| The macrolide antibiotics such as ERYTHROMYCIN, Clarithromycin, and Azithromycin promote motility by acting on the __ receptor. |
|
Definition
|
|
