Exam 4: GI Pharmacology Flashcards Preview

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Flashcards in Exam 4: GI Pharmacology Deck (108):
1

Histamine is stored in:

Vesicles of mast cells and circulating basophils

2

Histamine is released in response to:

Antigen/antibody reactions and certain drugs

3

Histamine is synthesized by:

Decarboxylation of histadine

4

Roles of histamine:

Inflammatory mediator
Regulation of gastric acid secretion
Regulation of neurotransmission

5

Histamine receptors:

H1, H2, H3

6

Histamine and the BBB:

Does *not* cross BBB, no CNS effects

7

H1 and H2 antagonists function by:

Blocking the response to histamine, not the actual release

8

Sites/effects (5) of H1 receptor activation:

Lungs: bronchoconstriction/↑ airway resistance
Vascular smooth muscle: dilation/hypotension/erythema
Vascular endothelium: ↑ capillary permeability/edema
Peripheral nerves: sensitization/itching, pain, sneezing
Heart: slows AV node conduction/↓ HR

9

Sites/effects (4) of H2 receptor activation:

Airways: relaxation of bronchial smooth muscle
Coronary vasculature: vasodilation
Heart: + inotrope/chronotrope
Stomach: activates proton pump of parietal cells to ↑ H+

10

Sites/effects of H3 receptor activation:

Heart and presynaptic, postganglionic SNS fibers
Inhibits synthesis/release of histamine (inhibitory receptor!)

11

Effect of H2 antagonists on H3 receptors:

Cross-antagonizes H3 receptors, which *promotes* histamine release

12

Anesthetic consideration with H2 blockers:

If given alongside histamine-releasing drugs, can cause ↑ histamine release d/t H3 antagonism

13

Structure of histamine receptors:

Seven-transmembrane GPCRs

14

First generation H1 antagonists:

Sedating; activate muscarinic, serotonin, and α receptors

15

Second generation H1 antagonists:

Non-drowsy; less CNS effects

16

Indications for H1 antagonists:

Rhinitis
Conjunctivitis
Urticaria
Pruritis
Motion sickness
Chemotherapy N/V
Insomnia

17

*Ineffective* uses for H1 antagonists:

Systemic anaphylaxis
Asthma

18

Characteristics of first-generation H1 antagonists:

Lipophilic
Neutral at physiologic pH (cross the BBB!)

19

Examples of first-generation H1 antagonists:

Diphenhydramine
Hydroxyzine
Chlorpheniramine
Promethazine
Doxepin

20

Characteristics of second-generation H1 antagonists:

Albumin binding
Ionized at physiologic pH (do not cross BBB)

21

Examples of second-generation H1 antagonists:

Loratidine
Desloratidine
Acrivastine
Fexofenadine
Cetirizine

22

PK of H1 antagonists:

Well-absorbed
Cmax: 2-3 hours
Protein binding: 78-99%
Metabolism: CYP450
E1/2t: variable (2-24 hrs)

23

A/E of H1 antagonists:

CNS toxicity/sedation
QT interval prolongation
Anticholinergic effects

24

MoA of H2 antagonists:

Competitive antagonism of H2 receptors to suppress gastic acid secretion via ↓cAMP

25

Examples of H2 antagonists:

Cimetidine (least potent)
Nizatidine
Ranitidine
Famotidine (most potent)

26

Effect of H2 antagonists on gastric emptying/tone:

None

27

Prophylactic dosing of cimetidine before GA induction:

300mg PO/IV 1-2 hours prior

28

Prophylactic dosing of famotidine before GA induction:

20-40 mg PO or 20 mg IV am of surgery

29

Prophylactic dosing of ranitidine before GA induction:

150 mg PO or 50 mg IV

30

Indications for H2 antagonists:

GERD
Duodenal ulcer disease
Chemoprophylaxis pre-GA

31

Effect of H2 antagonists on gastric pH and volume:

NO effect on pH of gastric fluid already present
Unpredictable effect on volume

32

Chemoprophylaxis for patients allergic to contrast dyes:

H1 and H2 blocker combined

33

PK of H2 antagonists:

Rapid absorption and extensive first-pass effect
Cmax: 1-3 hrs (oral)
Protein binding: 13-35%
E1/2t: 1.5 - 4 hrs

34

H2 antagonists and the BBB:

All cross the BBB!

35

Clearance of H2 antagonists:

Nizatidine: renal
Cimetidine, ranitidine, famotidine: hepatic

36

Clearance of H2 antagonists:

Nizatidine: renal
Cimetidine, ranitidine, famotidine: hepatic

37

IV administration of H2 antagonists:

Rapid administration causes bradycardia and hypotension!

Cimetidine & ranitidine over 15-30 minutes
Famotidine over 2 minutes

38

Hepatic A/E of H2 antagonists:

Transient elevation in LFTs
Decreases metabolism of hepatic extraction drugs

39

Cimetidine slows metabolism of these drugs:

Lidocaine
Diazepam
Theophylline
Propranolol
Phenobarb
Warfarin
Phenytoin

Lift the LiD and use TP when you PeWP

40

Three risk factors for PUD:

H. pylori
NSAID use
Smoking

41

Three goals of PUD therapy:

Reduce gastric acidity
Enhance mucosal defenses
Eliminate H. pylori

42

Drug classes (4) used to inhibit/neutrailize gastric acid secretion in PUD:

H2 antagonists
PPIs
Anticholinergics
Antacids

43

Drug classes (3) used to protect the gastric mucosa in PUD:

Sucralfate
Colloidal bismuth
Prostaglandins

44

Drug class used to eradicate H. pylori in PUD:

Antibiotics

45

MoA of PPIs:

Block the K+/H+/ATPase (proton pump) leading to a total shutdown of acid release

Prodrug converted to active drug in parietal cell; forms covalent bond with proton pump

46

Examples of PPIs:

All of the -prazoles

47

PK of PPIs:

Rapidly absorbed
E1/2t: short
Hepatically metabolized
Crosses the placenta

48

A/E of PPIs:

Headache
GI disturbance
Nausea
Enteric infections
Long-term unknown: carcinoid tumor?

49

Indications for PPIs:

PUD w/ H. pylori
Hemorrhagic ulcers
PUD in patient needing NSAIDs

50

Clotting and pH:

Clot formation impaired in acidic environments; PPIs help ulcers clot and heal

51

Example of anticholinergic used for acid reduction:

Dicyclomine

52

Efficacy of dicyclomine:

Less effective than H2 blockers/PPIs

53

MoA of anticholinergics for acid control:

Decrease PSNS production of acid/gastrin-mediated acid production

54

Structure of sucralfate:

Salt of sucrose sulfate and aluminum hydroxide

55

MoA of sucralfate:

Forms a viscous gel that binds to (+) proteins (albumin/fibrinogen) thus sticking to areas of ulceration and protecting it

Does NOT alter pH; affords symptomatic relief

56

A/E of sucralfate:

Constipation; little systemic absorption

57

Disadvantages of sucralfate:

Large tablets, frequent administration

58

Drug interactions with sucralfate:

Binds to drugs and impairs their function

59

Colloidal bismuth as PUD therapy:

Coating agent; forms barrier to protect mucosa

Stimulates mucosal bicarb and PGE2

Impedes H. pylori growth

60

Misoprostol as PUD therapy:

Prostaglandin analogue that prevents NSAID-induced ulcers

Can cause abdo discomfort, diarrhea; contraindicated in pregnancy

61

Triple therapy for H. pylori:

Amoxicillin
Clarithromycin
PPI

62

Quadruple therapy for H. pylori:

Tetracycline
Metronidazole
PPI
Bismuth

63

Types of antacids:

Aluminum hydroxide
Magnesium hydroxide
Sodium bicarbonate
Calcium carbonate

64

Antacids increase gastric pH to:

> 5

65

Effects of antacids on ulcers:

↑ rate of ulcer healing, duodenal ulcer pain relief

66

A/Es of antacids:

Constipation
Diarrhea
Electrolyte abnormalities

67

PK of bicitra:

Onset: rapid
pH: 8.4 (unpleasant taste)

68

Dosing of bicitra:

15-30ml PO 15-30 minutes pre-op

69

Dosing of bicitra:

15-30ml PO 15-30 minutes pre-op

70

Disadvantage of bicitra:

Increases intragastric volume

71

Effects of prokinetic drugs:

Increases LES tone
Accelerates rate of gastric emptying
Enhances peristalsis

72

MoA of metoclopramide:

Dopamine antagonist; achieves post-synaptic release of ACh

73

Effects of metoclopramide on stomach:

Kinetic only; pH unchanged

↑ LES tone
↑ gastric/small bowel motility
Relaxation of pylorus/duodenum

74

Antagonist for metoclopramide:

Atropine/glyco

75

A/E of metoclopramide:

EPS effects
Prolactin secretion

76

Mechanism of anti-emesis effect of metoclopramide:

Blocks dopamine stimulation of CRTZ

77

PK of metoclopramide:

Rapid absorption
Onset (IV): 3-5 min
Cmax: 40 - 120 min
E1/2t: 2 - 4 hrs
40% excreted unchanged renally

78

Indications for metoclopramide:

↓ gastric volume
Antiemetic
Tx of gastroparesis
Symptom tx for GERD
? lactation

79

Pre-op dosing of metoclopramide:

10 - 20mg IV over 3-5 min
15-30 min pre-induction

Fast administration → cramping

80

PONV dosing of metoclopramide:

0.15 mg/kg IV

81

A/E of metoclopramide:

Cramping
Cardiac dysrhythmias
Sedation
Dry mouth
Dystonic EPS
↑ sedation with CNS depressants
May inhibit plasma cholinesterases
Akathesia

82

Contraindications for metoclopramide:

Parkinson's
Bowel obstruction
Pheochromocytoma
Seizure d/o
Phenothiazines (promethazine etc)

83

Examples of extrapyramidal symptoms:

Oculogyric crisis
Trismus
Torticollis
Akathesia

84

Role of serotonin in the gut:

90% in enterochromaffin cells n the gut; carry pain/nausea impulses

85

Synthesis of serotonin:

5-Hydroxytryptamine (5HT) synthesized from tryptophan

86

Examples of 5HT3 antagonists:

Ondansetron
Granisetron
Dolasetron
Tropisetron

87

MoA of 5HT3 antagonists:

Selective antagonism at GI vagal afferent and CRTZ receptors

88

Types of N/V best suited to 5HT3 antagonist use:

Chemo
PONV
Hyperemesis gravidarum

89

A/E of 5HT3 antagonists:

Headache with rapid IV push
Dysrhythmias
Slow clearance in liver disease

90

Dosing of ondansetron:

Adults: 4 - 8mg IV
Peds: 0.05 - 0.15 mg/kg IV (up to 4mg)

91

Dosing of granisetron:

Adults: 0.01 - 0.04 mg/kg

92

Dosing of dolasetron:

Adults: 12.5 mg IV

93

Dosing of tropisetron:

5 mg

94

Dosing of dexamethasone for PONV:

4 - 10mg IV

95

Examples of phenothiazines:

Prochlorperzine (Compazine)
Promethazine (Phenergan)

96

MoA of phenothiazines:

Interaction with dopaminergic receptors in CRTZ

97

PK of promethazine:

Onset: 5min
Duration: 4 - 6hr
E1/2t: 9 - 16hr
Hepatic metabolism

98

Contraindications for phenothiazines:

99

Indications for phenothiazines:

Blood transfusion rxn
Allergic rxn
Sedation
PONV

100

Incidence and timing of neurolept malignant syndrome:

0.5 - 1% of patients taking phenothiazines
24 - 72 hrs after dose
Usually young men

101

Presentation of neurolept malignant syndrome:

Tachy
Dysrthymias
BP alterations
LOC alterations
MH-like: muscle rigidity, hyperthermia, rhabdo, ANS instability

102

Tx of neurolept malignant syndrome:

Amantadine and Dantrolene

103

MH vs. NMS:

NDMR will produce flaccid paralysis in NMS but not in MH

104

Example of butyrophenones:

Droperidol

105

MoA of droperidol:

Inhibitis dopaminergic receptors in CRTZ

106

Dosage of droperidol:

0.625 - 1.25 mg IV

107

A/E of droperidol:

↓ BP
Peripheral α blockade
EPS
Akathesia
Dysphoria

108

Droperidol is black boxed due to:

QT prolongation, torsades