Anti-histamines and Gastrointestinal Drugs Flashcards
Where are histamine secreting cells found
most tissues; highest levels in respitory and GI tract.
Mast cells + what it treats
Mediates type 1 anaphylactic, immediate hypersensitivity allergic reactions involving IgE
treats things like: hay fever, red, hot swollen and itchy skin, hives, bronchospasm; or generalized causing anaphylactic shock
What is histamines role in the GI tract
To regulate gastic acid secretion, released by ECL cells.
-H2 receptors on acid-secreting cells
Role of Histamine in peripheral nervous system
-predominantly H1 receptors
-Itch + pain
-stimulation of somatic sensory cortex
Histamine in the CNS
-can act as a neurotransmitter or modulator
its effect: promotes wakefulness through H1 receptors
What histamine receptors are there
H1 + H2
What is its subtype and what do H1 receptors do
Gg: activation od phospholipase C, Calcium mobilization
-brain (excitatory)
-Blood vessels (endothelial cells- release NO, cause dilation of arterial smooth muscle)
-Other smooth muscle contraction
-heart= Increased blood flow
ANTAGONIST: used as treatment for allergic response, vertigo, insomnia
Cardiovasual role H1
Vasodilation of blood receptors
increases vascular permeability
-constricts smooth muscle
-increase heart rate
What is its subtype and what do H2 receptors do
Gs: activation of adenylyl cyclase
Brain (unknown)
-Blood vessels (minor dilation through smooth muscle)
-GI tract (minor increase in rate)
-Heart (minor increase in rate)
ANTAGONIST: used to reduce acid secretion by stomach exocrine glands
What is epinephrine and what does it do
It is a: physiological antagonist
-increases cAMP levels which inhibits Mast cell degranulation
-opposes actions of histamine in smooth muscle: Beta-adrenergic recepts induce bronchial dilation, caso constriction.
-Treatment for anaphylaxis
prevents/reverses cardiac collapse:increases Bp and heart contractility
What are the first generation of H1 receptor antagonists
Diphenydramine (benadryl) = most potent oal antihisamine
Dimenhydrinate (Dramamine): less drowsy, allergy/cold medications, reduces mucus secretions
what do the first generation of H1 receptor antagonists help with
-allergic rhinitis
-hay fever
-itching
-contract dermatitis
-insect bites
-conjunctivitis
-nausea +motion sickness
-NOT indicated for asthma
side effects from 1st generation of H1 antagonists
Antihistamine effects: sedation/sleep induction (from blocking H1)
Antimuscarinic effects-through nonspecific actions on muscarinic receptors
-Sedation (CNS effect): prominent.. tolerance is problem
-Drying of secretioins, urinary retention
-anti-parkinsons through muscarinic antagonism (CNS effect)
Other side effects:
-Topical local anesthetic (block NA+ channel)
-Anti-emetic (some anti-serotonin effects)
Drug interactions of First gen H1 antagonists
Other sedatives, anticholinergics, tricyclic antidepressants
What are the second generation H1 antagonist and how are they different + what do they do
Loratidine (Claritin) and Fexofenidine (allegra)
-Do not cross BBB
Side effects: not sedating, no anti-muscarinic effects
Clinical uses: non-drowsy allergy relief, not effective in motion sickness
Both have good oral bioavailability
What is the parietal cell responsible for
gastric acid secretion. Stimulated by Acetylcholine (M3 receptors) and H2 receptors
Where are parietal cells located
Corpus (body) of the stomach.
-parietal cells
-secrete acid
What do ECL, D, and G cells do (in gastric glands)
ECL: histamine releasing- STIMULATES acid secretion
D cells: somatostatin releasing; INHIBITS acid secretion
G cells: Gastrin releasing- STIMULATES acid secretion by parietal cells
what are some causes of peptic ulcer disease in order from most to least common
-H. pylori infection
-NSAIDS, aspirin
-stress ulcerations
-Zollinger-Ellison syndrome
What is Helicobacter pylori, who found it, and what is its epidemiology, what does it need to survive, and what are its disease mechanisms
a basteria; eradication prevents ulcer recurrence. Discovered by Barry Marshall
-Rought of transmission unclear
-primarily childhood acquired (inversely with SES)
-survives in narrow pH range (needs acidic environment)
-Increased gastric acid secretion
-increased pepsinogen secretion
-decreased mucin secretion
How to get rid of H pylori
-antibiotics
-reduce acid
(proton pump inhibitor, Omeprazole)
(H2 receptor antagonist, Cimetidine)
Omeprazole; dynamics + cokinetics
-proton pump inhibitor (PPI)
-irreversible inhibitor (covalently modifies a chain)
Adverse effects: headache, diarrhea occur infrequently
Pro-drug: requires CYP450 to become active and thus inhibits CYP metabolism of other substrates.. drug interactions
what does phase 1 drug metabolism do
-cytochrome p450 enzymes
-oxidize drugs
-different subtypes
-70% of all drug metabolism
What is the warning on Omeprazole
Do NOT take with Plavix (clopidogrel)
why: Omeprazole occupies the cytochrome p450 enzyme needed to activate clopidogrel
Result: Increased risk of heart attack
Cimetidine Dynamics and cokinetics
-Competitive H2 receptor antagonist
-selectively inhibits H2 receptors
Metabolized by: CYP450 (CYP inhibitor: can deplay metabolism of other CYP substrates)
Excreted by: kidney (reduce does in kidney failure)
Ranitidine
Recall 2020
-competitive H2 receptor antagonist
-selectively inhibits H2 receptors
-top choice: same mechanism as cimetidine, less CYP inhibition
What do NSAIDS do to elicit mucosal injury
Block COX-1
Misoprostol Pharmadynamics
-synthetic PGE (agonist for PGE receptor Ep3/4)
-Protects gastric mucosa
-stimulates bicarbonate and mucus secretion
-reduces acid secretion
-only used for prevention of NSAID- induced ulcers
Misoprostol pharmacokinetics and adverse effects
orally active
-rapidly absorbed and metabolized
-short half life
Adverse effects: can cause diarrhea, cramping, uterine contracting. CANNOT use with pregnant women, controversial for labor induction and for abortion
What are the inputs and outputs for nausea in the medulla
inputs: CNS, visceral afferents, metabolic
Outputs: ONLY TWO vomiting center, chemoreceptor trigger zone
Drugs/toxins associated with nausea/vomiting
-chemotherapeutic agents
-dopaminergic agents
-ethanol
Treatment for severe nausea/vomiting
Serotonin subtype 5-HT3; Ondansetron (Zofran) is a 5-HT3 receptor antagonist
What is Ondansetron uses
prophylaxis of chemotherapy and radiation-induced nausea and vomiting
- post-operative nausea and vomiting
Side effects of ondansetron 5-HT3 inhibitor
GI effects
-diarrhea
-constipation
CNS effects
-headache
-fever
-lightheadedness
-dizziness, drowsiness
-blurred vision
Rash
Muscle spasm
Cannabinoid CB1 receptor and 5-HT3 receptor
CB1 opposes 5-HT3
-THC is effective as anti-neasea agent following chemotherapy
treatment for motion sickness (vertigo)
antagonists of H1 and mACh
Anticholinerics: Scopolamine: m1 AChR antagonist applied as a patch for prevention. Side effects for antichlinergic= urinary retention, constipation, vision disturbances
antihistamines: specific for H1 receptor + must cross BB
-dimenhydrinate, meclizine= long lasting. Promethazine= more sedation
side effects: drowsiness, anticholinergic effects
BEST AS PREVENTATIVES
Drugs for neasea and vomiting
ondansetron, THC (dronabinol), dimenhydrinate
Diphenhydramine’s Major indication, mechanism, adverse effects, and PK +notes
MI: allergy, motion, sickness, sedation
Mechanism: H1 receptor antagonist
Adverse effects: Tolerance to sedating effect prevents usefulness as insomnia treatment
Pk notes: t 1/2 9hrs; interactions with other sedating drugs and anticholinergic
Dimenhydramine Major indication, mechanism, adverse effects, and PK +notes
Mi: motion sickness (vertigo) prevention
Mechanism: H1 receptor antagonist
Adverse effects: less sedating than dephenhydramine
Pk notes: t1/2 9 hours; prominent dry mouth anti-cholinergic
Loratidine
Major indication, mechanism, adverse effects, and PK +notes
MI: allergy
Mechanism: H1 receptor agonist
Adverse effects: no sedation, not effective for motion sickness
Pk+notes: doesn’t cross BBB;short and long acting forms
Cimetidine
Major indication, mechanism, adverse effects, and PK +notes
MI: peptic ulcer, GERD
Mechanism: H2 receptor antagonist
Adverse Effects: headache, diarrhea
Pk notes: CYP metabolism can inhibit metabolism of other drugs; and reduce dose kidney failure
Epinephrine
Major indication, mechanism, adverse effects, and PK +notes
MI: anaphylaxis
Mechanism: BAR agonist, physiological antagonist of histamine
Adverse effects: tachycardia, hypertension
PK+ notes: emergency treatment IM injection
Misoprostol
Major indication, mechanism, adverse effects, and PK +notes
MI: GI protechtant- prevention of gastric ulcers
Mechanism: PGE receptor agonist
Adverse effects: Diarrhea, abdominal pain
PK+notes: Short half-life; contraindicated in pregnancy
Ondansetron
Major indication, mechanism, adverse effects, and PK +notes
MI: Nausea/vomiting
Mechanism: 5-HT3 receptor antagonist
Adverse effects: GI effects, CNS effects, rash
PK+notes: Effective for preventative of chemotherapy-induced or postoperative neasea
endocrine disrupting chemicals with their impacts on health
-little evidence to prove exposures cause health impacts but…
-declines in male/female fertility
-abnormalities in M/F reproductive organs
-increases in thyroid cancer; relationship to other cancers
-increases
