GI, diuretics Flashcards
What is histamine
Naturally occurring endogenous amine, synthesized in tissues (decarboxylation of histadine)
Stored in vesicles of mast cells (skin, lung, gastric mucosa) and basophils
Released in response to antigen-antibody reaction
What does histamine regulate?
Regulates gastric acid secretion
Regulations neurotransmission (doesn’t easily cross BBB, no CNS effect)
Receptors H1, H2, H3
Do H1 and H2 antagonist inhibit the release of histamine or block the response to histamine?
Block the RESPONSE to histamine
What are the effects of activating H1?
Bronchoconstriction (asthma/bronchitis: inc airway resistance)
Vasodilation
Inc capillary permeability
Peripheral nerve sensitization (itching, pain, sneezing)
Heart: found in AV node, slow HR conduction
What are the effects of H2?
Found in gastric parietal cells, cardiac muscle, and mast cells
Inc HR and contractility
Vasodilate (offsets H1 constriction)
Bronchodilate
Stomach: activate cAMP, activate proton pump of parietal cells to secrete H ions, gastric acid secretion ->PUD, GERD
What are the effects of H3?
Heart and presynaptic postganglionic SNS fibers
Stimulation causes inhibition of synthesis and release of histamine
Activity impaired by H2 antagonists, avoid rapid administration, esp with a histamine releaser
H1 receptor antagonists first vs. second generation? What effects do they have? How are they bound? List examples of each.
First: sedation, activate muscarinic, serotonin and alpha receptors, lipophilic, neutral at physiologic pH, ex: diphenhydramine, hydroxyzine, chorpheniramine, promethazine, doxepin
Second: non-drowsy, decreases CNS toxicity, albumin binding, ionized at physiologic pH, ex: loratidine (claritin D), desloratidine, acrivastine, fexofenadine (allegra)
H1 receptor antagonist uses?
Rhinitis, conjunctivitis, urticaria, pruritis
(not effective for systemic anaphylaxis or asthma)
Motion sickness, chemotherapy-related N/V
Insomnia
H1 antagonist pharmacokinetics?
Excellent absorption
Protein binding up to 99%
Hepatically metabolized by CP450
E1/2t is variable (chlorpheniramine is over 24 hours, acrivastine is 2 hours)
H1 antagonist adverse effects?
CNS toxicity, sedative effects
Cardiac toxicity, QT prolongation
Anticholinergic effects, pupillary dilatation, dry eyes, dry mouth, urinary hesitancy
H1 antagonist vs. H2 antagonist uses?
H1 blocker for allergic rhinitis
H2 blocker to inhibit acid of gastric fluid secretion, used for duodenal ulcer disease, GERD, chemoprophylaxis
H2 antagonists MOA?
Competitive antagonism of H2 receptors by decreasing intracellular cAMP (and dec the secretion of H ions) to suppress gastric acid secretion by parietal cells
(NO effect on lower esophageal sphincter tone, gastric emptying, pH, or volume)
List some H2 antagonists.
Cimetidine (tagamet)- least potent 300mg
Nizatidine (don’t use on renal failure pts)
Ranitidine (Zantac) 150mg po/ 50mg IV
Famotidine (pepsid)- most potent 20-40mg
H2 antagonist pharmacokinetics?
Rapid absorption oral, first pass hepatic metabolism
Low protein binding, crosses BBB
Elimination 1/2t 1.5-4h
Nizatidine renal excretion
Hepatic metabolism by cimetidine, ranitidine, and famotidine
Rapid IV administration of cimetidine/ranitidine may cause what? So give these over 15-30 min
Also, give famotidine over 2 min
Bradycardia or hypotension
H2 antagonist adverse effects?
Cimetidine slows metabolism of lidocaine and dec metabolism of drugs that undergo extensive hepatic extraction (propranolol, diazepam) due to inducing P450
Transient elevation in LFTs
3 factors in PUD development?
Bacterial infection of H pylori
NSAID use
Smoking
3 goals of therapy for PUD
Reduce gastric acidity
Enhance mucosal defenses
Eliminate H pylori
What drugs inhibit acid secretion?
H2 antagonists
PPIs
Anticholinergics
What drugs neutralize gastric acid?
Antacids
What drugs protect gastric mucosa?
Sucralfate
Colloidal bismuth
Prostaglandins
What drugs eradicate H pylori?
Antibiotics
How do PPIs work?
Block K-H-ATPase (proton pump) which stops acid release
List PPIs.
Lasoprazole Pantoprazole (protonix) Esomeprazole (nexium) Omeprazole (prilosec) Rabeprazole
PPI pharmacokinetics?
Rapid absorption, short half-life
Prodrug converted to active drug in parietal cell
Hepatic metabolism by CYP2C193A4
Cross placenta
PPI adverse effects?
Headaches
GI disturbance, nausea
Enteric infections
PPI uses?
PUD with H pylori
Hemorrhagic ulcers
PUD in patient who requires NSAID use
Anticholinergics work on what?
Muscarinic Ach receptor antagonist
Decreases acid secretion
Less effective than H2 antagonists and PPIs
Anticholinergic adverse effects?
Dry mouth, constipation, blurred vision, cardiac arrhythmia, urinary retention
How does sucralfate work?
Complex salt of sucrose sulfate and aluminum hydroxide, forms a viscous gel that sticks to areas of ulceration
Protects ulcerated tissue from aggressive factors such as pepsin, acid, and bile salts
DOESN’T alter gastric pH, good for symptom relief
Sucralfate adverse effects?
Constipation
Little systemic absorption (it binds to other drugs)
How does colloidal bismuth work?
It is a coating agent used in PUD
Protects mucosa from acid and pepsin degradation (barrier formation and stimulation of mucosal bicarb and PGE2)
Impede growth of H. Pylori
What is Misoprostol? AE?
A prostaglandin analoague
Prevents NSAID-induced ulcers
AE: abdominal discomfort, diarrhea
CI in pregnancy
What would triple therapy of H Pylori include? Quadruple therapy?
Triple: Amoxicillin, clarithromycin, PPI
Quad: Tetracycline, metronidazole, PPI, bismuth
Antacids
Neutralize or remove acid from gastric content
Aluminum, calcium, magnesium salts
INC gastric pH over 5 (from 2.5)
Not first line for ulcers but inc rate of ulcer healing and pain relief
List some antacids. What are side effects?
Aluminum hydroxide Magnesium hydroxide Sodium bicarb (caution in cardiac pt) Calcium carbonate (tums) Side effects: constipation, diarrhea, electrolyte abnormalities
What does sodium citrate (bicitra) do?
It is a preoperative nonparticulate (clear) antacid therapy, causes less of a foreign body reaction if aspirated
Rapid onset, give 15-30 min prep, 15-30mL, pH of 8.4, unpleasant taste
Prokinetic drugs: what do they do?
Increase lower esophageal sphincter tone
Accelerate rate of gastric emptying
Enhance peristalsis
What is metoclopramide (reglan)?
Dopamine antagonist, kinetic only
Gastric pH unchanged
Cholinergic stimulation of GI tract: increase LES tone, increase gastric/small bowel motility, relaxation of pylorus and duodenum
Interactions with metoclopraminde?
Post-synaptic release of Ach GI actions opposed by atropine and glycopyrrolate
Dopamine receptor antagonism
May inhibit plasma cholinesterase
Metoclopramide pharmacokinetics?
Rapidly absorbed PO
Peak plasma concentration 40-120 min
E1/2t 2-4h
Renal excretion, 40% unchanged drug
Metoclopramide uses?
Decrease gastric fluid volume
Antiemetic
Treatment of gastroparesis
Symptom treatment of GERD
Metoclopramide dose?
10-20 mg IV over 3-5 min
15-30 min prior to induction
Child/mom dose: 0.15 mg/kg
Diabetic gastroparesis (full stomach) dose: 10 mg IV
Metoclopramide side effects?
CNS effects
Extrapyramidal effects
Stimulate prolactin secretion
Anti-emetic
Abdominal cramping (with rapid administration, push in 3-5 min)
Cardiac dysrhythmias, sedation, dry mouth
Metoclopramide contraindications?
BOWEL OBSTRUCTION
Parkinsons
Seizure disorder
Phenothiazines (these also create extra-pyramidal effects)
Serotonin (5HT): what is is synthesized from? Where is it located intrinsically?
5HT is synthesized from tryptophan
Important as a neurotransmitter with pain/nausea impulses
90% in the enterochromaffin cells (gut)
10% in CNS and platelets
Where can 5HT3 antagonists work? What are they used for?
Antagonism at peripheral (vagal afferents in GI) and central (CRTZ) receptors
Used as an antiemetic for postop N/V, chemotherapy, hyperemesis gravidarum
Name some 5HT3 antagonists and dosages
Ondansetron 4-8mg IV (Peds 0.05-0.15 mg/kg IV up to 4 mg)
Granisetron 0.01-0.04 mg/kg
Dolasetron 12.5 mg IV
Tropisetron
Side effects of 5HT3 antagonists
Headache with rapid IV administration (ondansetron)
Cardiac dysrhythmias- rare
Rely on liver metabolism (reduce dosage appropriately in liver disease)
Dexamethasone used for PONV prevention, what is the dosage?
Steroid
4-10mg IV
Name a couple phenthiazines. What are they used for?
Prochlorperazine (compazine)
Promethazine (phenergan)
Exerts anti-emetic effects by interaction with dopaminergic receptors in CRTZ
Phenergan taken off the market for what?
Neurolept malignant syndrome
24-48 h after dose
Presentation: tachy, cardiac dysrhythmias, alterations in BP, presents like MH (distinguish by effect of NDMRs which produce flaccid paralysis in NMS but not in MH)
Treat with amantadine and dantrolene
Droperidol
Inhibits dopaminergic receptors in CRTZ, for PONV, decrease BP, peripheral alpha blockade, EPS, akathesia, dysphoria, neurolept anesthesia
Black box for QT prolongation and torsades de pointe
Thiazides: what does it work on, what does it do? K wasting/sparing? Prototype: HCTZ (hydrochlorothiazide)
Works on the distal convoluted tubule
Impairs Na and Cl reabsorption
Peripheral vasodilation (anti-HTN)
K wasting
Thiazides anesthesia concerns?
Hypokalemia, hypochloremia, hypomagnesemia
Muscle weakness potentiates muscle relaxants
Nephropathy
Inc risk of dig toxicity
Fluid volume status
Loop diuretics: where do they work?
Act on ascending loop of henle, inhibits passive transport of Na/K/Cl from lumen
Prototype: Furosemide
Loop diuretic side effects?
Hypokalemia, hypochloremia
Presynaptic effect potentiates NDMRs
Enhances possibility of nephrotoxicity when administered with aminoglycosides and cephalosporins (ABX)
Dec renal clearance of lithium
Cross reactivity with sulfonamide allergy
Furosemide dose? Pharmacokinetics?
0.1-1 mg/kg
Extensive protein binding
Excreted by glomerular filtration and renal tubular secretion
Furosemide uses?
Mobilization of edema fluid- peripheral vasodilation precedes onset of diuresis
Reduction of ICP, dec venous return
Used for hypercalcemia/ parathyroid syndrome and oliguria
Osmotic diuretic
Mannitol is the prototype (must give IV)
Cleared from plasma by glomerular filtration, increases renal tubular fluid osmolarity and plasma osmolarity
Draws fluid from IC to EC space, inc intravascular volume (problem with poor LV function/pulmonary edema)
Osmotic diuretic clearance
100% by GF None reabsorbed (so don't use in renal failure)
Mannitol uses?
Differential diagnosis of oliguria
Prophylaxis for ARF
Reduces ICP
Reduces IOP
Mannitol dose? Anesthesia concerns?
0.25-1 g/kg IV
Works in 10-15 min, lasts 2 hours
Anesthesia concerns: pulmonary edema, hypovolemia, electrolyte changes
Which diuretics are potassium sparing?
Epithelial sodium channel blockers (triamterene) Aldosterone antagonists (spironolactone)
How does triamterene work?
Works on the collecting duct
Non-competitive antagonism of aldosterone, Na channel blockade
Can cause hyperkalemia
How does spironolactone work?
Competitive aldosterone antagonist (blocks aldosterone from reabsorbing Na and water and secretion of potassium)
Spironolactone uses?
K sparing
Treats heart failure, ascites, low-renin HTN, hypokalemia, Conn’s syndrome
It is a weak diuretic, usually combined with other diuretics
Carbonic anhydrase inhibitor: what does it do?
Prototype: acetazolamide (diamox)
Uses: glaucoma, altitude sickness, ICP
Blocks carbonic anhydrase, inc amounts of bicarb, Na, and water in the urine
(Carbonic anhydrase catalyzes H and bicarb released from CO2 and water. H is then excreted in exchange for Na on the renal luminal membrane and bicarb is reabsorbed with Na)
