Feb22 M3-Antacids and prokinetic drugs Flashcards
ulcers cause+consequence and therapeutic goal
cause: bacterial infections
consequence: higher acidity in stomach
goal: stop excessive acid in stomach
direct way of reducing stomach acid
PPI blocks H (out) K (in) ATPase on luminal surface of parietal cell
4 receptors on parietal cell basal side regulating HCl secretion + effect
- M3 (muscarinic R): activates Ca dep pathway to release more HCl
- gastrin R (Ca dep pathway too)
- histamine R (activates cAMP dep pathway to release more HCl)
- PG R (blocks Ca dep pathway)
drugs acting indirectly on parietal cell to reduce acid secretion and one acting to increase it
- musc antag
- CCK2 (gastrin) R antag
- histamine R antag
- NSAIDs increase it
direct way of neutralizing stomach acid
bases (chemistry). many drugs like that
final problem of stomach acidity (why block it)
acid activates pepsin. overtime destroys wall of stomach = ulcers
drug blocking stomach wall
sucralfate (helps mucous layer)
how to tackle main cause of peptic ulcer
Abx (bacterial infection): bismuch, metro, tetracycline
(imp?) 5 drugs used for ULCER therapy
- antacids to neutralize
- cimetidine (H2i)
- propantheline (M1 M3 blocker)
- adenylate cyclase blockers (cAMP = histamine pathway)
- PPI
problems with cimetidine + alternative
ranitidine (better H2i). less anti-androgenic effects, longer action, no drug interaction (no p450 interaction)
omeprazole (PPI) advantages (2)
- activated when needed only (more acid in stomach = activated more)
- forms disulfide bridge with the pump and changes its chemistry = acts longer
omeprazole side effects
gastric mucosa hyperplasia (to compensate): may lead to gastric CA (hyperplasia stim by gastrin release in response to high pH)
2 kinds of antacids
- systemic (bioavailable): bicarb.
2. nonsystemic (poorly absorbed): Ca, Mg, Al
systemic antacids side effect
alkaline blood
what makes antacids diff from one another
onset time, duration of action, constipation or laxative effect
4 kinds of antacids + how to choose
-Na and K
-Ca
-Mg
-Al
choose depending on medical condition
long and short acting antacids
long = Ca and Mg short = Na, K
sucralfate (mucosa protecting drug) mech of action
complexes with proteins on ulcer side to provide coating for mucosa (+ binds to pepsin)
gastroparesis def + condition where cna happen
damage to gastric nerves or SM (ex, diabetes) = more acidity in stomach bc delayed gastric emptying
workforce to drive GI tract is why
Ach innervation to SM (Ach on musc Rs)
prokinetic drugs acting in synaptic cleft
M3 agonists (bethanechol) AChEi (neostigmine)
prokinetic drugs acting downstream on the presynpatic neuron
D2R inhibitors (dopamine) (metoclopramide) so the negative effect of this pathway on Ach release is blocked
prokinetic drugs acting upstream on neuron presynaptic
- erythromycin (motilin R bindors): positive regul of firing
- serotonin R agonists (cisapride) positive effect on firing
bethanecol (musc agonist) side effect and prob
non specific .. heart relaxation (M2)
cholinergic drugs (bethanecol and neostigmine: M agonists and AChEi) side effects
stim GI secretions (acid included) (not just mvmt), reflex and asthma are problematic and exacerbated by them and heart prob too.
classical D2Ri drug and one more used now
metoclopramide. (acts on CNS so not too good) domperidone better
D2Ri drugs other effect (benefits that it’s non specific)
blocks emesis, more GI coordination, etc.
D2Ri side effects
increase prolactin and breast tenderness (gynecomastia, galactorhea, etc.)
serotonin agonist used upstream on neuron (prokinetic)
metoclopromide (also D2 antagonist) and it has a mixed 5HT4 agonist, 5HT3 antag effect
why cisapride not used as serotonin $ agoist
activates arrhythmia channel in the heart. can cause death + galactorrhea + extrapyr effects in the brain
5HT4 R signal transduction
GPCR activates cAMP, higher Ca in the cell
5HT4 R agonist side effects and why
-more stim of bladder (R is on SM too) and adrenals
good thing in cisapride and metoclopromide
block 5HT3 (and also D2 for metoclopromide) in CTZ = block emesis
serotonin agonists effects on GI tract
- more gastric contractions
- more gastroduod coordination
- lower sphincter in stomach contracts more
motilin R agonists (erythromycin) effect on GI tract
more LES contraction, GI contraction
paresis meaning
lack of GI movement
most important factor in how food moves down GI tract
how liquid the food is
constipation 3 causes
- functional disorders (damage to enteric nerves or muscles)
- drug treatments (opiates)
- low residue diet (residue = attracts water)
5 types of laxatives (SSELB)
- secretory or stimulant
- saline
- emollient
- lubricant
- bulk forming
principle of laxatives
goal is to activate Cl channels in GI tract (their pumping of Cl in lumen is what keeps water in lumen)
secretory laxatives (castor oil) mech (2)
- activate the PG receptor EP3 (Cl channels more active)
2. inhib water reabso in lower intestine
secretory laxative used in IBS and opioid induced constipation
lubiprostone
saline laxatives mech + examples
draw water in intestine by osmosis (Mg hydroxide, sodium phosphate, sodium sulfate)
emollient laxatives mech
attract water to stool (anionic surfactants. lower surface tension of stool)
EX: DOCUSATE
lubricant laxatives mech + ex
retard water abso, smooth transit, less transit TIME (faster velocity)
ex: mineral oil
bulk forming agents laxatives mech + example
form large hydrophilic masses (less viscosity of content + more bulk and water content)
Ex: Bran (fibres) OR psyllium husk
4 problems of laxatives
- damage to myenteric plexus + habituation (bc ENS used to working less)
- colonic atony
- too much Ca loss
order of things to do when need laxatives
- increase diet fibers and water
- bulk agents
- osmotic laxatives
- stimulants (secretory): more pharma ones are last resort
antidiarrheal drugs mech of action
act on intestinal neurons: more abso, less fluid secretion, more segmental contractions, less propulsive contractions + act on CNS
ex of antidiarrheals
opioids, morphine, codeine
morphine and codeine good and bad
good: segmental contractions more and propulsive less
bad: act on CNS… (crosses BBB)
SO ARE NOT USED for diarrhea in enteric infections
drugs used as antidiarrheal and why
loperamide and diphenoxylate (no CNS effects)
