Pharmacology week 3 Flashcards
(107 cards)
1
Q
What are the four H2 receptor antagonists used for GI issues
A
Cimetidine, ranitidine, famotidine, nizatidine
2
Q
Mechanism of action of famotidine
A
Inhibit acid production by reversibly competing with histamine for binding to H2 receptors on basolateral membrane of parietal cells
3
Q
Therapeutic uses of famotidine
A
Promote healing of gastric and duodenal ulcers
Treat uncomplicated GERD
Prevent occurrence of stress ulcers
4
Q
Adverse effects of famotidine
A
Diarrhea, headache, drowsiness, fatigue, muscular pain, constipation
5
Q
How does dopamine exert its inhibitory effects on GI motility
A
Suppression of ACh release from myenteric motor neurons → mediated by D2 dopamine receptors
6
Q
Mechanism of action of metoclopramide
A
5HT4 receptor agonism
Vagal and central 5HT3 antagonist
Sensitization of muscarinic receptors on smooth muscle
Dopamine receptor antagonism
7
Q
Effects of upper GI tract with metoclopramide
A
Increases LES tone and stimulates antral and small intestinal contractions
8
Q
Metabolism of metoclopramide
A
Undergoes sulfation and glucuronide conjugation by liver
9
Q
1st line therapy in px with gastroparesis
A
Metoclopramide
10
Q
Therapeutic uses of metoclopramide
A
Ameliorate nausea and vomiting that often accompany GI dysmotility syndromes
Prevention of chemotherapy induced emesis
11
Q
Main adverse effect of metoclopramide
A
Extrapyramidal symptoms
12
Q
Mechanism of action of domperidone
A
Dopamine D2 antagonist
13
Q
Metabolism of domperidone
A
Undergoes metabolism via hepatic CYP3A4, N-dealkylation, and hydroxylation
14
Q
Therapeutic use of domperidone
A
Gastroparesis
15
Q
Adverse effects of domperidone
A
Increased risk ventricular arrhythmias and elevates prolactin levels
16
Q
2 important effects of the fermentation of fiber
A
Production of short-chain fatty acids that are trophic for colonic epithelium
Increase in bacterial mass
17
Q
What happens when fiber is not fermented
A
Fiber that is not fermented can attract water and increase stool bulk
18
Q
Derived from seed of plantago herb
A
Psyllium husk
19
Q
Therapeutic use of Psyllium husk
A
Fiber supplementation for constipation
20
Q
Mechanism of action of Psyllium husk
A
Soluble fiber that absorbs water to form gel-like mass → bulkier stool that stimulates bowel muscles and makes it softer/easier to pass
21
Q
Adverse effect of Psyllium husk
A
Bloating
22
Q
Examples of stimulant irritant laxatives
A
Senna and glycerine
23
Q
What are the active components of senna and how are they activated
A
Sennoside A and B, which are activated by bacterial action in the colon, converting glycosides to active monoanthrones
24
Q
Long-term adverse effect of chronic senna use
A
Melanosis coli
25
What is the mechanism of action of rectal glycerin suppositories?
Local mucosal irritation → stimulates rectal contractions
Hyperosmotic → draws water into stool to soften it
Lubricant → eases stool passage
26
What risks are associated with repeated use of hypotonic and sodium phosphate enemas?
Hypotonic enemas → Hyponatremia
Sodium phosphate enemas → Hypocalcemia
27
Mechanism of action of bismuth subsalicylate
In low pH of stomach reacts with hydrochloric acid to form bismuth oxychloride and salicylic acid
Inhibits prostaglandins (salicylate), antimicrobial effect through toxin binding (bismuth), coating effect on mucosa (both)
28
Therapeutic uses of bismuth subsalicylate
Prevention and tx of traveler's diarrhea
Control of indigestion, nausea or diarrhea
29
Adverse effects of bismuth subsalicylate
Dark stools and black staining in tongue
CNS effects, tinnitus
30
Mechanism of action of loperamide
Increases small intestinal and mouth-to-cecum transit times
Increases anal sphincter tone
31
How does loperamide have antisecretory activity against cholera toxin and E coli toxin
Acts on Gi linked receptors to counter the stimulation of adenylyl cyclase activity by toxins
32
Dosing of loperamide
Adult dose is 4 mg initially followed by 2 mg after each subsequent loose stool, up to 16 mg/day
33
Therapeutic uses of loperamide
Effective against traveler's diarrhea
Used as adjunct tx in many forms of chronic diarrheal disease
34
Overdosage effects of loperamide
Constipation, CNS depression (children) and paralytic ileus
35
FDA black box warning of loperamide
Exceeding recommended dosage can result in cardiac events including torsades de pointes, cardiac arrest and death
36
Mechanism of action of octreotide
Analogue of somatostatin
Inhibits secretion of 5HT
37
Therapeutic uses of octreotide
Diarrhea associated with carcinoid tumors and VIP-secreting tumors
Variceal bleeding
Intestinal dysmotility
Pancreatitis
38
Long term effects of octreotide
Gallstone formation and hypo or hyperglycemia
39
Mechanism of action of cholestyramine
Bile acid sequestrants
Effectively bind bile acids and some bacterial toxins
40
Therapeutic uses of cholestyramine
Tx of bile salt-induced diarrhea → px with resection of distal ileum or after cholecystectomy
41
Where is the central emesis (vomiting) center located?
In the lateral reticular formation of the brainstem, adjacent to the chemoreceptor trigger zone (CTZ) and the nucleus of the solitary tract (NTS).
42
What is the role of the chemoreceptor trigger zone (CTZ) in vomiting?
It lacks a blood-brain barrier, allowing it to detect toxins in blood and CSF and relay signals to the emesis center to induce vomiting
43
Which nerves relay information from the gut to the emesis center?
Vagus nerve → via the NTS
Splanchnic efferents → via the spinal cord
44
Which brain regions are involved in the perception of nausea?
Insular cortex
Anterior cingulate cortex
Orbitofrontal cortex
Somatosensory cortex
Prefrontal cortex
45
Mechanism of action of ondansetron
5HT3 receptor antagonists: acts in NTS and CTZ regions
46
Metabolism of ondansetron
Extensively metabolized in liver by CYP1A2, CYP2D6 and CYP3A4, followed by glucuronide or sulfate conjugation
47
Gold standard for treatment of PONV
Ondansetron
48
Therapeutic effects of ondansetron
Effective against hyperemesis of pregnancy and PONV, but not against motion sickness
49
Adverse effects of ondansetron
Constipation or diarrhea, headache, light-headedness
Serotonin syndrome
50
Mechanism of action of aprepitant
NK1 receptor antagonists (receptors for neuropeptide substance P)
51
Contraindications for aprepitant
Contraindicated in px receiving cisapride, terfenadine, astemizole, pimozide
52
Therapeutic uses of aprepitant
Emetogenic chemotherapy, along with 5HT3 antagonist and dexamethasone
53
Injectable form of aprepitant
Fosaprepitant
54
Mechanism of action of dronabinol
Stimulation of CB1 subtype of cannabinoid receptors on neurons and around CTZ and brainstem emetic centers
55
Principal active metabolite of dronabinol
11-OH-delta-9-tetrahydrocannabinol
56
Therapeutic uses of dronabinol
Prophylactic agent in px receiving cancer chemotherapy when other antiemetic medications are not effective
57
Adverse effects of dronabinol
Complex effects on CNS → prominent central sympathomimetic activity
58
Mechanism of action of cinitapride
Triple serotonergic effect
5HT4 receptor antagonists
5HT1 receptor agonist
5HT2 receptor antagonist
59
Therapeutic uses of cinitapride
Functional dyspepsia
Delayed gastric emptying
GERD adjunct
Nausea and vomiting
Irritable bowel syndrome
60
Adverse effect of cinitapride
Hyperprolactinemia → galactorrhea or gynecomastia due to dopamine antagonism
61
Mechanism of action of flunarizine
Blocks T and L type calcium channels, preventing neuronal excitability and vasospasm
62
Therapeutic uses of flunarizine
Vestibular vertigo with nausea/vomiting
Prevention motion sickness
Meniere disease
63
Adverse effects of flunarizine
Neurological → sedation, fatigue, depression, extrapyramidal symptoms
Metabolic → frequent weight gain
64
Mechanims of action of pentofixiline
Inhibits phosphodiesterase (PDE) leading to increased AMPc levels in blood cells → decreased platelet aggregation and improves erythrocyte flexibility
65
Therapeutic uses of pentofixiline
Alcoholic hepatitis
Chronic mesenteric ischemia
66
Mechanism of action of pinaverio
Blocks voltage-dependent calcium channels in smooth muscle of GI tract, reducing calcium influx
67
Therapeutic uses of pinaverio
Irritable bowel syndrome
Functional GI disorders with spastic component
Biliary dyskinesia and spastic colitis
68
Mechanism of action of sibutramine
Inhibits reuptake of serotonin, norepinephrine, and dopamine in hypothalamus → this increases availability of these neurotransmitters
69
Therapeutic use of sibutramine
Obesity management as adjunct to diet and exercise in:
BMI >30
BMI >27 with comorbidities
70
Mechanism of action of phentermine
Acts primarily as norepinephrine releasing agent in hypothalamus
Increases levels of norepinephrine
71
Therapeutic use of phentermine
Short term adjunct in management of exogenous obesity
72
Mechanism of action of rimonabant
Selectively blocks CB1 receptors (inverse agonist) in:
CNS (hypothalamus)
Peripheral tissues (adipose tissue, liver, GI tract)
73
Therapeutic uses of rimonabant
Obesity management
Metabolic syndrome
Type 2 diabetes
Dyslipidemia
74
Most potent suppressors of gastric acid secretion
Proton pump inhibitors
75
S-isomer of omeprazole and R-enantiomers of lansoprazole
Omeprazole → esomeprazole
Lansoprazole → dexlansoprazole, rabeprazole and pantoprazole
76
Mechanism of action of omeprazole and pantoprazole
*PPIs block final step of acid production*
Activation in acid environment → prodrug diffuses into parietal cells of stomach and accumulates in acidic secretory canaliculi → activated by proton-catalyzed formation of tetracyclic sulfenamide → activated form binds covalently with sulfhydryl groups of cysteines in the H, K-ATPase, irreversibly inactivating the pump molecule
77
What do you do when the oral route of administration for PPIs is not possible
Parenterally with esomeprazole sodium, omeprazole sodium, pantoprazole
78
Metabolization of PPIs
Extensively metabolized by CYP2C19 and CYP3A4
79
True or false: Proton pump inhibition is reversible
FALSE: Irreversible. Acid secretion suppressed for 24-48 hrs until new proton pumps are synthesized and incorporated into luminal membrane of parietal cells
80
Therapeutic uses of omeprazole and pantoprazole
Promote healing of gastric and duodenal ulcers and treat GERD
In conjunction of antibiotics for H pylori eradication
Mainstay in tx of pathological hypersecretory conditions
81
Most common adverse effects of PPI use
Headache, nausea, abdominal pain, constipation, flatulence, and diarrhea
82
Effects of chronic use of PPIs
Increased risk of bone fraction and susceptibility to certain infections
83
What are antacids composed of
Hydroxy magnesium aluminate complex
84
What is the mechanism of action of antacids
Neutralize gastric acid (H⁺) in the stomach lumen by reacting with hydrochloric acid to form water and salts. This increases the gastric pH
85
Surfactant that may decrease foaming and hence esophageal reflux, is included in many antacids preparations
Simethicone
86
Therapeutic uses of antacids
Acid reflux (heartburn) and esophagitis
87
Adverse effects of antacids in a patient with renal insufficiency
Absorbed Al can contribute osteoporosis, encephalopathy, proximal myopathy
88
Milk-alkali syndrome
Alkalosis, hypercalcemia, renal insufficiency
89
How do olsalazine and balsalazide deliver 5-ASA without sulfapyridine-related side effects?
They are 2nd generation 5-ASA prodrugs that use azo bonds but replace sulfapyridine with either:
Another 5-ASA (olsalazine) or an inert compound (balsalazide)
These are activated by colonic bacteria via azoreduction
90
Potential sites of action of 5-ASA drugs
Activation of IL-1 and TNF-a production
Inhibition lipoxygenase pathway
Scavenging of free radicals and oxidants
Activation of PPAR-y
Inhibition NF-kB
91
Therapeutic uses of 5-ASA drugs
Inflammatory bowel disease
Mild-moderate active CUCI
Prevent relapses once remission achieved
Meselamine: active proctitis and distal CUCI
92
True or false: Sulfasalazine reversibly affects female fertility
False: Sulfasalazine reversibly decreased number and motility of sperm but does not impair female fertility
93
Px with IBD separated in 3 groups according to their response to glucocorticoids
Glucocorticoid-responsive → improve clinically within 1-2 weeks and remain in remission
Glucocorticoid-dependent → respond to glucocorticoids but then experience a relapse of symptoms as the steroid dose is discontinued
Glucocorticoid-unresponsiveness or steroid-resistant → do not improve, despite prolonged high-dose steroids
94
Most common administered glucocorticoid and used for induction of remission of moderate-to-severe Crohn
Prednisone
95
Widely used synthetic corticosteroid without significant mineralocorticoid activity, can provide temporary therapy for acute flare-ups of Crohn and CUCI
Triamcinolone
96
Cytotoxic thiopurine derivatives with off-label use for severe IBD or those who are steroid resistant
Mercaptopurine and azathioprine
97
Mechanism of action of azathioprine and mercaptopurine
Impairs purine biosynthesis and inhibits cell proliferation
Azathioprine converted to 6-mercaptopurine → metabolized to 6-thioguanine nucleotides
98
When is mercaptopurine used in the context of IBD
Used in glucocorticoid-unresponsive or glucocorticoid-dependent disease
99
What are the 3 metabolic fates of mercaptopurine
Conversion by XO to 6-thiouric acid
Metabolism by TPMT to 6-MMP
Conversion by HGPRT to 6-thioguanine nucleotides and other metabolites
100
What is the role of xanthine oxidase for mercaptopurine
Converts mercaptopurine to thiouric acid, which has no therapeutic activity
101
Most serious adverse effect of mercaptopurine
Pancreatitis
102
Mechanism of action of methotrexate
Inhibits dihydrofolate reductase → blocks DNA synthesis and causes cell death
103
Therapeutic use of methotrexate in IBD
Induction and maintenance of remission of Crohn
104
Mechanism of action of TNFa-antagonists (infliximab and adalimumab)
Bind to and neutralize both soluble and membrane-bound TNF-a, one of the principal cytokines of Th1 immune response characteristic of Crohn → prevents its binding to p55 and p75 receptors
105
Administration route of infliximab and adalimumab
Infliximab → IV
Adalimumab → Subcutaneous
106
Therapeutic use of infliximab and adalimumab
Acute and chronic tx of moderate-to-severe CUCI and Crohn with poor response to conventional therapies
107
Major serious adverse effects of TNFa antagonists
Infection resulting from suppression of inflammatory response
