pharm Flashcards
antimuscarinic agents
MOA: Competitively inhibits autonomic, postganglionic cholinergic recptors= Decreased GI motility and spasm Indication: Abd pain/spasm hyoscyamine dicyclomine clindinium chlordiazepoxide
Opioid Agonists
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
Eluxadoline
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.
5-HT3 receptor antagonist (for diarrhea)
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
Cl- channel inhibitor
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
Peripheral opioid antagonist
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
Alvimopan
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
Methylnaltrexone
Mu opioid receptor antagonist
tx: OPIOID INDUCED CONSTIPATION
Linaclotide
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
Lubiprostone
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
stimulants (irritants)
\+ 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
Osmotics
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
Salines
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
Bulk forming
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)
Stool Softeners (surfactant, emollient)
Docusate
Mineral oil
soften feces, inc fluid secretion and inhibit water reabsorption
Metronidazole (5-nitroimidazoles) MOA
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
Metronidazole spectrum
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)
Metronidazole adverse effects
metallic taste in mouth
dry mouth, nausea, HA
Disulfiram-like effect (anti-EtOH effect, induces emesis)
Tinidazole similar but somewhat better tolerated
C. diff infection
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)
H. pylori tx
Bismuth subsalicylate
Metronidazole
Tetracycline
Omeprazole
Entamoeba histolytica
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
Entamoeba histolytica tx
Eliminate invading trophozoites: Metronidazole AND Tinidazole
Luminal amebicide: Paromomycin or iodoquinol
asx carrier tx with luminal amebicide
Giardia lamblia
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
Entamoeba histolytica dx
flask shaped ulcer on histology
ova and Parasite in stool
STOOL AG
fecal leuk +
Giardia lamblia tx
supportive tx
Tinidazole
Nitazoxanide- inihibition of pyruvate-ferredoxin oxidoreductase enzyme (essential for anaerobes) a prodrug
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)
Cryptosporidium parvum tx
live within intestinal epithelial cells antidiarrheal agents: Loperamide (opioid agonist) fluid management Nitazoxanide Paromomycin
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
S. stercoralis tx
Ivermectin: intensifies GABD med transmission in peripheral nerves
Shouldnt be given with other GABA enhancing drugs
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
A. lumbricoides tx
Albendazole and mebendazole (broad spectrum)
- microtubule synthesis
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
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
Albendazole and mebendazole
hook worms
A. lumbricoides
whip worms
pinworms
pyrantel pamoate
NM blocking agent, causes release of ACh and - AChE
tx: pinworms (E. vermicularis)
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
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
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
Taeniae solium
cestode (tapeworm) HOOKS undercooked pork dx via proglottids and/or eggs in feces wt loss, malnutrition Cysticercosis-seizures, muscle, eye DO, (rare)
Taeniae saginata
cestode (tapeworm) SUCKERS
undercooked beef
mostly asx
proglottids/eggs in feces
Diphyllbothrium latum
tapeworm
ingestion of larve in raw freshwater fish
absorbs B12->pernicious anemia and neuro sx
few abd sx
proglottids/eggs in feces
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)
Cestode(tapeworm) tx
Praziquantel
Niclosamide (alt tx, not effective against hydatid cysts)
Albendazole
anti-motility agents may be used for diarrhea if:
No fever and non-bloody stools
not C. diff or EHEC
reactive arthritis occurs in
Salmonella
Campylobacter
Shigella
Yersinia
arthritis, urethritis, conjunctivitis
Alcohol gels are ineffective against
Norovirus
C. diff
Guillian-Barre Syndrome
Campylobacter jejuni infection
acute demyelinating polyneuropathy
symmetrical muscle weakness usually begins in legs and ascends
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)
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
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
Aluminum adverse effects
constipation
HYPOPHOSPHATEMIA: acute tx of hyperphosphatemia (calcium also)
renal osteodystrophy
encephalopthy
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
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
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
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
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
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)
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
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)
drugs for motion sickness
Scopalamine (antimuscarinic patch)
Dimenhydrinate (Dramamine, antihistamine)
Meclizine
Drugs for vertigo
Meclizine
Cyclizine
Diabetic Gastroparesis drugs
Metoclopramide (D2 receptor antagonist but also ACh stimulation in GI to enhance motility)
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
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
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)
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!
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
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)
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
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
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
