Advanced Pharmacology Midterm Exam with complete solutions.

Chapter 28 Additional patient variables: Angina and Concomitant Diseases and drugs to treat them Angina and Myocardial Infarction aspirin and beta blockers *ACE inhibitors are the drug of choice to treat angina in patients with diabetes or left ventricular dysfunction. Angina and Heart Failure ACE inhibitors are first line patients who cannot tolerate ACE inhibitors are being prescribed ARBs Hypertension and Angina lifestyle modifications are the first approach to treatment for patients with emphasis placed on weight control, reduction of sodium, saturated fat, cholesterol, and alcohol and increased physical activity. All drug classes used to treat angina are helpful in the treatment of hypertension. ACE inhibitors and direct renin inhibitors are useful in blood pressure control based on their vasodilating effects Beta blockers are no longer first line therapy in hypertension and CCBs are acceptable for patients with HTN especially African Americans Hypercholesterolemia Patients should strive for LDL levels less than 100mg and less than 70mg in the very high risk patients (diabetic, smoker, etc) lifestyle modifications are the first line approach. Beta blockers can negatively affect triglyceride and LDL levels Peripheral Vascular Disease BB's are contraindicated in patients with severe PVD. CCB's are the drug of choice for patients with angina and PVD Diabetes Mellitus Diabetic patients with angina should make every attempt to have a near normal A1C ACE inhibitors are drug of choice CCBs are also useful because of their lower effects on glucose metabolism, and they also may have some degree of renal protection BB's may mask the signs of hypoglycemia Asthma and COPD BBs may exacerbate disease but should only be avoided if the patient has severe or uncontrolled disease Erectile Dysfunction related to endothelial dysfunction and vascular damage similar to HTN and angina *treatment of HTN has also been associated with ED and may affect patient compliance (BB's and thiazide diuretics are the drug classes most associated with ED) **Nebivolol is a BB least likely to cause ED and may even improve ED symptoms ***ED meds (Viagra, Cialis) used in combination with nitrates can cause severe vasodilation resulting in hypotension and syncope. Chapter 28 Beta Blockers and Diabetes Mellitus beta blockers decrease insulin secretion and may mask the signs of hypoglycemia. The one sign that is not masked is diaphoresis, and patients with diabetes who are taking these drugs should be taught to test their blood glucose levels in the event of a diaphoretic episode. 00:02 01:17 Chapter 36 Treatment for Stage A Heart Failure initial focus is on reversing underlying pathologies. -lifestyle modification and avoidance of behaviors that may increase risk: smoking, poor diet, obesity, sedentary lifestyle, alcohol or drugs Drug therapy: ACE inhibitors recommended for patients with a history of atherosclerotic vascular disease, diabetes mellitus, HTN. Definitely start ACE inhibitor and possibly add a BB BB are also recommended to control HTN and prevent HF Treatment of Stage B heart failure Drug therapy is ACE inhibitor and beta blocker. If patient was already on a BB for HTN or angina, provider can leave them on the same med or switch it to a diff one Treatment of Stage C heart failure This is the first stage to be symptomatic *most of HF patients are at this stage all of the Class I recommendations for stage A and B are appropriate here * in addition moderate sodium restriction along with daily weight monitoring are indicated to facilitate the most effective use of drugs -Combination of 3 to 4 types of drugs: ACE inhibitors, BB's, cardiac glycosides (digoxin), and a diuretic Stage C patients who remain symptomatic despite optimal treatment therapy patients who remain symptomatic despite therapy with ACE inhibitors and beta blockers it is recommended to start aldosterone antagonists (spironolactone) per the NICE guidelines Dosing of diuretics goal with dosing is to increase the urine output and promote weight loss of 0.5 to 1 kg daily concurrent administration of NSAIDs can affect absorption of diuretics **is symptoms seem resistant to to standard doses of diuretic check creatinine clearance Digoxin indications used in patients with reduced systolic dysfunction (ejection fraction 40%) while receiving standard therapy with a BB and ACE inhibitor. The decision to begin patient on digoxin should only be made when there is clear evidence of systolic dysfunction Treatment for Stage D Heart failure these are patients with refractory end-stage HF -marked symptoms even at rest despite maximal medical therapy -ACE inhibitors and BB's in small doses these drugs are contraindicated if systolic BP is 80 or who show signs of peripheral hypoperfusion -referral to cardiac transplantation and heart failure program -infusions of vasoactive and positive inotropic agents are not recommended for these patients Patients with HF with preserved Ejection Fraction (HF-pEF) -half of the population have HF-pEF limited evidence to show benefit of ACE inhibitors and BB's -main underlying causes of HF-pEF include HTN and CAD, treatment should target these causes **As with all HF patients diuretics should be given in the presence of volume overload to improve symptoms **ACE inhibitors should be considered in diabetic patients and one additional risk factor or those with symptomatic atherosclerotic cardiovascular disease **Beta blockers should be used in all patients with prior MI or AFib requiring control of ventricular rate First line drugs of choice for heart failure ACE inhibitor, Beta blockers, diuretic MOA of ACE inhibitors that benefit heart failure ACEIs affect both preload and afterload through their vasodilating effects -decrease the incidence of remodeling by reducing the local generation and action of angiotensin II in heart muscle -prevent neurohormonal counterregulatory mechanisms that worsen HF through their action on the R-A-A system Patients taking ACEI's experience: -moderate increase in ejection fraction -decreased left-ventricular end diastolic filling pressures and improved myocardial energy metabolism Indications for use of beta blockers in patients with heart failure should be given to all patients with a recent or remote history of MI regardless of ejection fraction or presence HF -these drugs improve ventricular function through their action on the HF counter-regulatory mechanisms and have cardioprotective properties Drugs contraindicated in heart failure CCBs Drugs that increase the life expectancy in patients with heart failure two drugs in the aldosterone antagonist class (spironalactone and eplerenone) when added with a loop diuretic and an ACE inhibitor can increase the life expectancy Drugs for managing heart failure during pregnancy ACE inhibitors are contraindicated during pregnancy. It is best to avoid any drug for HF during pregnancy unless the benefits clearly outweigh the risk-- BB's are considered safe in later pregnancy Patient monitoring of heart failure 1. functional capacity, chiefly using the NYHA class, specific QOL questionnaires, or a maximal exercise test 2. Assessment of fluid status (daily weights, jugular venous distension, lung crackles, hepatomegaly, peripheral edema, and orthostatic BP) 3. Assessment of cardiac rhythm, by clinical exam (12 lead may be useful if arrhythmia is suspected) Holter monitor is class IIb and could be considered in patients who have a history of MI 4. lab assessment, including electrolytes and serum creatinine and urea with special attention to potassium and sodium Indications to use anticoagulant therapy for patients who have concomitant atrial fibrillation. Patient education for heart failure -lifestyle management and exercise instruction -information to specific drug therapy and reasons for the drug taken -all patients should be encouraged to get annual influenza vaccine -pneumococcal immunization should be provided at the diagnosis of HF if not previously vaccinated **For older adults if initial vaccination was at 65 years or younger, revaccination at 65 years or 5 years after initial immunization whichever is later should be done Chapter 40 Classes of Drugs used and their MOA's ... Nitrates nitrates provide more nitric oxide to vascular endothelium and arterial smooth muscle resulting in vasodilation. All parts of the vascular system (from larger arteries to large veins) relax in response to nitrates -increases the O2 supply to the heart Beta Blockers Binds with receptors on the heart at the SA node to decrease heart rate, in the atria and ventricle to decrease contractility, and conduction velocity, and at the AV junction to slow conduction Decrease the incidence of angina, decrease cardiac rhythm disturbances associated with rapid rhythms Calcium Channel Blockers directly block the influx of calcium at the onset of the cycle relax smooth arterial muscle -significant reduction in afterload -reduction in contractility ACE inhibitors MOA Inhibit ACE-- decrease angiotensin II-- decrease GFR (prevent constriction of efferent arteriole) Increasing levels of renin (loss of feedback) ACE inhibition-- prevents inactivation of bradykinin (vasodilator) Which drugs increase myocardial oxygen supply Nitrates, BBs, and CCBs Causes of hypertension primary HTN has no identifiable cause Which drugs to treat hypertension & BPH, MI, heart failure in African Americans? ... Chapter 1 ... Roles and responsibilities of APRN prescribers As of January 2015: -all states have title protection for NPs -only Oregon has mandated third-party reimbursement parity for NP services -only five states have joint control of practice and licensure between the board of nursing and board of medicine -in 17 states and the District of Columbia NPs have independent scope of practice and prescriptive authority -six states have full autonomous practice and prescriptive authority following a period of postlicensure/post-certification supervision or collaboration Advanced Knowledge The APRN role requires advanced knowledge to diagnosis, prescribe the appropriate drug, monitor the expected outcome, and incorporate a holistic assessment of the impact of disease and therapy on patient lives Clinical judgment in prescribing -Is there a clear indication for drug therapy? -What drugs are effective at treating this disorder? *The Agency for Health Care Quality (AHCQ) and the National Institutes of Health (NIH) publish disease specific treatment guidelines that include both pharmacological and nonpharmacological therapies -What is the goal of therapy with this drug? -Under what conditions is it determined that a drug is not meeting the goal and a different therapy or drug should be tried? **consider concurrent disease processes -Are there unnecessary duplications with other drugs that the patient is already taking? -Would an over the counter drug be just as useful as a prescription drug? -What about cost? -Where is the information to answer these questions? Chapter 1 Autonomy and Prescriptive Authority By January 2004 all states had recognized the NP title scope of practice and prescriptive authority in legislation - As of 2015 26 states allow independent practice and 21 states allow independent full prescribing (these are not written in stone and can be reversed) Chapter 2 ... Types of drug responses quantal and graded quantal: may or may not occur (convulsions, pregnancy, rash, sleep, death) graded: biological effects that can be measured (BP, heart rate, pain) Metabolism -important factor in determining drug activity -when drugs are metabolized, they are chemically altered by enzymes into new molecules, called metabolites -can increase or decrease the onset, duration of action and toxicity of a medication Where does metabolism of drugs occur? mostly in the smooth endoplasmic reticulum of cells in the liver -metabolism of drugs however can occur un every biological tissue **the liver is a major organ for drug metabolism because it contains high amounts of drug-metabolizing enzymes and because it is the first organ encountered by drugs once they are absorbed from the gastrointestinal tract First-pass metabolism Metabolism by the liver following oral administration of a drug. And is important in determining whether a drug can be orally administered Phase I Metabolism Oxidation, reduction, hydrolysis - also called non-synthetic reactions -many phase I metabolites are rapidly eliminated, whereas others go on to phase II reactions Phase II Metabolism also called synthetic or conjugation reactions because drug molecules are metabolized and something is added to the drug to synthesize a new compound -makes the metabolites more water soluble and more easily secreted by the kidneys Cytochrome P450 This reaction catalyzes the metabolism of a large number of diverse drugs and chemicals that are highly lipid soluble. **We inherit drug-metabolizing enzymes from our parents CYP34A prominent enzyme that is responsible for metabolism of a number of drugs metabolism and half life drugs tend to be administered at dosing intervals that are close to their half-life blood levels decrease 50% in one half-life -75% in 2 half-lives -and 87.5% in 3 half-lives Receptors Agonists drugs that produce receptor stimulation and a conformational change every time they bind. -do not need all of the available receptors to produce a maximum response (left over receptors are called spare receptors) Antagonists drugs that occupy receptors without stimulating them. -occupy a receptor site and prevent other molecules, agonists, from occupying the same site and producing a response -produce no direct response -the response we see following administration of antagonists results from their inhibiting receptor stimulation by agonists Pharmacokinetics ... Absorption greatest with IV injection- immediate drug action and complete absorption- disadvantage is once administered it can not be slowed or removed. Oral- most convenient and most common. Most go through a number of steps on the way to the bloodstream: stomach, small intestine, large intestine on their way to the colon. They then pass through the lining of the intestines to enter the systemic circulation. Once absorbed they travel to the liver where they may be metabolized on their way to the bloodstream. **Sublingual and buccal allow drugs to have a more rapid onset to avoid liver metabolism. Ophthalmic preparations sterile preparations, that are buffered and isotonic so they do not cause discomfort **Aural (ear) preparations do not meet the requirements for administration into the eye Distribution once the drug is absorbed it still must reach its site of action to produce effect. -can occur by transfer through the bloodstream, passive diffusion, or by transport systems Protein binding drugs can bind to a variety of proteins that are present in the bloodstream. These are often called plasma proteins -many plasma proteins are produced in the liver and their presence in the blood reflects liver function, nutritional status, and the effect of aging and disease. *Albumin is a major protein in the blood and is measured as part of a typical blood analysis. Binding to plasma proteins drugs bound to plasma proteins can freely circulate in the bloodstream rather than be distributed by passive diffusion from their site of absorption, so plasma protein binding helps normalize concentrations throughout the body. -drugs that are bound to plasma proteins can be protected from metabolism in the liver and from excretion by the kidneys, so plasma protein binding can extend the period of time that drugs can remain in the body What can alter plasma proteins? Disease states: Poor nutrition Cancer liver disease MI Stress infection Proteins/Drug interactions binding to proteins is also the basis for a number of drug interactions (pg 21). Drugs bound to plasma proteins cannot interact with their receptor. Ex: Warfarin is about 98% bound to plasma proteins; this means only 2% of the drug is unbound and available to produce a pharmacological effect. If a second drug is taken that binds to plasma proteins and displaces even a small fraction of the Warfarin it can have a dramatic effect. Excretion Renal The kidney is the primary organ of excretion for most drugs *general theme of metabolism is to produce drug metabolites that are more water soluble and more easily removed by the kidneys -the kidney can then remove these substances from the plasma and excrete them in the urine Biliary excretion in addition to metabolizing many drugs, the liver secretes about a liter of bile a day. -drugs can enter the bile and be excreted into the intestinal tract when bile is released to help digest food -only small amounts of drugs enter the the bile by diffusion digoxin is an example of a drug secreted into the bile enterohepatic cycling when drugs are excreted in bile and reabsorbed in the intestine -decreases the amount of drug that is actually excreted and extends the time that a drug remains in the body Chapter 3 ... Process of rational drug prescribing: 6 steps proposed by WHO Step 1: Define the patients problem Step 2: Specify the therapeutic objective Step 3: Choose the treatment Step 4: Start the treatment Step 5: Educate the patient Step 6: Monitor the patient Patient education should include- the purpose of the medication, instructions of administration, and potential adverse drug effects -should be tailored to the patient and presented in plain english (5th or 6th grade reading level) with an understanding that 9 out of 10 adults have difficulty reading health information Monitor Effectiveness The WHO model describes two types of monitoring: passive and active Passive monitoring occurs when the patient is educated on the expected outcome of the drug therapy and is instructed to contact the provider is the treatment is not effective or if adverse drug effects occur (common with antibiotics) Active monitoring occurs when the provider schedules a follow-up exam to determine the effectiveness of the drug therapy Factors influencing drug selection Bioavailabilty -metabolism of a drug (for example one excreted exclusively by the kidneys would be avoided in renal patients) -drug half-life to determine dosing schedule -drug safety (taking into consideration your specific patient) -Cost (both to the patient and the health care system) Patient factors/Drug selection patient factors that may affect prescribing include drug adverse effects that influence adherence, health beliefs, values, and current drug therapy that may interfere with the new drug -unnecessary duplications with other drugs -patients age -pregnancy -mental health diagnosis beta blockers have adverse drug reactions (ADRs) that include anxiety, depression and mental status changes. The drugs in this class that have a higher central nervous system penetration are more likely to have these ADRs. If a BB is to be prescribed for a patient with mental illness it is best to use one that is less lipophilic because this subset of the drug class is less likely to exhibit these ADRs Chapter 4 ... New drug approval process on average it costs a company approx $2.6 billion to get one new med from the lab to the shelf pre-clinical research biological screening and pharmacological testing use nonhuman studies to explore the activity and therapeutic potential of compounds. These tests involve the use of animals, isolated cell cultures and tissues, enzymes, and cloned receptor sites as well as computer models Clinical Studies an investigational new drug (IND) application is filed with the FDA prior to human testing. The IND application is a compilation of all known info about the compound. Unless the FDA says no the clinical tests can begin 30 calendar days after submission. Phase I: the first testing of a new compound in subjects for the purpose of establishing the tolerance of healthy human subjects at different doses; studying its absorption, distribution, metabolism, and excretion patterns in humans Phase II: is controlled studies performed on patients with the target disease or disorder to determine a compound's potential usefulness and short-term risks. A relatively small number of patients usually no more than several hundred subjects are enrolled in Phase II studies. Phase III: are uncontrolled and uncontrolled clinical trials of a drug's safety and efficacy in hospital and outpatient settings. gather precise information on the drug's efficacy for specific indications, determine whether the drug produces a broader range of adverse effects than those exhibited in the small study of populations of phase I and II studies and identify the best way of administering and using the drug for the purpose intended. Conditions of an Investigational New Drug (IND) while an IND is in effect the sponsor must report in writing to the FDA within 10 working days any serious and unexpected adverse reactions that may be drug related. Official labeling the legal distinction between a legend drug and an OTC drug is determined by a regulatory decision on whether adequate directions for the drugs proper use can be written for the layperson Off-label Use use of medications for indications other than their FDA approved use. Some insurance and medicare rarely cover prescriptions written for off-label use Chapter 5 ... Adverse Drug Reactions ADRs Pharmacological often predictable based on the drug's mechanism of action and is typically dose-related. -more common and compromise approx. 85% to 90% of reported ADRs (ex: hypotension from BB metoprolol, or flatulence from the fiber supplement psyllium) **Preclinical trials are now focusing on secondary adverse effects to predict what may occur when the drug is administered to humans Idiosyncratic Reactions unpredictable and may be more likely to result in mortality. Mediated by the immune system, receptor abnormalities, drug-drug interactions, abnormalities in drug metabolism, pharmaceutical variations, or unmasking of an abnormal biological system Most often these are mediated by the immune system when a drug molecule is recognized as a foreign substance Hapten Hypothesis describes how drugs may cause an immune-mediated hypersensitivity reaction The hypothesis suggest that drugs are haptens, that is, low-molecular-weight chemicals that can become antigenic when they covalently bind to a carrier molecule, which is usually a protein. Through this mechanism, individual patterns of metabolism may generate reactive metabolites that act as haptens to elicit an immune-mediated reaction. **Penicillin is an example of a hapten with a low molecular weight that is able to bind to a protein and result in a Type I hypersensitivity (anaphylaxis) reaction Immune-Mediated Adverse Drug Reactions Type I- IgE- mediated, immediate-type hypersensitivity Example: angioedema and anaphylaxis Type II- Antibody- dependent cytotoxicity Example: heparin-induced thrombocytopenia Type III_ Immune complex hypersensitivity Example: Arthus reaction to tetanus vaccine Type IV- Cell-mediated or delayed hypersensitivity Example: Drug rash, Eosinophilia and Systemic Syndrome ADRs Types A-F Type A are equivalent to pharmacological reactions and account for 85% to 90% of ADRs, are dose-dependent, and are predictable, where-as Type B reactions are idiosyncratic, account for 10%-15% of ADRs, are not dose-dependent and are not predictable. Type C result from chronic medication use Type D are delayed Type E are from drug-drug interactions Type F result from treatment failures