The GI System, Pharm: Sweatman Flashcards

1
Q

Describe the prevailing autonomic tone on GI wall and sphincter smooth muscle and the role of sympathetic, parasympathetic, serotonergic, dopaminergic, and opiate agonists/antagonists in its modulation.

A

Predominate autonomic tone is parasympathetic.
Contracts walls of GI tract, relaxes sphincters, and increases secretions all via M3 receptors. Cholinergic activity.

Sympathetic NS antagonizes actions of the PSNS.
Relaxes walls of GI tract via a2 and B2 receptors.
Contracts sphincters via a1 receptors.

Serotonin: Important transmitter or cotransmitter at excitatory neuron-to-neuron junctions in the ENS.

Dopamine: modulatory transmitter in ENS

Enkephalin and related opioid peptides: Inhibit Ach release and peristalsis. May stimulate secretion. Antidiarrheals can be agonists of these receptors.
Opiate agonists will cause constipation.

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2
Q

Explain the tx of inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and opiate-induced GI dysfunction.

A

IBS- lifestyle modifications. Adjunctive drug tx to control constipation or diarrhea, depending on symptoms.

IBD- for both Crohn’s and ulcerative colitis: Anti-TNFa mAbs. Infliximab, adalimumab, golimumab, and certolizumab (for Crohn’s only). The mAbs are used for corticosteroid and immunomodulator (MTX or thiopurine) refractory cases.

Opiate-induced GI dysfunction (can’t move food, poo, secretions)- Give laxatives

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3
Q

Describe the several ways in which non-GI drugs can produce adverse effects in the GI system.

A

Can cause cholinergic agonism or be AchE inhibitors, causing typical cholinomimetic AEs: “DUMBBELS”
Diarrhea, Urination, Miosis/muscle weakness, Bronchorrhea, Bradycardia, Emesis, Lactation, Salivation/sweating

Muscarinic antagonists:
Constipation, antiemesis, decr. glandular secretions, hypo/anhydrosis.

Opiates in particular, are associated with gastroparesis.
Metformin causes diarrhea bc inhibits Glu absorption in intestines. Glu acts as an osmotic and pulls water into stool.

MCC of C. diff diarrhea: Abx

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4
Q

Describe the role of Pg-p, CYP3A, and gastric pH in drug bioavailability and explain the effects of antacids, H2 blockers, and PPIs on concurrent meds.

A

P-glycoprotein (Pg-p) and CYP3A are both involved in 1st pass metabolism. V in their activity = dramatically ^ drug bioavailability.

Low pH (2) necessary for drug bioavailability.

Antacids, H2 blockers, and PPIs all reduce drug bioavailability by raising pH.
Antacids can also chelate Abx.
H2 blocker Cimetidine inhibits many CYPs, leading to altered bioavailability of concurrent meds that rely on CYPs for metabolism.

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