GI2- Ex2 Pharm Flashcards
1
Q
5HT receptor antagonist with patch
A
Granisetron
2
Q
5HT receptor anatagoinst only for IBS-D
A
Alosetron
3
Q
Causes prolonged QT time
Dont use w/
Which one high risk
A
Serotonin (5-HT3) receptor antagonists
Dont use w/ anti-arrhythmics or in patients w/ electrolyte imbalance
Dolasetron
4
Q
5HT receptor antagonist with extended-release SQ injection
A
Granisetron
5
Q
5HT receptor antagonist pharmacokinetics
A
All have short half lives
Except Palonosetron and Sustained release formulation of Granisetron (SQ)
- 24hr +
6
Q
What two drugs work well for delayed-CINV as a single dose
A
Long half life
Palonosetron & Granisetron (patch & SQ injection)
7
Q
5HT receptor antagonist
A
-setron
8
Q
Neurokinin (NK1) receptor antagonists
A
- pitant
9
Q
Neurokinin (NK1) receptor antagonists types (5)
A
Aprepitant (PO)
Fosaprepitant (prodrug, IV)
Netupitant (combo only w/ palonosetron, PO)
Fosnetupitant (prodrug, combo only w/ palonosetron, IV)
Rolapitant (PO/IV)
10
Q
Strength of antiemetic drugs
- 5-HT receptor antagonist
- NK1 receptor antagonist
- H1 receptor antagonist
- D2 receptor antagonist
- M1 receptor antagonist
- Cannabinoid receptor AGONST
A
1) 5-HT= Strong
2) NK1= Moderate
3) H1= Weak
4) D2= Weak to moderate
5) M1= Weak
6) Cannabinoid= strong
11
Q
Uses of antiemetic drugs
- 5-HT receptor antagonist
- NK1 receptor antagonist
- H1 receptor antagonist
- D2 receptor antagonist
- M1 receptor antagonist
- Cannabinoid receptor AGONST
A
1) 5-HT
- CINV
- Radiation induced RINV
- Post-operative PONV
- N/V of pregnancy (NVP)
2) NK1
- CINV
- PONV
3) H1
- Idiopathic, mild N/V
- PONV
- NVP (doxylamine/ B6)
- Motion sickness/ Vertigo
- CINV (add-on therapy)
- RINV (add-on therapy)
4) D2
- Idiopathic mild N/V
- Gastroparesis/ Dysmotility (metoclopramide)
- PONV
- NVP
- CINV & RINV (only weak; olanzapien used in combo)
5) M1
- Motion sickness
- End of life care for excessive secretions
6) Cannabinoids
- *CINV (treatment resistant scenarios)
- Appetite stimulation
12
Q
Only NT1 receptor antagonist used for porphylaxis of post-operative N/V (PONV)
A
Aprepitant
Given 3 hrs PRIOR to anesthesia
13
Q
Pharmacokinetics of NK1 receptor antagonists
A
Netupitant/ Rolapitant have moderate-major active metabolites, longer half lives
Inhibition of few key CYP450 enzymes
14
Q
Initial therapy for NVP
A
Doxylamine with pyridoxine (B6) PO
15
Q
HIstamine receptor antagonist (7)
A
1) Diphenhydramine (PO, IV, IM)
2) Dimenhydrinate (PO, IV, IM)
3) Hydroxyzine (PO, IM)
4) Promethazine (PO, IV, IM, PR)
5) Meclizine (PO) vestibular issues
6) Cyclizine (PO) vestibular issues
7) Doxylamine (PO) NVP only
16
Q
Drugs for vestibular issues
A
Histamine receptor antagonists
Meclizine and Cyclizine (PO)
17
Q
Doxylamine
A
Only used for nausea in pregnancy
18
Q
Receptor antagonists that has anti-cholinergic properties at level of CTZ
A
Histamine receptor antagonists
19
Q
Classic anticholinergic effects
A
Drowsiness (CNS depression) Dry mouth Constipation Urinary retention Blurred vision Decreased BP
20
Q
Hydroxyzine
A
H1 receptor antagonist
Converted to active metabolite
IM
21
Q
Promethazine
A
IV
22
Q
Dopamine Receptor Antagonists (4)
A
Phenothiazines
1) Chlorpromazine (PO, IV, IM)
2) Perphenazine (PO)
3) Prochlorperazine (PO, IV, IM PR)
4) Metoclopramide (PO, IV, IM, ODT)
23
Q
Metoclopramide
A
Blocks D2 receptor and
Stimulates acetycholine (ACh) in GI -enhancing GI motilitly (dysmotility use) & increases lower esophageal sphincter tone
24
Q
Muscarinic receptor blocker (1)
A
Scopolamine
- patch
72 hrs
Motion sickness
25
```
Stimulates acetycholine (ACh) in GI
-enhancing GI motilitly (dysmotility use) & increases lower esophageal sphincter tone
```
Metoclopramide
| Blocks D2 receptor
26
Cannabinoid receptor agonists (2)
1) Dronabinol (C-III) PO
| 2) nabilone (C-22) PO
27
Patient with diabetes that has peripheral nerve transmission issues such that GI tract isnt fxn is not sychronous, prescribe what
Metoclopramide
28
Reserved for treatment resistant CINV
Cannabinoids
29
Cannabinoids MOA
CB1 adn CB2 cannabinoid receptors are stimulated in VC/CTZ exert signal transduction through G protein-coupled receptors
Results in decreased excitability of neurons
Minimizing serotinon 5-HT3 release from vagal afferent terminals
Suppress Emesis and nausea feeling in the brain
30
Adverse effects Cannadbinoids (8)
1) Euphoria/ Irritability
2) Vertigo
3) Sedation/ drowsiness
4) Impaired congition/ memory
5) Alterations in perception of reality
6) Xerostomia (dry mouth)
7) Sympathomimetic (Increasd HR/BP)
8) Appetite stimulation
31
Pharmacokinetics of Cannabinoids
1) Dronabinol: large first pass effect metabolized to ONE active metabolite
2) Nabilone: metabolized to SEVERAL active metabolites
Short time of onset of activity
Long duration of action 24-36 hrs
32
High Emetogenic Regimen
3-drug regimen
1. NK1 receptor antagonist (-pitant)
2. 5-HT3 receptor antagonist (-setron)
3. Corticosteroid (Dexamethasone)
Give treatment regimen day of (prior to) chemotherapy (for acute) and for 3 days following chemotherapy (for delayed N/V)
A. May add olanzapine (D2)
- increase to 4-drug regimen
B. May add cannabinoid (4 drug)
C. Provide therapy for break through
D. Provide therapy for anticipatory
33
Moderate-Emetogenic Regimen
2 drug regimen
1. 5-HT3 receptor antagonist (-setron)
2. Corticosteroid (Dexamethasone)
Give treatment regimen day of (prior to) chemotherapy (for acute) and for 2 days following chemotherapy (for delayed N/V
A. May add NK antagonist or olanzapine (3 drug)
B. May add cannabinoid (4 drug after step A)
C. Provide therapy for break through
D. Provide therapy for anticipatory
34
Low Emetogenic regimen
1 drug regimen
1. Corticosteroid (Dexamethasone) or
2. 5-HT receptor antagonist or
3. Metoclopramide or
4. Prochlorperazine or
Give day of (prior to) chemo (acute)
A. Provide break through
B. Provide anticipatory
35
Minimal Emetogenic Regimen
0 drug regimen
A. Provide break through
B. Provide anticipatory
36
Break through
Add one agent from a different drug class to the current regimen
37
Anticipatory Emesis Regimen
Avoid strong smells
Relaxation exercises
Lorazepam PO beginning on night before treatment and repeated the next day 1-2 hrs before chemo begins
38
Motion sickness
Scopolamine (patch)
Dimenhydrinate
Meclzine
39
Vertigo
Meclizine or Cyclzine
40
Diabetic Gastroparesis
Metoclopramide
41
Pregnancy induce nausea/vomiting (NVP)
(stepped therapy)
1. Vitamin B6 or H1 antagonist w/ Vit B6 or 5-HT3 antagonist
2. Dopamine Antagonist
3. Steroid or Different dopamine antagonist
42
Antacids 3 groups
1) Low-systemic agents
- Aluminum salts
- Calcium salts
- Magnesium salts
2) High-systemic agents
- sodium salts
3) Supplemental agents
- simethicone
43
Antacids that work the fastest
Calcium and magnesium
44
Prodrug that tacts the surface tension ofthe little bubbles, lessens it breaks it up and makes one gigantic bubble makes it easier to pass
Simethicone
45
Adverse effects Antacids
- Aluminum
- magnetsium
- calcium
- sodium
1) Aluminum
- Constipation
- Hypophosphatemia
2) Magnesium
- Diarrhea
- Hypermagnesemia
3) Calicum
- Constipation
- Hypercalcemia
- Hypophosphatemia
- Kidney stones
4) Sodium
- Gas
- Hypernatreia
- Metabolic alkalosis
46
Antacids w/ other medications
AVOID
Take all antacids 1-2 hrs before other medications or 2-4 hrs after
47
Antiulcer agents (5)
1) H2 receptor antagonists
2) Proton Pump inhibitors
3) Surface acting agents
4) PGE analogs
5) Bismuth Compounds
48
Histamine type 2 blockers (4)
- TIDINE
1) Cimetidine (PO/IV)
2) Ranitidine (PO/IV)
3) Famotidine (PO/IV)
4) Nizatidine (PO)
49
Only HIstamine Type 2 blocker not IV form
Nizatidine
50
Adverse effects H2 blocker
Rare
Cimetidine
- decreases testosterone binding to androgen receptor
(Gynecomastia in men, breast development)
(Galactorrhea in women, liquid from breasts)
Blood dyscrasias in elderly
- Neutropenia
- Throbocytopenia
51
Drug interactions H2 blockers
Cimetidine: CYP450 inhbitior
Ranitidine
-10% of cyp450 inhibition
52
Contraindications for H2 blockers
Pregnancy
Use Ranitidine if must
53
Proton Pump Inhibitors (PPI's) 6
- PRAZOLE
1. Omeprazole (PO)
2. Esomeprazole (PO/IV) isomer
3. Lansoprazole (PO)
4. Dexlansoprazole (PO) Isomer
5. Pantoprazole (PO/IV)
6. Rabeprazole (PO)
54
Given enough of what has potential to make patients echolithidric
PPIs
55
PPI characteristics
Last 24 hrs
QD dosing
50-90% acid secretion
Takes several days to feel effects
56
PPI adverse effects
Diarrhea
| - At risk clostirdium difficile associated diarrhea (CDAD)
57
PPI drug interactions
Omeprazole (CYP450 inhibition)
58
PPI contraindicated
Pregnancy
If necessary Lansoprazole
59
Surface acting agent
Sucralfate
Has alumnium in it --> constipation
60
Covers ulcer like bandaid, cross-linking from interaction w/ stomach acid
Sucralfate
61
Sucralfate contraindictaions
Severe renal failure (aluminum)
Avoid aluminum antiacids
62
Drug interactions sucralfate
avoid taking w/ other drugs, get stuck in viscous membrane
take 2 hrs after other medications
4x day
63
Prostaglandin analog
-fxn
Misoprostol
Makes mucus, bicarb, good blood flow, good healing cell regeneration
64
Misoprostol indicated in
Patients on non-steroidals who cant stop
65
Misoprostol MOA
works on both parietal cell and superficial epithelial cell
1) H2 antagonist, effect on cAMP to tell HK ATPase pump to not release H
2) Stimulatory effect in epithelial cells, make mucus, bicarb, quality blood supply and tissue regeneration
66
off label use of misoprostol (3)
Contractions
Post partum hemorrhaging
Pregnancy termination
67
Misoprostol adverse effect
Diarrhea
68
Contraindications Misoprostol
Pregnancy (contractions/termination)
IBD
69
Bismuth compounds FXN
Anti-diarrheal
| Anti-microbial
70
Bismuth can be added in which situations
Ulcers w/ H. pylori
Situations w/ high resistance
71
Bismuth adverse effects
Constipation
Black stools
Lots of drug interactions
72
Dont use Bismuth salicylate in what patients
can lead to
those w/ asprin allergies & GI bleeding
--> renal failure
73
Treatment of H. pylori
Need at least 2 antibiotics and PPI or H2 blocker
10-14 days
Triple therapy (All BID)
1) PPI
2) Clarithromycin
3) Amoxicillin (or metronidazole)
(or metronidaole & tetracycline)
Quadruple Therapy (10-14 days)
- PPI at BID and all other QUID
1) PPI
2) MEtrnoidazole
3) Tetracycline
4) Bismuth subsalicylate
74
PUD in pregnancy w/o H.pylori
1) short course antiacids or sucralfate
2) Moderate symptoms
- Ranitidine
3) Severe symptoms
- Lansoprazole
75
PUD if NSAIDS at risk
NSAID no required
- D/C NSAID
- acetaminophin
NSAID required
- COX-2 NSAID and/or
- PPI or misoprostol
76
Gram positive spore forming anaerobic rod
Clostridium difficile (C. diff)
77
Severe diarrhea
Abdominal cramping
Fever
Red inflamed mucosa with areas of white exudate on surface of large intestine
Pseudomembranes
C. DIff
78
C. diff frequently associated with what drugs (4)
1. Fluoroquinoles
2. Clindamycin
3. Cephalosporins
4. Pencillins
79
Treatment for Severe CDI
Vancomycin
80
Treatment for mild CDI
Metronidazole
81
Treatment for recurrent CDI
Fidaxomicin
| Spares many anaerobic colonic flora
82
Vancomycin adverse effect
Red man syndrome
- hypotension
- flushing
- tachycardia
83
CDI treatment if patient is vomiting
Metronidazole
84
H. pylori tx (4)
1. Bismuth subsalicylate
2. Metronidazole
3. Tetracycline
4. Omeprazole (PPI)
85
GI Infections
- Bacteria (2)
- Protozoa (3)
- Nematodes (6)
- Platyhelminthes (5)
Bacteria
1) Clostrudium difficile
2) Helicobacter pylori
Protozoa
1) Entamoeba histolytic
2) Giardia lamblia
3) Cryptosporidium parvum
Nematodes
1) Necator americanus
2) Ancyclostoma duodenale
3) Ascaris lumbricoides
4) Stronglyloides stercoralis
5) Trichuris trichiura
6) Enterobius Vermicularis
Platyhelminthes
1) Scistosomas
2) Taenia solium
3) Taenia saginata
4) Diphyllobothrium latum
5) Echinococcus granulosus
86
Entamoeba histolytic life cycle
Trophozoite --> binucleated precyst --> tetranucleated cyst
87
During which part of entamoeba life cycle does invasion happen
Trophozoites
88
Liver abscess pathogen
Entamoeba histolytica
89
Tx of Entamoeba histolytic (2)
1) Eliminate invading trophozoites
- Metronidazole
- Tinidazole
2) Eradicate intestinal carriage of the organism
- Paromomycin
- Iodoquinol
90
Paromomycin MOA (3)
Bind to 30 S subunit
Irreversible inhibitor protein syn
3 mechanisms
1) inhibit initiation by fixing 50S and 30S to AUG start codon
2) Inhibit continuation of translation, promote early termination
- Inhibition of translation: inhibition of formation 70S
- Promote early termination: induce misreading of mRNA by binding 30S
3) Introduction of errors in protein synthesis, incorportation incorrect AA --> non functional proteins
91
Iodoquinol MOA
Used as a luminal amebicide
No effect extrainestinally
Unknown MOA
92
Iodoquinol contraindicated in
Patient w/ iodine sensitivity
Iodine group
93
Drug of choice for extraluminal amebiasis
Metronidazole
Tinidazole is better tolerated tahn metronidazole
94
Luminal agent of choice for intestinal carriage in US
Paromomycin
Remains in GI
95
Giardia lamblia life cycle
Trophozoite --> Cyst
96
Characteristics of Giardia lamblia
```
Coats small intestine interferes w/ fat absorption
Steatorrhea
No invasion of intestinal wall
No blood in stool
Gas and cramps
```
97
Giardia first line agent (FDA approved)
Tinidazole
98
Giardia agents
Tinidazole
Metronidazole (Not FDA approved)
Nitazoxanide
99
Nitazoxanide
- MOA
- type
- pharmacokinetics
- AE
Inhibition of pyruvate-ferredoxin oxidoreductase enzyme
-Essential for anaerobic energy metabolism
Prodrug
Rapidly absorbed, excreted in urine and feces
AE
- Nausea, anorexia, flatulence, increased appetitie, enlarged salivary glands
- YELLOW EYES, DYSURIA, BRIGHT YELLOW URINE
100
Inhibition of pyruvate-ferredoxin oxidoreductase enzyme
Nitazoxanide
101
Frothy smelly diarrhea
Gas
Cramps
Giardia
102
Bind to 30 S subunit
Irreversible inhibitor protein syn
3 mechanisms
1) inhibit initiation by fixing 50S and 30S to AUG start codon
2) Inhibit continuation of translation, promote early termination
- Inhibition of translation: inhibition of formation 70S
- Promote early termination: induce misreading of mRNA by binding 30S
Paromomycin
103
Yellow eyes
Dysuria
Bright yellow urine
AE to nitazoxanide
104
Metallic mouth
| Vomit w/ alcohol
Metronidazole
105
Metronidazole
- MOA
- AE
Anaerobic pathogen donates electron to metronidazole
When donated, highly reactive nitro radical anion formed
Ion mediates the killing of organism by means of radical mediated DNA damage
AE= Metallic mouth, vomit w/ alcohol
106
Vancomycin
- type
- MOA
- route
- AE
Glycopeptide
Cell wall synthesis inhibitors
Bind- D-alanyl-D-alanine terminus of cell wall precursor units w/ high affinity
Leads to inhibition of transglycoslyase and prevents extension and cross linking of the peptidoglycans
Poorly absorbed orally, IV
Red man syndrome: hypotension, tachycardia, flushing
107
Fidaxomicin
- type
- MOA
- AE
Macrolide
Not systemically absorbed
Protein synthesis inhibitor, reversibly binds 50S subunit
Prevents translocation of tRNA from A site to P site
Conformation change, indirect inhibition of transpeptidation
Can induce arrhythmias
Hypersensitivity: eosinophilia, fever
108
Tetracycline
- MOA
- route
- AE
Bind 30S subunit and prevent aminoacyl tRNA from entering acceptor A site
Inhibits synthenis by indirectly blocking polypeptide elongation
Incompletely absorbed in GI
Binds calcium
- Permanent discoloration of teeth
- Bone deformaties
109
Discoloration of teeth
| Bone deformity
Tetracycline
110
Contaminated water
Daycare
travelers
Diarrhea and abdominal pain
-Self limiting in immunocompetent
Life threatening diarrhea
Cryptosporidium parvum
111
Cryptosporidium parvum tx
Antidiarrhea agents
- Loperamide
Fluid management
Antimicrobial agents
-Nitazoxanide (preferred)
Paromomycin
112
Preferred drug for cryptosporidium parvum
Nitazoxanide
113
Nematodes
- diagnosed
- look
- extra note
Eggs in feces
Round worms
No immune response to worms
- response to dead worms and eggs
- elevation of eosinophils
114
Necator americanus and Ancylostoma duodenale
- look
- life cycle
hook worms
Penetrate the skin in-between toes
- larvae to lungs
- grow coughed up and swallowed
- adults in small intestine
- eggs in feces
- larvae live in soil
115
```
Diarrhea
Abdominal pain
Weight loss
Anemia
Itching at wound in between toes
```
Necator americanus
| Ancylostoma duodenale
116
Ascaris lumbricoides
| -life cycle
Consumption of eggs (contaminated food)
```
Larvae penetrate intestine and travel to lung
Grow cough up
Swallow
Adult worms in small intestine
Eggs in feces
Eggs hatch, larvae in soil
```
117
Abdominal cramping
Malnutrition
Worm invasion
Ascaris lumbricoides
Worm load so heavy can block GI tract
118
Stronglyoides stercoralis
- life cycle
- diagnosis
```
Larvae in soil
Penetrates human skin, travels to lungs
Larve in lungs, coughed up swallowed
Adult worms in small intestine
Release eggs
EGGS NOT PASSED IN STOOL
Larvae in stool
```
Hatched larvae can
1) autoinfect
2) Excrete in feces, infect (direct)
3) Excrete in feces, mature, lay eggs, new larvae infect (indirect)
119
```
Vomiting
Abdominal bloating
Diarrhea
Anemia
Weight loss
Enterotest
```
Risk w/
Strongyloides stercoralis
Risk w/ immunosuppressive medication --> severe auto infection
Prednisone and asthma
Enterotest: swallow a piece of string, pull it back out
120
Organism which eggs are not passed in stool
Stronglyloides stercoralis
121
Dont use immunosuppressive medication with what pathogen
Strongyloides stercoralis --> severe autoinfection
122
Trichuris trichiura
- type
- life cycle
- diagnosis
- unique descriptor
Whip worm
Ingestion of food w/ infective eggs
Eggs hatch in SI migrate to cecum and ascending large intestine
No larvae
No lung involvment
No eosinophilia
Football shaped worms
123
Enterobius vermicularis
- type
- life cycle
- transmission
- diagnosis
Pin worms
Eggs ingested
Pinworms mature in cecum and ascending large intestine
Female to perianal at night to lay eggs
Severe perianal itching
Scotch tape test
124
Organism w/ larvae in stool not eggs
Stronglyloides stercoralis
125
Autoinfect
Stronglyloides stercoralis
126
Nematode treatment
```
Albendazole
Mebendazole
Ivermectin
Thiabendazole
Pyrantel pamoate
```
127
Albendazole and mebendazole MOA
Inhibits microtubule synthesis, paralyzes worms, worms passed in stool
Prodrug
128
Thiabendzole
- MOA
- AE
Inhibits microtubule synthesis, paralyzes worms, worms passed in stool
Dizziness, nausea, vomiting
Irreversible liver failure
Fatal steven johnson syndrome
129
Ivermectin
- MOA
- route
- contraindicated
Intensifies GABA mediated transmision of singals in peripheral nerves of the nematode
Oral only
Not combine w/ drugs that enhance GABA activity
130
Pyrantel pamoate
| -MOA
Neuromuscular blocking agent, causes release of acetylcholine and inhibit of cholinesterase, paralysis worm
131
Irreversible liver failure
Thiabendzole
132
Neuromuscular blocking agent, causes release of acetylcholine and inhibit of cholinesterase, paralysis worm
Pyrantel pamoate
133
Intensifies GABA mediated transmision of singals in peripheral nerves of the nematode
Ivermectin
134
Inhibits microtubule synthesis, paralyzes worms, worms passed in stool
Albendazole
Mebendazole
Thiabendazole
135
Bind 30S subunit and prevent aminoacyl tRNA from entering acceptor A site
Inhibits synthenis by indirectly blocking polypeptide elongation
Tetracycline
136
Protein synthesis inhibitor, reversibly binds 50S subunit
Prevents translocation of tRNA from A site to P site
Conformation change, indirect inhibition of transpeptidation
Fidaxomicin
137
Bind- D-alanyl-D-alanine terminus of cell wall precursor units w/ high affinity
Leads to inhibition of transglycoslyase and prevents extension and cross linking of the peptidoglycan
Vancomycin
138
Drug for N. americanus
Albendazole
139
Drug for A. duodenale
Albendazole
140
Drug for A. lumbricoides
Albendazole or mebendazole
141
Drug for S. stercoralis
Ivermectin
142
Drug for T. trichiura
Mebendazole
143
Drug for E. vermicularis
Albendazole
Mebendazole
Pyrantel pamoate
144
Pathogen that does molecular mimicry posts antigens on surface, confuse host
Schistosoma spp. (blood flukes)
145
Schistosoma spp
- location
- moa
- special
- life cycle
- clinical
fresh water
Invades venous system through exposed skin
Survive for years, no immune rxn
-molecular mimicry
Eggs hatch fresh water
Larvae infect snail
Mature leave snail, infect humans (exposed skin)
Portal venous system
-Mating mature worms veins surrounding intestine and bladder to lay eggs
Eggs enter lumen to be excreted
```
Dermatitis (immediate)
Katayma fever (4-8 wks)
Chronic fibrosis (years)
```
146
Katayma fever
fever hives
enlarged liver and spleen
bronchospasms
Schistosoma
147
Chronic fibrosis pathogen
Schistosoma
148
Dermatitis pathogen
Scistosoma
149
Schistosoma tx
Praziquantel
150
Praziquantel
- MOA
- route
- AE
Increases permeability of nematode and cestodes cell membrane to calcium resulting in paralysis, dislodgement and death
Oral
Rapid
Throughout
AE
- Immediate: HA, dizziness, drowsiness, lassitude
- several days: fever, pruritis, skin rash
151
Cestodes
- type
- part found in feces
Flat worms
Gravid proglottids
152
Taenia
- 2 types
- attachment
- life cycle
T. solium= pork, hooks
T. saginata= beef, suckers
Pigs/cows ingest eggs from field contaminated w/ human feces
- larve into cysts
- humans ingest undercooked meat
weight loss
Malnutrition
153
Raw fresh water fish
Diphyllobothrium Latum
154
Diphyllobothrium Latum
- acquired
- life cycle
- clinical
Raw fresh water fish
Absorbs vitamin B12 (anemia)
155
Echinococcus granulosus
- type
- cycle
Extra intestinal tape worm infection
dog eat sheep meat, poop, sheep eat something near poop
Humans injest eggs from dog feces
Form hydatid cysts
156
Hydatid cysts
Echinococcus granulosus
157
Echinococcus granulosus cyst removal
Inject albendzole and ethanol to kill everythign with in
surgically remove
158
Cestode treatment
Praziquantel
Niclosamide
Albendazole
159
Niclosamide
Not effective against hydatid cysts
Inhibition of ox phos or stimualtion of ATPase activity
Oral
160
Inhibition of ox phos or stimualtion of ATPase activity
Niclosamide
161
Used for patients with compensated liver disease who do not want to be on long-term treatment
-Prenant next 2-3 years
Interferon-a
162
Cons of Inteferon-alpha treatment (4)
1. Parenteral administration
2. expensive
3. Side effects
- Flu like syndrome w/ fever, HA, chills, myalgia, malaise
4. Dangerous in decompensated cirrhosis
163
Interferon-alpha vs Pedylated interferon alpha -2a/2b
Interferon alpha-2b
- agents dont last long
Pegylated interferon alpha-2a
- Inferon has slower clearance
- longer half life
- Steady concentration
- Left frequently dosage
164
Endogenous Interferon alpha (3)
1. Protect nearby cells
2. signal macrophages and NK cells
3. Induce lysosome lysis of infected cell
165
Interferon alpha MOA (4)
1. Interferon alpha binds type 1 interferon receptor and activates JAK1 and TYK2
2. Activated JAK1 and TYK2 phosphorylate and type 1 interferon receptor
3. Phosphorylation of receptor leads to recruitment, phosphorylation and dimerization of siganl transducer and activator of transcrition 1 STAT1 and STAT2
4. STAT1 and STAT2 translocate to the nucleaus and activate the transcirption of interferion stimulated gens (ISGs)
166
ISGs inhibit viral replication at multiple steps (4)
1. ZAP
2. IFIT family
3. OAS-RNAseL pathway
4. PKR
167
Why do you not give Interferon alpha treatment to patients w/ decompensated cirrhosis?
As treat w/ interferon alpha, levels of ALT drop.
HBV DNA present
HBeAg present
As the cells start to lyse the level of ALT is going to spike
Bad w/ Decompensated cirrhosis
- If already have bad liver disease dont want to have spike to make disease even worse
- might send over edge
168
Nucleosides/ Nucleotides reverse transcriptase inhibitor (NRTI) MOA (2)
1) Inhibit Plus-strand synthesis by DNA polymerase
| 2) Inhibit Minus-strand syntheiss by reverse transcriptase
169
Which NRTI require converstion
Nucleosides have to be converted into triphospahte to be active
170
NTRIs list (5)
Nucleosides
1. Lamivudine
2. Telbivudine
3. Entecavir
Nucleotide
4. Tenofovir
5. Adefovir
171
Patient with impair purine/ pyrimidine kinase activity
Use Tenofovir ( nucleotide)
172
Factors that affect selection of antiviral nucleosides/nucleotides for HBV
1. Resistance profile
2. Efficacy (clearance of HBV DNA)
3. Usefulness w/ HIV co-infection
4. Pregnancy
173
First line treatment for wild-type HBV
Tenofovir
174
Used in patients with lamivudine, telbivudine or entecavir resistance
Tenofovir
175
Tenofovir
- characteristic
- AE
Resistance is rare
Nephrotoxicity
-Proximal renal tubule
176
First line HBV infection agent
| -characteristic
Entecavir
- Resistance rare in nucleoside naive patients
- 50% in patients resistant to lamivudine
- well tolerated
- limited SE
177
Use in patients with HBV and renal insufficiency
Entecavir
Better than Adefovir or tenofovir
178
HBV vs HCV treatment
HBV can not be fully eradicated
HCV can be cured
179
HCV
| - characteristic
RNA virus
| Can be cured
180
Tx for HCV through 2011
PEGylated interferon alpha plus ribavirin
181
Ribavirin
- what is it
- MOA (3)
- Use (2)
- Contraindications
Nucleoside
MOA not fully known
Interferes w/ synthesis GTP
Inhibits capping viral messenger RNA
Inhibits viral RNA-dep polymerase
Potentiates actions of PEGylated interferon alpha-2a and alpha-2b
Also upregulates interferon stimulated genes (ISGs)
Contraindicated
- patients w/ anemia
- PREGNANCY
182
HCV Tx new approaches (4, 3)
Target translation & processing step
- no generation of new viral particles
1) Protease inhibitors
- Simeprevir
- Telaprevir
- Boceprevir
- (and grazoprevir)
2) NS5B inhibitor
- Ledipasvir
- Elbasvir
- Velpatasvir
183
Protease inhibitors
Block the NS3 catalytic site or the NS3/NS4A interaction
184
Simeprevir
Second generation protease inhibitor
Administered in combination:
-Simeprevir + PEGylated interferon 2a or 2b + ribavirin
- Simeprevir + sofosbuvir +- ribavirin (chronic genotype 1 infection)
185
Telaprevir and Boceprevir
First generation protease inhibitors
Administed in combo w/ PEGylated interferon alpha-2a or alpha-2b + ribavirin (chronic genotype 1 infection)
Diminished clinical use due to simeprevir
186
Sofosuvir
novel NS5B inhibitor
Nucleotide analog
First N5Sb inhibitor available in US
Use in combo w/ other antivirals ledipasvir
Disrupts all genotypes
187
NS5B inhibitor
RNA dependent RNA polymerase needed for HCV replication
188
HCV drug that disrupts all genotypes
Sofosuvir
189
Ledipasvir
Elbasvir
Velpatasvir
Inhibit NS5A
All genotypes effective
Low barrier to resistance
Ledipasvir traditonally given in combination w/ ribavirin adn PEGylated interferon alpha -2a or 2b
190
HCV Tx FDA approval 2016
Genotype 1
- Ledipasvir + Sofosbuvir
Genotype 1, 2, 3
- Velpatasvir + sofosbuvir
- Elbasvir + grazopevir (once daily w/ fixed dosage)
191
Coinfection HBV and HCV
Severe liver damage
Decompensation cirrhosis
Greater incidence HCC
Treatment directed at predominant virus
PEGylated interferion alpha-2a or alpha 2b + ribavirin for 48 weeks
- effective against HBV infection
- just as effective against HBV and HCV co infection
192
HCV drugs
Interferons
- PEGylated interferon alpha-2b
- PEGYlated interferon alpha-2a
Nucleoside= ribavirin
Nucleotide= Sofosbuvir
Protease inhibitors
- Simeprevire
- Telaprevir
- Boceprevir
- Grazoprevir
NS5A Inhibitors
- Ledipasvir
- Elbasvir
- Velpatasvir
193
-asvir
NS5A inhibitor
194
-previr
Protease inhibitor
195
Ulcerative Colitis (UC) agents(4,1,3,1,4)
1) 5-ASA
- Sulfasalazine
- Mesalamine
- Olsalazine
- Balsalazide
2) Janus Kinase (JAK) inhibitors
- Tofacitinib
3) TNF-alpha inhibitors
- Adalimumab
- Golimumab*
- Inflixmab
4) Alpha-4 integrin inhibitors
- Vedolizumab
5) Corticosteroids
- Prednisone
- Dexamethasone
- Hydrocortisone
- Methylprednisone
196
Crohns Disease (CD)
1) IL-12/23 inhibitors
- Ustekinumab
2) TNF-alpha
- Adalimumab
- Certolizumab*
- Infliximab
3) ALpha-4 integrin inhibitors
- Natalizumab*
- Vedolizumab
4) Corticosteroids
- Prednisone
- Dexamethasone
- Hydrocortisone
- Methylprednisone
197
Sulfasalazine
Sulfapyridine + 5-ASA
SE w/ Sulfa part
198
Mesalamine
Single 5-ASA
199
Olsalazine
2 molecules of 5-ASA
200
Balsalazide
Inert carrier + 5-ASA
201
5-ASA MOA
Blocks cycloxygenase and all prostaglandin mediators down stream
Blocks Lipoxygenase and downstream leukotriene
Blocks both via arachidonic acid pathway
Also inhibit activation of NFkB
202
5-ASA contraindicated
All 5-ASA CI in ASA-allergic patients
Sulfasalazine CI in sulfonamide allergic patients
203
Use 5-ASA agents in
Mild to moderate U.C
204
Use only in active UC in women
Balsalazide
205
Use only for maintenance of UC
Olsalazine
206
IV inj TNF-alpha inhibitor
Infliximab
207
Mild to moderate U.C use
5-ASA agents (active and maintenance)
- Sulfasalazine
- Mesalamine
- except Olsalazien (maintance only)
- except balsalazide (only for active disease)
208
TNF-inhibitors (4)
| - derived
-mab
Adalimumab
Infliximab
Golimumab
Certolizumab
All monoclonal Ab derived from IgG except certolizumab
-recombinant humanized antibody freagment (Fab)
209
Recombinatn humanize antibody fragment (Fab) assoc w/
Certolizumab
210
TNF-alpha inhibitors MOA
Bind to an neutralizes membrane-associated and soluble human TNF-alpha mediated pro-inflammatory cell signaling
Ultimately blocking, leukocyte migration to site inflammation
211
TNF-alpha inhibitors SE
1) Worry about drugs suppressing immune system
- TB testing pre-therapy
2) Liver toxicity
- have baseline LFT, ALT/AST
3) Rare, dermatologic adn malignancies
212
Adalimumab
Moderate to severe UC & CD
213
Infliximab
Moderate to severe UC and CD
214
Golimumab
Moderate to severe UC ONLY
215
Certolizumab
Moderate to severe CD ONLY
216
Moderate to severe UC ONLY
Golimumab (TNF)
| Tofacitinib (JAK inhibitors)
217
Moderate to severe CD ONLY
Certolizumab (TNF)
Resistant
-Natalizumab (a-4)
-Ustekinumab (IL-12/23)
218
Moderate to severe UC and CD
Adalimumab (TNF)
Infliximab (TNF)
Vedolizumab (a-4)
219
TNF-alpha inhibitors maintenance dosing (4)
1) Adalimumab
- SQ every 2 wks
2) Infliximab
- IV infusion every 8 wks
3) Golimumab
- SQ every 4 weeks
4) Certolizumab
- SQ every 4 weeks
220
Alpha-4 Beta-7 inhibitors
-targets
Alpha 4 Beta 1 inhibitors
-targets
Can decreased lymphocyte migration and immune response to tissue damage adn inflammation that IBD patients have
MAdCAM-1
Inhibit most leukocytes except neutrophils
VCAM1
221
Alpha-4 Integrin inhibitors (2)
1) Natalizumab (IV)
- Recombinatnt IgG4 monoclonal Ab
- ALpha4beta1 (VCAM-1) & Alpha4Beta7 (MAdCAM-1)
2) Vedolizumab (IV)
- humanized IgG1 monoclonal Ab
- Alpha4beta7 (MAdCAM1)
222
Alpha -4 integrin inhibitors MOA
Limits integrins associated cella dhesion and subsequent transendothelial migration of leukocytes to cite of inflammation
223
Alpha-4 Integrin inhibitors SE
Natalizumab
- Infections
- Progressive multifocal leukoencephalopathy (assoc w/ John Cunningham virus), 3 risk factors
1) Treatment >2 yrs
2) Prior imunosuppressant tx
3) Anti-JC virus (JCV) Antibodies
Infusion related SE
Anti-medication antibodies
224
Progressive multifocal leukoencephalopathy PML
Alpha-4 Integrin inhibitor
| -Natalizumab
225
Natalizumab indications
Moderate to severe CD
| Not recommend in combination w/ immunosuppressants
226
Vedolizumab indications
Moderate to severe CD & UC
227
Alpha-4 Integrin inhibitors are use when
After inadequate response to convential or TNF-alpha therapy
Treatment resistance
228
Alpha 4 maintenance dosing
1) Natalizumab
- IV every 4 weeks
2) Vedolizumab
- IV every 8 weeks
229
Interleukin IL-12/23 inhibitors
- name
- type
- MOA
Ustekinumab
- fully human IgG1 monoclonal Ab
Bind to a P40 subunit of IL-12/23 receptor located on surface of T cells and NK cells
Thereby inhibiting signal transduction related activites and production of pro-inflammatory TH1 and TH17 cells
230
Interleukin IL-12/23 inhibitors
| -SE
Infections
| -TB testing therapy recommended
231
Moderate to severe CD for patients w/ intolerant or inadequate response (resistant) to conventional, steroids or TNF-alpha therapy
Interleukin IL-12/23
Ustekinumab
232
Dosing Interleukin IL-12/23 inhibitors
Ustekinumab
-IV as single infusion for induction
-SQ every 8 weeks (for maintenance)
233
Janus Kinase (JAK) inhibitors MOA
Bind to and inhibit free-floating and bound JAK1 and JAK3
Thereby ultimately inhibiting gene transcription and more cytokine release
234
JAK inhibitors
-SE (4)
Tofacitinib
-Oral
SE
- Lymphopenia/ lymphocytosis
- Neutropenia/ Anemia
- Fatigue
- Increased LDL & HDL
235
JAK inhibitors indications
| -dosage
Moderate to severe U.C
PO BID
Dont use w/ other drugs
236
Steroid agents Indications
Acute and/or Severe UC & CD uncontrolled by other conventional medications
NOT for maintenance of remission unless absolutely required
Use when have very acute very severe hospitalized requiring flair of their disease
Use in conjunction w/ other therapies
Lowest dose for shortest duration possible
237
Agents for Diarrhea (1,3,1,1)
1) Prostaglandin inhibitors
- Bismuth
2) Opiod Agonists
- Loperamide
- Diphenoxylate
- Eluxadoline
3) Serotonin (5HT3) antagonist
- Alosetron
4) Chloride channel inhibitors
- Crofelemer
238
Loperamide
- death
- MOA
- SE
Structurally related to opiods
No opiate like effects
OTC status
Cardiac toxicites --> death
Interferes w/ peristalsis (slows transit time)
-Direct action on circular and longitudinal muscles of intestinal wall
Dizziness, fatigure, urinary retention
239
Diphenoxylate
- Fun fact
- MOA
- SE
Opiate agonist
(similar to meperidine)
C-V
Atropine added to discourage abuse
- Cant spit or pee
Exert effect locally & centrally on GI smooth muscle cells; inhibits GI motility adn slows excess GI propulsion
SE= dizzy, drowsy, urinary retention
240
Eluxadoline
- Indication
- MOA
C- IV
Specific to GI tract, opiod receptors
Specifically for IBS-D
Agonist at opioid Mu & kappa receptors in GI tract
Antagonist at delta opioid receptors
-stomach, pancreas, biliary tract, secretions decreased
241
Eluxadoline SE
Hepatic/ pancreatic toxicity (increased enzymes)
| - Pancreatitis high risk w/o gallbladder
242
Eluxadoline contraindicated in (5)
1. Biliary duct obstruction
2. Sphincter of Oddi dysfunction
3. Alcoholism
4. History of pancreatitis
5. Severe hepatic impairment
243
Serotonin Antagonists
- MOA
- indicated
Alosetron
-Selectively blocks GI-based 5HT receptors
Chronic severe IBS-D not responsive to other conventional therapies (women)
244
Serotonin Antagonists SE
Constipation
Be concerned if over shoot --> Ischemic colitis
245
Alosetron contraindicated (5,3,3,1)
1) GI obstruction, perforation, stricture, adhesions or toxic megacolon
2) Diverticulitis, Crohns, UC
3) Impaired intestinal circulation, thormbophlebitis, or hypercoagulable state
4) Severe constipation; D/C immediately if develops
246
Cl- channel inhibitors
- from
- MOA
Crofelemer
- derived from dark red sap of Croton lechleri tree
MOA
- inhibits chloride ion secretion by blocking cAMP stimulated CFTR & Calcium activated (CaCC) chloride channels
- slows GI secretions
247
Crofelemer indicated in
Non-infection diarrhea in HIV/AID pts on anti-retroviral therapy
248
Abdominal pain drugs
Antimuscarinics
- Hyoscyamine
- Dicyclomine
- Clidinium/ Chlordiazepoxide
249
Antimuscarinics
- MOA
- Indications
- Se
Competitively inhibit autonomic, post-ganglionic cholinergic receptors
-decreases GI motility and spasms (pain)
Indications: Abd pain/ spasms, esp when assoc w/ IBS
SE: Classic anticholinergic
-Dry mouth, urinary retention, constipation, drowsiness, blurred vision
250
Meds for Constipation (2,3,1,1)
1) Laxative & Cathartic agents
2) Peripheral Opiod Antagonists
- Methylnaltrexone
- Naloxegol
- Alvimopan
3) Guanylate cyclase-C agonists
- Linaclotide
4) Selective chloride (C2) channel activators
- Lubiprostone
251
Non-infection diarrhea in HIV/AID pts on anti-retroviral therapy
Crofelemer
252
Linaclotide
- MOA
- Indications
- SE
Guanylate cyclase C agonist
Binds to GC-C on luminal surface or intestinal epitehlium and increases intracellular/extracellualr concentrations of cGMP
- Stimulate secretion of chloride/bicarb into lumin
- Activate CFTR
- Results in increased intestinal fluid and accelerated transit
IBS-C
Chronic idiopathic constipation (CIC)
SE:
- Diarrhea, GERD
253
Lubiprostone
- MOA
- Indication
- SE
Selective chloride (C2) channel activator
Prostaglandin analog
Increases intestinal fluid secretion by activating GI specific chloride channels (CIC-2) in luminal cells of intestinal epitehlium
IBS-C
CIC
Opiod induced constipation (OIC)
254
Peripheral opiods
- MOA
- Indications
Methylnaltrexone (IV/PO)
Naloxegol (PO)
Alvimopan (PO, hospital use only)
Block Mu-opioid receptor
Opiod induced constipation (OIC)
Alvimopan only for accelerating time to GI recovery following bowel resection surgery w/ primary anastomosis (prevention of postop ileus)
255
only for accelerating time to GI recovery following bowel resection surgery w/ primary anastomosis (prevention of postop ileus)
Alvimopan
256
Risk w/ Alvimopan
Risk of MI
REMS program requires use only in approved institutions for max of 15 doses
257
Cathartics
Quickly empty the bowel now
| Few hours
258
Laxative (5,4,2,4,2)
Can stimulate things, can soften things, can make osmotically draw in water
1) Stimulants
- Bisacodyl
- Castor oil
- Glycerin
- Senna
- Na Picosulfate
2) Osmotics
- Lactulose
- Mag citrate
- Polyethylene glycol (PEG)
- Sorbitol (glycerin)
3) Salines
- Mag. hydroxide
- Na phosphate
4) Bulk forming
- Dietary (fiber/ bra, fruits, grains, cereal)
- Psyllium
- Methylcellulose/ Carboxymethylcellulose
- Calcium polycarbophil
5) Stool softener
- Docusate
- Mineral oil
259
Bulk-forming/ Hydrophilic Colloidal agents
- MOA
- AE
- Interactions
Work to increase bulk-volume and water content, therby increasing GI motility
Bloating/ Obstruction
Lots of drug interactions
260
Stool softeners
- Known as
- 2 examples
- time
- MOA (2)
Known as surfactant or emollient laxatives
Docusate 'salts'
Mineral oil
Takes a few days for effect 1-3 days
Soften/lubricate feces via reduction in surface tension
Increased fluid secretion in GI tract
261
Stimulants (Irritants)
| -MOA (3)
```
Senna
Bisacodyl
Castor Oil
Glycerin
Sodium Picosulfate
(*- also has magnesium oxide/ anhydrous citric acid, converted to mag. citrate (osmotic)
```
Stimulate peristalsis
1) Irritant to enterocytes, GI smooth muscle leading to inflammation
- Na/K inhibition and/or increased in prostaglandin synthesis and secretion (via cAMP)
2) Promote water/ electrolyte accumulate in GI
- Castor oil is hydrolyzed to ricinoleic acid
3) Glycerin is a tri-hydroxyl alcohol and fxns as an irritant & an osmotic & lubricant agent
262
Stimulants
- Time
- AE
- CI
12-36 hrs
AE: cramping
- Urine discoloration (yellow-brown to red-pink) Senna
- fluid electrolyte disturbances
CI: GI obstruction, Ileus, impaction
263
Urine discoloration (yellow-brown to red-pink)
Senna
264
Stimulant and Osmotic, use to completely evacuate GI tract before surgery or scope
Bisacodyl & Glycerin (PR)
- Fast onset 0.5 -2 hr
Prepopik
- large dose PEG 3350 for pre-colonoscopy only
- given evening before w/ bisacodyl
265
Saline Agents
- 3 examples
- MOA
Magnesium salts
- Mag. sulfate
- Mag. hydroxide
Sodium phospahte
Magnesium/ Phospahte poorly absorbed, hyperosmolar solutions; osmotically retain water in GI tract
266
Saline agents
- Drug interactions
- Caution
Interactions: Diuretics (electrolyte balance)
Caution:
- renal disease (electolytes)
- CHF/ HTN (sodium)
267
Osmotic agents
- time
- AE
Lactulose
Magnesium citrate
Sorbitol
Polyethylene glycol (PEG-3350)
1-2 days
Electrolyte distrubance
268
Lactulose
Osmotic agent
Disaccharide of galactose and fructose aids in retaining fluid in GI
Also used for severe liver disease patients
- Hyperammonemia
- Change in pH traps ammonia in GI
269
Sorbitol
Osmotic agent
Non-absorbable sugar, hydrolyzed to short chain fatty acids retaining fluid in GI
Increased motility
270
Polyethylene glycol (PEG-3350)
Osmotic agent
Also use in bowel prep for scopes
Smaller doses for constipation (MIralax)
Isotonic solution of long chain PEGs not absorbed with retain water in GI
1-3 hrs large vol administration
0.5-3 days small dose
