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1
Q

antimuscarinic agents

A 
MOA: Competitively inhibits autonomic, postganglionic cholinergic recptors= Decreased GI motility  and spasm 
Indication: Abd pain/spasm
hyoscyamine
dicyclomine
clindinium 
chlordiazepoxide
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2
Q

Opioid Agonists

A

DIARRHEA: interfere with peristalsis
Loperamide (first line therapy for microscopic colitis)
Diphenoxylate (atropine added)
Eluxadoline (IBS-D) **hepatic and pancreatic toxicity, risk of pancreatitis in pt’s without gallbladder, CNS related euphoria/dizzy/cognition

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3
Q

Eluxadoline

A

opioid agonist used for IBS-D
SE: GI sx, hepatic and pancreatic toxicity, pancreatitis increased risk in pt w/out gallbladder, CNS
Contraindicated: biliary tract obstruction, ETOH, h/o pancreatitis, sever hepatic impairment.

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4
Q

5-HT3 receptor antagonist (for diarrhea)

A

Alosetron
Selectively blocks GI based 5HT3 receptors
antagonism in GI modulates regulation of visceral pain, colonic transit, and GI secretions
Tx: Chronic severe IBS-D (women)
Contraindications:
GI obstruction, perforation, stricture, adhesion, toxic megacolon
diverticulitis, CD, UC
impaired intestinal circulation, thrombophlebitis, hypercoagulable states
severe constipation (D/c alosetron immediately)
SE: constipation, DYSPEPSIA, GERD, nv
ISCHEMIC COLITIS

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5
Q

Cl- channel inhibitor

A

DIARRHEA
Crofelemer (derived from tree sap)
inhibits Cl- secretion by blocking cAMP stimulated CFTER and Ca2+ activation of Cl- channels
leads to dec fluid secretion
**Indicated for noninfectious diarrhea in HIV/AIDS (on antiretroviral therapy)
SE: Abd distension, increased liver enzymes and bilirubin, infections

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6
Q

Peripheral opioid antagonist

A

CONSTIPATION
mu opioid receptor antagonists

Methylnaltrexone: tx: OPIOID INDUCED CONSTIPATION

Alvimopan: prevention of post-op ileus only** only for accelerating time to GI recovery following bowel resection surgery w/ primary anatomoses
-carries risk of MI

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7
Q

Alvimopan

A

mu opioid receptor antagonist
prevention of post-op ileus only** only for accelerating time to GI recovery following bowel resection surgery w/ primary anatomoses
-carries risk of MI

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8
Q

Methylnaltrexone

A

Mu opioid receptor antagonist

tx: OPIOID INDUCED CONSTIPATION

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9
Q

Linaclotide

A

selective guanylate cyclase-c (GC-C) agonist
-binds GC-C on lumen of intestinal epithelia and increased IC/EC [cGMP] which + secretion of Cl-/HCO3- into lumen via activation of CFTER
results in inc intestinal fluid and peristalsis
tx: IBS-C and chronic idiopathic CONSTIPATION
SE: diarrhea, GERD, dyspepsia, n/v

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10
Q

Lubiprostone

A

selective Cl- channel activator
a PGE-1 derivative-> inc intestinal fluid by + GI specific Cl- channels (ClC2)
indicated for IBS-C, chronic idiopathic CONSTIPATION, and opioid induced constipation
SE: n/dyspepsia, dizzy

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11
Q

stimulants (irritants)

A 
\+ peristalsis, irritant to enterocytes
bisacodyl
castor oil (recinoleic acid)
glycerin (precolonoscopy, irritant, osmotic and lubricant)
senna (urine discoloration)
Na+
Picosulfate

**Contraindicated in GI obstruction/ILEUS/Impaction

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12
Q

Osmotics

A

Lactulose (also used for sever liver dz(hyperammonemia) change in pH traps ammonia in GI)
Mag Citrate
Polyethylene Glycol (PEG) Miralax (large doses used for bowel prep prior to scope, procedures, surgery)
Sorbitol (glycerin)

works in 1-2 days sooner if larger dose

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13
Q

Salines

A

Mag Hydroxide
Na+ phosphate

Magnesium and phosphate poorly absorbed, osmotically retain water in GI lumen

**interact with DIURETICS, use caution in renal dz, CHF, HTN

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14
Q

Bulk forming

A 
dietary fiber
Psyllium
Methylcellulose
carboxymethylcellulose
Ca polycarbophil

work to inc bulk volume and water content thereby inc GI motility
Drink lots of water to prevent bloating/obstruction
lots of drug interactions (psyllium and celluloses)

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15
Q

Stool Softeners (surfactant, emollient)

A

Docusate
Mineral oil

soften feces, inc fluid secretion and inhibit water reabsorption

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16
Q

Metronidazole (5-nitroimidazoles) MOA

A

a prodrug activated by susceptible organisms (anaerobic pathogens) - redox potential - electron donated to metronidazole - highly reactive nitro radical anion formed -kills organisms by radical mediated DNA damage.

then can be catalyticaly recycled

resistance: inc intracellular O2

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17
Q

Metronidazole spectrum

A

active against anaerobes
flagellated protozoa (T. vaginalis, G. lamblia)
E. histolytica
anaerobic cocci and anaerobic G (-) bacilli
Helicobacter and Campylobacter spp.
G+ bacilli (Clostridium sp) (C. diff)

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18
Q

Metronidazole adverse effects

A

metallic taste in mouth
dry mouth, nausea, HA
Disulfiram-like effect (anti-EtOH effect, induces emesis)

Tinidazole similar but somewhat better tolerated

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19
Q

C. diff infection

A

cessation of inciting abx (Ampicillin, Clindamycin, Fluoroquinolones)
supportive
Vancomycin (preferred tx for severe CDI) Oral only
Metronidazole (mild CDI, sometimes if cant tolerate PO
Fidoxamicin (tx for recurrent CDI, spares many anaerobic colonic flora)

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20
Q

H. pylori tx

A

Bismuth subsalicylate
Metronidazole
Tetracycline
Omeprazole

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21
Q

Entamoeba histolytica

A

trophozoites invade intestine mucosa- portal blood circulation - LIVER ABSCESS - pulmonary or brain abscess (often death)
**Pathogenic if RBCs in cytoplasm
India, Mexico, Colombia

causes: Dysentery and Liver abscesses (occasionally toxic megacolon or pneumatosis coli)
* **MCC dysentery in the world

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22
Q

Entamoeba histolytica tx

A

Eliminate invading trophozoites: Metronidazole AND Tinidazole

Luminal amebicide: Paromomycin or iodoquinol

asx carrier tx with luminal amebicide

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23
Q

Giardia lamblia

A

Trophozoit -> cyst “pear/kite shaped”4 flagella, 2 nuclei
interferes with fat absorption
asx or WATERY (malodorous diarrhea)persistent diarrhea

dx: ova parasites, stool ag detection, fecal leuk -
acquired: lakes/streams/camping, zoonosis, daycare, Russia, IgA deficient more susceptible

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24
Q

Entamoeba histolytica dx

A

flask shaped ulcer on histology
ova and Parasite in stool
STOOL AG
fecal leuk +

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25
Giardia lamblia tx
supportive tx Tinidazole Nitazoxanide- inihibition of pyruvate-ferredoxin oxidoreductase enzyme (essential for anaerobes) a prodrug
26
Cryptosporidium parvum
Oocyst with 4 motil sporozoites person to person self-limited diarrhea in immunocompetent **life-threatening intractable in immunosuppressed WATERY diarrhea (large volumes) risk factors: food/water, SWIMMING POOLS, daycare, milk (resistant to chlorine tx) Dx: stool ag or microscopy (modified acid fast, DFA)
27
Cryptosporidium parvum tx
``` live within intestinal epithelial cells antidiarrheal agents: Loperamide (opioid agonist) fluid management Nitazoxanide Paromomycin ```
28
Strongyloides stercoralis
Nematode enter through exposed skin: bare feet on soil often asx can hatch eggs in SI ->autoinfection (persist for life) GI sx, SOB, cough, perianal urticaria, migratory rash Risk: rural, immunocompromised (hyperinfection), specifically HTLV1 Rhabditiform larvae in stool ** eggs not passed in stool eosinophils in stool
29
S. stercoralis tx
Ivermectin: intensifies GABD med transmission in peripheral nerves Shouldnt be given with other GABA enhancing drugs
30
Ascaris lumbricoides
ingestion of eggs can get long and cause bowel obstruction or biliary tree, hepatic abscess, ascaris pneumonitis eggs excreted in feces abd cramping, malnutirition, worm invasion
31
A. lumbricoides tx
Albendazole and mebendazole (broad spectrum) | - microtubule synthesis
32
Necator americanus and Ancylostooma duodenale
Hookworms (penetrate skin) adults live in SI, suck blood and reproduce ->erosion, focal hemorrhage, anemia, itching at penetration site eggs excreted in feces tx: albendazole and mebendazole
33
Trichuris trichiuria
``` whip worm simple life: ingestion of eggs, stay in SI and reproduce for 1 year no eosinphilia or autoinfection abd pain and diarrhea eggs in feces ``` tx: albendazole and mebendazole
34
Albendazole and mebendazole
hook worms A. lumbricoides whip worms pinworms
35
pyrantel pamoate
NM blocking agent, causes release of ACh and - AChE | tx: pinworms (E. vermicularis)
36
Enterobius vermicularis
pinworms eggs ingested, mature in CECUM and ascending LI females migrate to perianal area at night and lay eggs severe perianal itching scotch tape test no eosinphilia
37
Schistosoma spp.
Trematodes: blood flukes freshwater (snails contaminate water), invade venous system thru skin live for years but eggs must reach water to hatch cause: BLOODY stools, bladder cancer, liver cysts esophageal varices, portal vein branch obstruction initial dermatitis->Chronic fibrosis Katayama fever japonicum and mansoni: in veins of intestineeggs in feces haematobium: reside in bladder veins, eggs in urine
38
Schistosoma tx
Praziquantel MOA: increased permeability of nematode and cestode cell memebranes to Ca2+ SE: immediate-HA, dizzy, drowsy, lassitude. after several days-low grade fever, pruritis, rash
39
Taeniae solium
``` cestode (tapeworm) HOOKS undercooked pork dx via proglottids and/or eggs in feces wt loss, malnutrition Cysticercosis-seizures, muscle, eye DO, (rare) ```
40
Taeniae saginata
cestode (tapeworm) SUCKERS undercooked beef mostly asx proglottids/eggs in feces
41
Diphyllbothrium latum
tapeworm ingestion of larve in raw freshwater fish absorbs B12->pernicious anemia and neuro sx few abd sx proglottids/eggs in feces
42
Echinococcus granulosus
EXTRAINTESTINAL tapeworm infxn dogs and sheep eggs hatch in intestine and larvae form HYDATID CYSTS in liver or lungs (hydatid sand on CT)
43
Cestode(tapeworm) tx
Praziquantel Niclosamide (alt tx, not effective against hydatid cysts) Albendazole
44
anti-motility agents may be used for diarrhea if:
No fever and non-bloody stools | not C. diff or EHEC
45
reactive arthritis occurs in
Salmonella Campylobacter Shigella Yersinia arthritis, urethritis, conjunctivitis
46
Alcohol gels are ineffective against
Norovirus | C. diff
47
Guillian-Barre Syndrome
Campylobacter jejuni infection acute demyelinating polyneuropathy symmetrical muscle weakness usually begins in legs and ascends
48
Hemolytic Uremic Syndrome
Enterohemorrhagic E. coli (0157:H7) (EHEC) (Shiga-like toxin) giving abx in EHEC will inc chance of HUS Shigella (shiga toxin) dysentery, abd pain, fever, seizures - >microangiopathic hemolytic anemia (schistocytes) - >Thrombocytopenia - >renal insufficiency (dialysis, supportive tx)
49
Immunosuppressed pt's
cryptosporidium, cystoisospora belli, cyclospora, salmonella, campylobacter, shigella, MAC, CMV, Herpes, adenovirus IgA def- Giardia Hemochromatosis- prone to invasive/fatal enteric infxns Vibrio, listeria, YERSINIA infections should avoid raw fish
50
AIDS with low CD4 count (diarrhea)
Mycobacterium, CMV, adenovirus, herpes, cryptosporiia, cystoisopora belli, microsporida, blastocystis agents transmitted via rectum: neisseria gonorrhea, treponema pallidum, chlamydia may cause proctocolitis
51
Aluminum adverse effects
constipation HYPOPHOSPHATEMIA: acute tx of hyperphosphatemia (calcium also) renal osteodystrophy encephalopthy
52
H2 receptor antagonists
-tidine Reversibly inhibit H2 receptors on basolateral membrane of pariental cell onset .5-2 hrs (faster than PPI) Cimetidine (weak antiandrogen, gynecomastia, galatcorrhea) Famotidine Nizatidine Ranitidine (can be used in pregnancy) GI and CNS SEs Rare: blood dyscariasis, relatively contraindicated in pregnancy
53
PPIs
covalently (irreversibly) bind sulfhydryl groups of H+/K+ ATPase, inhibiting gastric acid secretion several days to new steady state and effects for 24 hrs Omeprazole (avoid during pregnancy) Esomeprazole Lansoprazole (can be given to pregnant) Dexlansoprazole SE: diarrhea/dyspepsia/nausea, HA/dizzy Increased risk of C. diff!! Increased risk in kidney dz relatively contraindicated in pregnancy
54
Sucralfate (carafate)
CYTOPROTECTION crosslinks with stomach acid to create sticky polymer which adheres to epithelia around ulcer's crater + local prostaglandin and mucous production and epidermal growth factor Indicated for DUODENAL ULCERS but also: apthous ulcers, mucositis/stomatitis, radiating proctitis/ulcers, bile reflux gastropathy SE: constipation (aluminum hydroxide) Relative contraindications: severe renal failure (aluminum should be avoided), 2 hours after other meds
55
Misoprostol
a PGE1 analog provides protective PGE1 to gastric mucosa and dec gastric acid release. cytoprotection and inc mucosal defenses Indication: PREVENTION of NSAID-induced gastric ulceration in high risk pts **also pregancy termination w/ or w/out mifepristone cervical ripening, post-partum hemorrhage Contraindicated in pregnancy and IBD
56
Bismuth
anti-diarrheal, anti-microbial believed to prevent microbial attachment to mucosa OTC: reflux, indigestion, and diarrhea Rx: used in combo with abx (Clarithromycin and Amoxicillin or metronidazole or metronidazole) and PPI SE: constipation, black/dark stools Relative contraindications: antiplatelets and anitcoagulants (its a salicylate), severe renal failure Absolute contraindications: GI BLEEDING, Salicylate hypersensitivity
57
Serotonin (5HT-3) receptor antagonists
Blockade of the 5-HT3 receptors at vagal n. terminals and blocks signal transmission to CTZ. STRONG ANTIEMETIC: Used for pretty much all N/V (CINV, RINV, Post-op, pregnancy) Dolasetron (high risk, not used) Granisetron Ondansetron- Palonsetron (longer 1/2 life, for delayed CINV) *Alosetron SE: HA/Constipation/Diarrhea. **Serotonin Syndrome (dont use with other 5HT3 drugs) **Dose dependent QT prolongation (anti-arrhythmics)
58
Neurokinin (NK1) Receptor antagonists | Substance
-pitant, MODERATE antiemetic used in combo for CINV Aprepitant *only used for prophylaxis of post-op N/V Fosaprepitant (prodrug) Netupitant (combo only with Palonsetron) Fosnetapitant (prodrug) Rolapitant (active metabolite, longe 1/2 life) SE: dyspepsia, constipation, diarrhea, dizzy, fatigue, tired, drug interactions
59
Histamine (H1) receptor antagonists
WEAK antiemetic Blockage of H1 in VC and vestibular system varying levels of ANTICHOLINERGIC effects uses: idiopathic mild n/v, vertigo, motion sickness ``` Diphenhydramine Dimenhydrinate (motion sickness) Meclizine and Cyclizine (vertigo) Hydrozyine Promethazine Doxylamine (with B6 or pyridoxine for n/v in pregnancy) ``` SE: anticholinergic effects (drowsy, dry, constipation, urinary retention, blurred vision)
60
drugs for motion sickness
Scopalamine (antimuscarinic patch) Dimenhydrinate (Dramamine, antihistamine) Meclizine
61
Drugs for vertigo
Meclizine | Cyclizine
62
Diabetic Gastroparesis drugs
Metoclopramide (D2 receptor antagonist but also ACh stimulation in GI to enhance motility)
63
Dopamine (D2) receptor antagonist
weak-to-mod antiemetic anticholinergic effects Uses: idiopathic, mild n/v, gastroparesis, post op and pregnancy n/v Phenothiazines: Chlorpromazine, perphenazine, prochlorprazine. Metoclopramide (also inc GI motility for gastroparesis) Haloperidol and Olanzapine (antipsychotic) SE: anticholinergic, GT prolongating, dec BP
64
Muscarinic (M1) receptor blockers
Scopalamine- patch behind ear for MOTION SICKNESS WEAK antiemetic blocks ACh and M1 receptors in neural pathways from the vestibular nuclei in inner ear to brainstem and from reticular formation to VC. also used for end of life care for excessive secretions SE: anticholinergic effects
65
Cannabinoids
STRONG antiemetic Dranabinol + predominately CB1 (central) and CB2 (peripheral) binds GPCR and dec excitability of neurons (dec serotonin from vagal afferents) used for CINV and appetite + Nabilone (fewer doses)
66
5-ASA agents
-sala- for mild to mod UC Inhibition of PG and LT production via inhibition of COX and LIPOX inhibitors->dec PMN and macrophage chemotaxis Sulfasalazine Mesalalmine Olsalazine Balsalazide (only for active dz in males) SE: contraindicated in ASA allergy!
67
TNF Inhibitors
``` Binds TNF blocking leukocyte migration to site of infection Adalimumab (UC and CD) Infliximab (UC and CD) Golimumab (UC only) Certolizumab (CD only) ``` SE: infections, liver toxicity, HA/arthralgia/fatigue, Derm related, malignancy
68
alpha 4 integrin inhibitors
Active and maintenance of CD and UC Limits integrin-assoc cell adhesions and trans-epithelial migration of leukocytes to site of inflammation Natalizumab (CD) *not in combo with other immunosuppressants ->Progressive Multifocal Leukoencephalopathy (john cunningham virus) Vedolizumab (CD and UC)
69
IL-12 and 23 inhibitors
active and maintenance of mod-severe CD bind P40 subunit of IL12 and 23 blocking activation and differentiation of naive T cells and activation of NK cells Ustekimumab (only if other tx not working) SE: infections, allergy, HA/arthralgia/fatigue inc malignancy
70
JAK inhibitors
active and maintenance of mod-severe UC bind and inhibit free JAK 1 and 3, thereby inhibiting gene txn and more cytokine release. Tofacitinib SE: lymphopenia/lymphocytosis, neutropenia/anemia, Inc LDL/HDL, inc malignancy
71
Steroids for IBD
Indicated for acute and/or severe UC and CD (not for maintenance or remission unless absolutely required) use the lowest dose for shortest duration

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