Pharm Flashcards
What are the receptors targeted for NV?
5-HT3 R antagonists NK1 R antagonists H1R antagonists D2R antagonists M1R antagonists Cannabinoid R agonists
What are the 5-HT3R antagonists used for NV and what is their strength? (5) (remember the family name)
Dolasetron, granisetron, palonosetron, ondansetron, and alosetron (used for treatment R IBS-D exclusively)
Strong anti-emetic agents
What is the MOA of 5-HT3 R antagonists (setrons)
Block vagal n terminal 5-HT3R in CTZ (chemo trigger zone)
Block serotonin released from enterochromaffin cells from binding receptors
What are the clinical uses of 5-HT3R antagonists (setrons) and what are the major SE?
Uses- CINV, RINV, PONV, and NVP
SE- QT prolongation and torsade arrhythmias (for this reason dolasetron is not used as prophylaxis for CINV)
What are the kinetics of 5-HT3R (specifically at granisetron and palonosetron)
Setrons have short halflifes except for granisetron and palonosetron which have long half lives and are given as a single dose for delayed CINV
What are the drug interactions who have to pay attention to if you are using 5-HT3R antagonist (setrons)?
QT prolonging anti-arrhythmics
What are the NK1R antagonists used for NV? (4- think about family name)What is the strength?
Aprepitant, fosaprepitant, netupitant (given in combo w/ palonosetron), and rolapitant
Moderate anti-emetic agents
What is the MOA of NK1 R antagonists? (Pitants)
What are the therapeutic uses?
MOA- block NK1 (substance P) R in CZT, VC (vomit center), and vagal terminals in the gut
Uses- CINV (given in combo w/ glucocorticosteroids and setrons) and aprepitant and fosaprepitant are used as prophylaxis for PONV
What are the SE of NK1 R antagonists (pitants)? Think about dcd dfd
SE- dyspepsia, constipation, diarrhea, drowsy, fatigue, dizzy
What are the kinetics of NK1R antagonists and what drug interactions should you pay attention to?
Kinetics- netupitant and rolapitant have long half lives b/c they are metabolized into active compounds
Interactions- pitants are mild cyp450 inhibitors
What are the H1R antagonists used for NV? (7) what is their strength?
Diphenhydramine, dimenhydrinate, hydroxyzine, promethizine, meclizine, cyclizine, doxylamine (given w/ B6)
Weak anti-emetic agents
What is the MOA of H1R antagonists used for NV? What are their SE?
MOA- block H1R in VC and vestibular system and have anti-cholingergic effects in CTZ
SE- drowsy, dry mouth, constipation, urinary retention, blurred vision, and dec BP
What are the therapeutic uses of H1R antagonists? What are the kinetics of hydroxyzine and promethazine?
Uses- mild NV, PONV, motionsickness (dimenhydrinate, meclizine, cyclinzine), add ons for CINV and RINV
Hydroxyzine has long half life; promethazine has intermediate half life and low F (dec dose if switch from PO to IV)
What are the drug interactions to pay attention to for H1R antagonists?
Cumulative effect w/ other anti-cholinergic agents
What are the D2R antagonists used for NV? (4)What is their strength?
Phenothiazines- chlorpromazine, prochlorperazine, and perphenazine
Metoclopramide
Weak-mod anti-emetic agents
What is the MOA of D2R antagonists used for NV? What are the SE?
MOA- block D2R in CTZ w/ anticholinergic effects
Metaclopramide stim Ach activity in gut to inc GI motility and LES tone
SE- drowsy, dry mouth, constipation, urinary retention, blurred vision, dec BP, (arrhythmia and extra-pyramidal SE at high doses)
What is the kinetics of prochlorperazine?
What are the interactions to watch for w/ D2R antagonists?
Prochlorperazine has low F (dec dose if PO to IV)
Cumulative effect w/ other anti-cholinergic agents and QT prolonging anti-arrhythmic
What is the M1R antagonists used for NV? (1) What is its strength and clinical uses
Scopalamine
Weak anti-emetic used exclusively for motion sickness
What are the clinical uses of D2R antagonists?
Mild NV, diabetic gastroparesis (metoclopramide), add on for CINV, RINV, and PONV
What is the MOA of M1R antagonists? What are the SE? What are the interactions to pay attention to?
MOA- block Ach from stim MR between vestibular nuclei and brainstem and between RF and VC
SE- drowsy, dry mouth, constipation, urinary retention, blurred vision
Interactions- cumulative effect w/ other anticholinergics
What are the cannabinoids used for NV? (2)What is their strength and clinical uses
Dronabinol and nabilone
Strong-antiemetics used exclusively for treatment resistant CINV and for appetite stimulation
What is the MOA of cannabinoids for NV?
MOA- stim central CB1 and peripheral CB2 in VC and CTZ to inc signal transduction via GPCR to dec neuron excitability and dec serotonin release
What are the adverse effects of cannabinoids? What are the interactions to pay attention to?
SE- euphoria, irritation, vertigo, sedation, impaired cognition, altered perception, inc HR/BP, dry mouth, and hunger
Interactions- CNS depressants, CV agents, and sympathomimetics
What are the kinetics of cannabinoids?
Dronabinol is metabolized into one active compound
Nabilone is metabolized into many active compounds
Both are fast acting and long lasting
Acute CINV=
Chronic CINV=
Anticipatory CINV=
Acute- NV <24hr after treatment
Chronic- NV >24hr after treatment
Anticipatory- NV before treatment
What is the strong emetogenic regmine for CINV?
3 drugs- 5-HT3R and NK1 antagonists w/ dexamethasone (corticosteroid)
Given prior to and for 3 days after
If not effective, add cannabinoid
Provide therapy for breakthrough/anticipatory NV
What is the moderate emetogenic regime for CINV?
2 drugs- 5-HT3R antagonist and dexamethazone (corticosteroid)
Given prior to and for 2 days after
If not effective add NK1 R antagonist then cannabinoid
Provide therapy for breakthrough/anticipatory NV
What is the weak emetogenic regime for CINV?
Dexamethazone or 5-HT3R or metoclopramide or prochlorperazine
Given prior to
Provide therapy for breakthrough/anticipatory NV
Explain the 3 stepped therapy for NVP?
1- B6 plus 5-HT3R or H1R antagonists
2- D2R antagonists
3- steroid or different D2R antagonists
What are antacids used for? what are the classes and the examples for each?
Short term relief of GERD/PUD symptoms
Low systemic (Al, Mg, Ca)
High systemic (Na)
Supplemental (simethicone- surfactant to aid in gas expulsion)
What is the MOA of antacids?
MOA- bind H and create H2O, CO2, Cl salts (do not dec gastric acid secretion/production); at high doses inc LES tone
What are the properties of antacids?
Mg and Ca- fast acting, long lasting, good neutralizer
Na- fast acting, short lasting, ok neutralizer
Al- slow acting, short lasting, bad neutralizer
What are the SE of the different antacids?
Al- constipation and hypophosphatemia
Ca- constipation, hypophosphatemia, hypercalcemia, kidney sttone
Mg- diarrhea and hypermagnesemia
Na- gas, hypernatremia, and metabolic alkalosis
What are the interactions w/ antacids aka how should you take them?
1-2 hr before other meds or 2-4 hr after taking other meds
What are the drug classes used as anti-ulcers? (5)
H2R antagonists, PPI, surface acting agents, PGE analog, and bismuth compounds
What are the H2R antagonists used for anti-ulcers (tidines-4)
Cimetidine, ranitidine, famotidine, nizatidine
What is the MOA of H2R antagonists? What fast do you see the effects How fast do ulcers heal How much gastric acid production does it stop How often do you take
MOA- block H2R on parietal cells Prompt onset and relief of symptoms Ulcers heal in 4-8 weeks Moderately dec (20-50%) gastric acid production Take 1 or 2 a day
What are the adverse effects of H2R blockers? What are the interactions and CI?
SE- nausea, constipation, diarrhea, HA, drowsy
Interactions- cimetidine inhibits lots of cyp450 enzymes; ranitidine inhibits fewer
CI- pregnancy; use ranitidine if necessary
What are the PPIs? (6-Prazole); what is the MOA
Omeprazole, esomeprazole, lansoprazole, dexlansoprazole, pantoprazole, and rabeprazole
MOA- irreversibly inhibit H-K ATPase on parietal cells by bind sulfhydryl group
PPIs How quickly do you see the effects How fast do ulcers heal How much gastric acid is prevented What is the dosing frequency
See effects in a few days
Ulcers heal 4-8 weeks
Prevent majority (50-90%) gastric acid production
Take 1 a day
What are the adverse effects of PPI
What are the interactions and CI
SE- HA, dizzy, clostridium difficile assoc diarrhea (stop treatment immediately)
Interactions- omeprazole is cyp450 inhibitor
CI- pregnancy- use lansoprazole if necessary, never use omeprazole
What is the surface acting agent used to treat ulcers? What are its clinical uses?
Sucralfate
DU, apthous ulcers, radiation ulcers, bile reflux, and mucositis
What is the MOA of sucralfate? (2 major actions)
MOA- forms adhesive polymer that adheres to mucosal epi and covers ulcer preventing acid from entering; involved in cytoprotection by inc mucus and PG production
What are the SE of sucralfate? CI? What are the interactions aka how do you take it and how often?
SE- constipation due to Al
CI- renal dysfunction due to Al
Take 2 hr after other meds-4 times a day
What is the PGE analog used to treat ulcers? what type of ulcer and what are the off label uses?
Misoprostol is used to treat NSAID induced ulcer
Off-label- pregnancy termination, cervical ripening, and treat postpartum hemorrhage
What is misoprostols MOA
MOA- PGE analog that inc HCO3 and mucus production, mucosal blood flow, and dec gastric acid secretion- aka cytoprotection
What are the SE and CI of misoprostol
SE- diarrhea, HA,dizzy
CI- pregnancy and IBD
What are bismuth compounds activitys?
Anti-diarrheal
Anti-microbial- prevent H pylori from attaching to mucosa
Stim PG and mucosa production
What are the uses of bismuth compounds? What are the drug interactions aka when do you take?
Heartburn, indigestion, diarrhea, treat H pylori
SE- constipation and dark black stools
interactions- take 2 hrs after other meds
What are the CI and absolute CI for bismuth compounds
CI- anti-coagulants and renal dysfunction
Absolute CI- siacylate sensitivity (aspirin) or GI bleed
Explain H pylori treatment:
Combo therapy
Triple therapy
Quad therapy
Combo- always take 2 antibiotics and a HCl inhibitor
Triple (14 days BID)- PPI + clarithromycin + amoxycilin/metronidazole
Quad (10-14 days)- PPI (BID) + tetracycline + metronidazole + bismuth compound (rest QID)
Continue PPI after therapy until ulcers heal
Treating H pylori-
What if amoxicillin allergy?
R to metronidazole
R to clarithromycin
Amoxicillin allergy- use metronidazole
Metro R?- use tetra or quad of amoxy and clarithro
Clarithro R?- use tetra or amoxy
What are the treatment classes for UC?
What are the treatment classes for CD?
UC- 5-ASA, corticosteroids, TNFa inhibitors, a4 integrin inhib
CD- Il-12/23 I, corticosteroid, TNFa inhibitor, a4 integrin inhib
What are the 5-ASAs used for UC? (4-sala); what is their MOA
Sulfasalazine, mesalamine, olsalazine, balsalazine
MOA- inhibit COX and LIPOX to dec PG and leukotriene production; dec PMN and macrophage chemotaxis by inhibiting NFKB pathway
What are the SE of 5-ASA? What are the CI?
SE- general neuro and GI SE (not as bad if you dont take sulfasalazine)
CI- ASA or sulfa allergy
What are the therapeutic uses of the different 5-ASAs
Sulfasalazine/mesalamine- mild to mod UC- active/maintenance
Olsalazine- maintenance
Balsalazine- active
What are the TNF-a inhibitors used for IBD? (4) MOA?
Adalimumab, infliximab, golimumab, certolizumab
MOA- neutralize TNFa signaling to prevent expression of pro-inflammatory genes
What are the SE of TNFa inhibitors (5)
Infections- test for TB prior- stop if pt develops infection or sepsis
Liver dysfunction, arthralgia, headache, fatigue
What are the therapeutic uses for the individual TNFa inhibitors; what is the dosing frequency/form
Adalimumab- mod to severe UC/CD- SQ every other week
Infliximab- mod to severe UC/CD- IV every 8 wks
Golimumab- mod to severe UC- SQ every 4 wks
Certolizumab- mod to severe CD- SQ every 4 wks
What are the a4 integrin inhibitors used to treat IBD? (2) MOA
Natalizumab and vedolizumab
MOA- prevent cell adhesions, transmigration, and activation of immune cells
What are the SE of a4 integrin inhibitors (specifically just one of them)
Natalizumab is assoc w/ JCV infections -> progressive multifocal leukoencephalopathy (inc risk of if med for 2 years, have history of immunosuppressant use, or if anti-JCV Ab)
What are the uses of the a4 integrin inhibitors? Dosing frequency/form
Natalizumab- mod to severe treatment R CD- IV every 4wk
Vedolizumab- mod to severe treatment R CD/UC- IV every 8wk
What is the IL-12/23 inhibitor used to treat CD? MOA and therapeutic use
Ustekinumab
MOA- inhibit IL-12/23 R- prevent TH1/TH17 differentiation
Uses- mod to severe treatment resistant CD (active IV, maintenance SQ every 8wk)
What are the SE of ustekinumab (IL12-23 inhibitor for CD)
SE- infections-test for TB prior, infusion rxn, arthralgia, headache, fatigue
Explain glucocorticosteroid use for IBD? When is it used? What is the dosing? MOA? SE?
Used to treat active severe acute IBD uncontrolled by other therapies; give smallest dose for shortest period of time
MOA- bind cytoplasmic R to dec leukocyte infiltration, humoral suppression, and intefere w/ inflammatory mediators
SE- inc BP, lipids, glucose, fluid retention (monitor Na and K for renal or heart failure), bone/psychiatric/GI defects
What are the 3 opioid agonists used to treat diarrhea?
Loperamide, diphenoxylate, eluxadoline
Explain Loperamide MOA and SE
No analgesic properties
MOA- interfere w/ peristalsis via direct action on circular and longitudinal smooth m
SE- drowsy, dizzy, urinary retention
Diphenoxylate properties, MOA, and SE
Analgesic properties at high dose- mixed w/ atropine to prevent OD and abuse
MOA- acts on GI smooth m cells to dec GI motility
SE- more prominent drowsy, dizzy, and urinary retention
Eluxadoline used for?
MOA
SE
CI
Used for IBS-D
MOA- mu and kappa agonists- slow peristalsis
MOA- delta antagonist- dec stomach, pancreatic, and GB secretions
SE- liver and pancreatic toxicity, pancreatitis if pt lacks GB
CI- biliary obstruction, sphincter of oddi obstruction, liver/pancreatic dysfunction, and alcoholics
Alosetron
MOA
Use
SE (including black box label)
MOA- 5-HT3R antagonist
Use- chronic severe treatment resistant IBS-D
SE- constipation, GERD, and ischemic colitis (blackbox- doc must take IBS training, enroll in Rx program, pt must have followup before refill, and doc/pt must sign statement to adhere to treatment plan)
Crofelemer
MOA
Use
SE
MOA- inhibit cAMP from opening CFTR and Ca from stim CaCC (Cl channel inhibitor)
Use- non-infectious diarrhea in immunocompromised pt
SE- URI and inc ALT/AST/bilirubin
What are the 3 (4) anti-muscarinics used for IBS? What is the MOA and specific use of them? SE
Hyoscyamine, dicyclomine, clidinium/chlordiazepoxide
MOA- inhibit post-synaptic MR in GI to dec GI motility/spasms assoc w/ IBS
SE- drowsy, dry mouth, constipation, urinary retention, and blurred vision
Linaclotide
Use
MOA
SE
Linaclotide- used for chronic idiopathic constipation and IBS-C
MOA- stim GCC to inc cGMP and stim CFTR
SE- GERD
Lubiprostone
Use
MOA
SE
Lubiprostone- used for CIC, IBS-C, and opioid-induced C
MOA- stim CIC-2 Cl channel
SE- nausea, dyspepsia, dizzy
What are the 2 opioid antagonists used to treat opioid induce constipation? MOA?
Methylnaltrexone and naloxegol
MOA- mu antagonists
What are the bulk forming agents (4) MOA When are effects seen SE Interactions aka when do you take
Dietary fiber, psyllium, cellulose, and polycarbophil
MOA- inc bulk vol and water vol to stim GI motility
Effective in 2 days
SE- bloating
Take 2 hr after other meds
What are the stool softeners (2)
MOA
How long to be effective
SE
Docusate and mineral oil
MOA- surfactates that lubricate feces, inc GI secretion, and directly soften the stools
Effective in 1-3 days
SE- bloating and gas
What are the stimulants for constipation (5) MOA When effective? SE (just one of the stimulants) CI Which is used for colonoscopy
Senna, bisacodyl, castor oil, glycerol, and picosulfate
MOA- stim peristalsis via irritation by inhibiting NaK ATPase and inc PG production
Effective in 12-36 hr
SE- senna (discolored urine)
CI- GI obstruction
Picosulfate is used pre colonoscopy
What are the 2 saline agents used for constipation
MOA
Interactions to pay attention to
Mg salt, and Na phosphate
MOA- inc osmotic pull
Interactions- diuretics, renal dysfunction, CHF, or HTN
What are the osmotic agents (3)
MOA
When to they take effect
What is special about the last one and how fast does it work
Lactulose and sorbitol
MOA- inc GI fluid secretion
Effects in 1-2 days
PEG3350 (polyethylene glycol) used for surgery and colonscopy-effects in 1-3 hr
What are the two general classes of drug treatments available for HBV infection?
IFNa and nucleoside/nucleotides
What are the (3) IFNa treatments for HBV?
IFNa-2b, PEG IFNa-2a/b
What are the pros and cons of IFNa treatments for HBV?
Pros- short course, effective, rare to develop R, dec HBV DNA and HBeAg
Cons- parenteral, expensive, SE are very common, and can not give to decompensated pt
What is the MOA of IFNa treatments
IFNa binds R, activates JAK and TYK, phosphorylate R, recruit phosphorylate and activate STAT, STAT translocates to nucleus and results in transcription/translation of ISGs
ISGs inhibit viral protein synthesis and replication
Why can you not give IFNa to decompensated pt?
IFNa causes a transient inc in ALT leading to inflammation and fibrosis
What are the pros of using nucleoside/nucleotide treatment for HBV? What is the MOA
Better tolerated, better response, and can give to decomp pt
MOA- encode NRTI (reverse transcriptase inhibitor) that prevents viral replication; nucleosides must be converted to nucleotides by kinases to become active compounds
What causes resistance to nucleosides? Does it affect nucleotides?
Dec kinase activity (still responsive to nucleotides but can’t convert nucleosides to active form)
Mutant DNA polymerase
What are the two nucleotides, which is preferred, and what is an adverse rxn? (Class- fovir)
Tenofovir (1st choice, given if resistance develops to nucleosides, but can cause proximal renal tubule toxicity)
Adefovir
What are the 2 nucleosides, which is the preferred treatment and why, why is the other not used as often
Entecavir- 1st choice if pt has renal dysfunction
“Vudine”- resistance inc with use
What HCV treatment is a nucleoside given w/ PEG-IFNa
PEG-IFNa and ribavirin- low cure rate, ribavirin is a nucleoside that potentiates the affects of PEG-IFNa
What are the NS3 protease inhibitors used to treat HCV? How are they given?
“Previrs” are given either in combo with PEG-IFNa and ribavirin or in combo w/ ribavirin and sofobuvir
What is the NS5B inhibitor used to treat HCV? What is general MOA?
What are the NS5A inhibitors used to treat HCV? General MOA and how they are given
NS5B- sofosbuvir, nucleotide inhibits viral replication, given in combo
NS5A-“asvirs”, inhibit viral assembly, often given in combo w/ PEG-IFNa and ribavirin
Explain Clostridium difficile (gram stain, when it infects, what it causes, and via what toxins) what are the general treatments given (do not include the meds given)
Gram positive, opportunistic, causes pseudomembranous colitis (toxin B), and diarrhea (toxin A)
Treat- remove causative antibiotic, give fluids, and give fecal transplant
What are the 3 treatments for c diff and explain each and under what circumstances they are given
Vancomycin- for severe c diff, inhibits CW, PO, can cause red man syndrome
Metronadizole- for mild c diff or if pt cant take oral vancomycin, incorps toxic metabolites into bacterial genome, IV, can cause peripheral neuropathy/metallic taste/disulfiram rxn
Fidaxomicin- recurrent c diff, spares normal flora, targets sigma unit of RNA poly, given orally
Entemoeba histolytica (life cycle and invasion of host)
Trophozoite ->bicyst ->tetracyst
Trophozoite can invade mucosa (RBC in cytosol on stool sample)
Flask shaped ulcers-bloody diarrhea
Explain the 2 part treatment of e histolytica
Eliminate trophozoite- metronidazole (primary choice) or tinidazole
Eliminate luminal organism- paromomycin (luminal amebocide)
Giardia (life cycle, invasion, and major characteristic of disease)
Trophozoite -> cyst (does not invade mucosa-no bloody diarrhea)
Fatty, smelly, frothy diarrhea
Explain the treatment for giardia; explain the second choice treatments MOA and special SE
Tinidazole (fist choice)
Nitazoxanide (inhibits oxidoreductase involved in nrg metabolism- cause bright yellow eyes and urine)
Cryptosporidium
Life cycle and what the infections are commonly assoc w/
Cyst -> 4 sporozoites
Contaminated water, day care, travel, immunocompromised diarrhea
Explain the 2 part treatment of cryptosporidum; what about if pt is immunocompromised
Anti-diarrheal such as loperamide
Anti-microbial- nitazoxanide (1st choice) or paromomycin
HIV- anti-retroviral and nitazoxanide
N americanus and A duodenale
How they infect
S/S
Treatment (MOA and CI)
Penetrate skin -> eggs in stool
Diarrhea, abdominal pain, wt loss, iron deficient anemia, and intense itchiness at site of penetration
Treatment- albendazole/mebendazole (inhibit microtubule synthesis leading to paralysis, 1st pass effect, CI in pregnancy or cirrhosis)
Ascaris lumbricoides
General life cycle
S/S (2)
treatment
Contaminated food -> eggs in stool
Malnutrition and cramps
Albendazole or mebendazole
Strongyloides sterc
general life cycle
S/s
Treatment/MOA/CI
Penetrate skin-> larvae in stool
Diarrhea, abdominal pain, wt loss, anemia, itchiness, eosinophilia, lung involvement, autoinfection if on immunosuppressant like prednisone (asthma)
Treatment- ivermectin (gaba enhancer leads to paralysis, CI if pregnant or on other gaba enhancer)
Trich
Life cycle
S/s (hey arnold)
Treatment
Eggs in food -> lay 100s of eggs but no larvae no invasion, eosinophilia, lung involvment, or autoinfection
Diarrhea w/ football shaped eggs
Treat- mebendazole
Enterobius vermicularis
Special things about the infection
Eosinophilia?
Treatment 3 (include last ones MOA and CI)
Ingest eggs, itchy anus, scotch tape test
No eosinophilia
Albendazole, mebendazole, pyranfel (stim Ach, inhibit AchE, paralysis, CI w/ liver dysfunction)
Schistosoma blood fluke How it invades and where it is found How it evades host immune system 3 steps of disease Diagnosis- where are eggs and what clinical feature Treat- MOA, immune response, CI
Eggs found in fresh water (where they hatch), enter venous sytem via open wound
No immune response due to molecular mimicry
Dermatitis -> katayama fever -> chronic fibrosis
Eggs in stool/urine and eosinophilia
Treatment- praziquantel (Ca influx and paralysis, causes an immune response due to the dead fluke, CI in pregnancy
Taenia solium and sagigata
Food and how they invade
Special clinical feature of one of them
Treatment
Solium (pork-hooks) and sagigata (beef-suckers)
Solium is assoc w/ cysts in brain, seizure, meningitis, and hydrocephalus
Treat- albendazole and praziquantel
Diphyll latum
Fresh water fish -> eggs and epiglottids in stool
Treat- niclosamide inhibits oxphos
E granulosus
Hydatid cysts
Treatment- albendazole and praziquantel
