Exam I: GI, Antihyperlipidemic and Diuretic drugs Flashcards
Acid secretion in the stomach is stimulated by?
- Histamine (H2 receptors)
- Ach (M3 receptors)
- Gastrin (promotes histamine secretion by ECL cells)
If PPIs permanently turn of proton pumps, how is acid produced when PPIs are stopped?
New proton pumps must be synthesized
Histamine. Receptor? Synthesis? Antagonists?
Receptor - Binds to H2 receptors on parietal cells
Synthesis - Made by Enterochromaffin-like (ECL) cells
Antagonists - Similar structure to histamine reversible competitive inhibitors on H2 receptors
Acetylcholine. Receptor? When is it released?
Receptor - Muscarinic III receptors on parietal cells
Released when food is smelled during hunger prior to eating - vagus (vagal) nerve stimulation
Gastrin. Promotes the release of?
Promotes histamine secretion by ECL cells - indirect stimulation of acid production
How is gastric acid (HCL) secreted?
Secreted by parietal cells in the stomach via the proton pump (H+/K+ ATPase)
Prostaglandin (PGE2). Function in the stomach?
- Inhibit acid production
- Cytoprotective - stimulates epithelial cell to secrete mucous barrier around stomach
- Stimulate epithelial cells to release bicarbonate (neutralize acid)
Five causes of Peptic Ulcer Disease (PUD).
- H. pylori - gram negative bacteria that colonizes beneath mucosal barrier
- Chronic NSAID use
- Other drugs (ie. Bisphosphonates, corticosteroids, clopidogrel, warfarin)
- Hypersecretion of gastric acid like in Zollinger-Ellison syndrome - benign pancreatic tumor that secretes gastrin
- Stress ulcers (ie. no PO for ICU patients, disruption in mucous and bicarbonate secretion)
How exactly does H. pylori cause ulcers?
Produces an enzyme called urease (converts urea to ammonia which increases pH)
Describe two cytoprotective drugs.
- Sucralfate - Coat the stomach and ulcer (if present), prevents acid from coming in contact
- Misoprostol - synthetic PGE1, acts like prostaglandins (inhibit acid production, stimulate mucous and bicarbonate secretion)
Name two methods to eradicate H. pylori (HPI).
Clarithromycin Triple
Bismuth Quadruple
Clarithromycin Triple regimen. Drug names, strengths, duration and directions.
14 day regimen
- Clarithromycin 500mg po BID
- Amoxicillin 1 gram po BID
- PPI po QD taken 30 min before breakfast
Bismuth Quadruple. Drug names, strengths, duration and directions.
10-14 day regimen
- Bismuth subsalicylate 2 tabs po QID
- Metronidazole 250 mg po QID
- Amoxicillin 500 mg po QID
- PPI po QD taken 30 min before breakfast
M of a for H2RAs?
Secondary inhibition of vagal (Ach) and gastrin-stimulated acid secretion
When is acid secretion most effectively inhibited by H2RAs?
Basal and nocturnal - at bedtime
Treatment durations for H2RA management of PUD for duodenal ulcers (DU) vs gastric ulcers (GU).
DU - 6-8 weeks
GU - Full 8 weeks
Add 2-4 weeks to regimen for elderly patients or smokers, ulcers take longer to heal in these patients
Put ranitidine, cimetidine, nizatidine and famotidine in order from longest to shortest duration
1 and 2. Famotidine and Nizatidine - 10 hours
- Ranitidine - 6-10 hours
- Cimetidine - 6 hours
Famotidine comes in 20 mg and 40 mg. There are some patients that take 20 mg po QD.
True/False
False
Doses always add up to the treatment dose for H2RAs (in this case 40 mg)
20 mg po/IV BID
Which H2RA causes the most side effects? What are the most common side effects? (4)
Cimetidine
- CNS - headache, dizziness, confusion etc
- GI (most common) - diarrhea, constipation, nausea
- Nosocomial pneumonia
- 2.3 times greater risk of community-acquired pneumonia
DDIs for cimetidine specifically. (4)
- inhibits hepatic CYP enzymes - increased plasma concentration for warfarin, alprazolam, etc.
- Decreased hepatic blood flow - increased bioavailability of drugs with a high hepatic extraction ratio
- Additive myelosuppression (alkylating agents, antimetabolites, radiation therapy)
- Decreased bioavailability when taken with Al/Mg antacids (Mylanta, Maalox)
Famotidine and nizatidine do not inhibit CYP enzymes.
True/False
True
DDI for all H2RAs
Decreased bioavailability of ketoconazole because it needs acid to dissolve
Salicylates—decreased renal tubular secretion (competitive inhibition by all H2RAs)
PPIs onset of action? How long does acid secretion take to return after discontinued?
Onset of action - 1 hour
Full acid secretion returns after 4-7 days from the time a PPI is discontinued
Most common side effects of PPIs. (6)
- GI (most common) - abd pain, nausea
- CNS - headache
- 2.5 times higher risk of community-acquired pneumonia
- Osteoporosis and increased risk of fracture
- Hypermagnesemia
- Dose-dependent decrease in vitamin B12
Name the PPIs approved to treat PUD. (3, one is a combo)
- Omeprazole alone or with NaHCO3
- Lansoprazole
- Rabeprazole
DDIs of omeprazole specifically.
- Inhibition of CYP enzymes
- increased levels of warfarin, phenytoin etc.
- Decreased levels of omeprazole when taken with Rifampin or St. John’s wort (supplement)
DDIs for all PUD PPIs.
- Decreased bioavailability of ketoconazole, ampicillin, iron salts, digoxin, atazanavir.
- May increase risk of digoxin-associated cardiotoxicity secondary to hypomagnesemia
- Sucralfate - binds to GI drugs and delays absorption and decreases oral bioavailability of PPI
What is GERD?
Transient relaxation of the esophageal sphincter
What can trigger GERD symptoms? (4)
Obesity
Alcohol or tobacco use
Fatty, spicy foods
Some medications/drugs
What are some alarm symptoms of GERD? Why are the alarming?
Symptoms: Dysphagia, chronic sore throat, bleeding or anemia, unexplained weight loss
Alarming because the symptoms may be due to Barrett’s esophagus syndrome which increases risk of cancer
Name the PPIs approved to manage GERD. (6)
- Omeprazole
- Esomeprazole
- Lansoprazole
- Rabeprazole
- Pantoprazole
- Dexlansoprazole (Dexilant)
What is NERD? More likely to respond to PPIs?
Non-erosive reflux disease (NERD) is a type of gastroesophageal reflux disease (GERD) in which the esophagus is unharmed by stomach acid
Less likely to respond to PPIs compared to patients with Erosive Esophagitis (EE)
Use of OTC PPIs for acid reflux should not exceed what time period. Why?
No longer than 14 days every 4 months without doctor supervision.
Can mask a serious illness like esophageal cancer
Concerns about long term use of PPIs
- Osteoporosis and bone fracture (decreased calcium absorption)
- Community-acquired pneumonia
- C. difficile colitis
- Ischemic heart disease and acute MI (PPIs may decrease nitric oxide synthesis)
- Dementia (in mice PPIs increase amyloid-beta proteins in brain)
- Chronic renal failure (mechanism unclear)
- Gastric carcinoid tumors in mice
What is the most effective antagonists for nausea and vomiting?
Serotonin (5HT3) receptor antagonists
ie. Ondansetron
Name 4 antiemtics for cytotoxic drug-induced emesis.
Ondansetron** (most common antiemetic)
Metoclopramide
Promethazine
Dronabinol nabilone
Name the Neurokinin receptor antagonists used to delay vomiting following cytotoxic drug-induced emesis
Aprepitant** (most common antiemetic)
Can dolasetron mesylate be administered IV for CINV? Why or why not?
No
Due to the risk of dose-dependent QT interval prolongation
Which Serotonin (5HT3) receptor antagonists are not indicated for RINV?
Dolasetron
Palonosetron
Statins derive their name from?
Molds or fungi
“STATIN” pharmacological class. M of a?
HMG CoA Reductase Inhibitors
HMG CoA reductase is the rate limiting enzyme in cholesterol synthesis
By inhibiting this enzyme it leads to a compensatory increase in the expression of LDL receptors which stimulates LDL catabolism
“STATIN” drugs have a pleiotropic effect. What does this mean? What are the pleiotropic effects?
Pleiotropic effect –> multiple effects with one dose
Decreases inflammation at site of coronary plaque, inhibits platelet aggregation, and anticoagulant effects
How do “STATIN” drugs affect HDL, LDL and triglyceride levels?
Lowers: LDL (“Bad cholesterol”), Triglycerides
Raises: HDL (“Good cholesterol”)
Patients with Atherosclerotic Cardiovascular Disease risk factors do not need to take a “STATIN” if cholesterol levels are normal.
True/False
False
If a patient is at risk for ASCVD from a co morbid condition then they need to be on a “STATIN” drug
“STATIN” drugs can be used for primary and secondary prevention. What is the difference?
Primary prevention – Medication is given for a patient that has never had the targeted disease
Ex. Patient at risk for a heart attack but never experienced
Secondary prevention – Aims to reduce the impact of a disease that has already occurred and prevent it in the future
Ex. Patient has had a heart attack in the past. Medication is used to prevent a future heart attack.
Adverse drug reactions to “STATIN” drugs. (5)
Diarrhea
Arthralgia (joint pain)
Nasopharyngitis (swelling of nasal passages in the back of the throat)
Insomnia
Malaise (feeling tired, ill or uncomfortable)
Increased hepatic function tests
When are “STATIN” drugs most effective? Why? Name the exceptions to this.
Most statins should be administered before bedtime because cholesterol is synthesized when dietary intake is at its lowest.
Exceptions - Atorvastatin and Rosuvastatin - can be taken at any time
Why can Atorvastatin and Rosuvastatin be taken at anytime in the day as opposed to other “STATIN” drugs?
They have a longer half life than other statins
Can “STATIN” drugs be given to pregnant patients?
No
Category X
What to do if a patient complains of myalgia (muscle pain)?
Try a different statin
Remember –> the more lipophilic the statin the greater chance of muscle pain
What fruit do statins interact with?
Grapefruit
At certain doses, Simvastatin must be taken concurrently with what other type of drug?
Calcium channel blockers (CCBs)
High intensity statin therapy. On average how much is LDL lowered with a daily dose? Name the two drugs and dose ranges.
Daily dose lowers LDL on average 50% or greater
Atorvastatin 40-80mg
Rosuvastatin 20-40mg
Low intensity statin therapy.. On average how much is LDL lowered with a daily dose? Name the four drugs and dose ranges.
Daily dose lowers LDL on average less than 30%
Simvastatin 10mg
Pravastatin 10-20 mg
Lovastatin 20 mg
Fluvastatin 20-40 mg
Name the combination statin drugs. (3)
Advicor® - lovastatin + niacin ER
Simcor® - simvastatin + niacin ER
Vytorin® - simvastatin + ezetimibe
Name the three “Choles-“ drugs. Pharmacological class.
Bile acid sequestering agent
Cholestyramine
Cholestipol
Cholesevelam
Mechanism of action for Choles- drugs.
Forms a non-absorbable complex with bile acids and releases chloride ions in the process
Inhibits reuptake of intestinal bile salts and increases fecal loss of LDL-C
“Off label” uses of CHOLES drugs
Chronic diarrhea due to bile acid malabsorption (most common)
Hyperthyroidism
Pruritus associated with cholestasis
Adverse reaction to CHOLES drugs. (6)
Abdominal pain
Constipation
Flatulence
Abnormal hepatic function tests
Myalgias
Osteoporosis
Interactions and monitoring necessary for patients taking CHOLES drugs. (3)
Warfarin – monitor for decreased INR
Statins/fibrates – monitor for increased incidence of myalgias
Amiodarone – may decrease availability/effectiveness of amiodarone
Name the three FIBRATE drugs.
Gemfibrozil
Fenofibrate
Fenofibric Acid
Mechanism of action for FIBRATE drugs
Exact mechanism is unknown
In theory, inhibits lipolysis and decreases hepatic fatty reuptake as well as inhibit secretion of VLDL
FIBRATE drugs effects on LDL, HDL and triglyceride levels.
Very good triglyceride lowering agents
Also decrease LDL and increase HDL
FDA approved indications for FIBRATE drugs. (2)
Hypertriglyceridemia
Hypercholesterolemia
Off-label use of FIBRATE drugs.
Primary biliary cholangitis – autoimmune disease of the liver, the bile ducts in your liver are slowly destroyed
Adverse reactions to FIBRATE drugs. (4)
Increased serum transaminases (can be a signal of liver damage)
Abdominal pain
Abnormal hepatic function tests
Myalgias
DDIs for all FIBRATE drugs
All can increase incidence of myalgias when combined with statins
Gemfibrozil DDIs
Contraindications - All statins, ezetimibe, any CYP2C8 substrates (many antiretrovirals)
Also use with caution in patient on warfarin
OCUMABS drugs mechanism of action
PCSK-9 inhibitors
Human monoclonal antibodies that aid in clearance of LDL
Adverse effects of OCUMAB drugs
Pain/redness at injection site, flu or flu-like symptoms
Name the two OCUMAB drugs available.
Alirocumab (Praluent®)
Evolocumab (Repatha®)
Niacin (nicotinic acid, Vitamin B3) mechanism of action
Not fully understood, potentially related to inhibition of release of free fatty acids from adipose tissue
Increases HDL while lowering LDL and TG
Niacin (nicotinic acid, Vitamin B3) adverse reactions. (6)
Flushing
Pruritus (itch)
GI distress
Vomiting
Diarrhea
Hepatotoxicity
Omega-3 polyunsaturated Fatty acids mechanism of action
Reduction in hepatic production of TG-rich very low-density lipoproteins + reduction in hepatic synthesis of TG
Secondary - only used if 1st options fail
Omega-3 polyunsaturated Fatty acids adverse reactions
Diarrhea, nausea, fishy burps
Omega-3 polyunsaturated Fatty acids products available.
Lovaza® – high grade fish oil
Vascepa® – Icosapent Ethyl
Ezetimibe (Zetia®) mechanism of action
Cholesterol absorption inhibitor at the brush border of the small intestine
Ezetimibe (Zetia®) adverse reactions (4)
Diarrhea
Arthralgia (joint pain)
Fatigue
Increased serum transaminases
Clinical pearls for Ezetimibe (Zetia®) (2)
Generally used as adjunctive therapy with statins or in addition to dietary changes
Works primarily lowering LDL but also slightly lowers TG and raises HDL
PIB drugs are not currently on the market. Name three drugs that haven’t been approved.
Torcetrabpib
Anacetrapib
Evacetrapib
Mechanism of action for PIB drugs
Inhibits cholesterol ester transfer protein resulting in increases in HDL and decreasing LDL
Thiazides are 1st line of therapy for what disorder? Which drug is the exception?
Hypertension (HTN)
Metolazone is used for CHF patients to assist in fluid management
Loop diuretics are first line for what disorder?
Fluid management in CHF and other disorders with fluid retention such as cirrhosis
Alternative agent to treat hypertension
K-sparing diuretics are primarily indicated in patients with what disorder?
Systolic CHF
or resistant hypertension
Osmotic diuretics are generally used for what disorder?
Intracranial pressure reduction
Not hypertension
Off label used for diuretics. (3)
Calcium nephrolithiasis
Diabetes Insipidus
Osteoporosis
What is Diabetes Insipidus?
Condition in which the kidneys are unable to prevent the excretion of water resulting in extremely dilute urine
What is Nephrolithiasis?
Kidney stone disease
A condition in which individuals form calculi (stones) within the renal pelvis and tubular lumens.
Stones form from crystals that precipitate (separate) out of the urine.
Name the 4 THIAZIDE diuretic drugs. (Two don’t end in thiazide)
Chlorothiazide
Hydrochlorothiazide
Chlorthalidone
Metolazone
Thiazide drugs mechanism of action.
Inhibits reabsorption in the distal convoluted tubules causing increased excretion of sodium, potassium and water
Block reabsorption of Na+ and Cl- increasing their excretion
Also decrease Ca2+ excretion
FDA approved indications for thiazide drugs. (3)
Hypertension (HTN)
Fluid retention in HF – heart failure (mild)
Edema
Adverse drug reactions for THIAZIDES (6)
Orthostatic hypotension
Dizziness
Photosensitivity
Hyponatremia
Hyperuricemia
Leg cramps
When do patients taking THIAZIDE drugs need to be monitored?
Monitor patient closely if they are concurrently using dofetilide or lithium
Loop diuretics generally end in what suffix? What is the exception?
“-semide”
i.e. Furosemide, Torsemide
Exception: Bumetanide
Loop diuretics mechanism of action.
Inhibits reabsorption of sodium and chloride in the ascending loop of Henle which causes its natriuretic effect (sodium loss)
Loop diuretics adverse reactions. (6)
Similar to the thiazide diuretics
Orthostatic hypotension
Dizziness
Photosensitivity
Hyponatremia
Hyperuricemia
Leg cramps
Name the 5 potassium sparing diuretics.
Spironolactone
Triamterene
Eplerenone
Amiloride
Potassium sparing diuretic mechanism of action.
Competes with aldosterone for receptor sites in the distal renal tubules increasing sodium and chloride excretion while preserving potassium
Potassium sparing diuretic adverse reactions.
Similar to the thiazide diuretics with the exception of potentially causing gynecomastia
