GI Meds Flashcards
Histamine
Where/how its synthesized
Storage released in resp to
Synth in tissues, decarboxylation of histamine. Stored in vesicles in mast cells (skin, lung, gastric mucosa) and circ basophils. Released in rep to antigen-Ab rxn/drugs
Histamine
3 effects in body
Mediated by
Inflammatory mediator, reg gastric acid secretion, reg neurotransmission. Doesnt readily cross BBB (no cns fx). Receptors H1, 2, 3
H1 and H2 antagonists dont inhibit what, do what
Dont inhib release of histamine, block response to histamine
H1 does what overall
Smooth muscle contraction lung, gi, vascular, release of NO, sensory nerve stim
H1 fx
Lungs
Bronchoconstriction, asthma/bronchitis, inc a/w resistance
H1 fx vascular smooth muscle
Dilation leads to hypotension and erythema
H1 fx vascular endothelium
Peripheral nerves
Heart
Inc cap permeability, edema
Sensitization, itching, pain, sneezing
In AV node, slow HR by slowing conduction
H2 receptor
Where they are
Gastric parietal cells, cv muscle, mast cells
H2 receptor
Action in heart and coronary vasculature
+ inotropic/chronotropic. Inc rate and contrac. Vasodilated heart vessels, offsets H1 constriction
H2 receptor
A/w fx
Activ cell level in stomach
Relaxes bronchial smooth muscle
Inc camp, activates proton pump of parietal cells to secrete h ions
H2 receptor
Fx in stomach
Gastric acid secretion, PUD and gerd
H3 receptor locations
Stim causes what
Heart and presynaptic postganglionic SNS fibers
Inhib of synthesis and release of histamine
H3
Activity impaired by what, avoid what
H2 antagonists, leads to inc histamine release. Avoid admin of these agents w a histamine releasing drug like atracurium
H1/2 antagonists
Histamine receptors that they occupy, about inhibition
Transmembrane G protein coupled. Competitive and reversible inhibition
H1 antag used for
H2 antag used for
1- allergic rhinitis
2- inhib gastric acic fluid secretion
H1 receptor antag
Diff b/w first and second gen
1st- sedation, activ muscarinic, serotonin and alpha receptors
2nd- non drowsy, decreases cns toxicity
H1 receptor antag
Uses
Not used for
Rhinitis, conjunctivitis, urticaria, pruritis.
Not effec for systemic anaphylaxis or asthma
H1 receptor antag
Used for __ /___ AND ____ specific ones
N/v, motion sickness. Diphenhydramine, dimenhydrinate, meclizine, promethazine
H1 receptor antag for insomnia
Diphenhydramine and doxylamine
H1 antihistamines
About 1st gen: 2
5 ex
Lipophilic, neutral and physio pH.
Diphenhydramine, hydroxyzine, chlorpheniramine, promethazine, doxepin
2nd gen h1 antihistamines
About drug 2
Ex 4
Albumin binding, ionized at physio pH.
Loratidine, desloratidine, acrivastine, fexofenadine
H1 antag
___ absorption
Cmax when
Protein binding
Excellent
2-3hrs
78-99%
H1 antag
Metab by what
Cyp 450
H1 antihistamines AE
Toxicities 2
___ effects
CNS (sedative), cardiac (QTi prolong)
Anticholinergic: pupil dilation, dry eyes/mouth, urine ret
H2 antagonists
MOA
4 agents
Competitive antagonist at h2 receptor, suppresses gastric acid sec by parietal cells. Cimetidine, nizatidine, ranitidine, famotidine
H2 antagonists Decreases intracellular \_\_ Least potent Most potent No effect where
CAMP
Cimetidine
Famotidine
LES tone/gastric emptying
H2 antag work on which pump
H K atpase
H2 antagonists effects
Tx duodenal ulcers and gerd, chemoprophylaxis prior to induction of GA
Chemoprophylaxis doses/when to give
Cimetidine
300 mg po/iv 1-2hrs preop
Chemoprophylaxis doses/when to give
Famotidine
20-40 mg po/20 mg iv am of surgery
Chemoprophylaxis doses/when to give
Ranitidine
150 mg po or 50 mg iv
H2 antagonists
No effect where
No effect on gastric pH. Unpredictable volume effect
H2 antagonists
Metab
Cmax
Rapid oral abs, 1st pass metab, 50% bioavailability
1-3 hrs
H2 antagonists
Protein binding
BBB
Elim
15-35%
All 4 cross it
1.5-4 hrs
H2 antagonists
Which one renal exc
Metabolism primarily
Nizatidine
Other 3 hepatic metab
H2 antag SE
Which 2 things inc SE severity
May have transient elev of
Multisystem disease and inc age
LFTs
H2 Antagonists
Avoid rapid admin of __ and __, why
Give over what time period
Cimetidine and ranitidine
Hypotension and bradycardia
15-30 min
H2 antagonists
__ may be given over 2 min
Famotidine
H2 antagonists
Decreases metab of what
Drugs w hepatic metab. Propranolol and diazepam
H2 antagonists
Cimetidine may slow metab of __ and other __
Lidocaine, drugs
Goals of PUD therapy 3
Reduce gastric acidity, enhance mucosa, elim h pylori
Drug tx PUD
For acid
Mucosa
H pylori
H2 antag, PPI, and anticholinergics for acid sec inhib. Antacids to neutralize. Mucosa protection: sucralfate, bismuth, prostaglandins. Abx
PPI
Block what
K h ATPase
PPI
__ absorption
Conversion, where
Rapid
Prodrug to active drug in parietal cell canaliculus
PPI \_\_ bond w proton pump \_\_ half life Metab Crosses \_\_
Covalent
Short
Cyp 2c19 and 3a4
Crosses placenta
PPI
AE
HA, GI disturb, nausea, enteric infections. Long term unknown, maybe carcinoid tumors
PPI
Indic for what
PUD w h pylori
Hemorrhagic ulcers
PUD in pt who req nsaid use
Dicyclomine
MOA
__ effective than h2 antag and PPI
AE
Musc ach antag, dec acid sec
Less
Dry mouth, constip, blurry vision, cardiac arrhythmia, urine ret
Where anticholinergics work in parietal cell
Block acetylcholine and Gastrin
Sucralfate
What it is
How it works
Salt of sucrose sulfate and al oh. Forms gel that binds to + charged proteins (albumin and fibrinogen), sticks to ulcer areas. Protects tissue from pepsin, acid, and bile salts
Sucralfate
Doesnt do what
Does do what
AE
Doesnt alter gastric ph
Does relieve symptoms
Constip, little systemic absorp, big pills and frequent admin, drug interactions (binds to them)
Colloidal bismuth
Used in what
Protects how
PUD. Coating agent. Protects mucosa from acid and pepsin degradation, forms barrier. Stim mucosal bicarb and prostaglandin, impedes h pylori
Prostaglandins
Agent
Does what
AE/contra
Misoprostal, pg analogue. Prevents nsaid induced ulcers. Abd discomfort and diarrhea. Pregnancy
Tx h pylori
Triple therapy
Amoxicillin, clarithromycin, PPI
H pylori
Quadruple therapy
Tetracycline, metronidazole, PPI, bismuth
Antacids
Inc pH to what
5
AE of antacids, 4 agents
Constip, diarrhea, electrolyte abn
Al oh, mg oh, na hco3, ca co3
Na citrate/bicitra What kind of antacid Onset Dose PH
No particulate, clear
15-30 min to facial mixing and emptying
15-30 ml po
8.4
Reglan
MOA
__ only, __ unchanged
Dopamine antagonist
Kinetic, pH
Reglan
What it does to GI tract 3
Cholinergic stim. Inc LES tone, inc gastric/small bowel motility, relaxes pylorus and duodenum
Reglan
Post synaptic release of __
Opposed by what
Ach. Atropine and glyco
Reglan
___ effects
Stim __ secretion
__ __ effects
CNS effects, EPS
Prolactin
Anti emetic
Reglan Absorption Peak E 1/2 Excretion
Rapid po
40-120 min
2-4 hrs
Renal exc, 40% unchanged
Reglan uses
4
Dec gastric fluid vol
Antiemetic
Gastroparesis
Gerd symptomatic tx
Reglan periop
When/how to give before induction
10-20 mg iv over 3-5 min. 15-30 min prior to induction.
Periop reglan
Dose after delivery
Dose kids post t+a PACU
Dose pre induction w diabetic gastroparesis
0.15 mg/kg iv
0.15 mg/kg
10 mg
Reglan SE
Cramping if given in less than 3 min Cardiac dysrhythmias esp w zofran Sedation, dry mouth, EPS (Torric) Inc sedation of butyrophenones and phenothiazines May inhib cholinesterase
Reglan contraindications 4
Bowel obstruction
Parkinson’s disease
Seizure disorders
In combo w phenothiazines
5ht
Where 90% lives
10%
Drugs that antagonize here
Enterochromaffin cells in gut
CNS and plt
TCAs and phenothiazines
Ondanzetron
MOA
5ht3 antag. Selective antagonism at peripheral (vagal afferrent gi) and central receptors
5ht3 antag
Useful in which 3 settings
Chemo
Postop NV
Hyperemesis gravidarium
SE 5HT3 antag
Careful w what disease
HA w rapid admin
Cardiac dysrhythmias rare
Rely on liver metab, reduce in renal disease
PONV dosing
Zofran
Adults
Peds
4-8 mg iv
0.05-0.15 mg/kg (up to 4 mg)
PONV dosing
Granisetron
Dolasetron
G- 0.01-0.04 mg/kg
D- 12.5 mg iv adults
Steroids to prevent ponv/dose
Dexamethasone
4-10 mg iv
Phenothiazines
2 ex, how they work
Compazine and phenergan. Interact w dopaminergic receptors in Crtz
Phenergan
Onset iv
Use 4
5 min
Blood trans rxn, allergic rxn, sedation, PONV
Phenergan Duration 1/2 life Metabolism Contra
4-6hrs
9-16 hrs
Liver
Under 2 y/o (fatal resp depression/comatose states)
Neuroleptic malig syndrome
Occurs w what, when
0.5-1% rx phenothiazines. 24-72hrs, young men
Neuroleptic malig syndrome
Presentation
Tachy/dysrhythmias, alt bp, fluc LOC. Sim to MH W: muscle rigidity, high temp, rhabdo, autonomic instability
Neuroleptic syndrome
Tx
How diff from MH
Dopamine antag (amantadine) and dantrolene NDMR will produce rapid paralysis in NMS but not MH
Butyrephonones
Which one
MOA
Dose
Droperidol
Inhib dopaminergic receptors in crtz
0.625-1.25 mg IV for PONV
Droperidol
Effects
Use
Now what, why
Dec bp central effect, peripheral alpha blockade, EPS, akathesia, dysphagia
Neuroleptic anesthesia
Block box bc of torsades
