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Flashcards in Block 6 - L1-L3 Deck (194):
1

What are the etiologic categories of constipation?

1. Mechanical obstruction
2. Drug-induced
3. Metabolic
4. Neurologic
5. Functional

2

In order to have a bowel movement, you need the right combination of what four components?

1. Solid waste
2. Water content
3. Motility
4. Lubrication

3

What are the 6 classes of constipation medications?

1. Bulking agents
2. Osmotic laxatives
3. Stimulant laxatives
4. Detergent laxatives
5. Lubricants
6. Large volume enemas

4

What are the 2 bulking agents?

1. Dietary fiber
2. Psyllium (Metamucil)

5

How do bulk laxatives work?

They increase stool weight, cause retention of fluid in the stool, and stimulate peristalsis. They are effective within 12-24 hours.

6

What are the side effects of bulk laxatives?

Flatulence

7

What are two caveats of using bulk laxatives?

1. Requires increased fluid intake
2. Cannot be used in debilitated patients who cannot drink adequate fluid

8

What are the 2 categories of osmotic laxatives?

1. Nonabsorbable sugars
2. Saline and magnesium salts

9

What are the 2 nonabsorbable sugar osmotic laxatives?

1. Lactulose
2. Sorbitol

10

How do nonabsorbable sugar osmotic laxatives work?

These are synthetic disaccharides degraded by bacteria in the colon into sugars and acid. This increases osmotic pressure, increasing stool water content.

11

What are the side effects of nonabsorbable sugars?

Bloating, cramps, flatulence, taste sickly sweet

12

What are the 2 saline/magnesium salt osmotic laxatives?

1. Magnesium citrate
2. Magnesium hydroxide (MOM)

13

How do saline and magnesium salt laxatives work?

These are osmotically active particles that increase intraluminal volume and stimulate intestinal activity. Mg also stimulates CCK, which stimulates bowel peristalsis.

14

What happens when high doses of saline and magnesium salt laxatives are given?

Rapid bowel evacuation

15

What are the side effects of saline and magnesium salt laxatives?

Dehydration, electrolyte abnormalities, ischemic colitis (rare)

16

What are the contraindications of saline and magnesium salt laxatives?

Bowel obstruction, patients with renal failure, cautious use in CHF and liver failure

17

What is magnesium citrate indicated for?

Bowel prep

18

What can happen in sick patients who are given sodium phosphate agents?

Acute phosphate nephropathy (intratubular deposition of calcium-phosphate)

19

What is seen on histology in acute phosphate nephropathy?

Purple crystals in the renal tubules

20

What are risk factors for acute phosphate neprhopathy?

1. Advanced age
2. Renal insufficiency
3. Volume depletion
4. Medications (ACEIs, ARBs)

21

What is polyethylene glycol?

Osmotically active, non-absorbable laxative that retains water in the stool and leads to softer stool and more frequent bowel movements

22

What are the different formulations of polyethylene glycol?

1. Colyte and Golytely - large volumes, used for bowel prep
2. Miralax - small doses, used for constipation

23

What are the 2 stimulant laxatives?

1. Senna
2. Bisacodyl (Dulcolax)

24

How do stimulant laxatives work?

Stimulate myoelectrical activity and increase peristalsis

25

What are the side effects of stimulant laxatives?

1. Cramping
2. Melanosis coli (senna)

26

What is melanosis coli?

Chronic use of senna can cause apoptosis of cells in the colon, a pigment is produced, and this is engulfed by macrophages. The gut appears brown on colonoscopy.

27

What is the one detergent laxative (stool softener)?

Docusate (Colase)

28

How do detergent laxatives work?

Surfactant, increases penetration of fluid into stool (emulsifies feces, water, fat)

29

What is the indication for detergent laxative use?

Prevention of hard stool formation

30

What are the 2 lubricants?

1. Glycerin (suppository or enema)
2. Mineral oil (enema)

31

How does glycerin work?

1. Osmotic - softens and lubricates stool
2. Irritant - stimulates rectal contractions

32

How does mineral oil work?

1. Coats fecal material, softening and lubricating stool

33

Why should mineral oil NEVER be administered orally to sick, debilitated patients?

Can aspirate and develop lipoid pneumonitis

34

What is the indication for lubricant use?

Fecal impaction

35

How do large volume enemas work?

Soften stool by increasing water content, distend distal colon, and induce peristalsis

36

What is the indication for large volume enemas?

Fecal impaction

37

What is fecal impaction?

Copious amounts of stool in the rectum

38

How is fecal impaction diagnosed?

Digital rectal exam

39

Where is the vomiting center located?

Medulla oblongata

40

What are the 4 categories of stimuli that can lead to emesis and where to do they act?

1. Motion sickness and certain drugs -> vestibular apparatus
2. Increased intracranial pressure, learned associations, and memory -> cerebral cortex and limbic system
3. Chemical stimuli in CSF and blood -> chemoreceptor trigger zone
4. Chemotherapy and GI compression -> NT receptors in GI tract and vagus nerve stimulation

41

What receptors are involved in the vestibular system?

ACh and H1 (histamine)

42

What receptors are involved in the cortex?

We don't know

43

What receptors are involved in the chemoreceptor trigger zone?

D2 (dopamine), 5HT3 (serotonin), and NK1 (neurokinin)

44

What receptors are involved in the GI tract?

5HT3, mechanoreceptors, chemoreceptors

45

What receptors are involved in the vomiting center?

ACh, H1, 5HT2

46

List the anti-emitic drugs (7).

1. Dopamine receptor antagonists
2. Serotonin (5HT3) antagonists
3. Antihistamines
4. Anticholinergics
5. Corticosteroids
6. Benzodiazepenes
7. Cannabinoids

47

What are the 2 dopamine receptor antagonists?

1. Prochlorperazine (Compazine)
2. Metoclopramide (Reglan)

48

How does Prochlorperazine work?

Central dopamine receptor antagonist in the chemoreceptor trigger zone (CTZ); it may also block the vagus nerve peripherally

49

What are the indications of Prochlorperazine?

1. Opioid-related nausea and vomiting
2. GI disorders, inflammation, infection

50

What are the AE of Prochlorperazine?

1. Extrapyramidal effects (stiff neck, etc.)
2. Dystonic reaction

51

What are the indications of Metoclopramide?

1. Chemotherapy-induced nausea and vomiting (only the less emetogenic agents)

52

What is an additional MOA of Metoclopramide?

Promotes motility in upper GI tract

Normally dopamine receptors inhibit cholinergic smooth muscle stimulation. Blocking this effects leads to a prokinetic action, which increases pressure of LES and increases gastric emptying.

53

What is Metoclopramide used to for as a motility agent?

Treatment of UGi tract dysmotility (diabetic gastroparesis, gastric stasis)

54

What are the AE of Metoclopramide?

1. Extrapyramidal (tardive dyskinesia, dystonia, akathisia, parkinsonism)
2. Acute dystonic reactions (trismus, torticollis - treat these with an anticholinergic)

55

What is the 5-HT3 receptor antagonist?

Ondanestron (Zofran)

56

What are the indications fo Ondansetron?

1. Chemotherapy-induced nausea/vomiting and prophylaxis
2. Radiation-induced nausea/vomiting and prophylaxis
3. Post-operative nausea/vomiting

57

What are the AE of Ondansetron?

1. QT prolongation
2. Headache

58

What is the NK1 receptor antagonist?

1. Aprepitant

59

What are the indications of Aprepitant?

1. Prevention of nausea/vomiting with highly emetogenic chemotherapy (often combined with a 5HT3 receptor antagonist and dexamethasone)

60

What are the AE of Aprepitant?

Fatigue, dizziness, diarrhea

61

What is the H1 receptor antagonist?

Promethazine (Phenergen)

62

What is the indication of Promethazine?

Motion sickness treatment and prevention

63

What is the AE of Promethazine?

Sedation

64

What is the pure anticholinergic?

Scopolamine

65

What is the indication of Scopolamine?

Treatment of motion sickness

66

What are the AE of Scopolamine?

Confusion, urinary retention, acute narrow angle glaucoma, dry mouth

67

What are the two corticosteroids and when are they used?

Prednisone and dexamethasone

Nausea due to increased intracranial pressure

68

What are the two benzodiazepenes and what are they used for?

Lorazepam and diazepam; anxiety-associated nausea and vomiting

69

What is the cannabinoid and what is its mechanism?

Dronabinol (Marinol)

Cannabinoid receptor (CB1) agonist

70

What are the indications of Dronabinol?

Breakthrough chemotherapy induced nausea and vomiting

71

What are the AE of Dronabinol?

Euphoria, dysphoria, paranoid delusions, cognitive clouding, somnolence/sedation, hypotension

72

What are the major differences between protozoa and helminthic infections?

Protozoa: complete replication within the definitive host, clinical illness results from single exposure, treatment goal = eradication

Helminths: life-cycle involves more than the definitive host, repeated exposures necessary for disease, treatment goal = eradication OR worm burden reduction

73

What are the 3 types of hosts?

1. Definitive: harbors sexual parasitic stage
2. Intermediate: harbors larval or asexual parasitic stage
3. Incidental: not necessary for parasitic survival

74

What is gametogony?

Sexual development

75

What is schizogony?

Asexual development

76

What are the 5 plasmodium species that cause human malaria?

1. Falciparum
2. Vivax
3. Malariae
4. Ovale
5. Knowlesi

77

Which plasmodium specie is responsible for nearly all fatal disease?

Falciparum

78

Which plasmodium species have a dormant liver stage (hypnozoites)?

Vivax and ovale

79

What are the 4 types of malaria treatment agents?

1. Gametocide
2. Sporonticide
3. Tissue Schizonticide
4. Blood Schizonticide

80

What category of malaria drugs destroys the sexual forms of the parasite in the blood and thereby prevent transmission of the infection to the mosquito?

Gametocide (primaquine and artemesinins)

81

What category of malaria drugs prevent the development of oocysts in the mosquito and thus ablate transmission?

Sporonticide (pyrimethamine, proguanil)

82

What are the 3 categories of malaria prophylaxis agents?

1. Terminal
2. Causal
3. Suppressive

83

What 3 variables are the basis of malaria treatment?

1. Infecting species
2. Clinical status of patient
3. Drug susceptibility of the species

84

Many antimalarial drugs work on what part of the organism?

The digestive vacuole

85

Discuss the use and effects of Chloroquine.

Ued for prophylaxis and treatment; schizonticidal in blood to all species (not active against exoerythrocytic phase)

86

What is the MOA of Chloroquine?

The chloroquine base diffuses into the food vacuole and becomes protonated, raising the pH of the normally acidic vacuole and reducing the rate of heme polymerization. This results in oxidative damage and death of the parasite.

87

Resistant in ___ to Chloroquine is widespread.

P. falciparum

88

What are the AEs of Chloroquine?

Pruritis, nausea, vomiting, abdominal pain, anorexia, malaise, blurred vision (rare)

89

Discuss the use and effects of Mefloquine (chloroquine derivative).

Used for prophylaxis and treatment of all forms of malaria (particularly chloroquine-resistant falciparum); schizonticidal in blood; MOA like chloroquine

90

What are the AE of mefloquine?

Nausea, vomiting, sleep and behavioral problems, neuropsychiatric toxicities

91

What are the contraindications of mefloquine?

Seizures, psychiatric diagnosis, arrhythmia

92

What are the drug interactions of mefloquine?

Quinine, quinidine, halofantrine

93

What is Atovaquone?

Naphthoquinone antibiotic

94

What is Malarone?

Proguanil + Atovaquone

95

What is the MOA of Atovaquone?

Inhibition of parasite mitochondrial electron transport

96

Why is Atovaquone often given with proguanil?

Normally, resistance develops quickly when used alone. It is quite effective when used in combination with proguanil.

97

What is the MOA of doxycycline?

Protein synthesis inhibition

98

What is doxycycline the drug of choice for?

Prophylaxis against mefloquine-resistant P. falciparum (and other multi-drug resistance)

99

What is quinine/quinidine the drug of choice for?

Treatment of severe disease with chloroquine-resistant P. falciparum malaria

100

Why is quinine/quinidine used with a second agent such as doxycycline?

To shorten duration and limit toxicity

101

What are the AE of quinine/quinidine?

GI, cinchonism (headache, nausea, visual disturbances, dizziness, tinnitus)

102

Can quinine be used in pregnancy?

Yes

103

What is Primaquine used for?

Treatment of exoerythrocytic forms of vivax and ovale malaria; gametocidal

104

What is Primaquine the drug of choice for?

Radical cure after chloroquine

105

What is the MOA of primaquine?

Probably similar to chloroquine

106

What are the AE of Primaquine?

Nausea, abdominal pain, cramps (infrequent); hematologic arrhythmias (rare)

107

What are the contraindications of Primaquine?

Granulocytopenia, G6PD deficiency

108

What is Artemisinin?

Rapidly acting schizonticide derived from old herbal therapy

109

A second agent is often used with Artemisinin to prevent ___.

Recrudescence (ACT = artemisinin combination therapies)

110

What is the MOA of Artemisinin?

Production of toxic free radicals in the parasite food vacuole

111

What are the main drugs used to prevent malaria?

Mefloquine, Malarone (atovaquone + proguanil), doxycycline

112

What drug should be given for chloroquine-sensitive P. falciparum infections?

Chloroquine

113

What drug should be given for P. vivax and ovale infections?

Chloroquine + primaquine

114

What drugs should be given for uncomplicated chloroquine-resistant P. falciparum infections?

1. Malarone
2. Artemether-lumefantrine
3. Quinine + doxy or tetra or clinda
4. Mefloquine

115

What drugs should be given for complicated chloroquine-resistant P. falciparum infections?

1. Quinindine + doxy or clinda
2. Artemisinin

116

How is amebiasis treated when there is an asymptomatic intestinal infection?

Not treated in endemic areas

Luminal agents (Iodoquinol, Paromomycin, Diloxanide furoate)

117

How is amebiasis treated when there is colitis, liver abscess, and/or ameboma?

Metronidazole + luminal agent

118

Material aspirated from an amoebic liver abscess resembles ___.

Anchovy paste

119

What is the drug of choice for extraluminal (tissue) amebiasis?

Metronidazole

120

What is the MOA of metronidazole?

Ferredoxin-linked processes reduce nitro group to a product that is lethal against anaerobic organisms

121

What are the AE of Metronidazole?

Nausea, vomiting, metallic taste, disulfuram-like reaction

122

What are the drug interactions with Metronidazole?

Anticoagulants, alcohol, anticonvulsants

123

What is Iodoquinol used for and what is its MOA?

Luminal amebic infections, other intestinal protozoa; MOA unknown

124

What are AE of Iodoquinol?

Neurotoxicity and nausea/vomiting

125

What are the primary treatment agents for Giardiasis?

Metronidazole and nitazoxanide (furazolidone and albendazole are alternate)

126

What are the management principles of Cryptosporidiosis?

1. Lactose-free diet
2. Antimotility agents
3. Restoration of immune response in HIV

127

Why is Cryptosporidiosis tough to treat?

It is an intracellular pathogen

128

What are some agents active against Cryptosporidiosis?

Nitazoxanide and Paromomycin

(Azithro and clarithro may be active)

129

What is the most effective agent to treat Toxoplasmosis?

Pyrimethamine

130

What must be added to Pyrimethamine in treating Toxoplasmosis?

Folinic acid

131

What drugs can be used to treat Leishmaniasis?

1. Sodium stibogluconate
2. Amphotericine B
3. Liposomal amphotericine B
4. Miltefosine

132

What is the mainstay of treatment for cutaneous and visceral leishmaniasis?

Sodium stibogluconate

133

What are the AEs of sodium stibogluconate?

GI, fever, HA, myalgias, arthralgias, rash, QT prolongation

134

What drugs are used to treat African Trypanosomiasis?

1. Pentamidine (does not cross BBB)
2. Suramin (does not cross BBB)
3. Melarsoprol
4. Eflonithine

135

What is the first line treatment for hemolymphatic Trypanosomiasis disease?

Suramin

136

What are the treatment options for American Trypanosomiasis?

1. Nifurtimox
2. Benznidazole

137

What is the drug of choice for acute Chagas disease?

Nifurtimox

138

What are the AE of Nifurtimox?

GI, rash, CNS

139

Chagas disease, Leishmaniasis, and sleeping sickness are caused by parasites characterized by the presence of ___.

Kinetoplasts (circular mitochondrial DNA colections)

140

Broadly, what are the contraindications of helminth treatment?

Pregnancy, GI tract ulcers

141

What is neurocysticercosis?

Disease of nervous system caused by taenia soliuma

142

When do symptoms of neurocysticercosis appear?

When cysts die, lose osmoregulation, and swell or leak Ag, causing inflammations

143

What are the three stages of cyst involution in neurocysticercosis?

1. Colloidal (fluid is turbid and scolex degenerates; capsule is thick with surrounding edema)
2. Granular (wall thickens, scolex is mineralized)
3. Calcification

144

How is Neurocysticercosis treated?

Albendazole and Praziquantel

145

Which helminths is Albendazole useful for?

1. Pinworm
2. Ascariasis
3. Hookworm
4. Tichuriasis
5. Strongyloidiasi
6. Echinococcus
7. Neurocysticercosis

146

What is the effect of Albendazole on calcified brain cysts in neurocysticerocosis?

None

147

What are the AE of Albendazole?

Minimal in the short term, elevated aminotransferases and GI effects in the long term

148

Which helminths is Praziquantel useful for?

1. Schistosomiasis
2. Chlonorchiasis
3. Paragonimiasis
4. Neurocysticercosis

149

What are the AE of Praziquantel?

HA, drowsiness, dizziness, abdominal pain

150

Why must Praziquantel be swallowed whole?

The drug is emetogenic

151

What are the contraindications of Praziquantel?

Ocular cysticercosis (inflammation)

152

Which helminths is Mebendazole useful for?

1. Ascariasis
2. Hookworm
3. Pinworm
4. Taeniasis
5. Trichinosis
6. Strongyloides

153

What are the AE of Mebendazole?

Minimal GI, neutropenia, hepatic (long term), hypersensitivity

154

Which helminths is Pyrantel pamoate useful for?

1. Pinworm
2. Ascaris
3. Hookworm
NOT trichuriasis or Strongyloidiasis

155

What is the MOA of Pyrantel pamoate?

Luminal agent that leads to depolarizing neuromuscular blocking, causing release of ACh and inhibition of cholinesterase (worm paralysis)

156

What is the DOC for filariasis?

Diethylcarbamazine

157

What is the DOC for onchocerciasis?

Ivermectin

158

What is the DOC for strongyloides?

Ivermectin

159

What i the MOA of Ivermectin?

Paralyzes nematodes and arthropods by intesnsifying GABA-mediated signals

160

What are the AE of Ivermectin?

Mild hypersensitivity from worm death, but severe Mazotti reactio in onchocerciasis

161

What are the symptoms of GERD?

Heartburn, regurgitation, vomiting, pain on swallowing, vocal cords changes, acid taste in throat

Less common: stomach pain, non-burning chest pain, difficulty swallowing, chronic sore throat, and/or cough

162

How is mild GERD treated?

Dietary changes and non-prescription medications

163

What drugs are used to treat GERD?

Antacids and histamine antagonists

164

What are antacids used for and what is their MOA?

Short-term relief; neutralizes gastric acid and reduces delivery to the duodenum

165

What are some antacids?

Tums, Maalox, Mylanta

166

What are the AE of antacids?

Ingestion of large amounts can lead to hypercalcemia, alkalosis, and renal impairment = milk-alkali syndrome

167

What is the MOA of Histamine-2 receptor antagonists?

Reduce production of acid in the stomach by blocking the H2 receptors on the pareital cell

168

What are H2 receptor antagonists used for?

PUD

169

What are the 4 H2 receptor antagonists?

Ranitidine, Famotidine, Cimetidine, Nizatidine

170

What two barriers can H2 blockers cross?

BBB and placental barrier

171

What are rare AE of H2 receptor antagonists?

1. Gynecomastia and impotence (cimetidine)
2. Hematopoietic and immune effects (B12 deficiency and idiosyncratic myelosuppression)
3. CNS (confusion and agitation)
4. Hepatic effects
5. Cardiac effects (bradycardia, hypotension)
6. Renal (mild increase in creatinine with cimetidine)

172

H2 receptor blockers work at the ___ stage, whereas PPIs work at the ___ stage.

Initial; terminal

173

What is the MOA of PPIs?

Block acid secretion by irreversibly binding to and inhibiting the H-K ATPase pump that resides on the luminal surface of the parietal cell membrane

174

What are the 3 phases of activation of PPIs?

1. They are weak bases concentrated in the acid compartment of parietal cells.
2. The inactive prodrug is activated in the acid environment
3. A reactive sulfhydryl group then forms a disulfide bond with cysteine residue on the H-K ATPase pump, inactivating the enzyme.

175

PPIs work poorly in ___ patients.

Fating

176

What are the 5 PPIs?

Omeprazole, Lansoprazole, Rabedprazole, Pantoprazole, Esomeprazole

177

A single dose of PPIs can inhibit ___% of gastric acid secretion.

95

178

Why should H2 antagonists and PPIs not be given together?

H2 antagonists reduce efficacy of PPIs

179

PPIS are the DOC for what?

Zollinger-Ellison syndrome
GERD when not response to H2 antagonists

180

PPIs reduce absorption of ___ and increase absorption of ___.

Ketoconazol;e digoxin

181

Prolonged use of PPIs can result in what deficiency?

Vitamin B12 (need acid environment for B12 absorption)

182

What are the AE of PPIs?

Few and mild
Diarrhea, headache, drowsiness, muscle pain, constipation

183

What are mucosal protective agents?

Sucralate - sulphated polysaccharide complexed with aluminum hydroxide that polymerizes and binds electively to necrotic tissue, creating a barrier between the gastric contents and the mucosa

184

What is the indication for Sucralate?

Treating duodenal ulcers (non-NSAID related), suppression of H. pylori

185

___ promotes the absorption of the aluminum in sucralfate.

Citric acid

186

Sucralate should not be given with what 2 drugs?

Cimetidine and ranitidine

187

What other drug acts like sucralfate to bind necrotic tissue and create a barrier?

Colloidal bismuth (Pepto)

188

What is Misoprostol?

Used in the prevention of NSAID-induced gastroduodenal ulcers

189

Of the drugs used to treat GERD and ulcers, which are eliminated renally (or primarily renally)?

H2 antagonists (cimetidine is hepato-renal) + Carafate (Sulcralfate)

190

Of the drugs used to treat GERD and ulcers, which are eliminated hepatically?

PPIs

191

Of the drugs used to treat GERD and ulcers, which have the shorter half-life?

H2 antagonists (and Sulcralfate)

192

Which drugs are safe for pregnancy and lactation?

H2RAs (espeically cimetidine and ranitidine)

193

Which drugs should be avoided in pregnancy?

Antacids
Misoprostol (induces abortion)

194

How is H. pylori treated?

PPI + 2-3 antibiotics for 2 weeks