Flashcards in Block 6 - L1-L3 Deck (194):
What are the etiologic categories of constipation?
1. Mechanical obstruction
In order to have a bowel movement, you need the right combination of what four components?
1. Solid waste
2. Water content
What are the 6 classes of constipation medications?
1. Bulking agents
2. Osmotic laxatives
3. Stimulant laxatives
4. Detergent laxatives
6. Large volume enemas
What are the 2 bulking agents?
1. Dietary fiber
2. Psyllium (Metamucil)
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.
What are the side effects of bulk laxatives?
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
What are the 2 categories of osmotic laxatives?
1. Nonabsorbable sugars
2. Saline and magnesium salts
What are the 2 nonabsorbable sugar osmotic laxatives?
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.
What are the side effects of nonabsorbable sugars?
Bloating, cramps, flatulence, taste sickly sweet
What are the 2 saline/magnesium salt osmotic laxatives?
1. Magnesium citrate
2. Magnesium hydroxide (MOM)
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.
What happens when high doses of saline and magnesium salt laxatives are given?
Rapid bowel evacuation
What are the side effects of saline and magnesium salt laxatives?
Dehydration, electrolyte abnormalities, ischemic colitis (rare)
What are the contraindications of saline and magnesium salt laxatives?
Bowel obstruction, patients with renal failure, cautious use in CHF and liver failure
What is magnesium citrate indicated for?
What can happen in sick patients who are given sodium phosphate agents?
Acute phosphate nephropathy (intratubular deposition of calcium-phosphate)
What is seen on histology in acute phosphate nephropathy?
Purple crystals in the renal tubules
What are risk factors for acute phosphate neprhopathy?
1. Advanced age
2. Renal insufficiency
3. Volume depletion
4. Medications (ACEIs, ARBs)
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
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
What are the 2 stimulant laxatives?
2. Bisacodyl (Dulcolax)
How do stimulant laxatives work?
Stimulate myoelectrical activity and increase peristalsis
What are the side effects of stimulant laxatives?
2. Melanosis coli (senna)
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.
What is the one detergent laxative (stool softener)?
How do detergent laxatives work?
Surfactant, increases penetration of fluid into stool (emulsifies feces, water, fat)
What is the indication for detergent laxative use?
Prevention of hard stool formation
What are the 2 lubricants?
1. Glycerin (suppository or enema)
2. Mineral oil (enema)
How does glycerin work?
1. Osmotic - softens and lubricates stool
2. Irritant - stimulates rectal contractions
How does mineral oil work?
1. Coats fecal material, softening and lubricating stool
Why should mineral oil NEVER be administered orally to sick, debilitated patients?
Can aspirate and develop lipoid pneumonitis
What is the indication for lubricant use?
How do large volume enemas work?
Soften stool by increasing water content, distend distal colon, and induce peristalsis
What is the indication for large volume enemas?
What is fecal impaction?
Copious amounts of stool in the rectum
How is fecal impaction diagnosed?
Digital rectal exam
Where is the vomiting center located?
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
What receptors are involved in the vestibular system?
ACh and H1 (histamine)
What receptors are involved in the cortex?
We don't know
What receptors are involved in the chemoreceptor trigger zone?
D2 (dopamine), 5HT3 (serotonin), and NK1 (neurokinin)
What receptors are involved in the GI tract?
5HT3, mechanoreceptors, chemoreceptors
What receptors are involved in the vomiting center?
ACh, H1, 5HT2
List the anti-emitic drugs (7).
1. Dopamine receptor antagonists
2. Serotonin (5HT3) antagonists
What are the 2 dopamine receptor antagonists?
1. Prochlorperazine (Compazine)
2. Metoclopramide (Reglan)
How does Prochlorperazine work?
Central dopamine receptor antagonist in the chemoreceptor trigger zone (CTZ); it may also block the vagus nerve peripherally
What are the indications of Prochlorperazine?
1. Opioid-related nausea and vomiting
2. GI disorders, inflammation, infection
What are the AE of Prochlorperazine?
1. Extrapyramidal effects (stiff neck, etc.)
2. Dystonic reaction
What are the indications of Metoclopramide?
1. Chemotherapy-induced nausea and vomiting (only the less emetogenic agents)
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.
What is Metoclopramide used to for as a motility agent?
Treatment of UGi tract dysmotility (diabetic gastroparesis, gastric stasis)
What are the AE of Metoclopramide?
1. Extrapyramidal (tardive dyskinesia, dystonia, akathisia, parkinsonism)
2. Acute dystonic reactions (trismus, torticollis - treat these with an anticholinergic)
What is the 5-HT3 receptor antagonist?
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
What are the AE of Ondansetron?
1. QT prolongation
What is the NK1 receptor antagonist?
What are the indications of Aprepitant?
1. Prevention of nausea/vomiting with highly emetogenic chemotherapy (often combined with a 5HT3 receptor antagonist and dexamethasone)
What are the AE of Aprepitant?
Fatigue, dizziness, diarrhea
What is the H1 receptor antagonist?
What is the indication of Promethazine?
Motion sickness treatment and prevention
What is the AE of Promethazine?
What is the pure anticholinergic?
What is the indication of Scopolamine?
Treatment of motion sickness
What are the AE of Scopolamine?
Confusion, urinary retention, acute narrow angle glaucoma, dry mouth
What are the two corticosteroids and when are they used?
Prednisone and dexamethasone
Nausea due to increased intracranial pressure
What are the two benzodiazepenes and what are they used for?
Lorazepam and diazepam; anxiety-associated nausea and vomiting
What is the cannabinoid and what is its mechanism?
Cannabinoid receptor (CB1) agonist
What are the indications of Dronabinol?
Breakthrough chemotherapy induced nausea and vomiting
What are the AE of Dronabinol?
Euphoria, dysphoria, paranoid delusions, cognitive clouding, somnolence/sedation, hypotension
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
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
What is gametogony?
What is schizogony?
What are the 5 plasmodium species that cause human malaria?
Which plasmodium specie is responsible for nearly all fatal disease?
Which plasmodium species have a dormant liver stage (hypnozoites)?
Vivax and ovale
What are the 4 types of malaria treatment agents?
3. Tissue Schizonticide
4. Blood Schizonticide
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)
What category of malaria drugs prevent the development of oocysts in the mosquito and thus ablate transmission?
Sporonticide (pyrimethamine, proguanil)
What are the 3 categories of malaria prophylaxis agents?
What 3 variables are the basis of malaria treatment?
1. Infecting species
2. Clinical status of patient
3. Drug susceptibility of the species
Many antimalarial drugs work on what part of the organism?
The digestive vacuole
Discuss the use and effects of Chloroquine.
Ued for prophylaxis and treatment; schizonticidal in blood to all species (not active against exoerythrocytic phase)
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.
Resistant in ___ to Chloroquine is widespread.
What are the AEs of Chloroquine?
Pruritis, nausea, vomiting, abdominal pain, anorexia, malaise, blurred vision (rare)
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
What are the AE of mefloquine?
Nausea, vomiting, sleep and behavioral problems, neuropsychiatric toxicities
What are the contraindications of mefloquine?
Seizures, psychiatric diagnosis, arrhythmia
What are the drug interactions of mefloquine?
Quinine, quinidine, halofantrine
What is Atovaquone?
What is Malarone?
Proguanil + Atovaquone
What is the MOA of Atovaquone?
Inhibition of parasite mitochondrial electron transport
Why is Atovaquone often given with proguanil?
Normally, resistance develops quickly when used alone. It is quite effective when used in combination with proguanil.
What is the MOA of doxycycline?
Protein synthesis inhibition
What is doxycycline the drug of choice for?
Prophylaxis against mefloquine-resistant P. falciparum (and other multi-drug resistance)
What is quinine/quinidine the drug of choice for?
Treatment of severe disease with chloroquine-resistant P. falciparum malaria
Why is quinine/quinidine used with a second agent such as doxycycline?
To shorten duration and limit toxicity
What are the AE of quinine/quinidine?
GI, cinchonism (headache, nausea, visual disturbances, dizziness, tinnitus)
Can quinine be used in pregnancy?
What is Primaquine used for?
Treatment of exoerythrocytic forms of vivax and ovale malaria; gametocidal
What is Primaquine the drug of choice for?
Radical cure after chloroquine
What is the MOA of primaquine?
Probably similar to chloroquine
What are the AE of Primaquine?
Nausea, abdominal pain, cramps (infrequent); hematologic arrhythmias (rare)
What are the contraindications of Primaquine?
Granulocytopenia, G6PD deficiency
What is Artemisinin?
Rapidly acting schizonticide derived from old herbal therapy
A second agent is often used with Artemisinin to prevent ___.
Recrudescence (ACT = artemisinin combination therapies)
What is the MOA of Artemisinin?
Production of toxic free radicals in the parasite food vacuole
What are the main drugs used to prevent malaria?
Mefloquine, Malarone (atovaquone + proguanil), doxycycline
What drug should be given for chloroquine-sensitive P. falciparum infections?
What drug should be given for P. vivax and ovale infections?
Chloroquine + primaquine
What drugs should be given for uncomplicated chloroquine-resistant P. falciparum infections?
3. Quinine + doxy or tetra or clinda
What drugs should be given for complicated chloroquine-resistant P. falciparum infections?
1. Quinindine + doxy or clinda
How is amebiasis treated when there is an asymptomatic intestinal infection?
Not treated in endemic areas
Luminal agents (Iodoquinol, Paromomycin, Diloxanide furoate)
How is amebiasis treated when there is colitis, liver abscess, and/or ameboma?
Metronidazole + luminal agent
Material aspirated from an amoebic liver abscess resembles ___.
What is the drug of choice for extraluminal (tissue) amebiasis?
What is the MOA of metronidazole?
Ferredoxin-linked processes reduce nitro group to a product that is lethal against anaerobic organisms
What are the AE of Metronidazole?
Nausea, vomiting, metallic taste, disulfuram-like reaction
What are the drug interactions with Metronidazole?
Anticoagulants, alcohol, anticonvulsants
What is Iodoquinol used for and what is its MOA?
Luminal amebic infections, other intestinal protozoa; MOA unknown
What are AE of Iodoquinol?
Neurotoxicity and nausea/vomiting
What are the primary treatment agents for Giardiasis?
Metronidazole and nitazoxanide (furazolidone and albendazole are alternate)
What are the management principles of Cryptosporidiosis?
1. Lactose-free diet
2. Antimotility agents
3. Restoration of immune response in HIV
Why is Cryptosporidiosis tough to treat?
It is an intracellular pathogen
What are some agents active against Cryptosporidiosis?
Nitazoxanide and Paromomycin
(Azithro and clarithro may be active)
What is the most effective agent to treat Toxoplasmosis?
What must be added to Pyrimethamine in treating Toxoplasmosis?
What drugs can be used to treat Leishmaniasis?
1. Sodium stibogluconate
2. Amphotericine B
3. Liposomal amphotericine B
What is the mainstay of treatment for cutaneous and visceral leishmaniasis?
What are the AEs of sodium stibogluconate?
GI, fever, HA, myalgias, arthralgias, rash, QT prolongation
What drugs are used to treat African Trypanosomiasis?
1. Pentamidine (does not cross BBB)
2. Suramin (does not cross BBB)
What is the first line treatment for hemolymphatic Trypanosomiasis disease?
What are the treatment options for American Trypanosomiasis?
What is the drug of choice for acute Chagas disease?
What are the AE of Nifurtimox?
GI, rash, CNS
Chagas disease, Leishmaniasis, and sleeping sickness are caused by parasites characterized by the presence of ___.
Kinetoplasts (circular mitochondrial DNA colections)
Broadly, what are the contraindications of helminth treatment?
Pregnancy, GI tract ulcers
What is neurocysticercosis?
Disease of nervous system caused by taenia soliuma
When do symptoms of neurocysticercosis appear?
When cysts die, lose osmoregulation, and swell or leak Ag, causing inflammations
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)
How is Neurocysticercosis treated?
Albendazole and Praziquantel
Which helminths is Albendazole useful for?
What is the effect of Albendazole on calcified brain cysts in neurocysticerocosis?
What are the AE of Albendazole?
Minimal in the short term, elevated aminotransferases and GI effects in the long term
Which helminths is Praziquantel useful for?
What are the AE of Praziquantel?
HA, drowsiness, dizziness, abdominal pain
Why must Praziquantel be swallowed whole?
The drug is emetogenic
What are the contraindications of Praziquantel?
Ocular cysticercosis (inflammation)
Which helminths is Mebendazole useful for?
What are the AE of Mebendazole?
Minimal GI, neutropenia, hepatic (long term), hypersensitivity
Which helminths is Pyrantel pamoate useful for?
NOT trichuriasis or Strongyloidiasis
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)
What is the DOC for filariasis?
What is the DOC for onchocerciasis?
What is the DOC for strongyloides?
What i the MOA of Ivermectin?
Paralyzes nematodes and arthropods by intesnsifying GABA-mediated signals
What are the AE of Ivermectin?
Mild hypersensitivity from worm death, but severe Mazotti reactio in onchocerciasis
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
How is mild GERD treated?
Dietary changes and non-prescription medications
What drugs are used to treat GERD?
Antacids and histamine antagonists
What are antacids used for and what is their MOA?
Short-term relief; neutralizes gastric acid and reduces delivery to the duodenum
What are some antacids?
Tums, Maalox, Mylanta
What are the AE of antacids?
Ingestion of large amounts can lead to hypercalcemia, alkalosis, and renal impairment = milk-alkali syndrome
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
What are H2 receptor antagonists used for?
What are the 4 H2 receptor antagonists?
Ranitidine, Famotidine, Cimetidine, Nizatidine
What two barriers can H2 blockers cross?
BBB and placental barrier
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)
H2 receptor blockers work at the ___ stage, whereas PPIs work at the ___ stage.
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
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.
PPIs work poorly in ___ patients.
What are the 5 PPIs?
Omeprazole, Lansoprazole, Rabedprazole, Pantoprazole, Esomeprazole
A single dose of PPIs can inhibit ___% of gastric acid secretion.
Why should H2 antagonists and PPIs not be given together?
H2 antagonists reduce efficacy of PPIs
PPIS are the DOC for what?
GERD when not response to H2 antagonists
PPIs reduce absorption of ___ and increase absorption of ___.
Prolonged use of PPIs can result in what deficiency?
Vitamin B12 (need acid environment for B12 absorption)
What are the AE of PPIs?
Few and mild
Diarrhea, headache, drowsiness, muscle pain, constipation
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
What is the indication for Sucralate?
Treating duodenal ulcers (non-NSAID related), suppression of H. pylori
___ promotes the absorption of the aluminum in sucralfate.
Sucralate should not be given with what 2 drugs?
Cimetidine and ranitidine
What other drug acts like sucralfate to bind necrotic tissue and create a barrier?
Colloidal bismuth (Pepto)
What is Misoprostol?
Used in the prevention of NSAID-induced gastroduodenal ulcers
Of the drugs used to treat GERD and ulcers, which are eliminated renally (or primarily renally)?
H2 antagonists (cimetidine is hepato-renal) + Carafate (Sulcralfate)
Of the drugs used to treat GERD and ulcers, which are eliminated hepatically?
Of the drugs used to treat GERD and ulcers, which have the shorter half-life?
H2 antagonists (and Sulcralfate)
Which drugs are safe for pregnancy and lactation?
H2RAs (espeically cimetidine and ranitidine)
Which drugs should be avoided in pregnancy?
Misoprostol (induces abortion)