Final Flashcards
1
Q
What are the different types of macronutrients in the diet?
A
Carbohydrates - Seen in sugar, flour, fruits, vegetables, dairy products, cellulose, etc. This is a big energy source for humans.
Lipids - Triacylglycerol makes up more than 90% of dietary fat. These provide satiety, add flavor, and aroma to the diet. This is an efficient energy source.
Proteins - Meat
2
Q
What are the processes of macronutrient digestion and absorption?
A
Carbohydrates - α-amylase in the saliva and pancreatic juice hydrolyzes starch and glycogen into maltose and maltotriose. There are enzymes in the small intestine as well (Maltase converts maltose/maltotriose -> glucose; Sucrase converts sucrose -> Glucose and fructose; Lactase converts lactose -> glucose and galactose). We need these enzymes because only monosaccharides are absorbed in the body.
- Indigestible carbs may be broken down by bacterial enzymes which result in short-chain fatty acids, resulting in diarrhea, gas, etc.
Lipids - Fats need to be solubilized in order to be digested. This is done by bile acids. Gastric and pancreatic lipases hydrolyze triacylglycerol to fatty acids and monoacylglycerol. Esterases are also used to hydrolyze monoacylglycerol and cholesterol ester.
Proteins - The low pH of gastric juice denatures proteins. Pepsins are also used for the digestion in the stomach. Peptidases on the surface on the intestine digest proteins to produce free amino acids and di- and tripeptides. Intracellular peptidases inside the intestine transport amino acids and hydrolyze the di and tripeptidases. Only free amino acids are released into the blood.
3
Q
What is the utilization of macronutrients after absorption?
A
Carbs - Used as a major energy source and is used to generate many metabolic intermediates.
Lipids - Chylomicrons deliver lipid to peripheral tissues. Muscle uses fat as an energy source, then excess fat is stored in adipose tissues.
Proteins - Used as an essential structural component. Also, they make up enzymes, hormones, plasma proteins, antibodies, and more. We are protein based.
4
Q
How are excess macronutrients converted and stored?
A
Carbs - Excess carbs are converted to glycogen and triacylglyerol
Lipids - Excess fat is stored in adipose tissues.
Proteins - Excess protein is used as a source of energy. Glucogenic amino acids are converted to glucose and ketogenic amino acids are converted to keto acids and fatty acids. Eventually, it’s converted to triacylglycerol to be stored in adipose tissue.
5
Q
How can you calculate the calorie contents of food?
A
Carbohydrates - 4 kcal/g
Lipids - 9kcal/g
Proteins - 4kcal/g
6
Q
What are the essential macronutrients?
A
Essential fatty acids: Used to synthesize eicosanoids.
- Omega-3 (ω-3) fatty acids: α-Linolenic acid (18:3) in vegetable oils, Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in fish oids.
- Omega-6 (ω-6) fatty acids: Linoleic acid in corn oil, Arachidonic acid in meat and fish.
Essential amino acids:
- Arginine, Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Threonine, Tryptophan, Valine.
- Conditionally essential: Cysteine, Glutamine, Glycine, Proline, Tyrosine
7
Q
What are the health consequences of having insufficient essential macronutrients?
A
Not enough essential amino acids: If we don’t get these from the diet, new proteins can’t be made without breaking down other body proteins.
No enough lipids: These are important in regulating BP, blood clotting, and immune functions, so we need these to keep out body processes balanced.
8
Q
What are human energy reserves?
A
- We have excess energy stored mostly as fat in adipose tissue.
- Glycogen in the liver is used to maintain blood glucose levels.
- Glycogen in the muscle is used for exercise
9
Q
What is the regulation of metabolism under well-fed, early fasting, and fasting states?
A
Well-fed: Insulin is released and is chemoregulating everything. Glycolysis is happening to break down glucose, glycogen is being made from the glucose. Amino acids are being broken down to make other products, fatty acids are being made. No glucose is being made!!
Early fasting: Glucagon is released (not insulin). Glycogen is being broken down to supply the body with glucose. Gluconeogenesis is happening due to the Cori and Alanine cycle. No amino acids are being broken down.
Fasting: Glucagon is released. The liver is working really hard to make glucose. Protein is used as a major carbon and nitrogen source (use Alanine and Glutamine). Lipolysis is happening in adipose tissue so that we are using fat as energy. Ketogenesis is happening because the amount of glucose in the body is not sufficient to supply the brain. We also see hypothyroidism.
10
Q
What is caloric homeostasis in a human?
A
Caloric homeostasis is when we have constant availability of fuels in the blood so that our body has whatever resources it needs.
Glucose is heavily regulated. If it falls below 1.5mM, coma and death will happen. If we have too much, it can cause dehydration, hyperglycemic coma, and other complications.
11
Q
What are examples of malnutrition?
A
Marasmus - Inadequate intake of both protein and energy, causing a thin wasted appearance. The child will be small for his/her age.
Kwashiorkor - Inadequate intake of protein with adequate energy intake. This happens mainly in children 1-3 years old. They can’t synthesize proteins (inc. digestive enzymes), so they aren’t able to break down carbs. They will have lots of swelling, which makes them deceptively plump.
12
Q
What do these mean: EAR, RDA, AI, and UL
A
EAR - Estimated average requirement. This represents the amount of nutrient that satisfies 50% of the population.
RDA - Recommended dietary allowance. This is 2 standard deviations away from the EAR (so it satisfies 98% of the population).
AI - Adequate intake. This is used when scientific evidence isn’t enough to set an EAR, so approximations of average nutrient intake are from a healthy population.
UL - Tolerable upper intake levels. If you pass this amount, there will be toxicity.
13
Q
What are the fat-soluble vitamins and what are the water-soluble vitamins?
A
Fat soluble - Vitamin A, D, E, K
Water soluble - Vitamin Bs, C
14
Q
What are the biochemical roles of the 7 B vitamins + Vitamin C?
A
- Thiamin (B1): Thiamin pyrophosphate functions as a cofactor in enzymatic catalysis. Thiamin triphosphate functions within the nerve impulse in peripheral nerve membranes.
- Riboflavin (B2): Precursor of cofactors that are used in redox reactions (FAD, FMN).
- Niacin (B3): These are converted to the cofactors NAD and NADP.
- Pyridoxine (B6): Converted to cofactor pyridoxal phosphate that functions in transamination reactions of AA metabolism, synthesis of neurotransmitters, and synthesis of sphingolipids.
- Biotin (B7): Is a cofactor in activation of CO2 in carboxylase enzymes.
- Folic acid (B9): converted to a one-carbon carrier in enzyme reactions. Used in the synthesis of amino acids and nucleotides and is essential for DNA synthesis and cellular proliferation.
- Cobalamin (B12): Required for two reaction in humans.
- Vitamin C: Ascorbic acid. Cofactor for several oxidases and is a reducing agent.
15
Q
What diseases can result from deficiency of a vitamin?
A
Vitamin A: Deficiency can result in night blindness.
Vitamin D: Rickets in young children, osteomalacia in adults.
Thiamin (B1): Severe deficiency is called beriberi.
Niacin (B3): Severe deficiency is called pellagra.
Pyridoxine (B6) has mid and severe deficiency symptoms.
Folic acid (B9): Deficiency can result in increased risk of birth defects.
Cobalamin (B12): Causes accumulation of homocysteine and methylmalonic acid, which causes anemia and neurological damage.
Vitamin C: Capillary fragility can result from a mild deficiency. Scurvy may result from a severe deficiency.
Calcium: Osteoporosis
Iron: Anemia
Iodine: Goiter (enlargement of thyroid gland), cretinism (severely stunted physical and mental growth).
Zinc: Poor growth and impairment of sexual development. Also may cause poor wound healing, dermatitis, and impaired immune function.
Copper: Anemia, bone demineralization, blood vessel fragility.
16
Q
What are the symptoms of vitamin or mineral deficiencies?
A
Thiamin (B1) deficiency, Beriberi, is characterized by muscular atrophy and weakness.
Riboflavin (B2) deficiency has symptoms including angular cheilitis, glossitis, and scaly dermatitis.
Niacin (B3) deficiency, Pellagra, has characteristics of dermatitis, diarrhea, and dementia
Mild Pyridoxine (B6) deficiency has symptoms of irritability, nervousness, and depression. Severe pyridoxine deficiency is seen with peripheral neuropathy and convulsions.
Folic acid deficiency can be seems in patients who are anemic. They can also cause birth defects (neural tube defect).
Capillary fragility (from mild Vit C deficiency) has symptoms of easy bruising and decreased immunocompetence. Scurvy (severe Vit C deficiency) has symptoms of decreased wound healing, osteoporosis, hemorrhaging, and anemia.
Ca2+ deficiency may cause osteoporosis or muscle cramps.
17
Q
What are common food sources for vitamins and minerals?
A
Vitamin A: Dark green and yellow vegetables, liver, egg yolk, butter, whole milk.
Vitamin D: Vit D milk, saltwater fish, liver, egg yolk
Vitamin E: Vegetable oils rich in polyunsaturated fatty acids
Vitamin K: Green vegetables, Vit K2 is synthesized by intestinal bacteria.
Riboflavin (B2): Milk, meat, eggs, cereal products.
Niacin (B3): Meats, peanuts, enriched cereals.
Pyridoxine (B6): Meat, vegetables, whole-grain cereals
Biotin (B7): Found in lots of food sources.
Folic acid (B9): Rich in lots of food sources.
Calcium: Dairy products, nuts, beans, seeds, seaweeds.
Iodine: Added to salt. Good natural source is seafood.
18
Q
What populations are at risk of vitamin deficiency?
A
- Populations that rely exclusively on polished rice for food or alcoholics are at risk to get beriberi (Thiamin deficiency)
- Chronic alcoholics also are at risk of Riboflavin deficiency.
- Alcoholics, pts with severe malabsorption, and the elderly are on very restricted diets.
- If raw egg white is consumed regularly or is a woman is pregnant the person may be at risk of biotin deficiency.
- Alcoholics are at risk of folic acid deficiencies.
- Patients with severe malabsorption diseases and long term vegetarians are at risk of cobalamin deficiencies.
- Smokers may be at risk of a vit C deficiency.
- Low-income children and adult females are at risk of a calcium deficiency.
- Menstruating females are at risk of an iron deficiency.
19
Q
What is the pharmacological mechanism of warfarin?
A
Warfarin inhibits the Vit K epoxide reductase that activates vitamin K. Without the active Vitamin K Hydroquinone, The carboxyglutamate is not made, which is needed for blood clotting.
20
Q
What are the biochemical roles of the 4 trace minerals?
A
Iodine: Synthesis of thyroid hormones.
Zinc: Needed for metalloenzymes and zinc finger proteins.
Copper: Needed for many enzymes.
Selenium: Used during translation.
21
Q
What are the biochemical roles of the 4 fat soluble vitamins?
A
- Vit A: Retinol, retinal, retinoic acid. Retinol can act as a light sensor. Retinoic acid can function as a steroid hormone that regulates cell growth and differentiation. Carotenoids are effective antioxidants.
- Vit D: Function as steroid hormones that maintain calcium homeostasis. It is produced in the skin from sun exposure.
- Vit E: Tocopherols and tocotrienols. These are antioxidants that protect unsaturated fatty acids. They reduce the risk of CVD by preventing the oxidation of LDLs.
- Vit K: Needed for post-translational modification of glutamic acid residues to carboxyglutamic acid residues, which allow proteins to bind to Ca2+. They are essential for blood clotting and bone mineralization.
22
Q
What are the biochemical roles of calcium and iron?
A
- Calcium: Makes bones, is a second messenger, required for enzymes, essential for blood coagulation and muscle contraction.
- Iron: Required for O2 transport, energy metabolism, cell proliferation, immune defense.
23
Q
What are some important parts of GI anatomy and what is the physiological control of acid secretion in the stomach?
A
Anatomy:
- Stomach (the acid sterilizes the contents we eat): The lower esophageal sphincter is important. If it’s too lose, the acid will go up into the esophagus. The stomach has a multi layer lining of muscle that facilitates digestion.
- Duodenum: This is where digestion begins. Digestive enzymes start to break down food.
- Jejunum
- Anal canal
Physiological control of GI secretions: First, G-cells produce gastrin. This gastrin travels through the blood stream and bind to ECL cells in the fundus of the stomach. In the ECL cell, histamine is released and it binds to receptors on the intestinal parietal cells (along with some gastrin and ACh). This binding pulls K+ out of the stomach and exchanges it for H+. This is the proton pump that contributes to the acidity of the luminal acid secretion. When the acid reaches a certain point, somatostatin is produced and shuts down gastrin production.
24
Q
What salts are used as antacids (4), what is their acid neutralizing capacity, and what side effects are associated with them?
A
Antacids - Ingest a weak base to reduce the acid content of the stomach.
NaHCO3 - High neutralizing capacity, side effects include systemic alkalosis and fluid retention
CaCO3 - Moderate neutralizing capacity, side effects include hypercalcemia, kidney stones, and milk-alkali syndrome; Ex. Tums
Al(OH)3 - High neutralizing capacity, side effects include constipation and hypophosphatemia
Mg(OH)2 - Diarrhea
25
What is the mechanism by which PPIs inhibit acid secretion and how can you recognize their chemical structure?
PPIs irreversibly inhibits the ATPase that exhanges K+ for H+ in the parietal cells. This means the acid is not produced.
PPIS all have the S=O that ends up covalently binding with the H+ pump. They also have the double ring structure. These are prodrugs that are activated by acidic pH inside the parietal cell.
Ex. Esomeprazole, lansoprazole, Pantoprazole
Some risks: infection, Vit B12 defiency, Ca2+ deficiency
26
What is the role of mucosal protective agents and what is their mechanism of action?
Sucralfate polymerizes to form a protective barrier at the ulcer site. Misoprostol is a prostaglandin analog that has cryoprotectant effects, like enhanced mucus and bicarbonate secretion, and reduced acid secretion.
Ex Misoprostol, Sucralfate
27
What is the rationale for antibiotic treatment of ulcers?
Many ulcers are use to an infection by gram-negative bacteria. They break the mucus down which provide an opportunity for an H. Pylori infection. So, antibiotics would work to eradicate this infection.
Common antibiotics used: Metronidazole, Tetracycline, Amoxicillin, Clarithromycin
28
What are examples of drug classes that increase GI motility (2) and what are their mechanisms of action?
Laxatives - Bulk and osmotic laxatives draw water into the stool by forming polymer chains, which stretches the intestine, leading to contraction and relaxation. Stool softeners get incorporated into the stool to make passage easier and decrease water absorption. They also lubricate the lower bowl to reduce fecal impaction. Secretory/stimulant laxatives cause irritation of the mucosa, which affects fluid secretion/absorption balance and induces peristalsis.
Prokinetics - These act on the cholinergic motor neuron. Metoclopramide is a D2 receptor antagonist that leads to an increase in ACh release. Prucalopride is a 5HT4 receptor agonist. It's a GPCR that leads to increased cAMP, which releases ACh (smooth muscle stimulated). Chloride Channel Activators, Linaclotide (GC-C) and Lubiprostone (ClC2) for example, lead to increased Cl- in the gut, leading to increased Na+, leading to increased H2O, which stimulates peristalsis. Sodium/hydrogen exchanger inhibition causes more Na+ to be in the lumen, leading to peristalsis.
29
What are examples of drug classes that reduce the GI motility (2), and what are their mechanisms of action?
Antidiarrheals - Opiates, like Dihenoxylate and Loperamide, inhibit presynaptic cholinergic nerves, leading to slowed peristalsis to increase water and electrolye absorption. 5HT3 receptor antagonists decrease colon motility.
Anti-emetics - 5HT3 receptor antagonists (ex. ondansetron) block the activity of afferent nerves from stomach and the SI, which activate the trigger center in the CNS. NK1 antagonists (ex. Aprepitant, Netupitant, and Rolapitant) antagonize receptors in the chemoreceptor trigger zone. Antihistamines/anticholinergics antagonize the muscarinic stimulation of peristalsis. Antipsychotics (D2 receptor antagonists) have anti-emetic, sedative, and antimuscarinic/antihistamine effects.
30
What is gastroesophageal reflux disease (GERD)?
GERD is when passage of gastric contents into the esophagus cause symptoms and/or damage to the esophagus.
31
What is the pathophysiology of GERD?
The lower esophageal sphincter usually relaxes when you swallow, then immediately closes up. With GERD, the sphincter is not as quick to close, and the liquid/acid can cause erosion in the esophagus and even food can come back up.
Increased acid production and gastric pressure, along with decreased esophageal clearance and gastric emptying contribute to the pathogenesis of GERD.
32
What are the symptoms (typical and atypical) and alarm symptoms of GERD?
Typical symptoms: Heartburn, regurgitation, belching, bloating, nausea, early satiety, hypersalivation, trouble sleeping
Atypical symptoms: Chronic cough, non-allergic asthma, hoarseness, dental enamel erosion, globus sensation
Alarm symptoms: Difficulty breathing, involuntary weight loss, vomiting, blood in stool, dysphagia, choking, chest pain, continual pain, painful swallowing
33
What are the risk factors and stressors of GERD?
Risk factors: overweight/obesity, diet, smoking, diabetes, asthma, pregnancy, delayed stomach emptying.
Food triggers for reflux: Coffee, chocolate, fatty foods, alcohol
Food triggers for heartburn: Spicy foods, acidic foods, carbonation
Medication triggers: Aspirin/NSAIDs, bisphosphonates, potassium chloride, iron, chemotherapy, anticholinergics, calcium channel blockers, tricyclic antidepressants, narcotics, barbiturates/benzodiazepines, nitrates, estrogen and progesterone
34
How do you diagnose GERD?
Do a clinical history to help paint a full picture. If the patient has typical mild symptoms, clinical history + response to treatment = diagnosis. With pts who have alarm symptoms or those who don't respond to therapy within 8 weeks of a PPI, consider other tests.
- Treat first, test later
- Other diagnosis tests: endoscopy, pH probe test, bernstein test, manometry
35
What are the non-pharmacological treatment options for GERD?
Lifestyle modifications
- Smoking cessation
- Exercise & weight loss
- Eat small, frequent meals
- Raise the head of the bed
- Eliminate trigger foods & increase water
- Avoid laying down after meals
36
What is the mechanism of action and use of GERD treatments?
We want to neutralize the acid and reduce gastric acid secretion.
PRN medications: Symptoms are just a couple of times per week. (refer if OTCs don't work within 14 days)
- Antacids: Weak bases that neutralize gastric acid. Quick onset. Ex. Tums (Ca), Milk of Magnesia (Mg), Mixed
Scheduled medications:
- H2RAs: Reversibly inhibit histamine receptors. Ex. Famotidine, Cimetidine; Used for mild to moderate GERD, take 10-60 mins before a meal. Treatment is 6-12 weeks.
- PPIs: Irreversibly inhibits proton/potassium ATPase activity. Full effect is in 3-5 days
- Prokinetics: Enhance gastric motility/increases speed of gastric emptying. Blocks DA/5HT receptors.
37
What are the medical options for the treatment of GERD?
Surgery - Reinforces the lower esophageal sphincter. The top of the stomach is wrapped around the lower esophagus. This reduces regurgitation and acid back-flow.
Who qualifies? - If pt is contraindicated to PPI or if PPI + lifestyle modifications don't control symptoms.
These don't prevent cancer and they don't prevent the need for long-term medications.
38
What are the treatment options for special populations in GERD?
Pregnancy: Lifestyle modifications
1. Antacids
2. Sucralfate & H2RAs (ranitidine, famotidine, cimetidine)
Last. PPI only for complications of GERD or treatment failure.
Lactation: PPIs and H2RAs are present in breastmilk, but there's low risk to infants at standard doses.
Infants/Children: Non-pharm includes thickening of formula/foods, decreasing the volume of intake, milk free diet, and positioning therapy
- PPIs and H2RAs can be used for 4-8 weeks if child is diagnosed for GERD for esophagitis.
- Children shouldn't use antacids chronically, and aluminum shouldn't be used in children under 12.
- Simethicone and probiotics are safe and OTC.
39
What is the dosing, MOA, side effects, and drug interactions for antacids?
Dosing: PRN
- Tums: 1-4 tablets PRN up to 4x per day.
- Milk of Magnesia: 5-15 mL PRN
MOA: Neutralize acid.
Side effects: Nausea/Vomiting
- Calcium side effects: constipation, Milk-Alkali syndrome
- Mg side effects: Diarrhea, accumulation
- Al side effects: Constipation, confusion/neurotoxicity
Drug interactions: Take meds 2 hours before or 4-6 hours after antacids.
- HIV meds
- Digoxin
- Levothyroxine
- Azole antifungals
- Tetracyclines
- Fluroquinolones
- Steroids
- Iron
40
What is the dosing, MOA, side effects, and drug interactions of H2RAs?
Dosing: every day or twice a day
- Famotidine: 20, 40mg
- Cimetidine: 200, 400, 800mg
MOA: Reversibly inhibit histamine receptors.
Side effects: Headaches, dizziness/fatigue, constipation/abdominal pain, somnolence/confusion, agitation, thrombocytopenia
Drug interactions:
- Cimetidine has so many drug interactions it's not used anymore.
** adjust the dose with pts who have renal impairment
41
What is the dosing, MOA, side effects, and drug interactions PPIs?
Dosing: Once daily dosing
MOA: Irreversibly inhibits proton/potassium ATPase activity. Prodrug.
Side effects: Headache, dizziness, constipation, diarrhea, nausea, abdominal pain, long-term concerns. These are pretty well tolerated.
Drug interactions: The most inhibition is with omeprazole and esomeprazole
- Reduce absorption of Ca2+, Vit C, and Iron.
- These increase effect: Methotrexate, phenytoin, warfarin
- These decrease effect: Iron, bisphosphonates, HIV drugs
** don't take OTC longer than 14 days at a time, Rx is used for 8 weeks, no tolerance seen, can increase to BID if needed, switch to different PPI if the first doesn't work.
42
What are some risks and concerns associated with PPIs?
- C. diff: Highest risk is in pts who are older, chronic med conditions, also on broad spectrum antibiotics. For this reason, we want to use these at the lowest dose for the shortest duration.
- Bone density decrease/fractures: Increasingp pH may decrease calcium absorption, leading to fractures. Pts may want to be on calcium and Vit D supplements.
- Memory impairment
- Low B-12 and Mg lab values
43
What is the dose, MOA, and risks of metoclopramide?
Metoclopramide:
Dosing: 10-15mg QID 30 mins before meals
MOA: Enhances motility/increases gastric emptying; blocks DA/5HT receptors
Risks: Tremors, depression, HTN, proarrythmic effects
** mainly used in pts with comorbid gastroparesis
44
What is the pathophysiology of PUD?
PUD - Open sore in GI mucosa that extends into muscularis mucosae (gastric or duodenal).
When the aggressive factors (pepsin, NSAIDs, H. pylori, and gastric acid) outweigh protective factors (blood flow to mucosa, bicarbonate, prostaglandins and mucus), ulcers can form.
45
What are the risk factors associated with the development of PUD?
Risk factors for H. pylori -
- Birth in developing country
- Low socioeconomic status
- Crowded/unsanitary living conditions
- Unclean food/water
- Exposure to gastric contents
- Close contact within households
46
How do pts with PUD present clinically?
Signs and symptoms: 70% are asymptomatic
- Intermittent symptoms: abdominal pain, nausea, bloating, abdominal fullness, weight loss, early satiety.
Gastric ulcer: Acid production in response to food irritates the ulcer
Duodenal ulcer: Pain occurs 2-3 hours after eating as the food passes through the stomach and into the duodenum.
47
What is the MOA, dosing, and adverse effects for Bismuth quad therapy?
MOA: bismuth has topical bactericidal effects which improves ulcer healing by inhibiting aggressive factors and increasing protective factors.
Dosing: Different brands have different dosing. 10-14 days.
- Metronidazole 250mg QID
- Tetracycline 500mg QID
- Bismuth subsalicylate 262.4mg 2 tabs QID
- PPI BID
Adverse effects:
- Bismuth: darkening of stools and tongue
- Metronidazole: Avoid alcohol due to disulfiram-like reaction (vomit)
- Tetracycline: Photosensitivity
- Levofloxacin: Tendon rupture, mental status change, QTc prolongation
48
What is the treatment of PUD when caused by H. pylori and NSAIDs and how do they differ?
H. pylori - PPI + 2-3 antibiotics; PPI BID is the backbone of therapy
1. Bismuth quad therapy (PPI, bismuth, tetracycline, metronidazole) for 10-14 days.
- Levofloxacin triple therapy PPI BID
Maybe. Probiotics prophylaxis as a supplement to increase eradication rates.
NSAIDs - Treatment for 8 weeks if NSAID was stopped, 12 weeks if continued.
1. PPIs: Daily dose
2. H2RAs
3. Sucralfate: forms barrier over an open ulcer; treatment only
49
How do you make a treatment plan for a patient with PUD (inc. dose, duration, monitoring, and education)?
- If the patient has antibiotic resistance, poor medication adherence, short duration of therapy, high bacterial load, or low intra-gastric pH, these may alter the therapeutic outcome.
- If one antibiotic doesn't work, use a different one
- Determine if H. pylori or NSAIDs caused. If H. pylori, do bismuth quad therapy, if NSAID, do PPI.
Education: proper drug administration, avoid/management of adverse effects, avoid triggers, comply with treatment, reduce NSAID-relate complications
50
What is the MOA, dosing, and adverse effects for misoprostol?
MOA: prostaglandin E1 analog that increases mucus and bicarbonate secretion, surface active phospholipids, and gastric mucosal blood flow. Also inhibits acid secretion.
Dose: 200mcg QID with food
Side effects: diarrhea, abdominal cramping, N/V, flatulence, headache, BBW: abortifacient
** for prophylaxis only
51
What are the four main classifications of diarrhea?
Acute: Less than 14 days of diarrhea.
Persistent: More than 14 days of diarrhea.
Chronic: More than 30 days of diarrhea.
Chronic idiopathic: More than 4 weeks of loose stool with no identifiable cause.
52
What are the different pathological mechanisms (4) associated with diarrhea?
- if secretions or reabsorption isn't balanced, then you may end up with either constipation or diarrhea.
1. Secretory - Change in active ion transport by either a decrease in Na+ absorption or an increase in Cl- secretion into the lumen, drawing more water in the stool. Seen with large stool volumes (>L/day), not altered by fasting.
2. Osmotic - Poorly absorbed substances are retained in the intestinal fluids, resulting in an influx of water and electrolytes into the lumen. This improves with fasting.
3. Exudative - This is a subset of secretory (messed up ion transport), secondary to inflammatory diseases of the bowel. This is characterizes by large stool volumes.
4. Altered intestinal transit - Moving too fast through the intestine, not enough time to absorb the fluid.
53
What are 3 infectious organisms that are commonly associated with causing diarrhea?
Bacterial - Salmonella, E. coli
Viral - Norovirus
54
What is the impact of diarrhea in the US and around the world?
Disrupts quality of life
Leading cause of death in children in 3rd world countries.
55
What are the clinical pictures, etiology, and treatment for acute diarrhea, chronic diarrhea, traveler's diarrhea, and drug-induced diarrhea?
Acute:
- Clinical presentation: Small intestinal cramps, abdominal pain, N/V, head ache, chills
- Treatment: No fever/systemic symptoms: fluid replacement, loperamide/diphenoxylate/absorbent, and diet; Yes fever/systemic symptoms: check for parasites and if positive, use appropriate antibiotics. If negative, do symptomatic treatment.
Chronic:
- Clinical presentation: Weight loss, anorexia, weakness
- Treatment: Refer!! If diagnosis, treat the specific cause; If no diagnosis: Replete hydration, D/C potential drug inducer, adjust diet, Loperamide or absorbent.
Traveler's diarrhea:
- Clinical presentation: Acute watery diarrhea, duration 2-3 days.
- Etiology: Infective, usually by bacteria
- Prevention: Bottled water, no prophylaxis antimicrobials (rifaximin if necessary), bismuth subsalicylate, be cautious
- Treatment: Oral rehydration solutions; Mild: Loperamide or BSS; Moderate: Maybe antibiotic, maybe loperamide as monotherapy or adjunct; Severe: Antibiotic treatment (single dose preferred), maybe loperamide as adjunct.
Drug-induced:
- Clinical presentation: Ranges from mild inconvenience to life-threatening antibiotic associated.
- Etiology: Decreases transit time leading to irregular absorption and secretion, alteration of bowel flora.
- Treatment: D/C causative agent, oral rehydration fluids, loperamide if needed.
56
What are the appropriate questions to ask a patient when they are complaining of diarrhea?
1. When did symptoms begin?
2. Frequency, consistency, and color of stool?
3. Have you had similar bouts in the past?
4. Any fever, N/V, malaise?
5. Presence of abdominal pain and/or cramping?
6. Anyone else with similar symptoms?
7. Any recent travel outside of the US?
57
What are the non-pcol options for management of diarrhea?
- Manage the diet: Most important with osmotic diarrhea, BRAT diet (bananas, rice, applesauce, toast); Don't stop the feeding in children with bacterial diarrhea
- Fluid/electrolyte replacement: Re-hydrate and prevent electrolyte disturbances. Ex. Pedialyte
58
What are the different therapeutic indications, advantages, disadvantages, side effect, and key pt counseling points for these diarrhea therapeutic agents: antimotility drugs, absorbents, antisecretory agents
Antimotility drugs: Activate mu opioid receptors to reduce peristalsis and increase segmentation.
- Shouldn't be used long term, not to be used with C. diff
- Ex. Loperamide, Diphenoxylate/Atropine (Lomotil)
- Loperamide has cardiac risk associated, so it's important not to exceed 16mg/day.
Absorbents: Adsorb nutrients, toxins, drugs, and digestive juices to provide symptomatic relief. Used for some pts with chronic diarrhea if they have trouble forming solid stools.
- Effectiveness is unproven.
- Ex. Psyllium (Metamucil)
Antisecretory: Reduces secretions in the gut
- Ex. Bismuth subsalicylate (don't use in pts who shouldn't take salicylates, also has antimicrobial and anti-inflammatory effects).
Also use antibiotics when needed (Bactrium, nystatin, azithromycin, etc.) and get recommended vaccines (rotarix, dukoral, typhim) to prevent.
59
What are the common causes of constipation and what medications lead to constipation?
- Lack of privacy (LTCF)
- Increased psychological distress
- Disease states: Diabetes, Parkinson's, CNS injury or disease, MS
- Medications: Analgesics/Opioids (Mu receptor agonist), NSAIDs (inhibition of PGs), Antacids, Anticholinergics, Iron, etc.
60
What is the normal physiology of defecation and what is the pathophysiology of constipation?
Normally, the presence of stool is sensed, the diaphragm, abdomen and rectal muscles are contracted, the EAS is relaxed, and the puborectalis muscle is relaxes, resulting in the stool coming out.
In pts with constipation, there is prolonged colonic transit time, leading to discoordination of abdominal rectoanal and pelvic floor muscles. There's a paradoxical increase in sphincter pressure. These things lead to an inadequate amount of abdomino-rectal propulsive forces, so the stool doesn't come out.
- Slowed GI transit time
- The movement of water in and out of the stool is too long due to transit time, resulting in for water being absorbed in the GI, leading to hardened stool.
61
What is the clinical picture, etiology, and treatment for acute vs. chronic constipation?
Acute:
- Clinical picture: Less than 3 bowel movements/week, stools are dry and hard, BMs are painful and the stools are difficult to pass.
- Etiology: Usually due to a change in condition or drug
- Treatment: ASAP relief: Mg citrate, large doses of PEG, enemas, suppositories; relief in 6-24 hours: MOM, PEG, Bisacodyl/senna tablets.
Chronic:
- Clinical picture: Symptoms last for >6 weeks, may respond to laxative tx but it returns after that is stopped.
- Etiology: Main causes are normal transit "functional" symptomaic (most common, pt just feels constipated), slow transit, evacuation disorder. May be caused by poor fluid intake, decrease calorie intake, failure to heed defecation reflex, etc.
- Treatment: 1. Relieve acute constipation first (diet stuff too); 2. Bulk-forming laxative + adequate fluid intake; 3. PEG/sorbitol/lactulose; 4. Stimulant laxative; 5. Lubiprostone, Linaclotide, Prucalopride, Plecanatide
62
Given a patient who is about to undergo a GI procedure, what are the different regimens we can use to cleanse the bowel?
Prep: Clear liquid diet (jello, broth, popsicles, gatorade, etc.) starting in the afternoon/evening prior to the procedure, drink large quantities of fluids.
Hyperosmotics: Go LYTELY
- Mix 1 bottle of Miralax into 2 bottles of gatorade & refrigerate; Drink 8oz ever 10-20 minutes over 1 hours, then wait 30 mins, then drink the second bottle
Saline laxatives: Bisacodyl
- 4 x 5mg tabs at noon.
63
What are the non-pcol treatment options for constipation?
- High-fiber foods (add slowly; goal: 20-30g per day); Prunes, Kiwifruit
- Encourage pts to defecate first thing in the morning and 30 minutes after meals.
- Vibrating capsule
64
What different treatments can we use for constipation? What are the side effects, and MOAs for these treatments? (bulk, surfactants, lubricants, saline, hyperosmotics, Lactitol, stimulants, Cl channel activator, Guanylate-C receptor activator)
Bulk laxatives: Forms emollient gels which retain water, swell, and stimulate BMs
- Side effects: Gas
- Ex. Psyllium, Methylcellulose, calcium polycarbophil
Surfactant/Emollient: Decreases fecal surface tension, stool softener
- Side effects:
- Ex. Docusate
Lubricant: Lubricates lumen of colon
- Side effects:
- Ex. Mineral oil, Magic Mousse
Saline Laxatives: Draws fluid into the colon which stimulates motility
- Side effects:
- Ex. Milk of Magnesia, Mg Citrate
Hyperosmotic agents: Draws fluid into the colon due to high concentration of sugar, PEG, or glycerin
- Side effects: Minor nausea, cramping
- Ex. PEG, Sorbitol, Lactulose
Lactitol: Draw water into stool
- Side effects: URIs, flatulence, diarreha, elevated CPK
Stimulant laxatives: Stimulate enteric nerves which stimulate the contractions and mobility; also increases fluid and Na secretion into the lumen
- Ex. Senna, Bisacodyl, Castor oil
Chloride channel activator: Activates chloride channels in the small intestine resulting in Na influx, which increases fluid movement into the intestinal lumen.
- Side effects: Nausea, diarrhea, headache
- Ex. Lubiprostone
Guanylate Cyclase-C receptor activator: Increases chloride and bicarb secretions into the intestinal lumen, also inhibits sodium absorption.
- Side effects: Diarrhea
- Ex. Plecanatide (this is for last stage use).
65
What are the pros and cons of the different constipation drug treatment classes?
Bulk laxatives:
- Pros: Softens stools better than docusate, well tolerated with few side effects
- Cons: Taste, must have adequate fluid intake, gas formation, impact on drug absorption, not ideal for bedridden pts.
Surfactant/Emollient:
- Pros: Safe, helps prevent hard stools
- Cons: We don't know the efficacy, not effective for active constipation
Lubricant:
- Pros: Lubricates/softens stool
- Cons: Poor patient acceptance (oily), only effective in the prevention of constipation, may decrease absorption of fat-soluble vitamins, tastes horrible
Saline laxatives:
- Pros: Used for acute management of constipation, quick onset, most economical
- Cons: Bad taste, Avoid in renal pts!!
Hyperosmotic agents:
- Pros: Well tolerated, softens while stimulating BM, excellent for chronic constipation
- Cons: 1-3 day onset at usual doses, sweet taste of some agents
Stimulant laxatives:
- Pros: 6-12 hours onset, works in pts with motility disorders, drug of choice for opioid induced constipation
- Cons: Risk of nausea and cramping, avoid long-term continuous use in patients with normal GI motility
Chloride channel activator:
- Pros: Used in pts who don't respond to or tolerate other laxatives.
- Cons: expensive
66
When should relief be expected for different constipation therapeutics? Monitor? When to refer?
Enema, bisacodyl/glycerin suppository: ASAP w/in 1 hour
Citrate of Mg, Large doses of PEG: 3-6 hours
Bisacodyl/Senna tablets: 1 day
Hyperosmotic agents: relief in 1-3 days
Acute: follow up in 1-2 days
Chronic: follow up in 1-2 weeks
Refer if: Symptoms for more than 2 weeks, black/tarry stools, marked abd pain or discomfort, fever, severe N/V, family history of IBD or colon cancer, drastic change in symptoms
67
What questions do we ask pts who are inquiring about therapy for constipation?
1. How long have you been constipated?
2. How often do you normally have a bowel movement?
3. What is the size and color of your stools?
4. Have you noticed period of constipation mixed with diarrhea?
5. Have you noticed a change in the caliber of stool?
6. Do you have gas?
7. Has your appetite or weight changed?
8. What have you tried so far?
68
What is the epidemiology and pathophysiology of Irritable Bowel Syndrome (IBS)?
Epidemiology: Impacts 5-15% of the US population, but it's usually just mild. Females are 2x more likely to have it than men.
Pathophysiology: Abdominal pain associated with abnormal bowel movements. IBS can be constipation-predominant or diarrhea-predominant, or it can alternate between the two.
- It's believed to be due to somatovisceral and motor dysfunction of the intestine.
- Involves host factors, environmental factors, and luminal factors.
69
What is the diagnostic criteria for IBS?
- Recurrent abdominal pain or discomfort for at least 1 day/week in the previous 3 months.
- Must have at least two of the following: Increase in pain related to defecation, associated with a change in frequency of stool, associated with a change in appearance of stool.
- Symptom onset should occur at least 6 months prior to the diagnosis.
No biomarkers of disease are known. Celiac disease screening is indicated if the pt have IBS-D or IBS-M. A colonoscopy is not needed unless there are alarm features. (rectal bleeding, weight loss, iron deficient anemia, nocturnal symptoms, family history of colorectal cancer, IBS, or Celiac disease), onset at age greater than 50 years.
70
What are the different subtypes of IBS? (4)
Undefined (IBS-U)
Mixed symptoms (IBS-M)
Constipation predominant (IBS-C): Less than 3 stools/week, straining, incomplete evacuation
Diarrhea predominant (IBS-D): More than 3 stools/day.
Symptoms for all types - Abdominal pain, cramping, distention, flatulence, passage of mucus, extreme urgency.
- Non-GI symptoms include urinary symptoms, lower back pain, fatigue, dyspareunia
71
What are the pharmacotherapy options based on the IBS subtype?
Fiber, bulk-forming agents, laxatives: for IBS-C
- Soluble fiber psyllium (increase stool volume)
- Polyethylene glycol (osmotic laxative)
Anti-spasmodic therapy: best for IBS-D, IBS-C
- Hyoscyamine (blocks ACh action on parasympathetic receptors)
- Dicyclomine (blocks ACh action on parasympathetic receptors)
SSRIs: consider for IBS-C
TCAS: consider for IBS-D
Anti-diarrheal agents: IBS-D
- Loperamide (inhibits peristalsis and GI secretions)
Opioid receptor agonist: IBS-D
- Eluxadoline (mu opioid receptor agonist)
5-HT3 receptor antagonists: IBS-D
- Alosetron (5-HT3 receptor antagonist, results in decreased visceral sensitivity and gastric motility)
Rifaximin: IBS-D; Symtpoms relief seen, may cuase dizziness, fatigue, peripheral edema
72
How can you develop a treatment plan for management of IBS-C and IBS-D?
IBS-C:
1. Increase fiber and fluid intake, avoid foods that make it worse
2. Add bulk-forming laxative
3. Consider adding anti-spasmodic or anticholinergic agent for GI symptoms
4. Consider lubiprostone or linaclotide to tx of constipation and abdominal pain
5. Psychotherapeutic behavior modification, consider antidepressents
6. Consider serotonin-4 agonist as last line
IBS-D:
1. Dietary modifications; Eliminate caffeine and lactose (may add bulk laxatives to promote normal stools)
2. Add loperamide or anti-spasmodic agent
2a. Replace with eluxadoline if pain persists ($$$)
2b. Consider rifaximin ($$$)
3. Add serotonin-3 antagonist (Alostron)
4. Physotherapeutic behavior modification, consider antidepressants.
73
What are the advantages and disadvantages of the agents used to treat IBS? (Fiber/Bulk-forming laxatives, anti-spasmodics, antidepressants, pro-secretory, antidiarrheal, opioid receptor agonist, 5-HT3 antagonist)
Fiber, bulk-forming agents and laxatives:
- Soluble fiber psyllium: Improves global symptoms in IBS-C, but some fiber contains FODMAPs which can worsen symptoms
- Polyethylene glycol: Improves global symptoms in IBS-C
Anti-spasmodic therapy:
- Hyoscyamine: Helps with the post-meal abdominal pain, gas, bloating, and fecal urgency, but use caution in elderly, may cause dizziness, somnolence, blurred vision.
- Dicyclomine - Improves abdominal pain, but avoid in elderly
Antidepressants:
- TCAS: Most beneficial in patients with IBS-D and it can reduce visceral sensitivity and decrease stress, can cause constipation, dry mouth, drowsiness, weight gain, and there's risk fo QT-prolongation.
- SSRIs: Reduce visceral sensitivity, may cause transient N/V, sexual dysfunction, sedation, and insomnia.
Pro-secretory agents:
- Lubiprostone: Improves global IBS-C symptoms, can cause N/V, headache, contraindicated if suspected intestinal block, avoid in pregnancy
- Linaclotide: May cause diarrhea, no use in children 17 and under.
Anti-diarrheal agents:
- Loperamide: No effect on abdominal pain, but it's effective at reducing diarrhea, may cause constipation.
Opioid receptor agonist:
- Eluxadoline: Slows motility and relieves pain, may cause dizziness, euphoria, fatigue, constipation, pancreatitis
5-HT3 receptor antagonist:
- Alosetron: May cause constipation, ischemic colitis
74
What are the differences between nausea, vomiting, and retching?
Nausea - Sickness at the stomach, and inclination to vomit
Vomiting - The ejection of matter forcibly from the stomach through the esophagus and mouth
Retching - Making movements of vomiting without effect
75
What are 5 common causes of nausea and vomiting?
- GI disorders (influenza, food poisoning, ulcers, cholecystitis, etc.)
- CNS disorders
- Pain (acute or chronic)
- Excessive intake of anything (food, alcohol, etc)
- Pregnancy (80% of pregnant women, begins 4th-7th week after last menstrual period, but usually resolves by the 20th week)
- Treatment-induced (cancer chemo, radiation, anesthesia, NC associated with procedures)
76
What are common complications and related assessments associated with severe, prolonged nausea and vomiting?
- Patient discomfort
- Dehydration
- Malnutrition
- Aspiration pneumonia
- Anxiety; anticipatory NV
- Decrease QOL
77
What drugs are likely to induce nausea and vomiting?
- Anti-neoplastic agents
- Opioids
- Aspirin, NSAIDs, etc
- Iron
- Some antibiotics (tetracycline, erythromycin, etc.)
- Estrogens
- Anti-parkinsons meds
- SSRIs
78
How would you perform an assessment of a patient's complaint of nausea and vomiting and determine which patients need to be referred for further evaluation?
- How long have you had NV?
- What color is your vomit?
- How often do you vomit?
- Is the vomiting related to eating? If so, what foods and how soon after eating?
- Do you have nausea without vomiting?
- Is the nausea associated with abdominal pain, constipation, diarrhea, lost of appetite, etc.?
79
Given a pt is about to undergo surgery, what are key factors that can increase the risk of post-operative nausea and vomiting (PONV)?
Patients with multiple risk factors are at the highest risk for PONV.
- Common with older, inhaled agents
Risk factors:
- Females > Male
- Non-smoking status
- Hx of PONV
- Hx of motion sickness
- Anesthetic risk factors: Use of volatile anesthetics, nitrous oxide, if the surgery is a laparoscopy, craniotomy, ENT.
80
What is the role of various non-pharmacologic interventions for the management of nausea and vomiting and in what patients can these measures be recommended?
- Determine the cause. Put the gut to rest through a clear liquid diet and/or IV hydration.
- Dietary: Avoid fatty, fried, sweet, and spicy foods. Eat food that is cold or at room temp.
- Physical: Avoid unpleasant sights, sounds, and odors that may aggravate NV, fresh air, avoid sudden movements, dim lights.
- Acupressure - for pregnancy or chemotherapy
81
What are the different therapeutic indications, pros/cons, and side effect/AEs associated with the anti-emetics we can use?
Antihistamines-anticholinergics: For moderate to severe NV
- Meclizine, Dimenhydramine, Scopolamine: Block histamine and/or muscarinic receptors in the CTZ and NTS centers. Side effects include drowsiness, sedation, dry mouth, constipation, blurred vision.
Phenothiazines:
- Prochlorperazine, Promethazine, Chlorpromazine: Dopamine inhibition at CTZ. Side effects include dizziness, sedation, dry mouth, hypotension, EPS
Serotonin antagonists:
- Ondanstron, Granisetron, Palonosetron, Dolastron: Serotonin inhibition at CTZ, VC, GI tract. Side effects include mild headache, dizziness, fatigue, constipation.
- Ondansetron and Granisetron are the cheapest and have various dosage forms, the other two are brand only $$$.
Neurokinin-1 Antagonists:
- Aprepitant, Fosaprepitant, Rolapitant: NK receptor inhibition at CTZ, VC, and GI tract. May cause fatigue, hiccups, constipation, and decreased appetite.
82
How would we decide therapy for pts with post-operative nausea and vomiting, motion sickness, NV associated with gastroenteritis or influenza, or nausea associated with pain?
Post-operative N/V: Try to prevent.
- Low risk (0-1 risk factor), no treatment necessary
- Mod to high risk (2+ risk factors): Tx with 1 or 2 agents (5-HT3 agents are DOC), drugs are administered at the end of the procedure.
- Highest risk (3+ risk factors): Always use 2 agents. 5-HT3 + metoclopramide or aprepitant.
- Breakthrough: Use agent from a different class if within 6 hours of original dose.
Motion sickness: Focus on prevention.
- Scopolamine patch
- Dimenhydrinate (Dramamine) PO
- Meclizine
NV secondary to gastroenteritis or pain: Treat symptoms while treating the cause.
- Ondansetron IV/ODT/PO
- Promethazine IV/IM/PO
83
How should we plan to monitor patients for therapeutic effects, side effects, and desired outcomes for pts treated for N/V?
Monitoring for efficacy: look at volume, frequency and duration, nausea rating, ability to eat, PRN doses of anti-emetic agents, QOL ratings.
Toxicity: Sedation/drowsiness, dizziness, diarrhea, headache, anticholinergic SE, EPS.
84
What are the difference between macules, papules, and pustules?
Macules - Changes in skin color
Papules - Skin gets elevated
Pustule - Is pus is present
85
What are the differences in these properties of ointments? Occlulsive, humectant, emollient, proctective
Occlusive - Promotes retention of water in the skin
Humectant - Causes water to be retained because of its hygroscopic properties
Emollient - Softens the skin, soothes irritation in the skin or mucous membranes
Protective - Protects injured or exposed skin surfaces from harmful or annoying stimuli
86
What is the order of these in terms of most hydrating to least hydrating? Cream, Gel, Ointment, Lotion, Foams/Solutions/Sprays
```
Ointment
Cream
Lotion
Gel
Foams/Solutions/Spray
```
87
What are the pros/cons of Ointments, Creams, Gels, and Lotion/Foams/Solutions/Spray
Ointment -
- Pros: Greatest hydrating ability, removes scales, is protective, better bioavailability of ingredients, longer duration of action
- Cons: Greasy and messy, not water washable (soap needed), poor patient acceptance, not ideal for hairy areas
Cream -
- Pros: Some are water washable, greater patient acceptance, can be used in hairy areas
- Cons: Not as hydrating as ointments, more frequent administration
Gel -
- Pros: Non-greasy, water washable, easy to apply to hairy areas, high patient acceptance
- Cons: Drying, more frequent administration, more likely to sting (EtOH)
Lotion/Foams/Solutions/Spray -
- Pros: Non-greasy, water washable, easy to apply to hairy areas and scalp, high patient acceptance
- Cons: Can be drying, lower bioavailability, more frequent administration
88
What are some characteristics of the two drug-induced skin disorders?
1. Hypersensitivity/allergic rxn - Systemic, seen on trunk of arms and legs
- Bilateral
- Macular lesions, may progress from rash to hives.
2. Photosensitivity -
- When exposed to sunlight, the deposit of the drug causes the skin to react much worse.
- Localized to where the skin is exposed to the sun.
- Phototoxic (results in local sunburn due to a photochemical reaction)
- Photo allergic (drug or its metabolite induces cell mediated immune response which produces a papular or eczematous contact dermatitis). This one looks a little more patchy.
89
What do we do if theres an ADR involving skin reactions?
1. Stop the drug
2. Systemic antihistamine
3. Systemic and/or topical corticosteroids
4. Soothing baths or soaks
90
What is cellulitis? What are the signs and symptoms, and treatment?
Cellulitis - Infection near the break in skin
Symptoms: Red, warm, swollen, fever if systemic). Tends to be unilateral.
Treatment: Refer! Need oral antibiotics or IV antibiotics in severe cases.
91
What is head lice? What are the signs and symptoms, and treatment?
Head lice - (Pediculosis), due to pediculus humanus capitis on the scalp.
Symptoms: Scalp redness and scaling, pruritus, most common in kids 3-12 yo.
Treatment: Refer (Rx products usually work better).
- Permethrin 1%, Malathion, Oral ivermectin, Spinosad, Topical ivermectin
- OTC medications
- Prevention: Check the others in the house, wash everything to reduce spread.
92
What is herpes zoster? What are the signs and symptoms, and treatment?
Herpes zoster - (shingles). Viral infection usually seen in adults over 40yo who previously had chicken pox. It is contagious and triggered by stress, old age, and immunosuppresion.
Symptoms - Unilateral, painful skin lesions (papules). These will progress to scabs.
Treatment: Refer!
- Oral valacyclovir, famciclovir. These lessen the intensity and shorten the course of the infection.
- Prevention with Vaccine: Shingrix
- May need non-steroidal or Opioid for pain.
93
What is dry skin (xerosis)? What are the signs and symptoms, and treatment?
Dry skin - very common. More common as you get older. Elderly patients and pts with frequent bathing are at risk for this.
Symptoms - Rough, dry scales and cracks. Itchy.
Treatment -
- Emollients (best used right after bathing). These are DOC for itching and they restore the barrier and skin function. Ex. Vaseline, Lubriderm, Eucerin.
- Other agents to reduce itching: Menthol and camphor, pramoxine, aluminum acetate, hydrocortisone.
- Dr. Martin's Rules of 3's: No more than 3 bathes/showers per week, use tepid water, bath for 3-5 minutes, pat dry, apply copious amount of emollients within 3 mins, apply emollients at least 3 times daily.
94
Who is at risk for topical fungal infections? What are the signs and symptoms, and should we refer or treat?
Risk - Infants, elderly, immunosuppressed, incontinent, obese.
Signs - Localized, red rash
Treatment -
- Most can be treated OTC
- Refer if systemic symptoms or if pt is immunosuppressed.
- Treatment is 4 weeks or longer (slow to grow... slow to go)
95
What is a topical candida infection? What are the signs and symptoms, and treatment?
Topical candida infection - fungal infection. Most common in moist areas in humid conditions. Also common in obese pts.
Treatment - Refer if systemic or if they are immunocompromised.
- Hygiene
- OTC Topical antifungal creams (clotrimazole, terbinafine, miconazole).
- Rx products - Nystatin, Ciclopirox, Ketoconazole.
- Dry the affected areas.
96
What are the treatment options for diaper rashes?
- Remove the irritant by increasing frequency of diaper changes
- Keep the areas clean with mild soap and water
- Antifungal agents/corticosteroid (refer for Rx)
- Protectants: Zinc oxide, Destin, Aveeno, Butt paste)
97
What is impetigo? What are the signs and symptoms, and treatment?
Impetigo - Staph or strep infection.
Symptoms: Crusty skin lesions.
Treatment: Refer to PCP
- May be prescribed topical antibiotics if it's a small area (mupirocin, retapamulin)
- Oral abx may be prescribed.
98
What is tinea pedis? How can we treat it?
Tinea pedis - Often spread in pools/showers.
Treatment -
- Topical antifungals
99
What is tinea corporis? What are the signs and symptoms, and treatment?
Tinea corporis - Ring worm.
Symptoms: Small, circular, red scaly areas
Tx:
- Topical antifungals
100
What is scabies? What are the signs and symptoms, and treatment?
Scabies - Sarcoptes scabiei infestation seen primarily in children and adolescents.
Symptoms - Raised lines caused by mites burrowing under the skin. Lots of itching
Treatment - Refer!
- Permethrin 5% cream
- Crotamiton
- Oral ivermectin
101
What are the 3 types of skin cancer? Who is most at risk and what are the treatment options?
Basal cell carcinoma - Most common
Squamous cell carcinoma - Sun-exposed
Melanoma - Most deadly
Risk - Caucasians with light eye and hair color.
Tx: Refer
- Removal of lesion
- Chemotherapy
- Radiation
102
What are the different severe drug-induced cutaneous reactions?
Stevens-Johnson syndrome and Toxic epidermal necrolysis-
Toxic skin reaction that is characterized by epiderma detachment and erosive mucosal lesions. This happens due to a drug protein complex reaction that leads to T-cell activation which migrates to the dermis and releases cytokines.
- SJS associated with anticonvulsants and antibiotics, etc.
- Usually occur within the first 4 weeks of treatment.
DRESS - Drug reaction with eosinophilia and systemic symptoms
AGEP - Acute generalized exanthematous pustulosis
Erythema multiforme - Red rash with darker outer layer
103
What layers of the skin are inflamed in a dermatitis reaction? What are the three types of dermatitis?
The upper two layers of skin (epidermis and dermis).
Acute: Blister formation. The itching is intense. Ex. Contact dermatitis.
Sub-acute: Less liquid like. More associated with dryness and crusting. Itching is common but it's less intense. Ex. Atopic dermatitis.
Chronic: Epidermal thickening, exaggerated skin markings, less itching, Ex. Any long standing acute or sub-acute dermatitis.
104
What are the two types of acute contact dermatitis? What are some general treatment principles?
- Look at the pattern and the part of the body that is involved.
1. Allergic
2. Irritant: Non-immunologic. More common than allergic. The reaction will be within a few hours. Common irritants include metals, cosmetics, and adhesives.
- Stop the itch-scratch cycle. The treatment we pick should be based off of the pts ability to carry out the treatment.
105
How do we treat poison ivy?
Contact dermatitis. The issue is being exposed to the resin of the poison ivy. This resin can stick around for 2 weeks, so whenever you tough that resin again, the lesions will occur.
Prevention is key - Ivy-Block (protectant, re-apply every 4 hours).
Treatment: Topical therapy is OK is <10% BSA is involved.
- Best treatment: Topical corticosteroids!!
- Remove the source
- Calamine lotion
- Topical antihistamines
- Oral antihistamines
106
What is the MOA of topical corticosteroids? What is the recommended dosing for acute dermatitis?
Anti-inflammatory - Increases the expression of anti-inflammatory genes and indirectly inhibits inflammatory transcription factors, such as NFkb, to decrease the expression of pro-inflammatory genes
Anti-mitotic - Inhibits cell proliferation
Immunosuppressive - Inhibition of humoral factors involved in the inflammatory response
Apply BID - QID x 3-14 days.
107
What is the recommended dosing for oral corticosteroids for treatment of acute dermatitis that covers more than 10% BSA?
- Prednisone 40-60 mg per day, taper every 3 days.
- Minimum of 10-14 days of treatment
- Avoid dose packs!! They don't provide treatment for a long enough period of time.
108
What is atopic dermatitis?
It's the most common form of eczema (sub-acute dermatitis). Usually, it's pretty easy to treat, but if it's severe, it can cause significant QOL issues.
Symptoms - Itching, symmetrical red papules or plaques, scaling, overall dryness of skin
In infants, it's common to see the dermatitis on the face. Then, as the pt gets older, we start to see it on the neck and creases of arms and legs, then we see it on hand, neck, arms, and legs.
- It's important to identify the triggers (like detergents, infections, allergens, etc.)
109
What is the stepwise treatment of atopic dermatitis?
1. Non-pcol measures: Emollients, eliminate triggers, trim fingernails, etc.
2. Topical therapy: Topical corticosteroids, topical calcineurin inhibitor therapy, topical JAK inhibitor, etc.
3. Systemic therapy: Phototherapy, oral immunosuppressant therapy, oral JAK inhibitors, injectable biologic agents
110
What is the management of moderate to severe atopic dermatitis?
Acute flares: Med potency TCS BID for up to 3 days beyond the clearance of the lesions.
Refractory: Phototherapy or oral immunosuppressive therapy. If none of that works, consider an emerging biologic agent.
Maintenance therapy: Basic measures + daily application of low dose TCS or 2-3 times weekly TCS or other topical anti-inflammatory agent. Also need a written action plan for what to do when flare ups occur.
- The vehicle of the TCS impacts the delivery and potency of corticosteroids. Only 2% is absorbed when it's applied to normal intact skin, but occlucion can enhance the penetration by up to 10x.
111
What is important to know about low vs. high potency topical corticosteroids?
```
High potency steroids (class 1) - Do not use on face!! These have the most anti-inflammatory properties. You also want to avoid using these for more than 2 weeks at a time, and no more than 50g per week.
- Ex. Betamethasone ointment
```
```
Low potency steroids (class 6-7) - Use on face, groin, genitals, axilla. These are safest for long-term maintenance use.
- Ex. Hydrocortisone.
```
112
What is the MOA of topical calcineurin inhibitors (TCI)? What are 2 examples of these?
Block pro-inflammatory cytokine agents
Ex. Pimecrolimus, tacrolimus
- These can be used on any area, including the face. There's no risk of atrophy.
- $$$
- Side effect: burning
- These are 2nd line treatment and are for intermittent use only (only moderate AD).
113
What is the MOA of Crisaborole 2% ointment and when would it be used?
Phosphodiesterase-4 inhibitor (non-steroidal)
- Used as an alternative to TCS and TCIs (steroid phobia)
- Used for mild or moderate AD (not mod-sev).
114
What is the first biologic indicated for moderate-severe AD? What's the MOA?
Dupilumab (Dupixent)
MOA: Human monoclonal antibody against IL-4 receptor a. It inhibits signaling of IL-4 and IL-13.
- $$$$$
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What is stasis dermatitis? How do we treat it?
It's dermatitis due to poor circulation and is most common around the ankles.
- Aching, swelling, discomfort.
- Hyperpigmentation (darkening of the skin due to retention of Fe++ in the skin)
Treatment:
- TCS for itching
- Emollients for all pts
- Oral abs only for local infections (cephalexin 250-500mg TID).
- To relieve swelling: elevate feet and legs, support stockings, compressive bandages.
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What do we do for chronic dermatitis?
- Same treatment as subacute
| - Topical corticosteroids and emollients for dry lesions. Try to avoid long term TCS use tho.
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What is seborrhic dermatitis? How do you treat it?
Erythema with greasy, yellow scaling seen most commonly along the hairline and on the face.
Treatment:
1. Medicated shampoos - Use them correctly with lots of contact time. Ex. OTC products first like head & shoulders.
2. Low strength TCS for lesions on the face and ears.
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What is the definition of acne? What things exacerbate acne?
A common chronic inflammatory disease of the sebaceous glands and hair follicles of the skin characterized by comedones, papules, and pustules. It's clearly associated with the number of androgens present.
Exacerbate acne:
- Oil-based cosmetics, emotional stress, irritation/physical pressure, drugs (androgenic steroids).
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What is a comedone?
Comedone - Hair follicle plugged with sebum, keratin, and dead skin. Bacterial colonization is trapped in the sebum.
Propionibacterium acnes is the bacteria in acne and it converse TGs to FFAs, which cause the irritation of local cells resulting in inflammation.
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What are the four major functions of pharmacotherapeutic agents for acne?
1. Antimicrobial
2. Anti-inflammatory
3. Decreased sebum production
4. Keratolytic/Comedolytic
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What is the general treatment of acne or all patients?
- Follow a regular skin cleansing regimen using a mild facial soap BID
- Minimize the use of products that cause irritation or stinging
- Use tepid, not hot, water to clean affected areas
- Know that there is no quick fix.
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How do we treat mild-moderate acne vs. severe acne?
Mild-moderate: Topical retinoid +/- antibacterial (can do oral if needed)
Severe - oral isotretinoin (reduces sebum production and shrinks sebaceous glands). Use for severe acne or when patients have failed other treatments.
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What are the 5 common adverse effects of topical agents for acne?
```
Erythema
Scaline
Burning
Flare
Resistance
```
(Tretinoin are the ones with the most adverse effects)
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When do we use oral abx for acne?
If topical therapy hasn't worked or if the pt has significant inflammatory lesions.
- These decrease bacteria and inflammation.
- We want to limit tx to 6-8 weeks due to resistance
- Minocycline/Doxycycline are the most common. (don't use in kids (turns teeth brown) or pregnant women).
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When do we use hormonal therapy for acne?
These are ideal for females who's acne flares during the menstrual cycle. And when initial treatments don't work.
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How do we dose isotretinoin (for acne) and what are some important points about it?
0.5-2mg/kg/day in 2 doses with food for 15-20 weeks.
- Acne will get worse before it gets better
- If acne flares after >2 months off tx, and a 2nd course may be used.
- Effectiveness increases with higher doses.
- Side effects are a big deal for this. Skin, musculoskeletal, and other issues can happen. Not for pregnant women (category X) and may cause depression/suicide.
- don't take a vit A supplement.
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When should we follow up with acne patients?
Follow up 2-6 months to see if the treatment has been successful.
- Lengthening acne free periods is key.
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What is rosacea? What are the symptoms? What are the 4 subtypes?
Rosacea - a common, chronic, progressive inflammatory dermatiosis based upon vascular instability.
Symptoms: Facial flushing/blushing, telangiectasia (dilated capillaries in the skin).
Triggers: Foods, temperature, weather, drugs (vasodilators), etc.
Subtypes:
1. Telangiectatic: Visibly dilated blood vessles on nose/cheeks
2. Papulopustular: Resembles acne
3. Phytmatous: Enlarges sebaceous glands, especially on the nose.
4. Ocular - Watery eyes, bloodshot eyes
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What are the treatment options for rosacea?
Lifestyle modifications: Avoid triggers, avoid excessive exposure to the sun, use mild soaps and cleansers
- Topical meds should be allowed to penetrate the skin for 5-10 minutes before applying make-up.
Mild: Avoid triggers, topical Abx (if pustular), topical retinoids
Moderate: Oral abs, topical retinoids
Severe: Oral isotretinoin, laster treatments.
For topical antibiotics: Metronidazole 1% is the treatment of choice!!! Apply BID
Topical retinoids: Azelaic acid!!
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What is psoriasis? What are the 3 types of psoriasis?
Psoriasis - Chronic autoimmune inflammatory skin disorder that is characterized by a T-lymphocyte mediated disease and keratinocyte proliferation.
- Thickened, bilateral red patches covered by silvery-white scales.
- Classified as limited (<5% BSA) or generalized (moderate 5-10& BSA, severe >10% BSA)
Types:
- Plantar
- Psoriatic
- Pustular
Triggers:
- Stress, environment, injury, infection, smoking, drugs, diet
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What are the treatment options for psoriasis?
- Sun: a little sun may be a good thing (too much can cause irritations)
- Baths
- Emollients
- Keratolytics
General approach:
- Topical therapy (1st line: emollients, corticosteroids, calipotriene/calcitriol, etc.)
- UV phototherapy
- Systemic therapy
- Biologic therapy
*don't use corticosteroids for too long. Alternate between the options to prevent tolerance
For severe disease:
1. Biologics: SC injection!!!
2. Systemic therapy: oral therapies (plethora of options)
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What do these peds terms mean? Pediatric, neonate, infant, child, adolescent, Pre-term, term, extremely low, very low, and low birth weight, corrected age
Pediatric: From birth up to ~18 years.
Neonate: Birth to 28 days of life
- Pre-term: < 37 completed weeks gestational age
- Term: 37 weeks gestation age or greater (usually 40 weeks)
Weight:
- Extremely low birth weight: <1000g at birth
- Very low birth weight: <1500g at birth
- Low birth weight: <2500g at birth
Corrected age = postnatal age - weeks born early
- ex. baby born at 28 weeks gestational age = 12 weeks premature. If she is 16 weeks old, then 16-12 = 4 weeks corrected age.
Infant: 28 days/1 month up to 12 months
Child: 1-11 years
Adolescent: 12-18 years
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What are the pharmacokinetic and physiological differences (heart rate, blood pressure, respiratory rate) between pediatric patients and adults?
Absorption: Neonates have thinner skin, greater density of capillaries in the muscle, and decreased skeletal muscle blood flow/contractions. They generally have a slower rate of enteral absorption. They have increased gastric pH which can either increase or decrease absorption of drugs. They cannot solubilize or absorb lipophilic drugs.
Distribution: Increased total body water and extracellular fluid, and decreased protein binding.
Metabolism: The liver takes time to mature. It's slower in neonates, but is faster is children, then gets slower in adults.
Excretion: We would expect more than 1mL/kh/hr of urine from pediatric patients. GFR will increase with age.
- eGFR = 0.413 x height in cm/Scr
SCr: Lower in infants due to infants not having much muscle.
Heart rate: Goes down with age
Blood pressure: Goes up with age
Respiratory rate: Goes down with age
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How can you assess renal function for a pediatric patient and apply that information when making dosing recommendations?
Calculate the creatinine clearance: GFR = 0.413 (height in cm/Scr)
Use that to asses what dosing to use.
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How can you utilize drug information resources to make appropriate dosing recommendations for pediatric patients? What are the dosing ranges for APAP and ibuprofen?
The best drug-resource is the Lexi-Comp Pediatric & Neonatal Product.
- Pay attention to headers, because neonates get different dosing than infants and children and adults.
- Do not exceed adult dosing, be mindful of units, be sure to know what the resource is telling you.
Acetaminophen range: 10-15mg/kg/dose q4-6h (32mg/mL suspension (160mg/5mL))
Ibuprofen range: 5-10mg/kg/dose q6-8h (20mg/mL (100mg/5mL))
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What are appropriate dosage forms and routes of administration for pediatric patients?
- Children can typically swallow tablets and capsules around 7-8 years old. Some capsules can be open, some tablets can be crushed, but not all.
- There are many unpleasant oral medications, like metronidazole, clindamycin, prednisone, furosemide, etc.
- Commercially available liquids are easy to fill, but they may have limited concentrations available.
- Compounded liquids may be difficult to find pharmacies to fill, but they can be compounded to many concentrations.
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What is the difference between gastroesophageal reflux (GER) and gastroesophageal reflux disease (GERD)?
```
Gastroesophageal reflux (GER) - Passage of gastric contents into the esophagus. This is a normal physiologic process in healthy infants/children.
- Caused by relaxation of lower esophageal sphincter.
```
Gastroesophageal reflux disease (GERD) - gastric reflux causes troublesome symptoms or complications (irritability, feeding difficulties, poor weight gain)
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What are some age appropriate signs and symptoms of GERD in pediatric patients?
GERD symptoms affect 2% of 9 year old children and 5-8% of 10-17 year old children.
- Symptoms differ between infants and children.
- Most children older than 4 show classic heartburn symptoms similar to adults.
GERD symptoms in infants:
- Regurgitation
- Feeding difficulties
- Hematemesis (vomiting blood)
- Irritability
- Failure to thrive
- Back arching
- Persistent cough
- Apnea/BRUE
GERD symptoms in children:
- Heartburn
- Vomiting
- Dysphagia
- Chest pain
- Persistent cough
- Wheezing
- Laryngitis
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What is the pathophysiology of diarrhea and constipation in children?
Diarrhea - 3 or more loose or liquid stools per day. Chronic diarrhea is more than 14 days consecutively. It may be due to infectious or non-infectious causes. It causes dehydration, electrolyte abnormalities, malnutrition, and negatively impacts quality of life.
Constipation - Infrequent passage of hard, uncomfortable stools that are distressing to the child. There's lots of causes, including anatomical, neurologic, obstructive, endocrine/metabolic, and functional (all other) causes.
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What is the appropriate management of GERD, diarrhea, and/or constipation, how should we monitor, and what are counseling points for pediatric patients?
GERD:
1. Non-pcol: feeding changes, positioning therapy (not for infants), lifestyle changes
2. Pcol Treatment: 1st is H2RAs (Famotidine) and alternative is PPIs (Pantoprazole, Omeprazole, etc.). Prokinetics are not used commonly (Metoclopramide)
- Avoid antacids in infants, but can be used for short term relief of occasional symptoms in children.
- H2RA/PPI side effects: Headache, diarrhea, abdominal pain, nausea. Don't want to use long term due to more serious risks.
Diarrhea:
- Non-pcol: Restore fluids and electrolytes, temporary diet modifications
- Dehydration treatment: Oral replacement therapy, IV rehydration if needed.
- Drug therapy used for supportive care: Loperamide (avoid if child is malnourished, severely dehydrated, or if they have bloody diarrhea)
- Don't use pcol therapy in cases of infectious diarrhea such as C. diff.
Constipation:
1. Glycerin suppository (no more than 3 days w/o referral)
- Avoid mineral oil, stimulant laxatives, phosphate enemas, and home-made remedies containing honey.
- Chronic constipation may require education -> disimpaction/cleanout (1. oral laxative 2. rectal 3. nasogastric)-> maintenance therapy (1. PEG 2. lactulose 3. Docusate) to establish regular bowel movements -> behavior modification
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What are scenarios requiring physician/specialist referral?
- Alarm symptoms (maybe it's more than just GERD): Bilious or projectile emesis, GI bleeding, vomiting beginning after 6 months of age, difficulty swallowing, history of food allergy, fever, diarrhea/constipation, lethargy, hepatosplenomegaly, etc.
- Lack of improvement after trialing first/second line drug therapy options
- Serious underlying medical conditions
- Constipation: Delayed passage of meconium (first baby stool), failure to thrive, bloody stools, severe abdominal distension, fistula
- Diarrhea: Blood in stool, fever, really young age, premature birth, change in mental status, persistent vomiting, etc.
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What are the 4 main pathways that can trigger vomiting in kids?
Blood-borne toxins (medications)
Motion (Vestibular pathway)
Mechanical( (Vagal)
Emotion (Fear, anxiety)
Classified as acute, chronic, or cyclic
143
T or F: Promethazine is the first line treatment choice in pediatric patients with vomiting issues
False, never use promethazine in patients less than 2 years old. It's associated with respiratory depression and may have enhanced toxicity in children.
144
What is important about amoxicillin/clavulanate in kids?
Clavulanate causes diarrhea. We really need pts to get less than 10mg/kg/day.
When we need to give high dose of amoxicillin/clav (90mg/kg/day), we need to use the 600mg/5mL formulation if possible. It's the highest ratio of amoxicillin to clavulanate, so it reduces the risk of diarrhea as much as possible.
145
How do we calculate fluid requirements in peds?
Up to 10kg: 100mL/kg
10-20kg: 1000mL + 50mL/kg for every kg greater than 10.
>20kg: 1500mL + 20mL/kg for every kg greater than 20.
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When do we refer for a cold? (9)
- Fever ≥ 102ºF
- Chest pain
- Shortness of breath
- Worsening symptoms
- COPD
- CV disease
- Chronic immunosuppression
- Elderly, frail
- Infants ≤ 3 months old
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when do we refer for a cough? (8+)
- Children < 4 years old
- Cough for more than 7 days
- Fever (adults > 103ºF, children > 102ºF)
- Think yellow, tan, or green mucus
- Cough worsens as cold or flu resolves
- Drug-induced cough
- Chronic diseases associated with cough
- Cough with dyspnea, angina, cyanosis, hemoptysis, weight loss, or night sweats
