Term
| How does histamine release acid from parietal cells? |
|
Definition
| Histamine binds to H2 --> cAMP/PKA mechanism activates the ATPase pump --> exchange of H+ for K+ and HCl builds up. |
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Term
| What is the H1 receptor responsible for? |
|
Definition
- Inflammation, contraction, AND relaxation!
- Histamine binds to H1 to release eNOS from endothelium via IP3
- NO uses cGMP to get rid of calcium in a cardiac muscle cell --> Relaxation
- Formation of prostacyclin through COX in epithelium - vasodilator
- Formation of TxA through COX in platelets - vasoconstrictor, dominates prostacyclin effects. Increase in BP!
- Binding to H1 --> production of NFkB --> inflammatory cytokines and inflammation. |
|
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Term
| What effect does histamine have on mast cells? |
|
Definition
| A resting mast cell has histamine granules inside it, degranulation happens when IgE is stimulated |
|
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Term
| What is the triple response? |
|
Definition
- Redness - vasodilation of arterioles due to H1
- Wheal - increase in vascular permeability
- Flare - Sub P release |
|
|
Term
| What are H1 receptor effects? |
|
Definition
- Vasodilation in the periphery
- Increase in vascular permeability - edema
- Contraction of bronchioles (IP3/DAG)
- Contraction of GI SM (IP3/DAG)
- Allergy symptoms
- Inflammatory PGs
- pain and itching
- N/V from CTZ and NTS, inner ear |
|
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Term
| What are H2 receptor effects? |
|
Definition
- Vasodilation
- Positive chronotropy and inotropy
- Stimulation of gastric acid release and pepsin release. |
|
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Term
| What kind of antagonists are H1 and H2 antagonists? |
|
Definition
|
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Term
| What are the responses to an H1 antagonist? |
|
Definition
- Decrease in edema, vasoconstriction
- Decrease in itching, pain, inflammation
- Relaxing of bronchioles
- Decreased allergies
- Penetrates CNS: sedation, Decreased N/V |
|
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Term
| Antihistamines have poor receptor specificity. What does that mean? |
|
Definition
- H1 blockade - sedation, decr cognition
- M3 blockade - anticholinergic effects
- Alpha blockade - hypotension, dizziness, reflex tachycardia
- Serotonin receptor blockade - Increased appetite and weight gain
- K channel blockade in phase 3 - Prolongs action/QT interval, torsades. |
|
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Term
| What first generation antihistamines have anti-emetic properties? What is their general rule? |
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Definition
- Diphenhydramine/Benadryl
- Dimenhydrinate/Dramamine
- Clemastine/Tavist
- Carbinoxamine/Clistin
- Cyclizine/Marezine
- Meclizine/Bonine or Antivert
- Hydroxyzine/Atarax
- Promethazine/Phenergan****
** No sedation = not anti-emetic |
|
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Term
| Are 2nd generation anti-histamine drugs anti-emetic? |
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Definition
| No! Do not cause sedation/do not cross the BBB |
|
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Term
| Where do antihistamines work to prevent N/V? |
|
Definition
Antagonize H1 and M1 receptors in the CTZ, NTS, and inner ear.
**Can be used in morning sickness |
|
|
Term
| What are side effects of antihistamines? |
|
Definition
- Anticholinergic: Sedation, dry mouth, dizziness, blurry and dry eyes, urinary retention, constipation
- Palpitation, exacerbation of glaucoma, HTN, impotence |
|
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Term
| What antihistamines are ethanolamines/what are their properties? |
|
Definition
- Benadryl/Diphenhydramine
- Dimenhydrinate/Dramamine
**Antihistamines and antiemetics w/ significant sedation
Pregnancy category B |
|
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Term
| What drugs are piperizines/what are their effects? |
|
Definition
- Meclizine/Bonine or antivert
- Cyclizine/Marezine
** weaker antihistamines, good anti-emetics. Some sedation |
|
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Term
| What anti-emetic is a phenothiazine/what are it's properties? |
|
Definition
Promethazine/phenergan
Weak DA blockade as well as M1 and H1. Very sedating.
Pregnancy Category C - can be used. Not used in cancer. |
|
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Term
| What is the MoA of H2 receptor antagonists? |
|
Definition
Inhibit gastric acid secretion in the stomach by blocking H2 receptors in parietal cells.
**For Tx of PUD and GERD |
|
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Term
| What drugs are H2 receptor antagonists? |
|
Definition
- Cimetidine/Tagamet - weakly androgenic, many drug interactions w/ CYP450
- Famotidine/Pepcid
- Nizatidine/Axid - more potent than tagamet
- Ranitidine/Zantac - more potent than tagamet
**Efficacy is relatively the same |
|
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Term
| What are H2 antagonists only moderately effective? |
|
Definition
Ach and Gastrin will still stimulate acid secretion from parietal cells.
BUT better than PPIs at inhibiting NOCTURNAL acid
**Can use w/ PPIs. 5 days to reach benefit. |
|
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Term
| Is there tolerance to H2 antagonists? Why? |
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Definition
| Yes! Blockade of H2 receptors --> upregulation. An increased pH stimulates gastrin release to bring pH down --> increases # of parietal cells and EC cells. CCKb receptors upregulated |
|
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Term
| What drugs are proton pump inhibitors? |
|
Definition
- Dexlansoprazole - Dexilant. Used to be Kapidex, changed because resembled other names.
- Esomeprazole - Nexium
- Lansoprazole - Prevacid
- Omeprazole - Prilosec
- Pantoprazole - Protonix
- Rabeprazole - Aciphex |
|
|
Term
| What are the components of a Prevpac? |
|
Definition
Lansoprazole
Amoxicillin
Clarithromycin |
|
|
Term
|
Definition
Selective, irreversible inhibitors of the H/K ATPase pump
ALL prodrugs - conversion to active drug in active parietal cell |
|
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Term
| Why are PPIs more effective than H2 antagonists? |
|
Definition
PPIs work on the pump, while H2 antagonists inhibit only histamine - gastrin and Ach can still work. Have longer half lives, once daily dosing. NO tolerance.
BUT - are prodrugs, must be in the parietal cell and protected from the acidity of the stomach. |
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|
Term
|
Definition
Passes through the stomach unionized, becomes ionized in the canalicular space, binds to cysteine residues of the ATPase pump, activating the PPI
**Longer duration - more sites inhibited on pump. |
|
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Term
| What is unique about PPIs? |
|
Definition
- Half life of parent is short, active drug is longer (24 hours)
- ONLY bind to active pumps
- Slow onset, takes about 5 days to reach steady state due to generating 25% new pumps each day.
- Take WITH food, do not cause achlorhydria |
|
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Term
|
Definition
| No! Inhibits the final step, so a build up of any enzyme will not affect the ATPase pump. |
|
|
Term
|
Definition
- Infections of GI tract
- reduced calcium absorption, for which acid is necessary. Do not take for more than 7 years. |
|
|
Term
| What are the indications for PPIs? |
|
Definition
- PUD - with antibiotics
- NSAID induced ulcers
- GERD
- Erosive esophagitis
- Zollinger-Ellison Syndrome |
|
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Term
| What is the MoA of Zegerid/Omeprazole + Bicarb? |
|
Definition
- Bicarb increases pH, but this drug is unionized in alkaline pH. INCREASED bioavailability.
**ONLY PPI approved for GI bleed in critical patients. |
|
|
Term
| What is the purpose of Prevacid Naprapac? |
|
Definition
Lansoprazole + Naproxen
Reduces the risk of NSAID induced GI ulcers |
|
|
Term
| What is the MoA of Soraprazan? |
|
Definition
| Potassium-competitive acid blocker - bound to ATPase. Was superior to PPIs but d/c. |
|
|
Term
| Where are prostaglandins found in the GI tract? |
|
Definition
| In the lamina propria - endogenously in the mucosa. |
|
|
Term
| What is the MoA of prostaglandin analogs? |
|
Definition
- Cytotec/Misoprostol.
- A prodrug that converts to PgE1 --> prevents release of acid and protects mucosa. Major side effect - diarrhea
** Used w/ NSAIDs, not to treat PUD or GERD. DO NOT GIVE TO PREGNANT WOMEN! |
|
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Term
| What drug is a cytoprotective agent? What is it's MoA? |
|
Definition
- Sucralfate/Carafate - Looks for the exposed surface of injured tissue, protecting it from acid and allowing healing.
**Does not affect acid secretion.
- May inhibit pepsin, release PGs. For ulcers or GERD |
|
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Term
| What is the MoA/uses for antispasmotic agents? |
|
Definition
- For GI spasms and diarrhea associated with IBS
- M3 antagonists. Bentyl also blocks BK and Histamine.
- Anticholinergic side effects --> Mydriasis/glaucoma |
|
|
Term
| What drugs are anti-spasmotic agents for IBS-D treatment? |
|
Definition
- Dicyclomine/Bentyl
- Hyoscamine/Levsin
- Chlordiazopoxide & Clidinium/Librax |
|
|
Term
| What are the effects of trans-scop? |
|
Definition
M1 antagonist (not histamine) for motion sickness, post-op, and opioid N/V. Anti-cholinergic side effects.
**Blocks M1 in the NTS and vestibular apparatus |
|
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Term
| What are the effects of blocking D2 receptors? |
|
Definition
- Increase Ach presynaptically
- Increase smooth muscle contraction
- Contract LES - decreased reflux
- Diarrhea
- Reduced N/V
**Pro-kinetic - increased motility. remember dopaminergic are inhibitory neurons. Blocking the block signal! |
|
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Term
| How does blocking D2 affect the LES? |
|
Definition
- LES is abnormally relaxed in GERD due to VIP or NO
- Block D2 - Ach increases - LES constricts |
|
|
Term
| What is the MoA of prochlorperazine/Compazine? |
|
Definition
- blocks DA2 in the CTZ and NTS
- Treatment of N/V from post-op and cancer -- can be more effective than phenergan.
**EPS side effects |
|
|
Term
| How could haloperidol/Haldol work for N/V, and why isn't it used? |
|
Definition
- DA2 antagonism - increases GI motility
- Not used due to EPS side effects - can be PRONOUNCED
- Increases prolactin - gynecomastia and galactorrhea |
|
|
Term
| What drug was a 5-HT4 agonist? |
|
Definition
- Zelnorm
- Was used to treat IBS-C. Withdrawn due to CV effects.
- Increases Ach - decreases HR and blood flow --> ischemia |
|
|
Term
| What are the effects of metoclopramide/Reglan? |
|
Definition
- DA2 antagonist - increase stomach and small intestine motility
- 5-HT 4 receptor agonist - Ach release
- Muscarinic agonist
- DA2 antagonist in CTZ/NTS
**Used for GERD, Diabetic gastroparesis, GI obstruction
**AE: SEDATION, EPS, prolactin. May result in tardive dyskinesia |
|
|
Term
| What drug can act as a motilin agonist? |
|
Definition
|
|
Term
|
Definition
5-HT3 receptor antagonists for IBS-D and N/V.
**Don't use agonists b/c would agonize everywhere
Most are indicated for N/V, 1st stage CINV, and pregnancy N/V |
|
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Term
| What drugs are Setrons/5-HT3 antagonists? |
|
Definition
- Ondansetron/Zofran
- Granisetron/Kytril
- Palonosetron/Aloxi
- Dolasetron/Anzemet
- Alosetron/Lotronox - only used for severe IBS-D. Can produce OBSTRUCTIVE constipation. |
|
|
Term
| What is the MoA of Setrons? |
|
Definition
- IBS - block sensory nerve and beginning of cholinergic nerve, decreasing motility
- Blocking the 5-HT3 channel in the NTS/CTZ |
|
|
Term
| What are the stages of CINV that can be treated with medication? |
|
Definition
1) acute CINV - withing first 24 hours, SEROTONIN related --> Setron Tx
2) Delayed CINV - 16-24 hours after chemo, can last 5 days. SUBSTANCE P related. |
|
|
Term
| What is the MoA for Aprepitant/Emend |
|
Definition
- Blocks NK1, the receptor for Sub P in the CTZ/NTS. Indicated for Delayed CINV
**hiccups |
|
|
Term
| How are steroids used to treat N/V? |
|
Definition
Dexamethasone is used for Tx w/ Setrons, Reglan, and Emend for CINV and PONV
HIGHER doses than to treat inflammation |
|
|
Term
| What is the MoA of Marinol/dronabinol? |
|
Definition
| A cannabinoid that decreases the release of Ach, decreasing GI motility and inhibiting Ach in the CTZ |
|
|
Term
| What is the MoA for trimethobenzamide/Tigan and emetrol? |
|
Definition
- Tigan - CTZ for PONV and gastroenteritis
- Emetrol - sugars produce an osmotic effect, inhibiting motility for the stomach flu. |
|
|
Term
| What is Octreotide/Sandostatin? |
|
Definition
A somatostatin analog that inhibits Adenylyl cyclase - inhibits GI hormones and GI organs including gastrin, CCK, secretin, motilin, serotonin, VIP
**Tx of portal HTN and esophageal varices
AE: gallstones, abdominal distention, hyperglycemia, constipation |
|
|
Term
| What must be present in IBD for pathology? |
|
Definition
NORMAL FLORA!
Crohn's - Cellular immunity
UC - Humoral immunity
**Defects in epithelium and mucosa |
|
|
Term
| What drugs are used to treat IBD and how do they work? |
|
Definition
- Azulfidine/Sulfasalazine - divides into sulfapyridine (no value) and 5-ASA(Mesalamine). Mesalamine inhibits cytokines, LTB4 --> no influx of PMNs. Incr adenosine. AEs due to sulfapyradine: GI
- Olsalazine/Dipentum - 2 5-ASA (Mesalamine) compounds
- Balsalazide/Colazal - huge capsules
- Mesalamine/ Pentasa or Asacol (EC capsules), Rowasa enema, Canasa suppository
***Mesalamine cmpds only indicated for ulcerative colitis |
|
|
Term
| What are the three types of patients w/ UC/CD when you give steroids? |
|
Definition
- Responsive - taper dose and remain in remission
- Dependent - relapse on D/C
- Unresponsive - No response
**Response seen in 1-2 weeks |
|
|
Term
| How do steroids help in IBD? |
|
Definition
Anti-inflammatory mechanism - decrease PMNs, inhibit PlA --> no PGs, decrease adhesion, DECREASE CYTOKINES
**Cortisol/Steroids upregulates IkB, inhibiting production of NFkB OR blocks ability to bind to DNA |
|
|
Term
| What steroids are used to treat IBD? |
|
Definition
- Hydrocortisone/Cortenema for UC
- Prednisone/Deltasone
- Methylprednisolone/Medrol
- Budesonide/Entocort EC - much less systemic effects than prednisone. Can be inhaled. |
|
|
Term
|
Definition
- Azathioprine/Imuran
- 6-Mercaptopurine/Purinethol
- Used to treat CD. Affects purine metabolism by replacing w/ 6-MP --> no normal cell division. A purine ANALOG.
** Decreased T and B cell activation, takes 2-3 months to work.. AE on the liver |
|
|
Term
| What is the MoA of Mycophenolate/Cellcept? |
|
Definition
| Inhibits IMP dehydrogenase, preventing GMP formation --> decrease in T and B cell formation. Less toxic than AZA |
|
|
Term
| How is MTX used to treat IBD? |
|
Definition
Doses for Crohn's - 15-25mg/week. High dose MTX inhibits DHFR - immunomodular activity.
***Decrease T and B cells. Causes liver toxicity and severe fatigue, myelosuppression |
|
|
Term
| What is the MoA of cyclosporine/Sandimmune? |
|
Definition
- A calcineurin inhibitor for the tx of severe UC when not responding to other therapy. Not for CD, only for short term.
**Binds to cyclophilin, the complex inhibits calcineurin. IL-2 cannot activate T cells.
***Major kidney toxicity, ischemia, gingival hyperplasia |
|
|
Term
| What are the effects of TNF? |
|
Definition
- Release of inflammatory cytokines
- prostaglandin release
- Bone resorption
- MMPs/cartilage breakdown
- Leukocyte accumulation
- Chemokine release |
|
|
Term
| What drugs are TNF antagonists? |
|
Definition
- Infliximab/Remicade - Works on both CD and UC
- Adalimumab/Humira
- Golimumab/Simponi
- Etanercept/Enbrel - does not work in IBD
- Certolizumab/Cimzia
**Work by neutralizing sTNF, TNF cannot bind to receptor |
|
|
Term
| How do you reduce the immunogenicity seen with TNF inhibits? |
|
Definition
|
|
Term
| What is Natalizumab/Tysabri? |
|
Definition
Targets integrins (alpha subunit), works in CD.
Prevents interaction of ICAM/VCAM.
**Increased #'s of PMNs in vascular space due to no migration - EXCEPT neutrophils |
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