Sweatman - GI System Pharm Flashcards
1
Q
What are the SYM and PARA receptors on GI tract smooth muscle? Actions (table)?
A
- SYM beta-2: probably through pre-synaptic INH of PARA activity
2
Q
What is the predominant autonomic tone in the GI tract? Ganglionic blockade?
A
- PARA
- Ganglionic blockade:
1. Reduced tone and motility
2. Constipation
3. DEC gastric and pancreatic secretions
3
Q
What are the consequences of cholinergic excess (table)?
A
- PARA agonists
- AchE inhibitors
4
Q
What are the consequences of cholinergic deficit (table)?
A
- Anti-muscarinics
5
Q
What is the enteric nervous system?
A
- Involved in sensorimotor control; afferent sensory neurons, motor nerves, and interneurons organized into 2 nerve plexuses:
1. Myenteric (auerbach’s): b/t longitudinal and circular muscle layers -> contraction/relaxation of GI smooth muscle
2. Submucosal (meissner’s): secretory and absorptive functions of GI epithelium, local blood flow, and neuroimmune activities
6
Q
What is the role of Ach in the ENS?
A
- Primary excitatory transmitter to smooth muscle and secretory cells
- Probably also the major neuron-to-neuron ganglionic transmitter
7
Q
What are the roles of dopamine and serotonin in the ENS? Metoclopramide?
A
- DOPAMINE: modulatory transmitter
- SEROTONIN (5-HT): transmitter or co-transmitter at excitatory neuron-to-neuron junctions
-
Metoclopramide: tx for N/V and gastroparesis -> 5-HT4 agonism, vagal and central 5-HT3 antagonism, possible sensitization of muscarinic receptors on sm m + D1, D2 (INH sm m contraction) antagonism
1. Pro-kinetic agent: coordinated contractions that enhance transit (largely confied to upper GI tract -> INC lower esophageal sphincter tone and stimulates antral/small intestinal contractions)
8
Q
What is the role of enkephalin in the ENS?
A
- In some secretomotor and interneurons
- INH Ach release and peristalsis -> may stimulate secretion
- Related to opioid peptides
9
Q
What is IBD? Drug target?
A
- Range of diseases: mostly Crohn’s, ulcerative colitis
- Dysbiosis of normal intestinal homeostatic relationship b/t intestinal mucosa and normal microbiome, leading to inflammatory rxn
1. Genetic predisposition
2. Disruption of physical barrier (mainly UC)
3. Microbe sensing dysfunction (Crohn’s)
4. Adaptive immune response dysregulation (both) - TNF-alpha INH: block interaction b/t TNF-alpha and receptor types 1, 2, and soluble receptors, neutralizing pro-inflam cell signaling and INH expression of inflam genes (ex: Infliximab)
10
Q
When should TNF-alpha INH be used in Crohn’s disease mgmt?
A
- Moderate-severe Crohn’s pts who have not had a response to adequate therapy with CCS or an immunomodulator
- Alternative to CCS
11
Q
When can Infliximab be used to treat UC?
A
- Mild-moderate disease that is refractory to CCS tx
- CCS-intolerant pts due to adverse effects
- Severe disease where standard tx has failed:
1. Adalimumab/Golimumab approval post-date this recommendation
2. Cetolizumab NOT approved for this indication
12
Q
What is the treatment algorithm for the tx of IBD (flow chart)?
A
- 5-ASA is Mesalazine, a salicylate that works only in the gut, minimizing side effects
- Topical CCS: enema, cream, or injections around fissure for localized delivery
- TNF-alpha AE’s: reactivation of latent TB, secondary malignancy, rashes, opportunistic infections; don’t use live vaccines while on these
13
Q
What opioid drug targets are implicated in GI physiology? How?
A
- B-endorphin is the preferred ligand for mu receptors
1. Morphine and Loperamide are agonists -> if used as anti-diarrheals, may cause constipation
2. Naloxone, etc. are antagonists
3. Responsible for analgesia, but can also cause respiratory depression (COD from OD)
4. Give laxatives to pts on opiates - Dynorphin ligand at kappa receptors in myenteric plexus = delayed transit, visceral antinociception (DEC sensitivity to pain)
- Enkephalin at delta receptors in myenteric plexus = delayed transit
14
Q
What are the clinical effects of the opiates in the GI tract?
A
- Focus on clinical effects and widespread distribution:
1. Gallbladder: biliary pain, delayed digestion
2. Gastroduodenum: anorexia, N/V
3. Small bowel: constipation, delayed digestion, hard/dry stool
4. Colon: bloating, distenstion, cramps, pain, spasm
5. Anorectum: incomplete evacuation and straining constipation
15
Q
What are some ways that drugs can induce diarrhea?
A
- Osmotic: meds draw water into the GI tract
- Secretory: Na+ absorption impaired, and Cl- and HCO3- ions secreted into the lumen
- Disordered motility: drugs affecting cholinergic tone
- Inflammatory: disruption of colonic flora, leading to C. diff or direct damage to gastric mucosa -> may occur after brief exposure, but risk INC w/duration, >1, repeated AB’s, or NG tube
- C. diff by disrupting acid-base envo/epi homeostasis: PPI’s, H2 antags, immunosuppressants, NSAIDs (direct epi damage + changes in Na+ permeability -> reduced bicarb, mucous, and inflammatory protection; PG INH, preventing repair mechs)
-
Fatty diarrhea: mal-digestion or absorption
1. Orlistat, cholestyramine: hypercholesterolemia
2. Octreotide: paradoxical (stops absorption of fat) -> tx of secretory diarrhea in pts w/carcinoid tumors, HIV-assoc
3. Metformin: 50% of pts; osmotic diarrhea via glu + a symptom of lactic acidosis
