Exam 1 Blueprint Pharm.PDF

Exam 1 Blueprint Students will be given 75 minutes for the exam. The following information should help you focus your studying. Some questions bridge different content areas so the numbers of questions in each category are approximate, but fairly accurate. For example, a scenario might require you...

Exam 1 Blueprint Students will be given 75 minutes for the exam. The following information should help you focus your studying. Some questions bridge different content areas so the numbers of questions in each category are approximate, but fairly accurate. For example, a scenario might require you to demonstrate your knowledge of pharmacokinetics when treating an older adult patient. Overall, the blueprint is a good representation of the material you’ll be tested on. Good luck! Content – Pharmacology of… # of Notes Questions Pharmacokinetics/ 9 · ​ Understand basic concepts such as Pharmacodynamics (PK/PD) first-pass metabolism, half-life, bioavailability, therapeutic index, steady state Pharmacokinetics (PK): what the body does with the drug, doses are determined by PK. Consists of: 1.​ Absorption: How well the body uptakes the drug. Movement of drug to blood from the site of admin 2.​ Distribution: how well the drug is transported to the site of action a.​ Volume of distribution (Vd): how much drug is circulating in the body/serum i.​ Drugs stay in bloodstream = low Vd ii.​ Drugs distribute widely (muscle/fat/BBB) = high Vd iii.​ The more unbound the drug is in the blood, the more it is distributed to tissues = higher Vd b.​ Only unbound/free drug can exert effect on the body c.​ Factors in distribution: i.​ Route of admin ii.​ Blood flow  iii.​ Lipid solubility increases transport through capillary walls and placenta iv.​ Blood brain barrier (dependent on the lipid solubility) v.​ Level of protein binding: may increase free/unbound concentration in the blood = more effect 1.​ The more protein bound the drug, the less it can distribute in the body well vi.​ pH 3.​ Metabolism: drug is transformed to be more excretable/conversion of drug into more water-soluble form (hydrophilic) in order to be excretable a.​ Usually involves liver b.​ Parent drug: initial drug before it goes through metabolism. Can be active or inactive c.​ Pro-drug/inactive: an inactive drug that needs to be metabolized into its active form (active metabolite) 4.​ Elimination: how well the drug is cleared from the body First pass metabolism: Drug is metabolized hepatically before it reaches the systemic circulation a.​ common in PO admin b.​ Transdermal avoids first pass c.​ If drug goes through significant first pass effect = need higher dose Half-life: Time for half of the total drug to be eliminated from the body -longer half life = stays in body longer, smaller dose -shorter half-life = more frequent dosing Bioavailability: proportion of drug dose that reaches systemic circulation a.​ IV drugs are 100% bioavailable b.​ bioavailability is affected by how well the drug is absorbed; some may not be absorbed due to enzymes in the liver/GI or secreted back into GI via proteins. Low solubility/low permeability plays a role. Therapeutic index: ratio between therapeutic effect to lethality of given amount. a.​ Higher ratio is better i.​ Ex: dose with undesirable effect/dose with desirable effect is 5:1 1.​ This is a good choice because you need 5x the given dose to be lethal/toxic 2.​ 1:1 = overdose/toxic 3.​ 2:1 = some chemo drugs have this ratio Steady state: amount of drug absorbed = amount of drug cleared. This is reached at 3-5 half-lifes. a.​ Example: sertraline half life is 26 hours. How long does it take to eliminate the drug from the body? -use average 4 half lifes -4x26/24 = 4.3 days Steady state concentration curve ​ Peaks = highest level of plasma concentration ​ Trough = lowest level of plasma concentration ​ Steady state achieved at 3-5 half lives (average of 4)  · ​ Know Phase I/II reactions and their purposes, changes over the lifespan Phase I (non synthetic reactions): Occrs via oxidation(CYP enzyme system)/ reduction/hydrolysis. a.​ Drugs can skip Phase I if they already have polar molecule groups b.​ Effect of Phase I: i.​ water soluble metabolites ii.​ chemically active compounds iii.​ substrates for Phase II c.​ Drugs can skip Phase I and go straight to Phase II i.e. Morphine Phase II (synthetic or conjugate reactions): Add hydrophilic (water soluble) groups to parent drug or Phase I metabolized drugs via glucuronidation. a.​ Effect of Phase II: i.​ makes drug inactive or active (if prodrug) ii.​ Makes drugs excretable as water-soluble compounds · ​ Understand PD at the receptor level Pharmacodynamics (PD): what the drug does to the body aka effect of drug via receptors/lock and key mechanism 1.​ Drug receptors:  a.​ Ion channels: sodium/potassium b.​ G protein: downgrade over time, play a role in rebound phenomenon (side effects that occur d/t suddenly stopping a med or reducing dose. These side effects were previously controlled by the drug) c.​ Transmembrane receptors: bind active hormones i.e. insulin, growth factors d.​ Intracellular receptors via DNA transcription (drug -> DNA -> RNA -> protein): i.e. corticosteroids, thyroid hormone, vit D e.​ Enzymes: drugs may inhibit or active enzymes i.e. statins, antibiotics 2.​ Drug response: a.​ Graded: dose-response curve. Most drugs the higher the dose the greater the response b.​ Quantal: rate of those within a certain population with a response; the response is present or not present 3.​ Drug actions a.​ Agonist: elicit a response when the drug binds to the receptor b.​ Antagonist: blocks receptor/ binding to the receptor does not allow a response c.​ Partial agonist: binds to and partially activates a receptor. When in presence of a full agonist it has antagonist qualities (receptor binding reduces response). · ​ Understand the components of the concentration-time curve  Onset time: drug starts to take effect MEC: minimum effective concentration MTC: therapeutic max/min toxic concentration, over this is toxic cMAX: peak concentration tMAX: time to peak concentration AUC (area under the curve): represents drug concentration in the body Prescribing 3 · ​ What are P-drugs/treatments? P-drugs: first line drug, well tolerated, most effective, “go-to”drug of prescriber. Drug of choice for a given condition. a.​ Is NOT the drug for an individual pt b.​ Drugs with high therapeutic index (TI) are ideal P-treatment: first line non=pharmacological approach · ​ Demonstrate ability to calculate correct pediatric doses 1.​ Usually weight based dosing- in kg 2.​ Initial dosing: (body surface area x adult dose)/1.73 m² = dose 3.​ PK varies by weight 4.​ BSA used to determine clearance · ​ Know basic components of a complete prescription Complete prescription:  1.​ Full name, title, address, and business hours phone number 2.​ Patient name and date of birth/pt address 3.​ Date that script was written 4.​ Rx: Drug name and strength 5.​ Sig: explicit directions for use 6.​ Disp: total amount of drug to be given from pharmacy 7.​ Diagnosis: use medical code for diagnosis for controlled substances only 8.​ Refills: write out number beside numerical number 9.​ DAW (dispense as written)- box to be checked if necessary 10.​Signature and DEA number Older adults 2 · ​ Understand physiologic changes with aging and their effects on pharmacokinetics Changes with aging: 1.​ Key points: a.​ Decreased kidney function b.​ Decreased clearance vis kidney and lungs c.​ Absorption: delayed gastric emptying/slowed GI motility d.​ Hepatic drug metabolizing with CYP450 system reduced by 30% e.​ Reduced liver function = inactivation of meds is reduced  f.​ Reduced renal elimination = reduced clearance 2.​ Absorption: rate is slowed a.​ Ex: effect on pH with use of PPIs 3.​ Distribution: a.​ increased body fat = increased drug storage b.​ Decreased body water compensation = increase of drug composition c.​ Decreased protein binding in plasma d.​ BBB permanently diminished 4.​ Metabolism: a.​ Decreased metabolism and decreased clearance of drugs d/t decreased liver size and blood flow b.​ Phase I CYP system decreased with age = slows onset of prodrugs and slows metabolism of active drugs c.​ Phase II uneffected 5.​ Excretion: a.​ Decreased renal clearance = increased adverse side effects b.​ Serum creatinine lower c.​ If drug is requires renal elimination, assess renal function Polypharmacy: taking 5 or more medications/more than 1 med per indication -medication reconciliation important Prescribing cascade: prescribe med for disease/disorder -> patient gets side effects -> treat side effects of med -you start to treat the side effects, not the initial problem BEERS drugs: list of meds for patients over 65 years old that carry increased risk of interactions, confusion, falls, side effects, toxicity (does not apply to end of life care). Pediatrics 2 · ​ Know physiological variation in infancy and childhood and implications for PK Physiological variations: 1.​ Neonates: 0-28 days a.​ Increased permeability of BBB b.​ Absorption: i.​ hepatic, pancreatic, and biliary systems slowed ii.​ Increased absorption of drugs absorbed in stomach, delayed/ reduced adoption in intestines iii.​ IM absorption slowed in neonates c.​ Clearance: low renal clearance = a lot of drug in system = toxicity risk 2.​ Infants: >28 days to 12 months a.​ Intestinal absorption increased due to increased blood flow to muscles, toxicity risk b.​ Transdermal absorption enhance in infants = increased risk toxicity of topical meds c.​ Increased body fat = decreased volume of distribution of lipophilic drugs d.​ Water accounts for greater percentage of body weight = higher dose of hydrophilic drugs required e.​ Less protein binding in infants until 10-12 months = increased distribution, so reduce dose as it is toxicity risk f.​ BBB not fully developed g.​ Great variability of metabolism i.​ Phase II metabolism reduced h.​ Elimination of drugs slowed 3.​ Children 1 or older: a.​ PK similar to adults  b.​ Faster drug metabolism (declines at age 2) = increased dosage and change in dosing interval 4.​ IN GENERAL: a.​ Immature drug absorption, protein binding, BBB, liver and renal function b.​ Organs not fully developed = low clearance = higher drug levels/prolonged effects c.​ Minimum effective concentration (MEC) longer with prolonged effects d.​ Adverse effects due to immature organs Ethics, Adherence, 3 · ​ Be able to application ethical Pharmacoeconomics principles to your role as a prescriber 4 ethical principles: 1.​ Justice: benefits and consequences should equitable, based on pt needs 2.​ Nonmalificene: do no harm 3.​ Autonomy: patient makes informed decisions (from pt education), consent is important. Acknowledge that the patient has the ability to make a decision we may not agree with. 4.​ Beneficence : do good, maximizing benefits and making efforts to enhance well-being Influence on prescribing: 1.​ Positive: a.​ Guidelines, policies, algorithms b.​ evidence /research c.​ Effectiveness d.​ cost 2.​ Negative: a.​ habit/custom b.​ P drugs c.​ Influence by peers, colleagues, and leaders d.​ Incentives  e.​ Lack of knowledge about alternatives · ​ Understand adherence Adherence: ratio of the number of drugs taken to the number of doses of a drugs prescribed aka medication possession ratio (MPR) a.​ Factors of adherence: cultural/personal beliefs, personal history, economic status, SDOH, literacy/education, adverse side effects, chronic conditions, is pt symptomatic?, polypharmacy b.​ Improving adherence: lowest number of doses per day, least expensive med, least side effects, effective communication, find mutual agreement, link med times with daily routine c.​ Non-adherence = bad patient outcomes i.​ Prevent non-adherence with education d.​ Improving adherence in pediatrics: give smallest amount of med concentration, provide written instructions, reminders/calendars, positive reinforcement · ​ Goals of pharmaco-economics Pharmaco-economics: assesses health care outcomes and cost in relation to using or not using healthcare good, services, or programs (Helps with determining drug coverage) a.​ Whos involved/perspectives: i.​ Society ii.​ Insurer iii.​ Health care organization iv.​ Patient b.​ Analysis of outcomes: i.​ Clinical ii.​ Economic iii.​ Patient reported outcomes iv.​ morbidity/mortality c.​ Applying pharaco-economics in practice: i.​ What's the evidence?  ii.​ How well defined was the question iii.​ Were alternatives ad comparisons explored iv.​ Is effectiveness well established v.​ Were costs/consequences considered Pharmacogenetics and CYP 2 · ​ Understand CYP activity enzymes (implications for PK of being normal, rapid, poor metabolizer, etc.) 1.​ CYP genotypes a.​ Diminished actively = poor metabolizer b.​ Increased activity -rapid metabolizer 2.​ Poor metabolizers (PM) a.​ Experience the most adverse drug effects b.​ Homozygous for dysfunction/deletion activity 3.​ Intermediate metabolizers (IM) a.​ Heterozygous alleles 4.​ Extensive metabolizers (EM) a.​ 2 fully functional alleles 5.​ Ultrarapid metabolizers (UM) a.​ 2+ active genes on same allele b.​ Non-responders to drugs at a normal dose -In metabolism, hepatic transformation involves CYP enzymes, aka Cytochrome P450 -Occurs during Phase I metabolism a.​ CYP1, CYP2, CYP3 metabolize drugs i.​ P450 Inducers: increases/enhance a CYP enzyme = drug is metabolized faster aka less drug in system/less effect ii.​ P450 inhibitors: decreases a CYP enzyme = drug is metabolized  slower aka more drug in system/toxicity risk/side effects · ​ Know common CYP enzymes involved in drug metabolism 1.​ CYP3A4 a.​ Has role in 50% of drugs metabolized by CYP enzymes b.​ Ex: antibiotics (macrolides), Benzos, Ca channel blockers, statins, opioids c.​ Inhibited by: grapefruit juice, erythromycin, ketoconazole d.​ Reduced activity by quetiapine and tamoxifen 2.​ CYP2C9: wairfran (S-isomer metabolized by CYP2C9), losartan, fluvastatin, sulfonylureas, NSAIDS a.​ Poor metabolizers clearance reduced by 70-80% for wairfran, need reduced dose and have higher risk of bleeding 3.​ CYP2C19 a.​ Metabolizes omeprazole (PPI) b.​ 3% white and 15-20% asians are poor metabolizers = reduce dose 4.​ CYP2D6 a.​ Codeine is metabolized to morphine i.​ Ultrarapid metabolizers = excessive morphine b.​ Dextromethorphan DXM i.​ Extensive metabolizers most  likely to experience effects ADRS, toxicities, 4 · ​ Know clinical presentation of hypersensitivity reactions different hypersensitivity reactions Type I: immediate drug reaction, drug allergy a.​ IgE mediated b.​ Minutes to hours c.​ s/s: urticaria (hives) anaphylaxis d.​ Antibiotics: PCN, beta lactams, cephalosporins Type II: cytotoxic, drug specific IgG or IgM antibodies a.​ s/s: thrombocytopenia, hemolytic anemia b.​ Methyldopa, heparin, PCN Type III: reactions that deposit immune complexes in blood serum, IgG/IgM a.​ s/s: lupus, serum sickness, vasculitis b.​ PCNs, sulfonamides, INH phenytoin, minocycline Type IV: non-immune, cellular: cytokines and T-cells a.​ s/s: rash, bullous or pustular skin eruptions b.​ PPD skin test · ​ Know drugs associated with serious adverse reactions PCN: accounts for 75% of anaphylaxis reactions a.​ Cross sensitivity with cephalosporins and carbapenems Sulfa-antibiotics (Bactrim w/ sulfamethoxazole): a.​ Most likely to cause Steven johnsons syndrome and toxic epidermal necrolysis i.​ prior hx = contraindication a.​ 60% people with AIDS have reactions b.​ Anaphylactic reactions, angioedema, serum sickness, and drug induced lesions c.​ Most people with sulfa allergy will tolerate: thiazide diuretics, furosemide (Lasix), sulfonylureas, celecoxib (celebrex) Aspirin/NSAIDS: aspirin exacerbated respiratory disease (AERD) a.​ Exposure to aspirin or NSAID causes rhinorrhea, congestion, conjunctivitis, bronchospasm, asthma b.​ Chronic idiopathic urticaria: aspirin and COX-1 worsen urticaria and angioedema c.​ Can cause IgE mediated reactions resulting in anaphylaxis and urticaria Contrast dyes (radiocontrast media): a.​ Reactions: urticaria, angioedema, bronchospasm, shock, death b.​ Prevention: i.​ identify pts w/ hx or family hx ii.​ Patients at risk = asthma , on beta-blockers, CV disease iii.​ Can pretreat with prednisolone and diphenhydramine Opioids: a.​ non-IgE mediated (itching, wheezing, urticaria) b.​ Usually not serious c.​ Pretreat with antihistamine d.​ Opioid OD: pinpoint pupils, CNS and resp depression, hypothermia Anticonvulsants: mild to severe rxn a.​ Severe reactions: SJS, TEN, anticonvulsant hypersensitivity syndrome, DRESS b.​ Aromatic agents: phenytoin, carbamazepine, phenobarbital, primidone; and newer meds: lamotrigine, oxcarbazepine, felbamate, zonisamide c.​ Cross reactions with aromatics = se nonaromatics such as: valproic acid, gabapentin, topiramate, or benzos · ​ Know classification of adverse drug reactions and be able to apply knowledge to a scenario 1.​ Adverse Drug Reactions (ADRs): unintended, harmful reactions to  meds, most are preventable but no med is risk free. Classifications: 1.​ DoTS: dose, timing, susceptibility a.​ Dose: i.​ Toxic: doses above therapeutic standard ii.​ Collateral: reactions at standard doses iii.​ Susceptibility reactions: reactions even at subtherapeutic levels b.​ Timing: i.​ Time independent ii.​ Time dependent 1.​ Rapid = administered too fast i.e. red man syndrome with vancomycin 2.​ First dose reactions i.e. ACE inhibitors 3.​ Early reactions = tolerance to meds over time i.e. headache with nitrate use 4.​ Intermediate = if no reaction at a certain point then it is unlikely to occur 5.​ Late = increased risk with repeated exposure i.e. corticosteroids , transdermal 6.​ Delayed = late onset even after discounting ie.  carcinogens and teratogens c.​ Susceptibility factors: i.​ Genetics ii.​ Age iii.​ Sex iv.​ Disease profile 2.​ Poisoning: adverse effect of taking a chemical at an excess amount a.​ Prevention = proper drug disposal b.​ HCP considerations: i.​ Unexplained symptoms? Consider exposure (ex: OD on opioids) ii.​ Potential exposures: supplements, complementary therapies, environmental toxins iii.​ Quantitative serum levels: ex: acetaminophen, ethanol, digoxin, salicylates, iron iv.​ Do not induce vomiting Hypertension (HTN) 6 ​ Common side effects and See table at last page for all monitoring associated with major classes drugs *** for HTN ADRs 1.​ Class: ACE inhibitors a.​ ADRs: Dry cough (ace cough), angioedema renal function decline, hyperkalemia b.​ BLACK BOX: fetal toxicity 2. Class: Angiotensin II receptor blockers (ARBs) ADRs: angioedema, hyperkalemia, renal decline, BLACK BOX: fetal toxicity 3. Class: Direct renin inhibitors  a.​ ADRs: do not use with ACEI/ARBs = causes hypoTN and hyperkalemia, DO NOT USE IN PREGNANCY 4. Class: Aldosterone inhibitor antagonists (mineralocorticoids) a.​ ADRs: · ​ Know first-line treatments for HTN and HF · ​ Be familiar with names of drugs in major drug classes 1.​ ACE Inhibitors “pril” meds a.​ Captopril b.​ Lisinopril c.​ Enalaprilat 2.​ Angiotensin II receptor blockers (ARBs) “sartan” a.​ Losartan b.​ Olmesartan c.​ Telmisartan d.​ Valsartan e.​ irbesartan 3.​ Direct renin inhibitors a.​ aliskiren · ​ Know MOA of major anti-hypertensive drug classes 1.​ ACE inhibitors a.​ MOA: inhibits angiotensin converting enzymes 2.​ Angiotensin II receptor blockers (ARBs) a.​ MOA: selective agents that block vasoconstrictive and aldosterone secreting effects of angiotensin II 3.​ Direct Renin inhibitors a.​ MOA: block enzyme renin  · ​ Be familiar with other indications/uses of antihypertensives (e.g. which can be used for HF, etc.) 1.​ ACE inhibitors = pril meds a.​ Other uses: i.​ HF ii.​ CKD iii.​ MI iv.​ L ventricular dysfunction after MI, renal issues, non ST acute coronary syndrome 2.​ Angiotensin II receptor blockers (ARBs) a.​ Other uses: i.​ HF ii.​ Acute coronary syndrome iii.​ Intolerant of ACE iv.​ Marfan's syndrome v.​ Diabetic neuropathy vi.​ L ventricular hypertrophy 3.​ Direct Renin Inhibitors a.​ Other uses: i.​ Obesity/metabolic syndrome 4.​ Aldosterone inhibitor antagonists (mineralocorticoids) a.​ Hyperaldosteronism b.​ HFpEF · Heart failure (HF) 3 · ​ Know which antihypertensives are used in or contraindicated in HF  Used in HF: Diuretics first line ACE “pril” /ARBs “sartans” Aldosterone antagonists: spironolactone Beta blockers “lol” SGLT2 inhibitors: “flozin” Nitroprusside Contraindicated in HF: Ca channel blockers: show no benefit Alpha adrenergic antagonists monotherapy Alpha adrenergic agonist: clonidine · ​ Know monitoring, major interactions associated with use of HF meds Monitoring: BP, HR, urinary output, kidney function, ECG Interactions: drugs that prolong QT interval or inhibit/induce CYP3AF ADRs: hypoTN, arrhythmias, thrombocytopenia, AKI, tachycardia, headache, cyanide toxicity in renal failure (nitroprusside), angioedema, hyperkalemia, antiandrogen actions, genital mycotic infections, nausea, increased cardiac workload Antibiotics 4 · ​ Know MOA for antibiotic classes · ​ -Know major allergic/hypersensitivity reactions associated with antibiotic drugs/classes Classes: 1.​ MOA: antimicrobials inhibit cell wall synthesis Ex: beta lactams i.​ Penicillins (PCN) 1.​ ADRs: never give to pt with SJS/TEN ii.​ Cephalosporins  1.​ More broad spectrum than PCN because more stable against beta lactams 2.​ ADRs: N/V/D, local irritation/thrombo phlebitis with IM, C diff infections, hemolytic anemia iii.​ Carbapenems 1.​ Ex: “penems” drugs 2.​ ADRs: GI, rash, seizure 3.​ Cross sensitivity with PCN is LOW iv.​ Monobactams v.​ Vancomycin 1.​ Give IV 2.​ ADRs: vancomycin flushing syndrome from histamine release = slow infusion and give antihistamine vi.​ Fosfomycin: first line for uncomplicated UTI 1.​ 3g PO x 1 dose vii.​ Bacitracin: nephrotoxic so only use topically a.​ Gen ADRs for cell wall inhibitors: viii.​ allergy sensitivity much less than reported ix.​ PCNs cross sensitivity with cephalosporin x.​ Generally safe in pregnancy and breastfeeding 2.​ MOA: Beta lactamase inhibitors, inhibit cell wall synthesis  a.​ Ex: i.​ Clavulanic acid ii.​ Amoxicillin + clavulanic acid = Augmentin iii.​ “Bactams”: sulbactam, vaborbactam, tazobactam, avibactam iv.​ Piperacillin + tazobactam = Zosyn v.​ Ampicillin + sulbactam = Unasyn vi.​ Ticarcillin + clavulanic acid = Timentin 3. MOA: Inhibitors of protein synthesis a.​ Tetracyclines i.​ ADRs: bind to and damage growing bones/teeth ii.​ Avoid use in pregnancy and in children under 8 iii.​ Ex: Doxycycline, minocycline, demeclocycline, glycylcycline Tigecycline: Black box warning b.​ Macrolides: i.​ Ex: erythromycin, azithromycin, clarithromycin (fewer GI side effects) , fidaxomicin, ketolides, clindamycin ii.​ ADRs: N/V/D, prolonged QT (torsades de pointes) c.​ Oxazolidines: i.​ ADRs: hematologic d.​ Aminoglycosides i.​ Ex: tobramycin, streptomycin, neomycin, gentamicin, amikacin, kanamycin ii.​ ADRs: nephrotoxicity, ototoxicity with use of > 5 days, elderly, renal insufficiency. 1.​ Neomycin allergy and skin irritation common 4. MOA: Inhibit folic acid biosynthesis  a.​ Sulfa drugs: sulfonamides i.​ ADRs: N/V/D, SJS, hemolytic anemia, growth of rickettsiae, kernicterus in newborns ii.​ Ex: Bactrim 5. MOA: inhibit DNA/RNA synthesis: a.​ Fluoroquinolones i.​ ADRs: n/v/d, QT prolongation, tendon rupture = BLACK BOX WARNING , rare liver injuries, muscle weakness (avoid in patients with myasthenia gravis), photosensitivity (wear sunscreen), C.Diff ii.​ Ex: “Floxacin” 1.​ Ciprofloxacin: BLACK BOX WARNING, use other drugs for UTIs/sinusitis 2.​ Ofloxacin 3.​ Levofloxacin 4.​ Gatifloxacin · ​ Understand the spectra of antibiotic coverage Gram positive/ negative Broad-spectrum: acts on gram negative AND gram positive Narrow-spectrum: acts on gram negative OR gram positive a.​ Helps against antibiotic resistance · ​ Identify key patient education associated with various antibiotics Bactericidal: results in bacteria death a.​ Required in: immunocompromised, endocarditis, sepsis, brain abscess, meningitis, osteomyelitis, infection of prosthetic device b.​ Low concentrations are bacteriostatic Bacteriostatic: limits/suspends growth/reproduction of bacteria, allowing immune system to kill bacteria  a.​ Duration of therapy must be enough to allow host defense mechanisms to kill bacteria but bacteria usually starts to grow again when antibiotic is removed b.​ High doses can act as bactericidal Empiric therapy: treats most likely pathogens Direct therapy Pathogen known, narrow spectrum, evidence strong, fewer ADRs, less costly Pharmacodynamics: minimum inhibitory concentration (MIC): lowest concentration of antibiotic that completely inhibits growth of specific organism in vitro. Used to determine sensitivity via Antibiogram Pharmacodynamics: minimum bactericidal concentration (MBC): lowest dose of bacteria that kills 99% Time dependent dosing: optimal effect based on duration that drug concentration is above MIC a.​ Aka how long the drug is free/unbound b.​ Dosing schedule reflects percentage of time needed for drug concentration to be above MIC Concentration dependent dosing: Peak concentration and area under the curve determine efficacy of antibiotics a.​ Aka increased rate of killing bacteria with increased concentration b.​ Drugs can have both time dependent and concentration dependent properties Antibiotic Stewardship: a system of informatics, data collection, personnel, and policy/procedures which promotes optimal selection, dosing, and duration of therapy for antimicrobial agents a.​ Purpose: limit inappropriate/excess antibiotic use, improve antibiotic  resistance, and improve/optimize clinical outcomes Antivirals 2 · ​ Understand appropriate use of oseltamivir (Tamiflu) Oseltamivir (Tamiflu): a.​ MOA: neuraminidase inhibitor b.​ Active against influenza A and B c.​ Should be started within 48 hours onset of symptoms but 12 is ideal d.​ Reduce duration of illness by one day, reduce risk of hospitalization/death/need for antibiotics · ​ Know principles of treatment for tuberculosis (TB) TB treatment: combo therapy REQUIRED a.​ Rifampin and isoniazid (INH) i.​ best for preventing resistance b.​ Pyrazinamide: i.​ Used first 2 months of treatment, shortens treatment to 6 months c.​ Ethambutol: i.​ To prevent rifampin resistance d.​ Quinolones: levofloxacin and moxifloxacin i.​ Used for resistant TB/TB does not respond to first line drugs Asthma and COPD 6 · ​ Know major MOA, therapeutic goals, boxed warnings/precautions, and major contraindications of major classes of inhaled drugs to treat asthma and COPD 1.​ MOA: beta 2 agonists, smooth muscle relaxation a.​ Therapeutic goal: bronchodilators b.​ ADRs: Tolerance can occur 2.​ MOA: Corticosteroids, alter expression of pro-inflammatory cytokines a.​ Therapeutic goal: increased responsiveness of B2 adrenergic receptors, decreased mucus production, and decreased airway edema. b.​ ADRs: hoarseness, dysphonia, thrush, HPA suppression c.​ Cigarette smoking decreases effectiveness d.​ Potent inhibitor of CYP3A4 3.​ MOA: Anticholinergics, competitive antagonist of muscarinic receptors a.​ Therapeutic goal: reverse cholinergic mediated bronchospasm b.​ ADRs: urinary retention, dry mouth, headache, and URIs 4.​ MOA: Leukotriene modifiers, receptor antagonists a.​ Therapeutic goal: moderate effect on muscle tone, lung function, and frequency of exacerbations b.​ ADRs: not commonly prescribed d/t eosinophilic granulomatosis, hepatotoxicity, hepatic failure, and neuropsychiatric effects 5.​ MOA: Biologic agents, target IgE pathway or interleukin pathway (high dose ICS) a.​ Therapeutic goal: to control moderate to severe asthma 6.​ MOA: Methylxanthines, anti inflammatory  a.​ Not commonly used today as there is risk for life threatening toxicity and DDIs · ​ Be able to identify first-line drugs for acute symptom control and those used for long-term control of asthma/COPD (e.g. LABA, LAMA, SABA, ICS, etc.) It will be useful to be familiar with common names of drugs in each drug class SABA: Short acting beta 2 agonists a.​ First line treatment for severe acute asthma i.​ albuterol ii.​ Also used for PRN intermittent bronchospasm LABA: long acting beta 2 agonists a.​ More lipid soluble than SABAs = stay in lung longer b.​ LABAs should NOT be used as monotherapy for chronic asthma c.​ Ex: i.​ formoterol ii.​ Salmeterol iii.​ Ultra LABA: vilanterol ICS: inhaled corticosteroids a.​ Most effective asthma Rx b.​ High topical potency without the systemic effect c.​ REDUCE DOSE OF BETA 2 AGONIST WITH ICS d.​ CYP3A4 inhibitors Anticholinergics: non selective antagonists at M1-M3 receptors a.​ Used in combo with SABA for acute asthma exacerbation b.​ Ex: i.​ Ipratropium bromide 1.​ Caution in patients with closed angle glaucoma ii.​ Tiotropium  1.​ Add on med in patients not well controlled with LABA and ICS iii.​ Umeclidinium: MOA = selective at M3 1.​ Umeclindium-fluticasona-v ilanterol combo , QD dosing Biologic Agents: high dose ICS a.​ Ex: “mab” i.​ Omalizumab ii.​ Mepolizumab iii.​ Reslizumab iv.​ Benralizumab v.​ Dupilumab vi.​ Tezepelumab Methylxanthines: a.​ Theophylline · ​ Be able to determine appropriate treatment when given the GOLD group and the table A Less 0-1 symptoms, exacerbatio low risk ns per year B More 0-1 symptoms, exacerbatio low risk ns per year C Less >2 symptoms, exacerbatio high risk ns D More >2 symptoms, exacerbatio high risk ns Treatments: A: Bronchodilator B: LABA or LAMA C: LAMA D: LAMA or LABA + LAMA or ICS + LABA Antihistamines 1 · ​ What are the major adverse effects of H1 blocking antihistamines (mainly first generation)? ADRs first gen H1 blocking histamines: a.​ Ex: diphenhydramine (benadryl) ADRs: SEDATION/DROWSINESS (distributes in CNS) and fatigue #1, N/V/D, increased/decreased appetite, epigastric distress, constipation b.​ HIGHLY anticholinergic = BEERS drug Law and rule 3 · ​ Understand components of physician collaboration, especially as it relates to prescribing Collaboration: When a CNS, CNM, and CNP must have a collaborating physician either in person or via tele-communication Supervision: CRNAs must be directed by and have a anesthesiologist in immediate presence Standard Care Arrangement (SCA): written formal guide for planning and evaluating care written by collaborator and APRN. APRN may not practice without the current SCA, scheduled for review at least every 2 years. Prescribing: -Influenced by committee by prescriptive governance (CPG) -may not exceed collaborators authority -DEA required and renewed every 3 years to prescribe scheduled drugs -Schedule II drugs may not be refilled -Schedule III and IV can only be refilled 5x in six months · ​ Know what is required to practice as an APRN in Ohio and in most states APRN licensure In Ohio: 1.​ RN  2.​ Graduate degree in nursing speciality (masters/doctorate) 3.​ Passed certification exam 4.​ Pharmacology course within five years, approved by BON, and instruction on state and federal laws about authority of prescribing 5.​ Renew every two years/must identify collaborating physician that within your speciality To be a prescribing APRN in Ohio: 1.​ RN license in state of Ohio 2.​ Current certification 3.​ APRN license 4.​ Standard Care Arrangement (SCA) · ​ Understand scope of practice Scope of practice: parameters of profession performance, responsibility, and accountability identified and defined by national professional organizations 1.​ CNM may not perform version, breech, or fae presentation except emergency 2.​ CRNA requires supervision 3.​ CNP may perform preventive and primary care services, provide services for acute illness, and evaluate and promote patient wellness 4.​ CNS may provide and manage complex health problems First line meds UTI: Fosfomycin TB: rifampin, isoniazid, pyrazinamide, ethambutol (need combo of all) Black box warning meds 1.​ Ciprofloxacin: use other drugs for UTIs/sinusitis 2.​ Tigecycline 3.​ Fluoroquinolones: tendon rupture 4.​ ACE inhibitors: Fetal toxicity Pregnancy Safe: 1.​ PCNs Not safe: 1.​ Tetracyclines HTN meds: Class MOA ADRs Drug names Other uses ACE inhibitors inhibits Dry cough (ace “Pril” HF angiotensin cough), Captopril CKD converting Enalaprilat MI angioedema renal enzymes Lisinopril function decline, hyperkalemia BLACK BOX: fetal toxicity ARBs selective agents angioedema, “Sartan” -HF that block hyperkalemia, Losartan -Acute coronary vasoconstrictive renal decline, Olmesartan -syndrome and aldosterone Telmisartan BLACK BOX: fetal Intolerant to ACE secreting effects Valsartan of angiotensin II toxicity -Marfans Irbesartan -Diabetic neuropathy -L ventricular hypertrophy Direct Renin Block enzyme -do not use with aliskiren Obesity Inhibitors renin ACEI/ARBs = Metabolic syndrome causes hypoTN  and hyperkalemia -DO NOT USE IN PREGNANCY Aldosterone Competes with -Gynecomastia Spironolactone HFpEF inhibitor aldosterone to -hypoTN Hyperaldosteron bind with -Hyperkalemia ism antagonists aldosterone (when used w/ (mineralocorticoid receptor ACE/ARB) s) -Do not use if creatine cl