Pharm III Final Exam PDF

Pharm III Final Exam HIV Viral Load: Speed of Train; CD4 < 200 = end of track (AIDS) Treatment Goals:...

Pharm III Final Exam HIV Viral Load: Speed of Train; CD4 < 200 = end of track (AIDS) Treatment Goals: Maximally/durably suppress plasma HIV RNA Restore/preserve immunologic function ↓ HIV morbidity + prolong duration + quality of survival Prevent HIV transmission NRTIs: Nucleoside/tide Reverse Transcriptase Inhibitors (NRTIs) “Nukes” FTC/TDF (Truvada) Inhibit action of virally encoded protein *Renal excretion for most: ABC/3TC (Epzicom) reverse transcriptase via replacing Caution CKD; Descovy > Truvada FTC/TAF (Descovy) nucleotides in elongating strand of viral 3TC/AZT (Combivir) DNA à early termination of viral DNA 1 NRTI + 2-combo NRTI only ABC/3TC/AZT (Trizivir) à rapid development of resistance! Tenofovir (TFV) HBV treatment T disoproxil fumarate b à TFV in plasma ↓ Bone mineral density (TDF) TAF à TFV in cells T alafenamide (TAF) Weight gain Emtricitabine (FTC) HBV treatment Do NOT combine 3TC + FTC Lamivudine (3TC) HBV treatment FTC: Skin discoloration Abacavir (ABC) No renal adjustment needed* HLA-B*5701 à fatal hypersensitivity Hola aBacavir Liver metabolism Alcohol ↑ levels, Sleep disturbances Zidovudine (ZDV, AZT) Newborns w/ perinatal HIV exposure Hyperpigmentation, myelosuppression (anemia, neutropenia), myopathy Stavudine (d4T) deripheral neuropathy Peripheral neuropathy Didanosine (ddI) Peripheral neuropathy, GI toxicity Common Themes FTC 3TC TFV = HBV That’s Cool D4t ddl = deripheral neuropathy ABC = Hola aBacavir, liver! NNRTIs: “non-Nukes” EFV/TFV/FTC (Atripla) Binding of NNRTI à Hepatotoxicity RPV/TFV/FTC (Complera) Δ in conformation of enzyme that Lipohypertrophy à abd, chest, neck interferes w/ ability to form viral DNA Efavirenz (EFV) Once daily on empty stomach Do NOT use w/ ATV/c or DRV/c (QHS to mitigate CNS) CNS: drowsy, insomnia, dreams, agitation Ew, No Kids Rash, QTc prolongation, False (+) drug test, drug abuse risk, Teratogenic risk in 1st 6w pregnancy Rilpivirine (RPV) Once daily w/ meal Depression, HA, rash, QTc prolongation Potential failure if RNA>100k or CD4 200 Efavirenz (EFV) + tenofivir disoproxil fumarate (TDF) + emtricitabine (FTC) Efavirenz (EFV) + tenofivir (TAF/TDF) + emtricitabine (FTC) Rilpivirine (RPV) + tenofivir (TAF/TDF) + emtricitabine (FTC) Common Themes EFV + RPV = QTs (ew no kids + fail if bad disease) Pharm III Final Exam PIs: Protease Inhibitors -navir DRV/Cobicistat (DRV/c) Inhibit HIV protease Risk MI, stroke, n/v/d (w/food), Hepatotoxic ATV/Cobicistat (ATV/c) /c or /r to inhibit CYP (metabolism) Lipodystrophy: gaunt face à fat mob Lopinavir/Ritonivir (LPV/r) Atazanavir (ATV) acid Unboosted for ART-naïve pts Jaundice, PR prolongation, stones NOT absorbed w/ acid-lowering tx eg. PPI Darunavir (DRV) danger ❤ QD in PI-naïve, BID for mutations Sulfa rash, ALT, hyperlipidemia, CV risk Lopinavir (LPV) loopy QD in PI-naïve, non-pregnant LFTs, asthenia, PR/QT prolongation, EtOH Indinavir (IDV) I don’t vant Early drug Nephrolithiasis Cobicistat (/c) Inhibit CYP metabolism to keep drug in system for longer, boost [c] PI Ritonivir (/r) /c: Inhibits renal secretion of Cr à ↑ Cr levels (no ↓ GFR) PI-based regimens: CrCl < 70 mL/min/1.73m2 à choose TAF > TDF Atazanavir/ritonavir (ATV/r) + tenofivir (TAF/TDF) + emtricitabine (FTC) Atazanavir/cobicistat (ATV/c) + tenofivir (TAF/TDF) + emtricitabine (FTC) Darunavir/ritonavir OR cobicistat (DRV/r/c) + tenofivir (TAF/TDF) + emtricitabine (FTC) Darunavir/ritonavir OR cobicistat (DRV/r/c) + abacavir (ABC HLA*B(-)) + lamivudine (3TC) INSTI: Integrase Inhibitors -gravir EVG/c/FTC/TDF (Stribild) Inhibit integrase Given 2h before OR 6h after EVG/c/FTC/TAF (Genvoya) à prevent viral DNA from becoming products w/ divalent cations DTG/ABC/3TC (Triumeq) a part of the host cell (eg. Mg, Al found in antacid, laxatives, BIC/TAF/FTC (Biktarvy) dairy, multivitamins) à ↓ levels INSTIs Doltegravir (DTG) High barrier to resistance Hyperglycemia, ↑ Lipase DTG/RPV (Juluca) Safe in pregnancy, pediatrics Raltegravir (RAL) Pill burden: no single-tablet regimen ↑ Cr phosphokinase (Myopathy) Hypersensitivity, SJS/TEN Carbotegravir (CAB) Injectable 600mg Qmo NOT for ART-naïve pts Long-acting approved for PrEP PO lead-in before injectable Elvitegravir (EVG) Requires /c for QD NOT for pregnancy ↑ LDL, ↑ triglycerides, GI upset, DDI Bictegravir (BIC) High efficacy/potency Well-tolerated, rare hypersensitivity Not enough evidence for pregnancy INSTI- based regimens: Safe for Viral Load < 100k + HLA*B-5701 (-) Raltegravir (RAL) + abacavir (ABC HLA*B(-)) + lamivudine (3TC) When ABC, TAF, TDF cannot be used: Raltegravir (RAL) + Darunavir/ritonavir (DRV/r/) Lopinavir/ritonavir OR cobicistat (LPV/r) + lamivudine (3TC) Entry/Infusion Inhibitors Enfuvirtide (T20, ENF) Binds to viral protein that helps w/ fusion Injection-site reactions En-jection, pnEumo SQ injection for multidrug-R strains Risk bacterial pneumonia Maraviroc (MVC) Targets human protein coreceptor Hepatotoxicity, Postural hypotension, MI RI P-hy Test Trofile: CCR5 vs. CXCR4 dizziness, URI infections, MI risk Ibalizumab iris Attachment inhibitor, humanized mAb Infusion rxn, IRIS (Trogaaaaarzo) Fostemsavir Attachment inhibitor QTc prolongation, ↑LFTs w/ HBV/HCV No Hep for Frost Lenacapavir Capsid inhibitor Ø: Strong CYP3A4 inducers No CYP for Lena Injection site reactions Pharm III Final Exam Initial Treatment for HIV Bikarvy: Bictegravir (BIC) + tenofovir alafenamide (TAF) + emtricitabine (FTC) NO pregnancy Tivicay: Dolutegravir (DTG) + tenofovir (TFV) + emtricitabine (FTC) OR lamivudine (3TC) Pill burden Symtuza: R-boosted darunavir (DRV/r) + tenofovir (TFV) + emtricitabine (FTC)/lamivudine (3TC) INSTI-free Triumeq: Dolutegravir (DTG) + tenofivir (TAF/TDF) + emtricitabine (FTC) OR lamivudine (3TC) (-) HLA*B, HBV Dovato: Dolutegravir (DTG) + lamivudine (3TC) NOT for HIV RNA >500k or HBV coinfection, awaiting testing Optimal ART: 2 NRTIs + INSTI 3rd drug choice between an INSTI, NNRTI, or PI should be guided by regimen’s efficacy, genetic barrier to resistance, adverse effects profile, and convenience Consider: Pretreatment HIV RNA level (viral load) Pretreatment CD4 cell count HIV genotypic drug resistance testing results HLA-B*5701 status for abacavir (ABC) à ↓ risk of hypersensitivity reaction Patient preferences, anticipated adherence to the regimen Do NOT use: Monotherapy NRTI, Dual NRTI, Triple NRTI alone Atazanavir (ATV) + indinavir (IDV) = hyperbilirubinemia Didanosine (ddI) + stavudine (d4T) = peripheral neuropathy Didanosine (ddI) + tenofovir (TDF) = pancreatitis OR lactic acidosis Virologic Failure: Resistance testing (during regimen OR within 4w of d/c) More accurate if HIV RNA > 1000 copies/mL Indications Upon entrance into care Virologic failure during potent combination ART All pregnant women w/ HIV Suboptimal suppression of viral load s/p initiation of potent combination ART Acute HIV infection before initiating tx (determine if a drug-R virus transmitted) After testing: Check resistance, address underlying causes, consider reinitiation OR Initiate new regimen OR Intensify 1 therapy or boost Genotypic Presence of mutations known to cause drug resistance à tx-naïve Comparing HIV-1 pol gene w/ a wild-type gene Guide therapy in patients w/ virologic failure while on their 1st or 2nd regimen Phenotypic Test for inhibitory concentration needed to ↓ HIV replication by 50% (IC50) à complex Values are reported as fold changes in sensitivity (X ↑ in IC50) resistance Sensitive: 10x Special Considerations Vaccinations Flu, pneumococcal, HAV/HBV, Meningococcal ACWY, HPV, COVID-19 NO live vaccines if CD4 < 200 (eg. MMR, VZV, rotavirus, yellow fever) Pregnancy ART initiated during pregnancy should have 2 NRTIs + INSTI OR PI/b MC combo: Dolutegravir (DTG) + TAF-FTC/3TC, TDF-FTC, ABC-3TC If established regimen: Consider replacing elvitegravir/c (EVG/c) w/ /r or PI combo Efavirenz (EFV) before 8 weeks Ppx: Vertical NO injectable CAB/r, NO breastfeeding; Infants can have ppx + nevirapine (NVP) Transmission HIV in labor: IV Zidovudine (ZDV/AZT) if HIV RNA >1000 near delivery Low-risk Infants: Zidovudine (ZDV/AZT) within 6-12h High-risk Infants: Nevirapine (NVP) + Zidovudine (ZDV/AZT) + lamivudine (3TC) DDI Food effects on ARV absorption DRV, ATV, EVG, RPV require food for absorption Fatty food ↑ EFV absorption à adverse effects Red Flag Potent CYP3A4 inhibitor: PIs, macrolides, many azole antifungals Drugs CYP3A4 inducer: rifamycins, many anti-convulsants CYP3A4 substrates : antiarrhythmics, warfarin, QTc-drugs, ergotamines, erectile dysfunction agents, benzos, opiates Pharm III Final Exam Opportunistic Infections: *all HIV infected should be screened for latent TB CD4 Value Disease à Ppx < 250 Coccidiomycosis à Fluconazole < 200 PCP à Bactrim (TMP-SMX) < 150 Histoplasmosis à itraconazole if in S. America < 100 Toxoplasma à Bactrim (TMP-SMX); Cryptococcus < 50 MAC à macrolide? (azithromycin) HIV Prophylaxis PrEP Prophylaxis in HIV(-) to prevent infection: Truvada (TDF-FTC) or Descovy (TAF-FTC) Time to Effect: 7d s/p receptive anal, 21d s/p vaginal TDF-FTC: 2-1-1 (2-24h loading dose, 24h after, continue 2d QD after encounter) CAB-LA: for ease/compliance, risk for renal/bone dz; may develop INSTI-R Monitoring: HIV test Q90 d, serum Cr/UA for GFR < 60, HBV PEP Occupational post-exposure if suspected HIV(+) patient: NRTIs + INSTI Dolutegravir (DTG) + TFV-FTC Raltegravir (RAL) + TFV-FTC nPEP Nonoccupational post-exposure if suspected HIV(+) partner: NRTIs + INSTI Raltegravir: Dolutegravir (DTG) + TDF-FTC cheaper, BID Raltegravir (RAL) + TDF-FTC Dolutegravir: QD, $$ Adherence >95% < 95% adherence = risk virologic failure (if not NNRTI- or boosted PI-) ↑ CD4 response Factors that affect adherence: complexity of regimen ↓ viral load Comorbidities Side effects Lack of knowledge Drug Interactions Metabolism CYP3A4 is most abundant CYP450 isoenzyme for most PIs, NNRTIs, EVG, MVC PI/c are inhibitors of CYP450/3A4 NRTIs, RAL, ENF not prone “resistant” to drug interactions INSTIs chelate w/ cations (polyvalent Ca, Ma, Al) à ↓ PO absorption! Monitoring Viral Load Key goal is undetectable VL, achieved by 16-24w Virologic Failure > 200 Measure 2-8 w after initiating ART à decline >1 log (10x) from baseline Measure Q 4-8w until undetectable If stable ART à measure Q3-6mo Change in ART à measure 2-8w to confirm potency CD4 Q3-6mo: 1st 2 y tx OR viremia develops while on ART OR CD4 < 300 After 2y tx: Annual if CD4 = 300-500 Avg. ↑ 100/y until plateau/stabilization Labs Lipids: pre-tx baseline; 4-8 weeks after starting applicable new ART Chem: At 2-8 weeks; then every 3-6 mos CBC: every 3-6 mos (more often on AZT) Resistance: if VL>500-1000 on tx, or within 4 weeks of d/c Urinalysis: annual; q6mo if on TDF Lactate: if symptomatic and on AZT, ddI, d4t HLA-B*5701: Before ABC Tropism assay: if VL >1000 (Monogram Trofile) or lower VL (Monogram Trofile DNA) + considering MVC Changing Treatment Switch if SE/AE unmanageable; Do NOT switch unless new regimen will be as active as current one (aka NO drug resistance!) Pharm III Final Exam Pediatrics Age classifications: Neonates 4; adult levels by age 2-3yo (PO absorption) ↓ biliary fxn (lipophilic), slowly motility(duration), rectal size/expulsion (suppository) Percutaneous: absorbed better due to thinner stratum corneum + surface area (topical) IM: lower m. mass and tone (injection) Distribution Water-soluble drug: larger distribution in neonate (80% water) > infant à higher dose ↑ VD for water-soluble (↑ dose gentamicin); ↓ VD for fat-soluble (↓ dose benzos) ↓ levels of proteins in 1st year of life: ↑ bioavailability of protein-bound drugs Albumin binds acidic drugs; Alpha 1 glycoprotein binds basic drugs Drugs can displace bilirubin from albumin à jaundice, hyperbilirubinemia ↓ blood volume; ↑ permeability of BBB in neonates à concern for kernicterus Metabolism Hepatic drug metabolism slower due to underdeveloped enzymes/pathways Phase I: CYP450 enzyme reactions ↑ à larger doses per kg due to 2x adult activity Enzyme levels Phase II: enzymes facilitate elimination from the body; normalize by ~6mo kid > adult Sulfation: well-developed; alternate pathway for acetaminophen in neonates until puberty ↓ Glucuronidation: acetaminophen ↓ Conjugation w/ acetyl co-A in first month of life (sulfonamides) ↓ Carboxylation + Oxidation + Hydroxylation + Esterification CYP450 DDI Inducer: Phenytoin (3A4) Inhibitor: Voriconazole/posaconazole Rifampin Amiodarone Carbamazepine Fluoxetine St. John Wort Terbinafine Elimination Systemic excretion credited to kidneys (GFR newborn = 40 mL/min/m; adult ~3mo) ↓ GFR, tubular secretion (↑ until 6mo), reabsorption ↓ clearance of penicillin, aminoglycosides, cephalosporins Renal Fxn Kidneys immature in structure/function; nephrogenesis starts at 9w, done by 36w Not proportional à GFR ↑ rapidly in 1st 2w life, but clearance ↓ (5-15 ml/min) Schwartz CrCl ml/min/1.73m2 = [k X Height in cm] / SCr Equation Pre-term Infant (LBW < 1 year) k=0.33 Term Infant (Term < 1 year) k=0.45 Estimate GFR Child or Adolescent Girl (1-18 yo) k=0.55 Adolescent Boy (13-18 yo) k=0.70 *Bedside: CrCl (ml/min/1.73m2) = [0.413 X Height in cm] / SCr ADHD in Peds: ↓ core sx + meet realistic, achievable, measurable goals (3-6 at a time) Monitor: cardiac dz (BP, HR, EKG), CBC, LFT, weight/appetite, growth; if misuse (used up Rx) Amphetamines 1st line stimulant tx >6y Requires Schedule II rx Methylphenidate Blocks transporter reuptake Long, intermediate, short-acting Dextroamphetamine of NE + dopa to keep in synapse Amoxetine SNRI; less abuse potential? Black box: suicidal thinking Clonidine Alpha-2-adrenergic agonist Fewer SE, safer for sig. comorbidities Guanfacine Last line; XR can be adjunctive tx Sepsis + Meningitis in Peds 0-1 mo Ampicillin + Gentamicin OR Ampicillin + Cefotaxime 1-3 mo Ampicillin/Vancomycin + Cefotaxime/Ceftriaxone* à Kernicterus (Ceftriaxone can displace bilirubin from albumin) > 3 mo Ceftriaxone + Vancomycin Bacterial ppx Prevent H. influenza + N. meningitidis in high-risk, nursery, daycare, household Rifampin Ceftriaxone Cipro (no fluoro-R N. meningitidis) Pharm III Final Exam RSV in Peds Nirsevimab (Beyfortus) IgG1 mAb: passive immunization Hypersensitivity rxn, rash, local site 1st season: halothane > nitrous oxide) Guedel’s Stage I analgesia: patient initially experiences analgesia w/o amnesia Classification Stage II excitement: delirious, may vocalize but is completely amnesic Stage III surgical anesthesia: slowing of RR + HR à apnea 4 planes based on ocular movements, eye reflex, & pupil size Stage IV medullary depression: circulatory + respiratory support à CNS ↓ including vasomotor center in medulla + respiratory center in brainstem Awareness in GA Sedation w/ midazolam à amnesia: fail to form memory of event when awake Volatile anesthesia at depth > 0.7 MAC OR titration to BIS < 60 Inhaled Anesthesia Via gas exchange in alveoli; rapid onset/induction + rapidly terminated Volatile Halothane Enflurane Isoflurane Liquid administered using vaporizers Desflurane Sevoflurane ↓ vapor pressures + ↑ boiling points ANE = Still have pain Gaseous Nitrous oxide Xenon Gas at room temperature ↑ vapor pressure + ↓ boiling points IV Procedural Anesthesia Facilitate rapid induction + replaced inhalation as preferred method; MC in monitored care + ICU Propofol Lipophilic + Cross BBB rapidly (~40sec) NO analgesia à often w/ fentanyl Long-term sedation in ICU NO egg or soybean allergy Sedative + amnesic Major: hypotension, burning Minor: green discoloration urine + hair ETomidate Procedural sedation + amnesia NO analgesia à often w/ fentanyl Rapid sequence intubation (ET) Painful injection Immediate onset; duration: 5-15min Myoclonus, respiratory depression, Safe for hypotension adrenal suppression, n/v Benzos Alone or w/ opioid Repeated doses accumulate in adipose Midazolam Minimal sedation à prolonged sedation Anxiolysis + amnesia New: Remimazolam Short-Acting Bind to opioid receptors in CNS Only one w/ analgesia Opioids to inhibit ascending pain pathways Fentanyl Alfentanil SLOW IV push Remifentanil Administration Current drugs are not ideal à produce all not only 5 desired effects unconsciousness, amnesia, analgesia, autonomic reflexes inhibition, m. relaxation High flow O2 Balanced anesthesia employing multiple drugs (15L face mask) Inhaled anesthetics, sedative-hypnotics, opioids, neuromuscular blocking drugs If short-acting agent unavailable: midazolam then fentanyl for procedural sedation Pharm III Final Exam Other IV Procedural Anesthesia Ketamine Dissociative sedative; trance-like state Tachycardia, hypertension, Sedation, analgesia, amnesia laryngospasm, emergence reactions, + Midazolam Preserves upper airway m. tone nausea/vomiting, ICP + IOP, salivation if aggressive Brief pain procedure eg. fx reduction or lac Methohexital Barbiturate; suppress reticular activating center in brainstem, cerebral cortexà sedation Ketofol 2 synergistic meds; lower doses of each used Nitrous Requires well-ventilated room w/ scavenging system Which Healthy: Propofol (elderly pick; fast-acting but go low/slow) > Etomidate Drug? Hypotension risk: use etomidate or ketamine Risk airway/respiratory: ketamine Neuromuscular Blocking Agents Depolarizing ACh stimulates all cholinergic receptors t/o PNS/SNS Succinylcholine Binds directly to postsynaptic ACh of motor endplate à continuous stimulation à transient fasciculations à muscular paralysis Ø: personal or family h/o malignant hyperthermia à risk hyperkalemia myopathic metabolic disorder w/ sympathetic hyperactivity, muscle rigidity, acidosis, hyperthermia à tx cooling, sedation, dantrolene Non-depolarizing Rocuronium: Rapid sequence intubation when succinylcholine contraindicated -curonium OR when prolonged NM blockade required Vecuronium: Alternative Pancuronium: NOT for rapid sequence intubation; longer onset + duration also cause tachycardia + histamine release NMBA Train of 4: electrical impulses over 2” at 0.5” intervals to discrete muscle group Monitoring # twitches detected = intensity of blockade 0 = profound; strong but fade in 3rd/4th twitch = partial SCh noncompetitive + will not “fade” à constant 4 stimulations Reversal Neostigmine 0.06-0.08 mg/kg IV after 40% neuromuscular fxn returns ACh-ase inhibitor allows ACh to continue to stimulate neuromuscular junction Sugammadex rapid Opioids: Fentanyl, Dilaudid/Hydromorphone (rapid onset), Morphine (long DOA) Absorption Absorbed when taken orally Distribution Widely distributed; cross placenta; faster crossing of BBB = ↑ addictive Metabolism Hepatic enzymes; CYP2D6: codeine, oxycodone, hydrocodone; alcohol ↑ levels Elimination Via kidney; elimination HL ↑ in pts. w/ liver disease *Remifentanil: plasma metabolism + tissue esterase; short HL DDIs Sedative hypnotics: ↑ CNS depression, esp. respiratory depression Antipsychotics: ↑ sedation; ~respiratory depression; ↑ cardiovascular effects Monoamine Oxidase Inhibitors: relative contraindication to all opioid analgesics due to ↑ incidence of hyperpyrexia coma, hypertension MOA μ, δ, κ receptors: involved in antinociceptive + analgesic mechanisms Physiologic: endogenous endorphins β-endorphin, enkephalins, dynorphins Ionic: inhibit synaptic activity via activating receptor à G-proteins + phospholipase C Acute Effects Analgesia Sedation & Euphoria Respiratory Depression Antitussive Actions Nausea & Vomiting GI Effects Smooth muscle Miosis Misc: Flushing/Pruritis Clinical Use Analgesia Cough Suppression: Codeine & DXM Acute Pulmonary Edema: Morphine Tx diarrhea: Diphenoxylate, loperamide Anesthesia Dependence: Methadone & Buprenorphine Nociceptive Drugs APAP 1st line nociceptive pain 4g/day max NSAIDs Nociceptive musculoskeletal pain Alternatives: Antidepressant (TCA, SNRI) Myofascial pain Antiepileptic (Gabapentin, Pregabalin) Opioids Low risk for substance abuse Persistent pain despite trials Pharm III Final Exam Neuropathic Drugs Initial tx: antidepressants (TCA, SNRI) Ca channel ligands (gabapentin, pregabalin) adjunctive topical therapy (eg. topical lidocaine) when pain is localized Gabapentin Pregabalin Postherpetic Neuralgia NO TCA in heart dz, epilepsy, glaucoma TCA Alternative: capsaicin Duloxetine Venlafaxine Diabetic Neuropathy Alternative: gabapentins Amitriptyline TCAs NSAID Regional Pain Syndrome Alternative: topical lidocaine, capsaicin Bisphosphonate -dronate Carbamazepine Trigeminal Neuralgia Refractory: surgery Oxcarbazepine Slow TCA Amitriptyline Fibromyalgia Alternative: SNRI Primary Pain Control Tramadol Refractory analgesia Serotonin syndrome, Seizure Tapentadol Neuropathic pain, painful diabetic neuropathy ~GI Mixed mechanism Cyclobenzaprine Adjunct to rest/PT for m. spasm / MSK dz Do NOT use >2-3w NOT for MAO use (within 14d), hyperthyroidism, heart failure, arrhythmia, heart block, conduction disturbance, acute recovery s/p MI Ketamine Dissociative anesthetic IV agent Neuropathic, intractable chronic pain Tx-R depression + suicidal ideation Opioid Rx Percocet = oxycodone 5mg/APAP 325mg (CII) Vicodin = hydrocodone 5mg/APAP 325mg (CII) Vicoprofen = hydrocodone 7.5mg/ibuprofen 200mg (CII) Look at next slide 30mg hydrocodone = 20mg oxycodone PCA Patient-controlled analgesia (PCA) is useful in conscious patients who can cooperate with/understand instructions for use of PCA pump Allows self-dosing w/ opioids up to a predetermined limit ("lockout" interval) Acute Pain Mild Sprains, nonspecific LBP, dental extraction, headaches à APAP, NSAIDs (regularly scheduled dose = most effective) Moderate Laparoscopic surgery, fractures à regularly scheduled non-opioids + 3 day Rx of short-acting opioid Severe Major surgeries, compound fractures à 7 days of high-dose opioid + appt right after for eval Pharm III Final Exam Acute Perioperative Pain IV APAP 50kg: 650mg Q4h (Ofirmev) Max dose: 75 mg/kg/day Max dose: 4g/day Liposomal Dose based on size of surgical site NOT equivalent to bupivacaine HCl Bupivacaine Vol required to cover area (Exparel) Inject slowly into surgical site Opioids IV, IM, SQ, transdermal, transmucosal Somnolence, ↓ respiration, urinary Morphine Bolus IV for moderate pain retention, n/v due to trigger zone Hydromorphone Pt-controlled analgesia w/ lockout Fentanyl Histamine release follows morphine à flushing, tachycardia, hypotension, pruritus, bronchospasm GI slows à constipation + ileus Methylnaltrexone Methylnaltrexone: opioid antagonist doesn't cross BBB; tx ~opioid constipation Use standard therapy in all chronic pain + surgical patients aka “Bowel Regimen” Opioid Allergy Phenanthrenes: codeine, hydromorphone, levorphanol, morphine, oxycodone, hydrocodone, pentazocine Phenylpiperidines: meperidine, fentanyl Phenylheptanes: methadone, propoxyphene Rx Initial rx for an opioid drug to an adult for outpatient use is limited to 7-day supply Opioid rx for minors shall not exceed a 72-hour supply at any time Emergency Med: Antidotes N-Acetylcysteine APAP Atropine Organophosphates, carbamates Charcoal Most poisons Digifab Digoxin Dimercaprol Arsenic, Gold, Mercury Flumazenil Benzos Methylene Blue Drug-induced methemoglobinemia Naloxone Opioids Pralidoxime Anti-cholinesterase nerve agents Benzos Lorazepam Ethanol Withdrawal If refractory Delirium Tremens à Diazepam + IV Thiamine, Folate, phenobarbital, propofol Isotonic Saline + D5W Benzos Stimulant Withdrawal If severe or cocaine-induced HTN à phentolamine IV Benzos Hallucinogenic, Marijuana Capsaicin, hot shower Nuggets for Antiemetic w/ ↓ effect on QT à metoclopramide, prochlorperazine, droperidol *ECG EM AFib w/ RVR + ↓ BP à Ca+BB or CCB à 10mg diltiazem If ↓ EF à diltiazem, metoprolol If CrCl < 30: avoid nitrofurantoin DDI Warfarin + Fluoroquinolones, Metronidazole, TMP-SMX Warfarin + Azithromycin, Doxycycline Methadone + Fluoroquinolones (QT prolongation) ACEI, ARB, K-sparing Diuretic + TMP-SMX Vasopressor Vascular tone to MAP >65mmHg à NEpi, Dopamine Central line > peripheral to ↓ tissue excavation Arterial cath: BP monitoring NEpi tones NEpi: septic shock Epi: anaphylaxis Epi pen Dopamine: bradycardia rocks shock Vasopressin: +septic Phenylephrine: neurogenic Inotrope 💪 ↑ Pump function, contractility, CO s/p fluid resuscitation à Dobutamine, Milrinone Dobutamine: late-stage HF cardiogenic shock Milrinone: pump Ino U can Pharm III Final Exam Crystalloids Water, dextrose, NaCl, other electrolytes Isotonic solution Fluid resuscitation: depletion correlates w/ ↓ cardiac fxn + organ hypoperfusion 0.9% NS or LR 1L administered = 250 mL intravascular space Hypotonic solution Maintenance of IV fluids: unable to tolerate PO Dextrose 5% (D5W) Kids: 100mL/kg 1st 10kg, 50mL/kg next 10kg, 20mL/kg the rest Adults: 20-40 mL/kg/day 1L administered = 100 mL intravascular space Colloids Packed RBCs, plasma, semi-synthetic starch or glucose à volume expanders (cannot cross capillary) 25% albumin Exception: 5x oncotic pressure of plasma Fluid shift from out à in vascular space Sodium: Raise slowly Tolvaptan Hyponatremia < 125; Normovolemic/Edematous Selective drug Toll Fluid restriction Conivaptan Hyponatremia < 125; Volume depleted Up to 4 days of use Skinny Conni 1st replace vol w/ 0.9% NS, Na+ admin ↓ Serum Na Hypernatremia > 145 (fever, burn, infxn, renal/GI) If rapid correction: 2 If CKD à hemodialysis Loop Furosemide IV Ca cardiac Surgery Cefazolin (Ancef) MC SSIs: S aureus, coag (-) staph Allergy: gentamicin, cipro, 2g dose within 60m prior to incision levothyroxine, aztreonam Repeat intraop dosing > 2 T½ (~2h) Or blood loss > 1500 mL + Vancomycin if SSI due to MRSA Clean Uninfected operative wound w/ no inflammation + closed wound Clean Contaminated Operative wound w/ viscus entered in controlled conditions Contaminated Open fresh incidental wound, operation w/ break sterility or gross spillage Dirty Old traumatic wound w/ devitalized retained tissue, FB, or fecal/infection Pharm III Final Exam Parenteral Nutrition: thru veins - but if gut works, use it! (EN > PN) Indications Clinically malnourished: immediate PN, preoperatively in surgery Well-nourished ↓ serum albumin < 3.5 Loss >10% can wait 7d H/o poor intake NPO x 5-7 days due to illness Goals ↓ surgical mortality ↓ surgical complications/infection ↓ catabolic state + restore anabolism ↓ hospital LOS Speed healing + recovery OR patient Hold Total Parenteral Nutrition (TPN) during surgeries >1.5h 2h preop: ↓ TPN rate @ 50% x 1hr before; start D10 infusion at TPN rate 6h postop: TPN rate @ 50% x 1h then ↑ TPN slowly (monitor blood sugar) Preop Consider TPN if no PO x 3-5 days Postop TPN if pt cannot yet PO x 5-7d malnourished x 7-10d well-nourished Correlation Factor 1.10 ventilator 1.15 bedridden 1.25 normal Stress Factors 1.3 low 1.5 moderate 2.0 severe 1.9-2.1 for burn Calorie Obesity: 18-20kcal/kg/day of IBW Normal: 25-30kcal/kg/day Requirements Elective surgery: 28-30kcal/kg/day Severe injury: 30-40kcal/kg/day Extensive trauma/burn: 40-45kcal/kg/day Peripheral Vein Must not exceed 900 mOsm/L; MC central line preferred Types 2 in 1 all nutrients in same bag, except lipids à risk hyperTG, dyspnea, cyanosis 3 in 1 all nutrients mixed to form lipid emulsion à avoid excessive Ca Mg Central Line Caloric requirements: 25-35 kcal/kg/day if BMI < 30 Regimen Fluid requirements: 30-35 mL/kg/day or 2500-3500 mL/day Protein/AA requirements: 0.8-2g/kg/day Calculate remaining calories: admin 20-30% total cal lipid, remainder dextrose Medications Generally should not be added, especially Ceftriaxone: precipitates Ca Exception: Phenytoin: change pH of PN regular insulin Propylene Glycol, Ethanol (eg. furosemide, diazepam, digoxin, etoposide) Iron dextran (trivalent cations destabilize lipid emulsion in 3 in 1) Monitoring Infection, peripheral vein thrombophlebitis, infiltration, fluid status Nutritional status: prealbumin (normal 16-40, moderate malnutrition 11-16) Electrolyte, acid-base imbalances Metabolic alkalosis: Na + K as Cl salts Metabolic acidosis: Na + K as acetate à bicarbonate salts Respiratory acid-base disorders: underlying cause or adjust ventilator settings Pharm III Final Exam Enteral Nutrition: G/J tube Indications Hemodynamically stable pts at risk of malnutrition w/ anticipated no PO x 1-2w Contra- Complete intestinal obstruction GI fistula (high-output >500mL/d) indications Extreme short bowel Severe v/d Hemodynamic instability Intestinal ischemia Orogastric Nasal/facial trauma Sinusitis NG Tube MC short-term enteral access Stomach decompression Prolonged use: sinusitis, ulceration Gastric ileus Ø NG; risk aspiration Preferred ↓ risk of infection EN > PN Avoid GI mucosal atrophy Prevent bacterial translocation (gut bacteria can cross weakened intestinal barrier) Complications Improper tube placement or displacement Clog: prevent by flushing w/ warm water, cola, pancreatic enzymes, NaHCO3 Aspiration pneumonia: elevate head of bed 30-45°; monitor gastric residuals Administration Liquids should be diluted w/ 2-3x med volume of Drugs Mix crushed tabs/capsules w/ 10-15mL sterile water, inject separately Do NOT crush sustained-release or enteric-coated pills To help bioavailability: D/c tube feedings before + after drug administration Consider feeding tube location + subsequent drug absorption Pharm III Final Exam Transgender Med Spironolactone Transgender Women Monitor K à hyperkalemia Estrogen Monitor E2 Testosterone Transgender Men Monitor serum TE Before GAHT 1. Confirmation of the attainment of the age of consent 2. Confirmation preferably from MHP or Registered Clinical Psychologist 3. Confirmation that the patient can understand the consequences and possible risks associated and is capable of taking hormones in a responsible manner 4. Affidavit affirming the name and the preferred gender (optional) 5. Documented dressing in confirmation of the appropriate gender (real-life experience) >3 mo duration is preferable but not mandatory 6. PE: Height, weight, BP, examination of breasts & genitalia (with due consent) 7. Labs: Basic for all, some additional tests may be necessary 10. Informed consent for GAHT including the risks and benefits. 11. Counselling for healthy lifestyle w/ body weight, substance abuse (smoking) 12. Control of other comorbidities if coexisting (eg. hypertension and diabetes). 13. Counselling for the option of cryopreservation of oocytes and embryos 14. Counselling against self-medication Suppression of GnRH analogs, antiandrogens, antiestrogens, medroxyprogesterone acetate Puberty Along w/ GAH Hospice Care: end-stage illness or