NSG 531 Advanced Pharmacology Exam 3 Study Guide with Verified Answers

NSG 531 Advanced Pharmacology Exam 3 Study Guide with Verified Answers thrombogenesis and selective cox-2 inhibitors - ANS cox-1 found in platelets makes TXA2 which causes vasoconstriction and platelet aggregation cox-2 found in endothelial cells - makes prostacyclin which causes vasodilation and inhibits platelet aggregation people that were taking cox-2 were having thrombotic effects and having heart attacks cox 1 platelets cox2 immune cells cox 1 acts on arachidonic acid and it makes TXA2 which is stronger cox-2 inhibitrs platelelt aggregation if you selectively inhibit cox-2 you are tipping the balance in favor of TXA 2 vasoconstriction and platelelt aggregation cytokine inhibitors - ANS humira, remicaid antigen presenting cell presents the antigen to the T cell, activates macrophages, releases inflammatory cytokines such as tumor necrosis factor alpha those durgs are TNF alpha monochromal antibodies - bind to the TNF alpha released by the antibodies and prevent it from producing inflammatory effects anakirna blocks action of IL1 antagonist receptor for cytokines the problem with this is that you could inhibit your immune system by blocking those binding sites leukotriene inhibitors - ANS drugs that bind to the receptor for leukotriene and lock those sites up - or we can give a drug that blocks the LOX enzyme itself flag inhibitors - inhibits the formation of leukotriene statins as anti-inflammatory drugs - ANS inhibit the cholesterol synthesis pathway HMG CoA is inhibited by the statins blocking the pathwya by blocking that early in the pathway you also inhibit isoprenoids which are inflammatory byproducts pediatric issues of GI absorption - ANS gastric pH at birth is 6-8 gradually declines until adult values reached by 2-3 years of age evidence that active and passive transport do not fully develop until four months not known when efflux pumps or intestinal P450 enzymes develop slowed gastric emptying evidence that switch from breast milk to formula induces hepatic P450 enzymes what does a high gastric pH at birth effect? - ANS base drugs will be better absorbed and acidic drugs will not - kids are the opposite of adults describe issues of GI transport in pediatrics - ANS because of the transporter proteins not being developed in infants a drug will struggle if it is dependent on transportation across the gut into the circulation via transporter proteins describe issues of efflux pumps in GI for pediatrics - ANS pumps develop at different ages - depending on whether that drug is able to bind to the efflux pump and back into the intestine will effect whether or not it will end up in circulation pediatric issues of intramuscular absorption - ANS decreased skeletal muscle blood flow and inefficient movement may decrease absorption may be offset by increased capillary density skeletal muscle mass is still relatively low and they can't make the same efficient movements as adults - this decreases absorption pediatric issues of percutaneous absorption - ANS increased percutaneous absorption d/t thin stratum corneum and increased skin hydration increased percutaneous absorption also r/t higher body surface area describe issues of ratio of body surface area to weight between infants to adults - ANS covering a similar percentage of the newborn's body with a skin absorbable substance will lead to a larger dose per unit of body weight compared to an adult ratio of body surface area to weight is 3x higher in infant - example if you cover a similar percentage of a newborn's body when compared to adults with an absorbable substance you could be giving a higher dose 2 fold pediatric issues of drug distribution - ANS increased TBW as percent weight and increased ECF increased weight-adjusted Vd and relatively increased loading decreased plasma protein concentration - contributes to increased Vd Increased bilirubin due to increased RBC turnover and immature liver why does decreased plasma protein concentration lead to increased volume of distribution in peds - ANS because less drug is binding to plasma proteins because the children are relatively hypoalbuminemic compared to adults why do peds have increased bilirubin - ANS because the liver is not mature enough they can't always convert RBC to conjugated bilirubin that can be eliminated they tend to have unconjugated non water soluble bilirubin that hangs around longer - it can then bind to plasma proteins so bilirubin will then comptete with drugs for plasma protein binding sites if the bilirubin has a higher affinity for the plasma protein you see jaundice if the drug has higher affinity for the plasma protein then you have higher plasma concentrations of the drug pediatric issues of biotransformation - ANS reduced phase I and phase II reactions reduced glucuronidation - cause of chloramphenicol-induced gray baby syndrome with phase II we get concerned about being able to conjugate glucoronic acid to a drug - major phase II reaction pediatric issues of elimination - ANS reduced GFR in neonates and premmies tubular secretion is 20-30% of adult values and reaches adult levels at 30-40 weeks reduced tubular reabsorption don't eliminate as well as adults due to lower kidney function if you have reduced GFR you are going to filter less and therefore reabsorb less clinical implications of pediatric issues - ANS clearance determines maintenance doses - lower maintenance doses than adults hepatic and renal function mature with age need to increase daily doses to prevent subtherapeutic concentrations regular clinical assessment and TDM if a child is going to be on a drug for a very long time over time that dose is going to have to be titrated up as they mature due to growth and development Geriatric issues of absorption - ANS increased gastric pH (promotes base and inhibits acid absorption) slower rate of absortpion variable changes in bioavailability: decreased gut active transport - transporters slow down with age decreased first pass effect - liver function slows with age - they don't absorb as much but what they do absorb is less susceptible to first pass which will effect dose decreased gut P450 Geriatric issues of distribution - ANS TBW and lean body mass decrease - reduced volume of distribution reduced albumin concentration - increase the distribution of the drug because less will be bound to albumin reduced loading doses geriatric issues of biotransformation - ANS liver mass and blood flow decrease with aging phase I declines little change in phase II this can be an issue for drugs that have substantial first pass effects - when they make the first pass through the liver they become more polar and lose a lot of activity so because of the phase I effects you're accounting for first pass effects that aren't going to be as present so a normal dose for a 50 year old may then be toxic geriatric issues of elimination - ANS reduced cardiac output reduced GFR reduced tubular secretion geriatric issues of pharmacodynamics - ANS changes in receptor sensitivity decreases in receptors decreases in certain neurons reduced homeostatic adjustments Describe how geriatrics are effected by changes in receptor sensitivity - ANS example of benzo - more receptive to sedative effects because the receptor site is not as tightly regulated - it will open up the chloride channel more than it did when you were 30 describe how geriatrics are effected by decreases in receptors - ANS example - beta agonists - beta receptors decrease so you need to give a greater dose because you are stimulating fewer receptors describe how geriatrics are effected by decreases in certain neurons - ANS example such as dopaminergic and cholinergic so what happens if you give an anticholinergic drug? that person will be much more susceptible to the anticholinergic effects because their cholinergic transmission is already reduced before the drug in geriatrics - would you give more or less of an antagonist - ANS you would give less because there are less receptors to block in geriatrics - would you give more or less of an agonist - ANS you would give more because there are less receptors to stimulate Describe effects of G6PD deficiency - ANS affects 400 million people worldwide G6PD normally maintains RBC levels of reduced glutathione which protects RBCs from oxidative stress certain drugs can decrease RBC concentration of reduced glutathione such as sulfas INH ASA if someone is G6PD deficient then they can't restore reduced concentration of glutathione to normal levels results in ghost cells - they have lost their hgb but still have a cell membrane basically results in people that now have hemolytic anemia benefits to being deficient though is that you are protected against malaria Describe effects of Factor V Leiden and oral contraceptives - ANS Factor V is the 5th factor in the blood coagulation pathway converts prothrombin to thrombin thrombin has a way of turning off additional activation of prothrombin into thrombin thrombin induces the production of protein C which then inhibits Factor V - negative feedback loop oral contraceptives increase factor V and increase the resistance of factor V to protein C - this is in a normal woman that doesn't have factor V leiden if she has factor V leidin it can still activate thrombin and it can still lead to the activation of protein c but it is resistant to the inhibitory effects of protein C making her more susceptible to not turn off prothrombin effects making her more likely to have a clot add in the effects of the oral contraceptive and factor V leiden and she is even more at risk for stroke What is unique about redheads and anesthesia - ANS they require more they have a mutation in melanicortin receptor 1 describe the effects of atypical pseudocholinesterase - ANS if we were giving a polarizing blocker it binds to the receptor and opens it keeping it open and the initial response is contraction but with prolonged depolarization the muscle becomes flacid in order to reverse it we stop giving it and wait - pseudocholinesterase will metabolize the blocker and get rid of it if they have atypical pseudocholinesterase they have a reduced affinity for the substrate - the atypical pseudocholinesterase will not bind as well to the succinylcholine we will see prolonged effects of the neuromuscular blockade prolonged paralytic effects variability in acetylation of drugs - ANS phase II reaction if you add an acetyl group to a drug it will become more water soluble and be able to be excreted if plasma concentrations are low then they are fast acetylators if they are higher they are slow acetylators if someone is a rapid acetylator then they are resistant to a drug that is acetylated What are the effects of a defective CYP 2D6 - ANS decrease in biotransformation therefore increased plasma concentration what are the effects of an extra copy of CYP 2D6 - ANS increases the biotransformation therefore increased plasma concentrations Describe genetically why asians metabolize alcohol differently - ANS point mutation in ALDH so they do not successfully convert acetaldehyde to acetate effects - flushed, hypotension, malaise we want people to feel this way with antibuse - aversive therapy Describe malignant hyperthermia - ANS o a potentially lethal complication of a rare inherited muscle disorder o may be triggered by inhaled anaesthetics and depolarising muscle relaxants o calcium floods the cell binds to ratidine receptors then floods out and we get muscle contraction o acidosis develops + body temp rises → tachycardia, cardiac arrhythmias, hypotension, decreased cardiac output and cardiac arrest temperature gets high very quickly o muscle contraction and rigidity high temp stop surgery cool them give muscle relaxant acute intermittent porphyria - ANS porphyrins are pigments genetic mutation in PGBD leads to accumulation of PBG S/S - abdominal pain, neuropathy, psychiatric manifestations certain drugs can induce ALA synthase which increases ALA and PBG accumulation and can percitate an episode (anticonvulsants, barbituates) genetic variants relevant to warfarin - ANS CYP 2C9 - variants can decrease biotransformation vitamin K epoxide reductase - allows us to recycle vitamin k - mutation decreases its activity (anticoagulation effect) lower doses of warfarin are needed Type I hypersensitivity reaction - ANS IgE mediated IgE expressed on surface of cell - cross link 2 IgE receptors and you get bronchoconstriction, hives, eczema Type II hypersensitivity reaction - ANS IgG mediated cytotoxic hypersensitivity often seen in RBCs lysis blood transfusion reactions type II hypersensitivity reactions - ANS Immune complex mediated hypersensitivity also called serum sickness inflammatory response at the point where the antigen antibody complex binds to the basement membrane activates compliment and starts activating an inflammatory response at that site Which hypersensitivity reactions are fast and slow - ANS Type I, II, III fast within minutes Type IV is slow - couple of days Type IV hypersensitivity reaction - ANS cell mediated has to work its way through the lymphnodes example - the TB test, contact dermatitis EP is a 38-year-old female patient that comes in for diabetes education and management. She was diagnosed 12 years ago and states lately she is not able to control her diet although she continues a 1600 calorie diet with appropriate daily carbohydrate intake (per dietitian prescription) and walks 40 minutes every day of the week. She states compliance with all medications. She denies any history of hypoglycemia despite being able to identify signs and symptoms and describe appropriate treatment strategies. PMH: T2DM, HTN, obesity, depression, s/p thyroidectomy due to thyroid cancer FmHx: Noncontributory SHx: (−) Smoking, alcohol use, past marijuana use while in high school Medications: Metformin 850 mg tid, glipizide 20 mg bid, lisinopril 20 mg daily, sertraline 100 mg daily, multivitamin daily Vitals: BP 128/82 mg Hg; P 72 beats/min; BMI 31 m/kg2 Laboratory test results: Na 134 mEq/L, K 5.4 mEq/L, Cl 106 mEq/L, BUN - ANS Exenatide - Exenatide (Bydureon) once weekly has been able to demonstrate weight loss and decrease A1C% by 0.7% to 1.2% in clinical trials; however it is contraindicated for EP due to the self-reported history of thyroid cancer. Dapagliflozin - Dapagliflozin (Farxiga) is contraindicated in this patient due to hyperkalemia which could be made worse by this drug. The package insert does not indicate a specific potassium concentration cut off to no longer use this medication; however, there are better choices in this patient. Sitagliptin - Sitagliptin (Januvia) is able to obtain an A1C goal of less than 7% based on clinical trials and currently the patient does not have any cautionary objective measures to not use this medication. DPP-IV inhibitors are weight neutral. DPP-IV inhibitors can be used in patients taking sulfonylureas; however, it may be recommended to reduce or stop the sulfonylurea dose. Acarbose - Acarbose (Precose) is not recommended for initial management and is associated with significant GI side effects. More information would be needed regarding fasting and post-prandial numbers. In addition, adding acarbose would only lower A1c by 0.8% at best and therefore would not achieve the desired A1C goal of <7% JR is a 68-year-old African American man with a new diagnosis of T2DM. He was classified as having prediabetes (at risk for developing diabetes) 5 years before the diagnosis and has a strong family history of type 2 diabetes. JR's blood pressure was 150/92 mm Hg. His laboratory results revealed an A1C of 8.1%, normal cholesterol panel, and normal renal/hepatic function were noted with today's laboratory test results. Past medical history: Hypertension (diagnosed 4 y ago) Hyperlipidemia (diagnosed 2 y ago) Pancreatitis (idiopathic) (acute hospitalization 3 y ago) Family history: Type 2 diabetes Medication: HCTZ 25 mg daily, simvastatin 10 mg daily Allergies: SMZ/TMP Vitals: BP: 150/92 mm Hg P: 78 beats/min RR: 12 rpm Waist Circumference: 46 in Weight: 267 lb Height: 5 ′ 6 ″ BMI: 43.1 kg/m 2 Despite improvements in the past six weeks due to lifestyle changes and exercise, drug therapy is to be started for JR's diabet - ANS Metformin is the drug of choice recommended for most patients with diabetes in addition to lifestyle modifications assuming no contraindications or intolerabilities are present upon evaluation. Metformin has also shown to provide positive weight neutral/loss effects in obese patients. It is crucial to know the renal status of patients commencing metformin therapy to limit the risk of lactic acidosis (JR is without contraindication). Since his entry A1C is >7.5%, dual therapy is indicated. There are several potential choices. The second step can be a dipeptidyl peptidase-4 inhibitor, it can be a glucagon-like peptide-1 (GLP-1) receptor agonist, it can be a TZD, it can be a sulfonylurea agent, it can be a SGLT2 inhibitor, or it could be basal insulin. Anything next can be tried depending on what suits the circumstance DPP4 inhibitors are weight neutral bet relatively benign side effect profile. Sitagliptin has been associated with case reports of pancreatitis, so this specific agent should be avoided. $$$ GLP-1 analog and has data to support an A1C reduction necessary to gain glycemic control and may assist with weight loss goals for this patient. New information suggests these agents may provide benefits in those with ASCVD. JR has a past history of pancreatitis and GLP-1 analogs are not recommended due to this contraindication TZDs have data to support an A1C reduction necessary to gain glycemic control, but are associated with weight gain, negative effects on lipids and increased risk of fracture. Until recently, TZDs have also been linked to increased CV events and use has fallen out of favor Sulfonylureas provide excellent A1C lowering, but are also associated with weight gain. They also have the potential to cause hypoglycemia, so patient education is crucial. Because of his allergies to "sulfa", use would be contr A patient with type 1 diabetes reports taking propranolol for hypertension. What concern does this information present for the provider? - ANS A patient with Type 1 DM is insulin dependent for glucose control and at high risk for hypoglycemic episodes. Propanolol causes prolonged hypoglycemic episodes. Needs to switch to ACE or ARB. A provider teaches a patient who has been diagnosed with hypothyroidism about a new prescription for levothyroxine. Which statement by the patient indicates a need for further teaching? a. "I should not take heartburn medication without consulting my provider first." b. "I should report insomnia, tremors, and an increased heart rate to my provider." c. "If I take a multivitamin with iron, I should take it 4 hours after the levothyroxine." d. "If I take calcium supplements, I may need to decrease my dose of levothyroxine." - ANS D. Calcium may reduce levothyroxine absorption. Further education is needed if the patient feels she can take half of a prescribed medication. MC has undiagnosed multiple gastric ulcers. Shortly after consuming a large meal and alcohol he experiences significant GI distress. He takes an OTC heartburn remedy. Within a minute or two he develops what he will later describe as "belching, nausea and a bad bloated feeling". Several of the ulcers began to bleed and he becomes profoundly hypotensive from the blood loss and is taken to the ED. Endoscopy confirms multiple bleeds; the endoscopist remarks that it appears as if the lesions had been literally stretched apart causing additional tissue damage. What did the patient most likely take (i.e. what was the OTC remedy)? - ANS I would accept Alka-Selzer. I contains NaHCO3 (as well as ASA). In the presence of HCL it Liberates CO2, that can cause gastric distention, belching and nausea. The reaction is fairly swift allowing little time for dissipation. Tums, its primary ingredient calcium carbonate which when taken cause a reaction with the stomach acid such as production of carbon dioxide gas which can cause bloating and the stomach to stretch to tear the ulcers open. On your way to this examination, you experience the vulnerable feeling that an attack of acute diarrhea is imminent! If you stop at a drug store, which anti-diarrheal drugs could you buy without a prescription even though it is chemically related to the strong opioid analgesic meperidine (but acts only on the peripheral opioid receptor)? - ANS Loperamide JA has multiple medical problems and is taking several drugs including theophylline, warfarin and phenytoin. His conditions were well controlled, but recently he started to experience some GI distress for which of his "well intentioned friends" gave him some medication. He presents to you with toxic effects of all his other medications and plasma levels of those medications elevated. What was most likely the medication he took? - ANS Cimetidine What lifestyle modifications should be recommended? - ANS -losing weight if overweight -elevating head of bed while asleep -eating smaller meals -avoid foods/meds that exacerbate gerd -stop smoking -stop drinking alcohol What medications / foods can contribute to GERD? - ANS -Medications: anticholinergics, barbituates, dopamine, estrogen, opioids, progesterone, theophylline, nitrates -Foods: cirus fruits/juices, coffee, tomatoes, spicy food, carbonated drinks Fried/fatty foods, garlic, onions, chocolate What is the most effective PPI or H2RA within each of these classes? - ANS -PPI- bismuth quadruple therapy combined with proton pump inhibitors -H2RA- Famotidine 80mg Other products such as antacids are also available. What are some of these and what is their place in therapy? - ANS -Reflux symptoms <2 times a week (infrequent) -Effective for immediate relief -Magnesium/Aluminum Hydroxide (Maalox)- can cause constipation -Alginic Acid Why would antibiotics be used for PUD caused by H Pylori? What is a typical regimen and duration of therapy? What patient specific factors should be considered and how should treatment be monitored? - ANS Considerations before regimen choice: -penicillin allergy -previous exposure to macroglide antibiotics Strongest Reccomendation: -Bismuth Quadruple Therapy 10-14 days *do not drink alcohol w/ metronidazole* -Salvage regimen should be different than first regimen Who would be a candidate for prophylaxis of NSAID induced ulcer and what agents are appropriate? What if the patient is on cardio-protective (low dose) aspirin? What if an NSAID induced ulcer does develop. How should it be treated? - ANS Candidate: -Candidates: Chronic Nsaid Use, Hx ulcers, Zollinger-Ellison Prevention Treatment- PPI, standard doses (most effective & best tolerated), Misoprostol (better than H2RA's, No Pregnancy) What if an NSAID induced ulcer does develop. How should it be treated? - ANS Ulcer Treatment- -PPI (most effective) -H2RA (Famotidone 40mg daily) -Sucralfate (binding paste, requires multiple doses, adverse med reactions, abdominal side effects) Who is a candidate for stress ulcer prophylaxis (SUP)? - ANS -ICU patients -Trauma, including spinal cord injuries -Mechanical ventilation -Thermal injuries >35% (almost half the body) Of the agents available to control the complications of diabetes mellitus, cardiovascular drugs, and particularly ACE inhibitors, have a pre-eminent place. Experimental and epidemiological data suggest that activation of the renin-angiotensin-aldosterone system plays an important role in increasing in the micro- and macrovascular complications in patients with diabetes mellitus. Not only are ACE inhibitors potent antihypertensive agents but there is a growing body of data indicating that also they have a specific 'organ-protective' effect. For the same degree of blood pressure control, compared with other antihypertensive agents, ACE inhibitors demonstrate function and tissue protection of considered organs. ACE inhibitors have been reported to improve kidney, heart, and to a lesser extent, eye and peripheral nerve function of patients with diabetes mellitus. These favorable effects are the result of inhibition of bo - ANS There is a "compelling" indication in patients with hypertension and DM. These should be the 1st class of antihypertensive medications used in those with DM + HTN Recommended for the treatment of the patient with CKD (modestly elevated (30-299 mg/24 h) or higher levels (>300 mg/24 h) of urinary albumin excretion), even in those without DM Delay progression of nephropathy in Type 1 with or without HTN and any degree of albuminuria Delay progression of nephropathy in Type 2 with or without HTN and microalbuminuriaReduce development of microalbuminuria (kidney disease) in Type 2 with or without HTN ARBs are considered a reasonable alternative for those intolerant of ACEI - ANS