Pharmacology Flashcards
What is the process of HCl secretion?
CO2 and water are converted to carbonic acid by carbonic anhydrase
HCO3 and H+ are also produced
HCO3 is pumped out fo the cell into the blood in exchange for Cl, which is pumped into the lumen
H+ is pumped into he lumen in exchange for K+ by the proton pump (H/K/ATPase)
H+ and Cl make HCl
Via which receptors do secretagogues cause secretion?
M3 muscarinic
G/CCK2
H2
What is the process that causes HCl secretion via M3 receptors?
ACh binds to receptor
Cause increased cAMP
Increases number of proton pumps
Increases acid secretion
What is the process that causes HCl secretion via G/CCK2 receptors?
Gastrin binds to receptor
Causes increase in intracellular calcium
Increases number of proton pumps
Increases acid secretion
What is the process that causes HCl secretion via H2 receptors?
Histamine from enterochromaffin cells binds to receptor
Increases cAMP
Increases number of proton pumps
Increases acid secretion
What is the mechanism of PPIs?
Irreversible inhibit proton pumps so H+ cannot be pumped into lumen, decreasing acid secretion
Where do PPIs not work, and what should be done to counter this?
In tubulovesicle proton pumps
Take 20 mins before eating because that is the time taken for proton pumps to move to the canalicular membrane
What are examples of PPIs?
Omeprazole
Lansoprazole
What are the side effects of PPIs?
Increased risk of infection, e.g. C. diff
Osteoporosis
What is the mechanism of H2 receptor antagonists?
Blocks H2 receptor so histamine cannot act on parietal cell to decrease acid production
How do H2 receptor antagonists compare to PPIs in terms of effectiveness, and why?
Less effective
H2 blocked but ACh and gastrin can still cause acid secretion
When are H2 receptor antagonists used?
If PPIs contraindicated, or not receptive to PPIs
What are examples of H2 receptor antagonists?
Ranitidine
Cimetidine
Famotidine
Nizatidine
What are the side effects of H2 receptors antagonists?
Masks symptoms of gastric malignancy
What is the mechanism of antacids?
Buffer HCl and make pH in the stomach more neutral
What is the mechanism of alginates?
Increase the viscosity of gastric juice and react with acid to produce a foam later that protects the oesophagus
What is the indication for antacid alginate combination?
OTC for short term symptomatic relief
What are examples of compound alginates?
Peptac
Gaviscon
Mucogel (antacid only)
What is the function of prostaglandins and somatostatin?
They reduce the effect of secretagogues and inhibit gastric acid secretion
What is the mechanism of NSAIDs?
Inhibit COX1
This causes decreased prostaglandins production
Less prostaglandins means more acid secretion
What are examples of NSAIDs?
Aspirin
Ibuprofen
Diclofenac
Naxaproxen
What is misoprostol, and what is its indication?
Prostaglandin agonist - prescribe at the same time as NSAIDs to prevent adverse effects and reduce the risk of ulcer
What is the pathology that causes diarrhoea?
Increased solutes in the lumen - water follows
What class of drug are synthetic opioids?
Anti-motility so also anti-diarrhoeal
What is the mechanism of synthetic opioids?
Opioid agonists
Inhibit ENS to decrease peristalsis and increase segmentation
Increase fluid absorption
What are the examples of synthetic opioids?
Loperamide (imodium) - used most often
Codeine phosphate
What are the contraindications for synthetic opioids?
(ABCD) Acute UC Babies C. Diff colitis Dysentery (or any bloody diarrhoea)
What is the mechanism of rehydration therapy?
Na and glucose in the rehydration salts is absorbed by SGLT1
Water follows and is absorbed too
What are causes of constipation?
Lack of fibre
Lack of physical activity
Drugs (e.g. opioids)
Obstruction
What is the mechanism of bulking laxatives?
Indigestible so add to faecal mass and cause the stool to absorb water
Increase the bulk of stool so peristalsis is stimulated
What are examples of bulking laxatives?
Ispaghula husk
Methylcellulose
Sterculia
What are the contraindications for bulking laxatives?
Bowel obstruction
Ileus
What is the mechanism of osmotic laxatives?
Cause osmosis, water travels into stool
Increase in bulk, peristalsis activated
What are examples of osmotic laxatives?
Lactulose
Macrogols
What are contraindications for osmotic laxatives?
Bowel obstruction
Heart failure, ascites, electrolyte disturbances
What is the mechanism of stimulant laxatives?
Stimulate intestinal motility and water secretion into lumen
Stimulate enteric nerves
What are examples of stimulant laxatives?
Senna
Glycerol suppository
What are the contraindications of stimulant laxatives?
Bowel obstruction
Prolonged use
What are the side effects of stimulant laxatives?
Abdominal pain
What is nausea?
Unpleasant sinking feeling hit throat or stomach
Involves pallor, sweating, salivation
Stomach and LOS are relaxes
What is retching?
Rhythmic reverse peristalsis
Involuntary abdominal and diaphragm contraction
No gastric content expelled
What is emesis?
Forceful expulsion of gastric/intestinal contents out of mouth
What are the events of vomiting?
- Intestinal slow wave activity stops
- Retrograde contraction from ileum to stomach
- Glossitis is closed and breathing stops to prevent aspiration
- LOS relaxes
- Diaphragm and abdominal muscles contract
- Gastric contents ejected
What can iatrogenic vomiting be caused by?
Chemotherapy
General anaesthetic
Drugs, e.g. morphine and SSRIs
Post-op
What are the consequences of vomiting?
Dehydration
Loss of gastric protons and chloride causing metabolic alkalosis and can lead to hypokalaemia
Oesophageal damage
What are examples of anti-emetics?
5-HT3 antagonists
Muscarinic acetylcholine
Histamine H1 antagonists
Dopamine receptor antagonists
What is the mechanism of 5-HT3 antagonists, what is an example, and what are they used for?
Block 5-HT3 receptors to reduce vomiting in the vomiting centre
Ondansetron
Nausea due to chemo
What is the mechanism of muscarinic acetylcholines, what is an example, and what are they used for?
Unclear
Hyoscine, scopolamine
Proplylaxis of motion sickness
What is the mechanism of histamine H1 antagonists, what is an example, and what are they used for?
Blocks H1 in the vestibular nuclei
Cyclizine
Proplylaxis of nausea due to inner ear pathology
What is the mechanism of dopamine receptor antagonists, what is an example, and what are they used for?
Block dopamine system, are pro-kinetic
Domperidone, metoclopramide
Drug induced vomiting
What is an example of an indication for metoclopramide?
With morphine in MONA+T acute heart attack management