GI Pharmacology Flashcards
What is the product/function of Parietal Cells?
HCl for Protein Digestion, Sterilization, and Nutrient Absorption
What is the product/function of Superficial Epithelial/Neck Cells?
Mucus and Bicarbonate for gastroprotection
What is the product/function of ECL cells?
Histamine, which promotes HCl secretion
What is the product/function of G cells?
Gastrin, which promotes HCl secretion
What are the key regulatory of paracrine, endocrine, and neuronal acid seretion?
Paracrine –> Histamine
Endocrine –> Gastrin
Neuronal/Neurocrine –> Acetylcholine
What are the Direct/Indirect regulators of acid secretion from the parietal cells?
Gastrin and Acetylcholine
Directly stimulate the Parietal Cell
Indirectly stimulate the ECL Cells
What are the 3 key roles of prostaglandins?
- Mucus and Bicarbonate secretion
- Suppression of HCL secretion
- Increase gastric blood flow
What type of ulcer has the greatest frequency?
Duodenal Ulcers
Stress Ulcer (Definition)
Peptic ulcer caused by illness, systemic trauma, neuronal injury, emotions
Cushing Ulcer (Definition)
Stress ulcer associated with Head Trauma or Brain Surgery
Ischemic Ulcer (Definition)
Ulcer caused by hemorrhage, multi-system trauma, severe burns (Curling ulcer), heart failure, sepsis
What are the two most common causes of ulcers in the U.S.?
NSAIDs (COX inhibition) and H. pylori
Symptoms of an ulcer
1. Abdominal Pain (particularly after a meal)
- Nausea
- Vomiting, vomiting blood
- Bloody, tarry school
- Indigestion
- Weight loss
- Fatigue
Antacids (Therapeutic Goals)
Neutralize the acid in the stomach to a pH > 4
End products: Salt, Water (sometimes CO2)
No Target Receptor
Sodium Bicarbonate - NaHCO3 (Rate of Reactivity, Specific Adverse Effects)
Rate of Reactivity: FAST
Specific Adverse Effects: Metabolic acidosis, excessive NaCl absorption, Gas/Bloating (CO2__)
Calcium Carbonate - CaCO3 (Duration of Action, Rate of Reactivity, Specific Adverse Effects)
DoA: 1-2 hours
RoR: MODERATE
SAE: Acid Rebound (Feed forward mechanism causing INCREASED acid production after long-term use), Gas/Bloating (CO2), Hypercalcemia (large doses), Hypophosphatemia (Rare)
Magnesium Hydroxide - Mg(OH)2 (Rate of Reactivity, Specific Adverse Effects)
RoR: SLOW
Specific Adverse Effects: Osmotic Diarrhea (due to excess Salt in intestines), Hypermagnesemia (large doses over an extended period of time)
Aluminum Hydroxide - Al(OH)2 (Rate of Reactivity, Specific Adverse Effects)
RoR: SLOW
SAE: Constipation (slows down smooth muscle peristalsis), Aluminum toxicity (impaired RENAL FUNCTION), Hypophosphatemia, Bone Resorption, Hypercacelmia
Duration of Action of Antacids
Very SHORT (1-2 Hours)
***Have to take them very frequently, therefore, will see a Decrease in Compliance
Two common Adverse Effects of Anatacids
- Reduced Drug Bioavailability
- Enteric Infection
Therapeutic Uses of Antacids
GERD, Peptic Ulcers, Dyspepsia
Anatacids are used as adjunctive therapy with____
PPIs
Antacids are equally efficacious as _____ at treating GERD (heal rate = ___%) and Peptic Ulcers (heal rate = ___%)
Antacids are equally efficacious as H2-Receptor Antagonists at treating GERD (heal rate = 50%) and Peptic Ulcers (heal rate = 80%)
H2-receptor Antagonists
- Type of inhibition/Selectivity
- What is blocked?
- Competitive and Highly Selective
- Blocks Indirect action of Gastrin and Acetylcholine; Does not block direct action of Gastrin and Acetylcholine
What do all H2-receptor Antagonist names end in?
They all end in -tidine
H2-receptor Antagonists
Drug Names (4 of them)
- Cimetidine (Tagemet)
- Ranitidine (Zantac)
- Nizatidine (Axid)
- Famotidine (Pepcid)
H2-receptor Antagonists
- Duration of Action
- Common Adverse Effects
DoA: 10 hours or 6 hours OTC
CAE: Headache, diarrhea, fatigue, constipation, infection, drug kinetics, bradycardia (IV), hypotension (IV)
H2-receptor Antagonists
- Specific Considerations for Cimetidine
- CNS Effects (confusion, hallucinations, agitation)
- Endocrine Effects (inhibition of androgen receptors, inhibition of estradiol metabolism, increase prolactin levels)
- Inhibition of hepatic CYB metabolism (Inhibits cytochrome P450 activity, which leads to high potential of drug-drug interactions)
H2-receptor Antagonists
- Key Difference from Antacids
- Key Advantage compared to Antacids
- Must be absorbed into the BLOODSTREAM to take effect
- Have to be administered LESS often
(Equally efficacious as antacids at treating GERD and Peptic Ulcers and can additionally treat Gastritis)
Proton Pump Inhibitors (PPIs)
- Key Advantage over H2-receptor Antagonists
- Antagonizes the proton pump, so is able to block both Direct and Indirect actions of ACh, Histamine, and Gastrin
Proton Pump Inhibitors (PPIs)
- Mechanism of Action (5 things)
- Activated by low pH
- Acid-labile drug is absorbed into the BLOODSTREAM by GI
- Concentrates at the site of action (Parietal Cells)
- Irreversibly binds/inhibits proton pump
- Activation of pump requires new synthesis
What do all Proton Pump Inhibitors end in?
All PPIs end in -prazole
Proton Pump Inhibitors (PPIs)
- Drug Names
- Omeprazole (Prilosec)
- Lansoprazole (Prevacid)
- Rabeprazole (Aciphex)
- Esomeprazole (Nexium)
- Pantoprazole (Protonix)
Proton Pump Inhibitors (PPIs)
- Duration of Action
DoA: 24 hours (takes 3-4 days of dosing to reach max effect)
Proton Pump Inhibitors (PPIs)
- Common Adverse Effects
***Extremely SAFE***
- Decreased drug bioavailability
- Diarrhea, headache, abdominal pain (1-5%)
- Decreased nutrient absorption (Vitamin B12, Iron, Calcium, Zinc)
- Enteric and Respiratory infections
Why does it take 3-4 days for PPIs to reach maximum effect?
It takes 3-4 days for the body to exhaust its supply of proton pumps, which are waiting in the tubulovesicular network to be brought to the apical surface and inactivated by the PPI
***This is why you initially supplement w/ Antacids or H2-receptor Antagonists***
Proton Pump Inhibitors (PPIs)
- Therapeutic Uses
GERD
Peptic Ulcers
Dyspepsia
Gastritis
Hypersecretory Diseases
NSAID-associated Ulcers
H. pylori-associated Ulcers
Proton Pump Inhibitors (PPIs)
- Effectiveness
- Most Efficacious Inhibitors
(GERD Heal Rate = 90%)
(Peptic Ulcer Heal Rate = 90%)
Muscoal Protective Agents
- Drug Names
Sucralfate (Carafate)
Misoprostol (Cytotec)
Bismuth subsalicylate (Pepto-Bismol)
Mucosal Protective Agents
- Mechanism of Action
Sucralfate and Bismuth subsalicylate both create a physical barrier and stimulate mucus and HCO3- secretion from the gastric mucosa
Misoprostol (a prostaglandin derivative) stimulates mucus and HCO3- secretion from the gastric mucosa, but DOES NOT form a physical barrier
Mucosal Protective Agents
- Duration of Action
6 hours
Mucosal Protective Agents
- Common Adverse Effects - Sucralfate
- Other Adverse Effects
- Constipation, Impaired Drug Absorption
- Caution w/ Renal Insufficient Patients
***Constipation (inhibition of smooth muscle contraction) and Renal Toxicity due to presence of Aluminum***