GI Pharmacology Flashcards
1
Q
What is the product/function of Parietal Cells?
A
HCl for Protein Digestion, Sterilization, and Nutrient Absorption
2
Q
What is the product/function of Superficial Epithelial/Neck Cells?
A
Mucus and Bicarbonate for gastroprotection
3
Q
What is the product/function of ECL cells?
A
Histamine, which promotes HCl secretion
4
Q
What is the product/function of G cells?
A
Gastrin, which promotes HCl secretion
5
Q
What are the key regulatory of paracrine, endocrine, and neuronal acid seretion?
A
Paracrine –> Histamine
Endocrine –> Gastrin
Neuronal/Neurocrine –> Acetylcholine
6
Q
What are the Direct/Indirect regulators of acid secretion from the parietal cells?
A
Gastrin and Acetylcholine
Directly stimulate the Parietal Cell
Indirectly stimulate the ECL Cells
7
Q
What are the 3 key roles of prostaglandins?
A
- Mucus and Bicarbonate secretion
- Suppression of HCL secretion
- Increase gastric blood flow
8
Q
What type of ulcer has the greatest frequency?
A
Duodenal Ulcers
9
Q
Stress Ulcer (Definition)
A
Peptic ulcer caused by illness, systemic trauma, neuronal injury, emotions
10
Q
Cushing Ulcer (Definition)
A
Stress ulcer associated with Head Trauma or Brain Surgery
11
Q
Ischemic Ulcer (Definition)
A
Ulcer caused by hemorrhage, multi-system trauma, severe burns (Curling ulcer), heart failure, sepsis
12
Q
What are the two most common causes of ulcers in the U.S.?
A
NSAIDs (COX inhibition) and H. pylori
13
Q
Symptoms of an ulcer
A
1. Abdominal Pain (particularly after a meal)
- Nausea
- Vomiting, vomiting blood
- Bloody, tarry school
- Indigestion
- Weight loss
- Fatigue
14
Q
Antacids (Therapeutic Goals)
A
Neutralize the acid in the stomach to a pH > 4
End products: Salt, Water (sometimes CO2)
No Target Receptor
15
Q
Sodium Bicarbonate - NaHCO3 (Rate of Reactivity, Specific Adverse Effects)
A
Rate of Reactivity: FAST
Specific Adverse Effects: Metabolic acidosis, excessive NaCl absorption, Gas/Bloating (CO2__)
16
Q
Calcium Carbonate - CaCO3 (Duration of Action, Rate of Reactivity, Specific Adverse Effects)
A
DoA: 1-2 hours
RoR: MODERATE
SAE: Acid Rebound (Feed forward mechanism causing INCREASED acid production after long-term use), Gas/Bloating (CO2), Hypercalcemia (large doses), Hypophosphatemia (Rare)
17
Q
Magnesium Hydroxide - Mg(OH)2 (Rate of Reactivity, Specific Adverse Effects)
A
RoR: SLOW
Specific Adverse Effects: Osmotic Diarrhea (due to excess Salt in intestines), Hypermagnesemia (large doses over an extended period of time)
18
Q
Aluminum Hydroxide - Al(OH)2 (Rate of Reactivity, Specific Adverse Effects)
A
RoR: SLOW
SAE: Constipation (slows down smooth muscle peristalsis), Aluminum toxicity (impaired RENAL FUNCTION), Hypophosphatemia, Bone Resorption, Hypercacelmia
19
Q
Duration of Action of Antacids
A
Very SHORT (1-2 Hours)
***Have to take them very frequently, therefore, will see a Decrease in Compliance
20
Q
Two common Adverse Effects of Anatacids
A
- Reduced Drug Bioavailability
- Enteric Infection
21
Q
Therapeutic Uses of Antacids
A
GERD, Peptic Ulcers, Dyspepsia
22
Q
Anatacids are used as adjunctive therapy with____
A
PPIs
23
Q
Antacids are equally efficacious as _____ at treating GERD (heal rate = ___%) and Peptic Ulcers (heal rate = ___%)
A
Antacids are equally efficacious as H2-Receptor Antagonists at treating GERD (heal rate = 50%) and Peptic Ulcers (heal rate = 80%)
24
Q
H2-receptor Antagonists
- Type of inhibition/Selectivity
- What is blocked?
A
- Competitive and Highly Selective
- Blocks Indirect action of Gastrin and Acetylcholine; Does not block direct action of Gastrin and Acetylcholine
25
What do all **H2-receptor Antagonist** names end in?
They all end in **-tidine**
26
**H2-receptor Antagonists**
Drug Names (4 of them)
1. Cime**tidine** (Tagemet)
2. Rani**tidine** (Zantac)
3. Niza**tidine** (Axid)
4. Famo**tidine** (Pepcid)
27
**H2-receptor Antagonists**
1. Duration of Action
2. Common Adverse Effects
**DoA:** 10 hours or 6 hours OTC
**CAE:** _Headache_, diarrhea, fatigue, constipation, infection, drug kinetics, bradycardia (IV), hypotension (IV)
28
**H2-receptor Antagonists**
1. Specific Considerations for **Cimetidine**
1. **CNS Effects** (confusion, hallucinations, agitation)
2. **Endocrine Effects** (inhibition of *androgen receptors*, inhibition of *estradiol metabolism*, increase *prolactin levels*)
3. **Inhibition of _hepatic CYB metabolism_** (Inhibits **cytochrome P450 activity**, which leads to high potential of **drug-drug interactions**)
29
**H2-receptor Antagonists**
1. Key Difference from Antacids
2. Key Advantage compared to Antacids
1. Must be **absorbed into the BLOODSTREAM** to take effect
2. Have to be **administered LESS often**
(Equally efficacious as antacids at treating **GERD** and **Peptic Ulcers** and can additionally treat Gastritis)
30
**Proton Pump Inhibitors (PPIs)**
1. Key Advantage over H2-receptor Antagonists
1. Antagonizes the proton pump, so is able to **_block both_** **Direct and Indirect** actions of ACh, Histamine, and Gastrin
31
**Proton Pump Inhibitors (PPIs)**
1. Mechanism of Action (5 things)
1. Activated by **low pH**
2. Acid-labile drug is **absorbed into the BLOODSTREAM** by GI
3. Concentrates at the site of action (**Parietal Cells**)
4. **Irreversibly binds/inhibits** proton pump
5. Activation of pump requires new synthesis
32
What do all **Proton Pump Inhibitors** end in?
All **PPIs** end in **-prazole**
33
**Proton Pump Inhibitors (PPIs)**
1. Drug Names
1. Ome**prazole** (Prilosec)
2. Lanso**prazole** (Prevacid)
3. Rabe**prazole** (Aciphex)
4. Esome**prazole** (Nexium)
5. Panto**prazole** (Protonix)
34
**Proton Pump Inhibitors (PPIs)**
1. Duration of Action
**DoA:** 24 hours (takes _3-4 days_ of dosing to reach _max effect_)
35
**Proton Pump Inhibitors (PPIs)**
1. Common Adverse Effects
\*\*\*Extremely **SAFE**\*\*\*
1. Decreased drug bioavailability
2. Diarrhea, headache, abdominal pain (1-5%)
3. Decreased nutrient absorption (Vitamin B12, Iron, Calcium, Zinc)
4. Enteric and Respiratory infections
36
Why does it take 3-4 days for PPIs to reach maximum effect?
It takes 3-4 days for the body to exhaust its supply of proton pumps, which are waiting in the tubulovesicular network to be brought to the apical surface and inactivated by the PPI
\*\*\*This is why you initially **supplement w/ Antacids** or **H2-receptor Antagonists**\*\*\*
37
**Proton Pump Inhibitors (PPIs)**
1. Therapeutic Uses
GERD
Peptic Ulcers
Dyspepsia
Gastritis
Hypersecretory Diseases
NSAID-associated Ulcers
H. pylori-associated Ulcers
38
**Proton Pump Inhibitors (PPIs)**
1. Effectiveness
1. **Most Efficacious Inhibitors**
(GERD Heal Rate = 90%)
(Peptic Ulcer Heal Rate = 90%)
39
**Muscoal Protective Agents**
1. Drug Names
Sucralfate (Carafate)
Misoprostol (Cytotec)
Bismuth subsalicylate (Pepto-Bismol)
40
**Mucosal Protective Agents**
1. Mechanism of Action
**Sucralfate** and **Bismuth subsalicylate** both create a _physical barrier_ and _stimulate mucus and HCO3-_ secretion from the gastric mucosa
**Misoprostol** (a prostaglandin derivative) _stimulates mucus and HCO3-_ secretion from the gastric mucosa, but DOES NOT form a physical barrier
41
**Mucosal Protective Agents**
1. Duration of Action
6 hours
42
**Mucosal Protective Agents**
1. Common Adverse Effects - **Sucralfate**
2. Other Adverse Effects
1. Constipation, Impaired Drug Absorption
2. Caution w/ _Renal Insufficient Patients_
\*\*\*Constipation (inhibition of smooth muscle contraction) and Renal Toxicity due to presence of **Aluminum**\*\*\*
43
**Mucosal Protective Agents**
1. Common Adverse Effects - **Misoprostol**
2. Other Adverse Effects
1. Cramping, Diarrhea
2. Abortificient (stimulates smooth muscle contractions, so could induce uterine contractions)
44
**Mucosal Protective Agents**
1. Common Adverse Effects - **Bismuth subsalicylate**
2. Other Adverse Effects
1. Blackening of Stool and Tongue
2. High doses - _Salicylate Toxicity_
45
Reasons to use **Mucosal Protective Agents**
1. Generalyl **2nd line agents** to PPIs
2. **Sucralfate** --\> prevents stress-related bleeding when you _DO NOT want to prevent acid secretion_ (hospitalized patient who is at risk for infection)
3. **Misoprostol** --\> _NSAID-associated ulcers_
4. **Bismuth subsalicylate** --\> _H. pylori_-associated ulcers, _Travelers diarrhea_, _Dyspepsia_ (indigestion)
46
**H. pylori** **and Gastric Ulcers**
1. 70 to 90% of patients with ________ are infected with H. pylori
2. **Transmission** of H. pylori
70 to 90% of patients with **Gastric or Duodenal Ulcers** are infected with H. pylori
2. **_Orally_** via **Fecal Matter** (tainted water) or transmitted from stomach to mouth from **GERD or belching**
47
**H. pylori and Gastric Ulcers**
1. **Treatment** of H. pylori (Triple Theory)
2. Key of Treatment
1. PPI --\> Clarithromycin --\> Amoxicillin
(Can used _Metronidazole_ in place of Amoxicillin if there is a penicillin allergy)
2. **Two antibiotics** given due to the **high resistance of H.pylori** \*\*\*Know\*\*\*
MUST USE 3 drugs --\> suppress acid secretion and two antibiotics
Old Triple Theory (Bismuth subsalicylate, _Tetracycline_, Metronidazole)
Quadruple Therapy --\> New Triple Theory + Bismuth subsalicylte
48
Summary of Antacids, H2-receptor Antagonists, PPIs, and Mucosal Protective Agents
49
**Serotonin (5-HT)**
1. Function in the GI System
1. (Within the **Enteric Nervous System**) Stimulates **gastric motility** by inducing the release of **Ach** by neurons onto **GI smooth muscle**
50
**Acetylcholine**
1. Function in the GI System
2. Regulation
1. Binds to **Muscarinic (M3) receptors** and induces **conraction** of the **GI smooth muscle**
2. Concentrations regulated at _neuromuscular junction_ by **Acetylcholine esterase** (AchE)
51
What is the function of **Dopamine (D2) receptors** in the GI system?
**Pre-synaptic** receptors involved in regulating the release of neurotransmitters:
**Stimulate D2 receptor** --\> **_DECREASED**_ acetylcholine production --\> _**DECREASED_** **motility**/neuronal firing/smooth muscle contraction
52
What is the function of the **Motilin Receptor (MR)** in the GI system?
Motilin is a hormone that is released and **promotes motility in the UPPER GI tract (stomach, duodenum)**
\*\*\*Has less effect as you move lower
53
**Metoclopramide (Reglan)**
1. Mechanism of Action
2. Used to Treat
3. Adverse Effects
**MoA:** D2 Antagonist
\*\*\*Promotes **_Motility_**\*\*\*
**Use:** GERD, Impaired Gastric Emptying, Dyspepsia, Antiemetic
**AE:** CNS (restlessness, drowsiness, insomnia, anxiety), \*\*\*_Altered Motor Function (Parkinsonian Symptoms)_\*\*\* due to blocking of Dopamine
54
**Bethanechol (Urecholine)**
1. Mechanism of Action
2. Used to Treat
3. Adverse Effects
**MoA:** M3 Agonist
\*\*\*Promotes **_Motility_**\*\*\*
**Use:** GERD, Gastroparesis
**AE:** Cholinergic side effects
55
**Neostigmine (Prostigmin)**
1. Mechanism of Action
2. Used to Treat
3. Adverse Effects
**MoA:** AchE inhibitor
\*\*\*Promotes **_Motility_**\*\*\*
**Use:** Non-obstructive: urinary retation and abdominal distension
**AE:** Cholinergic side effects
56
**Erythromycin (Erythrocin)**
1. Mechanism of Action
2. Used to Treat
3. Adverse Effects
**MoA:** Motilin Receptor Agonist
\*\*\*Promotes **_Motility_**\*\*\*
**Use:** Gastroparesis
**AE:** Erythromycin-mediated side effects (alterations of the normal gut flora)
57
**Laxatives (Bulk-Forming)**
**e.g. Wheat Bran, Psyllium (Konsyl-D, Metamucil), Methycellulose (Citrucel), Polycarbophil**
1. Mechanism of Action
1. **Plant cell walls (fiber)** that are RESISTANT to digestion by GI system --\> forms **gel-like substance** that pushes on colonic wall and leads to **mass peristaltic contractions**
\*\*\*Take with _a lot of water_\*\*\*
58
**Laxatives (Stool Softener)**
**e.g. Glycerin and Mineral Oil**
1. Mechanism of Action
1. Two Theories:
a. Penetration of water/lipids into the stool
b. "coats" the stool with oil
59
**Laxatives (Osmotic Agents)**
**e.g. Magnesium Hydroxide (Milk of Magnesia), Sorbitol, Lactulose, Polyethylene Glycol (PEG)**
1. Mechanism of Action
1. **Non-absorbable s****ugars and salts** used to alter the osmotic pressure and pull water into the colon
60
**Laxatives (Stimulant)**
**e.g. Anthraquinone derivatives (Aloe & Senna), Castor Oil, Diphenylmethane derivatives (Phenophthalein)**
1. Mechanism of Action
1. Three Theories:
a. Stimulation of the _ENS_
b. Inducing a _leaky mucosa_
c. _Inhibiting sodium uptake_ by the gut
61
**Methylcellulose (Citrucel)**
1. Mechanism of Action
2. Absorption
3. Use
4. Adverse Effects
**MoA:** BULK-FORMING; Fiber --\> adds bulk and retains water
**Absorption:** *Poor*
**Use:** *Constipation, Minimize Straining, Prior to Surgical and Endoscopic Procedures*
**AE:** Gas/Bloating
62
**Glycerin (Colace)**
1. Mechanism of Action
2. Absorption
3. Use
4. Adverse Effects
**MoA:** SURFACTANT; Coats and Penetrates fecal material
**Absorption:** *Poor*
**Use:** *Constipation, Minimize Straining, Prior to Surgical/Endoscopic Procedures*
**AE:** Nutrient Malabsorption
63
**Laculose (Enulose)**
1. Mechanism of Action
2. Absorption
3. Use
4. Adverse Effects
**MoA:** OSMOTIC; Change osmotic pressure
**Absorption:** *Poor*
**Use:** *Constipation, Minimize Straining, Prior to Surgical/Endoscopic Procedures*
**AE:** Gas, Electrolyte Flux
64
**Senna (Ex-Lax)**
1. Mechanism of Action
2. Absorption
3. Use
4. Adverse Effects
**MoA:** STIMULANT; Stimulate ENS
**Absorption:** *Poor*
**Use:** *Constipatio, Minimize Straining, Prior to Surgical/Endoscopic Procedures*
**AE:** GI irritation
65
**Tegaserod (Zelnorm)**
1. Mechanism of Action
2. Absorption
3. Use
4. Adverse Effects
**MoA:** SEROTONIN AGONIST
\*\*\*STIMULATES\*\*\*
Serotonin (5-HT) stimulates **pre-synaptic** **5-HT4 receptors** --\> release of NT (e.g. **Ach**) in ENS --\> **_INCREASED motility**_ and _**DECREASED**_ _**pain_** (via decreased firing of extrinsic sensory neurons to the CNS)
**Absorption**: 10%
**Use:** _Chronic_ idiopathic constipation
**AE:** GI, CV \*\*\*Not available for general use - a **LAST DITCH EFFORT TYPE OF DRUG**\*\*\*
66
**Lubiprostone (Amitiza)**
1. Mechanism of Action
2. Absorption
3. Use
4. Adverse Effects
**MoA:** CHLORIDE CHANNEL ACTIVATOR
Activates **Chloride Ion Channel 2 (CIC-2)** --\> **_INCREASED**_ luminal concentration of _**chloride in the gut_** --\> accumulation of sodium and water --\> motility
**Absorption:** Poor \*\*\*Accesses the **apical/lumenal side**, is NOT absorbed into the bloodsteram\*\*\*
**AE:** Nausea/Vomiting, Diarrhea
67
**Methylnaltrexone (Relistor)**
1. Mechanism of Action
2. Absorption
3. Use
4. Adverse Effects
**MoA:** Mu-OPIOID RECEPTOR ANTAGONIST
**Blocks _PERIPHERAL_ Mu-opioid receptors** (normally activated by opioids (e.g. morphine) and lead to DELAYED intestinal motility) --\> prevents pain treatment-associated/post-surgical constipation
**Absorption:** \*\*\***Poor CNS penetration** allows pain management and prevention of constipation
**Use:** Opioid-induced constipation during palliative care
**AE:** Abdominal pain, Flatulence, Nausea, Diarrhea
68
**Alvimopan (Entereg)**
1. Mechanism of Action
2. Absorption
3. Use
4. Adverse Effects
**MoA:** Mu-OPIOID RECEPTOR ANTAGONIST
**Blocks _PERIPHERAL_ Mu-opioid receptors** (normally activated by opioids (e.g. morphine) and lead to DELAYED intestinal motility) --\> prevents pain treatment-associated/post-surgical constipation
**Absorption:** **\*\*\*Poor CNS penetration** allows for pain management and prevention of constipation
**Use:** Postoperative **_Ileus_** in hospitalized patients with bowel resection
**AE:** GI similar to _Methylnaltrexone_
\*\*\*Can cause **_Myocardial Infarction_** (so only short-term use, 7 days or less)
69
**Antidiarrheal Agents (Opioids)**
1. Mechanism of Action
Frequently administered **Orally**
**MoA:** only have **_peripheral effects_** (do not cross BBB/do not enter CNS) to minimize abuse potential
Alter **GI Smooth Muscle by:**
a. Decreasing peristalsic contractions
b. Increasing segmental (mixing) contractions
c. Increasing internal anal sphincter tone
d. Decreasing perception of GI distension
70
**Antidiarrheal Agents (Bismuth Subsalicylate)**
1. Mechanism of Action
Administered **Orally**
**MoA:** primarily mediated by **salicylate inhibition of _prostaglandin synthesis_** \*\*\***IN CONTRAST** to what is occurring in the **STOMACH**
Also _Bismuth_ compounds _absorb bacterial toxins_
71
**Antidiarrheal Agents (Bile Salt Binding Resins)**
1. Mechanism of Action
**MoA:** _reduce the osmotic pressure_ in the lumen of the large intestine by **binding the unabsorbed bile salts**
72
**Antidiarrheal Agents (Octreotide)**
1. Mechanism of Action
Is a synthetic peptide (somatostatin analogue) so it has to be given **IV** or **subcutaneously**
**MoA:** activates **somatostatin receptor**, increasing fluid absorption and _decreasing motility_
73
**Loperamide (Imodium)**
1. Mechanism of Action
2. Use
3. Adverse Effects
**MoA:** OPIOID AGONIST
**Use:** Diarrhea (IBS)
**AE:** Constipation (VERY SAFE)
74
**Diphenoxylate (Lomotil)**
1. Mechanism of Action
2. Use
3. Adverse Effects
**MoA:** OPIOID AGONIST
**Use:** Diarrhea
**AE:** CNS Effects, Atropine Effects
\*\*\*Given with **Atropine** to miniize abuse\*\*\*
75
**Bismuth subsalicylate (Pepto-Bismol)**
1. Mechanism of Action
2. Use
3. Adverse Effects
**MoA:** _Inhibit PG Synthesis_ (Intenstinal), Absorb Toxins
**Use:** Non-specific diarrhea, Travelers diarrhea
**AE:** Salicylate Toxicity
76
**Cholestyramine (Prevalite)**
1. Mechanism of Action
2. Use
3. Adverse Effects
**MoA:** Bind BILE ACIDS and SALTS
**Use:** Impaired bile salt absorption-mediated diarrhea
**AE:** Bloating, flatus, constipation; Fecal impaction; _Impaired fat absorption/fat soluble vitamin absorption_
77
**Octreotide (Sandostatin)**
1. Mechanism of Action
2. Use
3. Adverse Effects
**MoA:** Somatostatin receptor agonist
**Use:** Secretory diarrhea
**AE:** Impaired pancreatic secretion, _Decreased GI motility (nausea, pain)_, Decreased gallbladder contraction, Glucose hemostasis
78
What are the key receptors that regulate an emetic response in the **Vestibular system?**
Histamine (H1) and Muscarinic (M1)
79
What are the **receptors** that are involved in an **emetic response**? (7 of them)
Histamine (H1)
Muscarinic (M1)
Dopamine (D2)
Neurokinin (NK1)
Serotonin (5-HT)
Chemoreceptors
Mechanoreceptors
80
**Ondansetron (Zofran)**
1. Mechanism of Action
2. Adverse Effects
**MoA:** 5-HT3 (Serotonin) Antagonist
**AE:** Headache, Dizziness, Constipation, _Prolonged QT Interval_
81
**Scopolamine (Transderm Scop)**
1. Mechanism of Action
2. Adverse Effects
3. Use
**MoA:** _M1_ Antagonist (Vestibular System)
**AE:** Antimuscarinic Effects
**Use:** _Motion Sickness_
\*\*\***Patch behind the ear**\*\*\*
82
**Metocloramide (Octamide)**
**MoA:** D2 Antagonist
**AE:** Extrapyramidal (**_Parkinsonian Symptoms_**)
83
**Dimenhydrinate (Dramamine)**
1. Mechanism of Action
2. Adverse Effects
3. Use
**MoA:** _H1_ Antagonist (Vestibular System)
**AE:** Drowsiness
**Use:** _Motion Sickness_
84
**Aprepitant (Emend)**
1. Mechanism of Action
2. Adverse Effects
**MoA:** NK1 Antagonist
**AE:** Fatigue, Dizziness, Diarrhea, **_CYP3A4 Interactions_** (leads to **drug-drug interactions**)
85
**Prochlorperazine (Compro)**
1. Mechanism of Action
2. Adverse Effects
**MoA:** M1D2H1 Antagonist (\*\*\***Last Resort**\*\*\*(severe conditions)--\> knocks out all receptors)
**AE:** Extrapyramidal, Drowsiness, Anticholinergic
86
**Lorazepam (Ativan)**
1. Mechanism of Action
2. Adverse Effects
3. Uses
**MoA:** GABA _Agonist_
**AE:** Drowsiness
**Uses:** _Indirect Antiemetic_, Anxiety, Chemotherapy
87
**Nabilone (Cesamet)**
1. Mechanism of Action
2. Adverse Effects
**MoA:** Cannabinoid _Agonist_
**Uses:** _Indirect Antiemetic_
**AE:** Dysphoria, Sedation, Increased Appetite
88
**Dexamethasone**
1. Mechanism of Action
2. Adverse Effects
3. Uses
**MoA:** Glucocorticoid _Agonist_ (**LAST RESORT** (Extreme situations))
**AE:** Weight Gain, Water Retention, Other corticosteroid effects
**Uses:** _Indirect Antiemetic_, Chemotherapy, Post-operative
\*\*\***Increases** the effectiveness of **5-HT antagonists**\*\*\*
89
How do **aminosolicylates** work?
**Topical**
\*\*\*DO NOT want systemic absorption - will NOT work\*\*\*
90
**Irritable Bowel Syndrome (IBS)**
1. Definition
2. Cause
3. Treatments
1. **Idiopathic chronic relapsing disorder** charactereized by abdominal discomfort (**pain, bloating, distension, or cramps**) in association with alterations in bowel habits (**diarrhea, constipation, or both**)
**Cause:** Uncertain
**Tx:** _Loperamide_ (reduces diarrhea), _Osmotic laxatives_ (relieves constipation), as well as _tricyclic antidepressants_ and _antispasmodics/antimuscarinics_ (relieves pain)
91
**Tegaserod (Zelnorm)** vs. **Alosetron (Lotrenex)**
1. Mechanism of Action
2. Use
3. Adverse Effects
**Tegaserod (Zelnorm)**
**MoA:** 5-HT**_4_** partial **_agonist_**
**Use:** IBS-**_constipation_** predominant
**AE:** GI (_pain_, dyspepsia, flatulence, nausea/vomiting, diarrhea), ***_CV (0.01%, MI and Stroke)_*** **\*\*\*Not available for general use - EMERGENCY only\*\*\***
**Alosetron (Lotrenex)**
**MoA:** 5-HT**_3 *ANT*agonist_**
**Use:** IBS-**_diarrhea_** predominant (works in **WOMEN only**)
**AE:** Constipation (29%), \*\*\****_Ischemic colitis (fatal)_***\*\*\*
92
**Inflammatory Bowel Disease (IBD)**
1. Key thing to think about
2. Two specific diseases
1. **INFLAMMATION**
2. _Crohn's Disease_ and _Ulcerative Colitis_
93
**Crohn's Disease** vs. **Ulcerative Colitis**
**Crohn's Disease:** an idiopathic inflammatory disorder that affects **_ANY PART_** of the GI tract
**Ulcerative Colitis:** a chronic inflammatory disease that causes ulcerations of the **_COLONIC/DISTAL_** mucosa of the GI tract
94
**Aminosalicylates (ASA)**
1. Mechanism of Action
**MoA:**
1. Inhibition of _COX_ production of _prostaglandins_
2. Interfere with _inflammatory cytokine production_ (i.e. IL-1)
3. Inhibit _NF-KB signaling_
95
How do **5-aminosalicylic acid (5-ASA)** compounds work?
They are administered **TOPICALLY** to the GI site; they _will not work_ if they are absorbed into the bloodstream
-Requires use of Proprietary Release Formulas (Jejunum, Ileum), Chemical Binding (Proximal Colon), and High Concentration Enemas (Distal Colon and Rectum)
96
Which two **5-aminosalicylic acid (5-ASA)** drugs are used to treat **Inflammatory Bowel Disease (IBD)**?
Sulfalazine
Mesalamine
97
Which two **Glucocorticoids** treat **IBD**, and what is their general mechanism of action?
Prednisone
Hydrocortisone
**MoA:** Suppress _inflammatory cytokines, signaling, etc._
98
How do **antimetabolites** work to treat **IBD**, and what is an example of one?
**MoA:** Suppress _cell proliferation_ of _immune cells_
**Example:** Methotrexate
99
**Anti-TNFa Therapy**
1. Mechanism of Action
2. Example
**MoA:** _TNFa monoclonal antibody_ (a protein) is administered IV or subQ --\> **binds and sequesters TNFa** --\> Inhibit TNFa-mediated immune response
**Example:** Infliximab
100
**Sulfsalazine (Azulfidine)**
1. Type of Agent
2. Use
3. Adverse Effects
**Agent:** Amicosalicylate (ASA)
**Use:** 1st line agent for _mild to_ _moderate_ ulcerative colitis
**AE:** Nausea, GI upset, headache, arthralgia, myalgia, bone marrow suppression, malaise (40% of patients cannot tolerate)
101
**Mesalamine (Pentasa)**
1. Type of Agent
2. Use
3. Adverse Effects
**Agent:** Aminosalicylate (ASA)
**Use:** 1st line agent for _mild to moderate_ ulcerative colitis
**AE:** Headache, Dizzines, Abdominal Pain
102
**Prednisone (Predone)**
1. Type of Agent
2. Use
3. Adverse Effects
**Agent:** Glucocorticoid (STEROID)
**Use:** _Moderate to Severe ***ACTIVE*** IBD_
**AE:** Glucocorticoid adverse effects
103
**Azathioprine (Azasan)**
1. Type of Agent
2. Use
3. Adverse Effects
**Agent:** Antimetabolite
**Use:** Maintenance of ***_REMISSION_*** of IBD (onset 17 weeks)
**AE:** Nausea, vomiting, bone marrow suppression
104
**Methotrexate (Rheumatrex)**
1. Type of Agent
2. Use
3. Adverse Effects
**Agent:** Antimetabolite
**Use:** Maintenance of ***_REMISSION_*** of Crohn's (onset 8-12 weeks)
**AE:** Low dose side effects uncommon, but include bone marrow depression and megaloblastic anemia
105
**Infliximab (Remicade****)**
1. Type of Agent
2. Use
3. Adverse Effects
**Agents:** Anti TNFa antibody
**Use:** Will look at 5-ASA compounds and Steroids **BEFORE LOOKING AT THIS**
Consider this when moving into the **Moderate to Severe IBD**
**AE:** Infection
