Antagonist
A drug or chemical that interferes with the physiological action of another, especially by combining with and blocking its receptor
Agonist:
Agonist
A drug or chemical that can combine with a receptor on a cell to produce a physiologic reaction typical of a naturally occurring substance.
Receptor:
Receptor
Any of various specific protein molecules in surface membranes of cells and organelles to which complementary molecules, eg hormones, neurotransmitters, may be bound.
Irreversible binding
Irreversible binding: An irreversible antagonist binds covalently to the receptor and cannot be displaced by either competing ligands or washing.
Side effect
Problems that occur when treatment goes beyond the desired effect. Or problems that occur in addition to the desired therapeutic effect
what is Abdominal discomfort indicative of
Peptic Ulcer (upto 1 in 8 people)
Gastro esophageal reflux
Vomiting
where do peptic ulcers form
Form in stomach (Stomach ulcer) or the digestive tract (duodenal ulcers).
symptoms of peptic ulcers
Pain intheabdomen/neck/navel/back. Bleeding Indigestion Heartburn Loss of appetite Vomiting Can no longer tolerate fatty foods
pain of peptic ulcer
Can last from a few minutes to a few hours
If a stomach ulcer usually startssoonafter eating a meal.
If the ulcer is in your small intestine, pain may start two to three hours after eating.
describe the pain of stomach ulcers
no typical symptoms and can cause no pain
how does plain work in stomach ulcers
get complication withoutpain.
where are neck cells
cardiac, pylori, fundus
where are chief cells found
fundus
where is parietal/oxyntic
fundus
what do the gastric glands secrete
gastric Juice ( HCL + enzymes + mucus
what does Neck cells secrete
mucus
what does Chief cells secrete
proteolytic enzymes (digestive)
what does Parietal / oxyntic cells secrete
HCL
how is acid secreted
H+ ion is pumped into the lumen, in exchange for K+ via proton pump
where is hydrogen ion generated and what happens after
Hydrogen ions are generated within the parietal cell from dissociation of water. The hydroxyl ions formed in this process rapidly combine with carbon dioxide to form bicarbonate ion, a reaction cataylzed by carbonic anhydrase.
what happens after Bicarbonate is transported out of the basolateral membrane in exchange for chloride
. The outflow of bicarbonate into blood results in a slight elevation of blood pH known as the “alkaline tide”. This process serves to maintain intracellular pH in the parietal cell.
how are Chloride and potassium ions are transported into the lumen of the cannaliculus and why is this important
conductance channels and such is necessary for secretion of acid.
what happens when hydrogen ions are pumped out of the cell into the lumen
this is done in exchange for potassium through the action of the proton pump; potassium is thus effectively recycled
what happens when there is an accumulation of osmotically active hydrogen ion in the cannaliculus
generates an osmotic gradient across the membrane that results in outward diffusion of water - the resulting gastric juice is 155 mM HCl and 15 mM KCl with a small amount of NaCl.
what causes peptic ulcers
Underlying mechanism
Disruption of stomach lining cause tissue damage by stomach acid
what pH is needed for healing
more than 3
mechanism of action of H.pylori
Urease (to produce NH3 + H2CO3)
Induces inflammation (Gastritis)
disrupts the lining of the stomach -> stomach acid infiltrates -> ulcer
how much of the population have H.pylori
50%
is H pylori negative or positive
negative
true or false Once infected bacteria may remain in the stomach for life
true
true or false Most people there are no symptoms
true
true or false can trigger ulcers in 10-25% of those infected
false Can trigger ulcers in 10-15% of those infected
what do PPI do
decrease H+ secretion by parital cells
what is interesting about the coating of PPI
Prodrugs,
enteric coating prevents rapid exposure to stomach HCl
However some use a bicarbonate coat to alter stomach pH and protect the PPI
what cells take up PPI
parietal cells
PPIs
Prodrugs,
enteric coating prevents rapid exposure to stomach HCl
However some use a bicarbonate coat to alter stomach pH and protect the PPI
Taken up by Parietal cells
At acidic pH conversion sulfenamides
Irreversible inhibition of H+-pump via ATPase
Proton Pump Inhibitors dose
Elimination half-life of PPIs
0.5 to 2.0 hr,
Single dose persists up to three days.
Due to
Accumulation of the drug in parietal cell canaliculi
the irreversible nature of proton pump inhibition
antagonist of H2 receptor targeting
Cimetidine, Ranitidine, Nizatidine
future of antagonist of H2 receptor targeting
Well tolerated generally
But replaced by PPIs due to better effect and safety profile
treatment of H.pylori
Eradication of Helicobacter pylori with antibiotics:Amoxicillin + clarithromycin
Amoxicillin + metronidazole
Combined therapy with PPI
can NSAIDS can cause ulcer formation?
yes
COX 1 inhibited by
NSAID .
COX 2nhibited by
NSAIDS
COX 2 INHIBITIORS
COX 1 examples
prostagladins
thromboxanes
COX 2 examples
prostaglandins
prostacyclins
Prostaglandin receptors eg PGE Misoprostol
prostaglandins
decrease gastric acid secretion
increase mucus and HCO3- stomach secretion
Both of these are important in maintaining the stomach lining
With NSAIDs Misoprostol can be given
Mechanism:
decrease cAMP in parietal cells proton pump activity decrease
what is vomitting
Vomiting a reflex triggered by a signal from the brain.
Frequency and signals to induce vomiting
Physical injury (remember retching as well) Electrolyte/fluid imbalance
internal causes of vomiting
headache viral infection heart attack severe pain abdominal source apprendictis hapatisis kidney or gallbladder issue pregnacy
external causes of vomiting
motion sickness
alchol poisoning
food poisining
medcinine
Motion sickness Muscarinic antagonists
(Hyoscine)
Not specific eg blurred vision, dry mouth, relaxes gut
Histamine antagonists
(Cinnarizine / Cyclizine / Promethazine)
Side-effects drowsiness + dry mouth
Pregnancy related sickness: Thalidomide
Originally a sleeping tablet
But then prescribed off-label for vomiting#
Caused phocomelia
Chemotherapy induced vomiting
5HT3 antagonists
Reduce activity of the vagus nerve – used to stimulate vomiting reflex
Few side effects
Ondanestron, Granisetron
Used in conjunction with dexamethasone to improve efficacy
Chemotherapy induced vomiting. Metoclopramide
Acts on CTZ and increases motility of digestive tract
But unwanted side-effects – disorders of movement, fatigue, stimulates prolactin release, and causes disorders of menstruation
Chemotherapy induced vomiting. Domperidone
Acts on both gut and CTZ
Does not cross blood brain barrier
Phenothiazines
Used after nausea induced by cancer/radiation therapy/ cytotoxic drugs
Unwanted side-effects common - dystonia (Neurological movement disorder) and tardive dyskinesia.
Conclusions
Peptic Ulcers are caused by Bacterial infection
Multiple mechanisms for targeting pH in the stomach
Vomiting is a reflex mechanism
There are multiple reasons for vomiting to occur, and therefore multiple sites for pharmacological intervention
cause of motion sickness
conflict between what ur eyes see and what your inner ears which help with balance, sense
prevention of motion sickness
more serious motion sickness can be treated with medication such as Hyoscine. Ginger has also been used as a treatment for centuriess
3-12 is when travel sickness happens, usually more men than women. true or false
true
30% have motion sickness regularly on journeys by road, sea or air. true or false.
true