Chamberlain College of Nursing:NR 566 Week 5 final study guide Latest,100% CORRECT

Chamberlain College of Nursing:NR 566 Week 5 final study guide Latest Chapter 18: Drugs Affecting the Hematopoietic System • Know the pharmacodynamics, pharmacotherapeutics clinical use, drug interactions and adverse drug reactions for: Anticoagulants • Pharmacodynamics • Oral anticoagulants such as warfarin (Coumadin) inhibit the hepatic synthesis of several clotting factors, including factor X. • Heparin inhibits the activity of several activated clotting factors by accelerating the activity of antithrombin III. • LMWH enoxaparin (Lovenox) potentiates the activity of antithrombin III and inactivates factors Xa and IIa (thrombin). • Dabigatran (Pradaxa) is a direct thrombin inhibitor. • Thrombin is required for the conversion of fibrinogen to fibrin in the clotting cascade, thus dabigatran's inhibition of thrombin prevents thrombi from forming. • Fondaparinux (Arixtra) is a selective inhibitor of antithrombin III and a factor Xa inhibitor. • Rivaroxaban (Xarelto) an anticoagulant, is a highly selective factor Xa inhibitor that inhibits thrombin formation and the development of thrombi. • Apixaban (Eliquis) is a selective inhibitor of factor Xa. • Aspirin antagonizes the cyclooxygenase pathway and interferes with platelet aggregation. • NSAIDs have this same action. • NSAIDs are not used as antiplatelet drugs, but this explains why concurrent use with anticoagulants is contraindicated • Ticlopidine (Ticlid) and clopidogrel (Plavix) reduce platelet aggregation by inhibiting the ADP pathway of platelets. • Unlike aspirin, they have no effect on prostaglandin metabolism. • Ticagrelor (Brilinta) reversibly interacts with the platelet P2Y12 ADP-receptor to prevent platelet activation. • Vorapaxar (Zontivity) is a protease-activated receptor-1 (PAR-1) antagonist, inhibiting thrombin-induced and thrombin receptor agonist peptide-induced platelet aggregation • Pharmacotherapeutics: • Precautions and Contraindications • All anticoagulants are contraindicated for patients who are hypersensitive to the drug or actively bleeding or who have hemophilia, thrombocytopenia, severe HTN, intracranial hemorrhage, infective endocarditis, active tuberculosis, or ulcerative lesions of the GI tract. • Heparins are contraindicated in advanced hepatic or renal disease. • They may be used in patients who are actively bleeding to treat DIC • Heparin is Pregnancy Category C: stillbirth, prematurity • Some heparin preparations contain benzyl alcohol: known to cause “gasping syndrome”: • fatal toxicity in neonates • Hyperkalemia may develop • Use for patient with DM or renal insufficiency requires care and frequent monitoring of aPTT • Has been associated with fatal medication errors r/t different strengths of preparations • JCo: anticoagulant therapy is a National patient Safety Goal: plan in place at each facility to reduce patient harm • LMWHs are contraindicated for patients with allergies to pork, sulfites, or benzyl alcohol; uncontrolled bleeding; and in patients who have antiplatelet antibodies • Renal impairment: cautious use • Body weight less than 50 kg associated with increased r/f bleeding: • enoxaparin dose adjustment • Cautious use: untreated HTN, retinopathy (HTN or DM caused), severe liver disease, recent Hx of ulcer, or malignancy • Not used for thromboprophylaxis in patients with mechanical heart values: especially pregnant (r/f heart value thrombosis) • Enoxaparin: Preg Cat B, tinzaparin: teratogenicity and fetal death, fondaparinux: Preg B • First line drug for women who require antithrombotic therapy during pregnancy: LMWH • Pharmacokinetics of LMWH is altered during pregnancy • Warfarin • Hepatic dysfunction potentiates response through impaired synthesis of coagulation factors • Use with caution: Hypermetabolic states produced by fever or hyperthyroidism increase responsiveness to warfarin: • r/t increased catabolism of vit K dependent coagulation factors • Increased r/f bleeding in older adults • Caution use based on balance between potential for decreased r/f thromboembolism and the risk for bleeding especially in those with dementia or severe cognitive impairment: Hx of three falls in the previous year or recurrent injurious falls, uncontrolled HTN, or non-adherent or unreliable • Warfarin is Pregnancy Category X: Crosses placenta and can cause hemorrhagic disorders in the fetus and serious birth defects • Safe during lactation • Rivaroxaban (Xarelto): Black-Box Warning: premature discontinuation of anticoagulants including rivaroxaban may lead to thrombotic events. • An increased risk of stroke is seen in patients with atrial fibrillation when transitioning to warfarin • Rivaroxaban is Pregnancy Category C and is not recommended for use in pregnant women. • Apixaban (Eliquis): Black Box warning premature discontinuation leading to thrombotic events • Although there are no well-controlled studies: Pregnancy Category B • Hypersensitivity to aspirin and cross-sensitivity with NSAIDs may occur, contraindicating the drug • Aspirin hypersensitivity is more prevalent in patients with asthma, nasal polyps, or chronic urticaria. • Reye syndrome has been associated with its use in children and teenagers who have influenza or chickenpox. • Reversible hepatotoxicity has occurred • Use with caution in liver damage, preexisting hypoprothrombinemia, or vit K deficiency • Preg Cat C and Cat D in third trimester • Avoid during lactation • Clopidogrel and ticlopidine: severe hepatic disease (r/f bleeding d/o), do not use in these patients • Not recommended for patients with GI d/o • Preg Category B • Ticlopidine: clearance increased with age, older adults increased sensitivity to this drug (closely monitor or ADRs) • Older adults: increased levels of clopidogrel: no dosage adjustments • In older adults clopidogrel is a safer drug • Ticlopidine: elevations in cholesterol and TC within 1 month of therapy: factor in HLD • Ticagrelor: Black-Box Warning to not use in a patient with active pathological bleeding or history of intracranial hemorrhage. • Ticagrelor should be discontinued 5 days prior to any surgery. • Dabigatran: Black-Box Warning concerning discontinuation increasing risk of thrombotic events. • There is no reversal agent available for dabigatran • Vorapaxar: Black-Box Warning to not use in patients with a history of stroke, TIA, intracranial hemorrhage, or active pathological bleeding. • Vorapaxar is Pregnancy Category B, with no congenital malformations found in animal studies • ADRs • All anticoagulants: excessive bleeding • Risk is higher early in therapy, with wide fluctuations in aPTT or INR, and older adults (especially women over 60) • Heparins: cause thrombocytopenia and anemia • More likely with bovine than with porcine • Early thrombocytopenia 2 to 3 days after starting therapy and delayed forms 7 to 12 days • Platelet below 100,000: d/c heparin • Enoxaparin antidote: protamine sulfate 1 mg for each mg of enoxaparin dalteparin and tinzaparin: 1 mg for each 100 anti-Xa IUs of dalteparin • Slow IV injection • Fondaparinux: no known antidote • Heparin has a short half-life: Tx is usually d/c of the drug • Protamine sulfate antidote for heparin OD • Warfarin: toxicity and OD Tx withholding one or more doses • Or 1 to 10 mg of vitamin K is the antidote for minor bleeding • 5 to 50 may be used for frank bleeding • Hemorrhagic skin necrosis in women and cyanotic toes in men have been reported • r/t transient inhibition in proteins S and C • Allergic reactions: symmetrical, maculopapular, erythematous lesions • Some are isolated and some confluent: face, neck, and torso • May not appear until 8 to 10 days • Ribaroxaban: bleeding is major ADR • No reversal agent • Back pain, upper ABD pain, osteoarthritis, dyspepsia, and fatigue • Apixaban: bleeding • No reversal agent • ASA: gastric erosions: increased r/f serious upper GI bleeding • More likely when used in combo with other anticoags such as warfarin • Salicylism (tinnitus) : serum levels above 200 mcg/mL • Toxicity: tinnitus, HA, hyperventilation, agitation, confusion, lethargy, diarrhea, and sweating • Ticagrelor: bleeding • Dyspnea: sometimes improves with use or must be d/c • HA, cough, dizziness, and nausea • Ticlopidine: reversible neutropenia at 3 weeks to 3 months after initiation of therapy • Severe neutropenia (450) or thrombocytopenia (80,000) d/c drug • Clopidogrel: ADRs similar to ASA, safe and effective • Dabigatran: bleeding • GI ADRs: dyspepsia and gastritis-like symptoms • Angioedema and thrombocytopenia • Vorapaxar: bleeding • Anemia, depression, and rashes or eruptions • Drug Interactions • Cephalosporins and PCNs given parenterally associated with coagulopathies, increased r/f bleeding when given with Heparin • Second and third gen cephalosporins and high doses of PCNs: increased r/f bleeding with Warfarin • Drugs that affect platelet functioning or cause hypoprothrombinemia (ASA, NSAIDS, dipyridamole, quinidine, and valproic acid: increased r/f bleeding • Heparin and LMWHs: similar drug interactions: also interact with antiplatelets including NSAIDS and dextran • Foods can effect anticoags • Warfarin: many drug interactions and increased INR monitoring within 4 to 7 days when other drugs are started or stopped even ABX • Vit K: antagonistic interaction with warfarin: decreases effectiveness • Inhibitors of CYP 1A2, CYP 2C9, or CYP 3A4 increase effect of warfarin • Inhibitors decrease the effectiveness of warfarin • Interacts with any other drug that increased bleeding: anticoags, antiplatelets, NSAIDS and SSRIs • ABX and antifungals may affect INR • Herbal Productions may increase bleeding: ginkgo biloba and garlic • Decrease effectiveness: St John’s wort, ginseng, and coenzyme Q10 • May influence metabolism of warfarin: St John’s wort, echinacea, ginkgo, goldenseal, AND GRAPEFRUIT JUICE • Dabigatran: rifampin (decreased levels of dabigatran) • Dronedarone increased dabigatran levels by 70 to 150% • CCB verapamil: increases dabigatran • Amiodarone increases dabigatran • Clopidogrel increases dabigatran • Ticagrelor: metabolized by CYP 3A4: avoid strong inhibitors ketoconazole, itraconazole, voriconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir, and telithromycin • Avoid inducers: rifampin, dexamethasone, phenytoin carbamazepine, and phenobarbital • Vorapaxar: avoid with CYP3A inhibitors • Avoid use of inducers (rifampin, carbamazepine, St John’s Wort, and phenytoin • Clinical Use and Dosing Prevention and Treatment of Thromboembolism • Warfarin: drug of choice for prevention of venous thrombosis, systemic thrombosis, and pulmonary embolism o For prevention: give dose sufficient for INR between 2 and 3 o Beginning dose is 10 mg daily for the first 2 days with a recheck of INR in two to three doses o ICSI guidelines: recommend starting warfarin at 5 mg/day with a range of 2.5 mg to 7.5 mg/day o Further dosing is based on INR o Lower initiation doses for: ▪ Older than 75 ▪ Multiple comorbid conditions ▪ Poor nutrition (low albumin) ▪ Elevated INR when off warfarin ▪ Elevated LFTS ▪ Changing thyroid status o If INR is greater than 2 after the first 3 doses, consider decreased the dose by one half o If INR raises rapidly: search for reasons: drug interactions, poor nutrition, infection, or systemic disease process • Acute PE, DVT, or acute systemic embolization: admit to hospital for IV anticoagulation o Heparin, LMWH, or SC fondaparinux and then placed on oral anticoags o Treat while waiting on Dx tests o Acute PE: heparin, LMWH, or fondaparinux for at least 5 days until INR is greater than or equal to 2 for 24 hrs o ACCP recommends staring warfarin on the first day of Tx in conjunction with heparin, LMWH, or fondaparinux or SX heparin o PE due to transient (reversible) risk factor is warfarin for 3 months • Superficial Vein Thrombosis: 45 days of prophylaxis with fondaparinux or LMWH o Lower limb of at least 5 cm in length o ACCP recommends fondaparinux 2.5 mg/day over prophylactic LMWH • Deep Vein Thrombosis: Divided the Tx of acute DVT into acute treatment of DVT of the leg and Tx of the upper extremity DVT o Leg or UE: short term Tx with SC LMWHs, SC fondaparinux, or IV or SC heparin for at least 5 days and until the INR is 2 for 24 hr o LMWH and SC fondaparinux: preferred over heparin o Warfarin: initiated on the first Tx day (like PE) • Idiopathic DVT: maintained on warfarin with target of 2.5 (range 2.0 to 3.0) for 3 months • Indwelling Cline: at r/f DVT o Tx is the same as for leg DVT o After Cath removed: 3 months of anticoags (Warfarin) • All other patients requiring anticoags therapy can be started on Warfarin as OPs o 10 mg/day or 5 mg/day, o Unless patient wt. is less than 110 lbs., over 75, or at ARF bleeding ▪ Start these patients on 2.5 mg/day o Steady state is achieved in 5 to 7 days: dosage adjustments are made ATT based on INR • Goal of therapy is an INR of 2 to 3 for all Tx durations • For patients with DVT or PE and CA: LMWH for 3 to 6 months o Referral for management • Air travel time longer than 8 hrs: increases r/f thrombus formation o Wear loose clothing, avoid tight clothing around the waist or lower extremities, good hydration, and frequent calf muscle exercises o At high risk for DVT: wear compression stockings 15 to 30 mm Hg during air travel • Immobility (bedrest): ambulation as tolerated o Use of compression stocking with 30 to 40 mm Hg for 2 years after DVT episode Prevention of Embolic Stroke in AFib • Low risk for stroke: ASA 75 mg to 325 mg daily • Intermediate risk for stroke: oral anticoags o Anticoags or a combination of ASA and clopidogrel • High risk for stroke: oral anticoags o ACCP recommends: 150 mg of dabigatran BID rather than warfarin • For patients with paroxysmal AFib at high risk for stroke: warfarin target INR between 2 to 3 • For AFib and mitral stenosis: follow recommendation of those at high risk o If valve replacement: follow recommendations for those with heart valves regardless of AFib • Apixaban: to reduce risk of stroke and systemic embolism in non-valvular AFib o 5 mg BID o For those older than 80, less than 60 kg, or crt 1.5 dose at 2.5 mg BID Mitral Valve Disease • Rheumatic MVD but no AFib and left atrial diameter of less than 55 mm: no therapy • Rheumatic MVD with left atrial diameter of greater than 55 mm or left atrial thrombus or AFib or previous embolism: warfarin target INR of 2.5 • Therapy is continued indefinitely in all cases Antithrombotic Therapy for Ischemic Stroke • Acute ischemic stroke or TIA: early (within 48 hours) ASA therapy at 160 to 325 mg • ACCP has three options for long term therapy after noncardioembolic ischemic stroke or TIA • 75 to 100 mg ASA/day • Combo of ASA (25 mg) and ER dipyridamole or clopidogrel • Patients with Hx of ischemic stroke or TIA with AFib: 150 mg dabigatran BID over warfarin Recurrent Embolism or Prosthetic Heart Valves • Warfarin: drug of choice o Therapy initiated and maintained the same as for prevention of venous thrombosis o Except that the target INR is valve dependent • For patients with additional risk factors (AFib, MI, left atrial enlargement, endocardial damage, and low EF) o 75 to 100 mg/day of ASA should be added to Warfarin protocol o The same is true for patients with caged ball or caged disc valves • Bioprosthetic valves in SR: 75 to 100 mg/day of ASA o Therapy is continued indefinitely for mechanical heart valves • For systemic embolization that recurs after 6 months of therapy: therapy is continues for an additional 12 months • Pregnant patients with MHV: require anticoags o Use one of three treatment regiments ▪ LMWH BID ▪ SC heparin every 12 hours ▪ Or SX heparin or LMWH until the 13th week of pregnancy then warfarin until close to delivery with LMWH or heparin is resumed o Warfarin is a known teratogen: may cause fetal hemorrhage o Women with MHV at high risk of thromboembolism: ASA 75 to 100 mg/day added to anticoags regimen o Women on warfarin planning on pregnancy: frequent pregnancy tests and substitution of heparin or LMWH when pregnancy is achieved o Anticoagulation specialist and perinatologist Prevention of MI • Several protocols are effective in prevention of MI in patients with and w/o CAD o Over 50 w/o symptomatic CVD: ASA 75 to 100 mg/day o Established CAD (1 year post ACS, with prior revascularization, coronary stenoses greater than 50% by angiogram, and/or evidence for cardiac ischemia on Dx testing): ASA 75 to 100 mg/day or clopidogrel (75 mg/day) o Patients with ACS who have undergone PCI with or w/o stent placement: dual therapy: 90 mg ticagrelor BID plus ASA 75 to 100 mg/day ▪ ACCP: recommends use of ticagrelor over clopidogrel in PCI • Patient who have experienced an MI: anticlot therapy o STEMI: fibrinolytics then ongoing therapy after hospital d/c • Post-AMI TX: • Anterior AMI w/ r/f LV thrombus who do not get a stent: warfarin (INR target 2 to 3) and ASA 75-100 mg/day • Patients with an acute MI who have a bare metal stent: triple therapy o Warfarin (INR target 2-3), ASA low dose, and 75 mg daily clopidogrel for a month after stent placement o Then warfarin and one antiplatelet drug for months 2 and 3 o After 3 months: d/c warfarin and replaced with dual antiplatelet therapy (90 mg ticagrelor BID plus ASA 75 to 100 mg/day for up to 12 months • Patients with DM: ASA 75 to 162 mg/day • Vorapaxar: approved for reduction of thrombotic CV events in patients with Hx of MI or with PAD o Patient takes one 2.08 mg tablet daily in addition to ASA or clopidogrel Prevention of Post-Operative Thromboembolism • J Co requires that all hospital have a formal active strategy to prevent venous thrombosis • LMWH, low dose heparin, or fondaparinux o Moderate-risk major general surgery, higher risk patients who are having a major procedure for CA, major vascular surgery, major gynecological surgery, major urological procedures, bariatric surgery, thoracic surgery, and many orthopedic surgeries • Length of Tx: determined by the type of surgery, ranging from a single dose to 10 days for most orthopedic procedures, to 28 days in high risk patients, patients undergoing major gynecological surgery, and patients having major surgery for CA • Hip or knee replacement: Apixaban 2.5 mg BID Perioperative Therapy of Patients on Warfarin or Antiplatelet Therapy • Stop Warfarin 5 days before surgery and resume 12 to 24 hours after surgery • For prevention of thromboembolism (MHV, AFib): may require parenteral anticoags perioperatively o Decision to bridge with heparin is determined by balancing r/f bleeding due to the surgical procedure and clotting risk due to the underlying d/o • Low bleeding risk: skin biopsies, cataract surgery, and most dental procedures can remain on warfarin o Dental procedures: tranexamic acid mouthwash can be used w/o interrupting anticoags therapy • Low risk thromboembolic risk (AFib w/o prior stroke or remote Hx of venous thrombosis): warfarin stopped 5 days prior to surgery and resumed that evening of surgery • High thromboembolic risk (PHV): bridging with LMWH or unfractionated heparin may be indicated • Antiplatelets: do not d/c before surgery • Rational Drug Selection • Cost can be significant • PO anticoags are preferred: no special equipment or skills to administer, less expensive • Brands are not interchangeable • Monitoring • Dosage adjustments of warfarin is by INR o Daily INRs initially to guard against excessive anticoagulation until therapeutic range for 2 days o Testing interval is then lengthened to 2 or 3 times weekly for 1 or 2 weeks o Self-testing is increasing in popularity: competency using the equipment o Computer assisted, validated, decision, support tools for warfarin dose regulation: more effective than traditional dosing at maintaining therapeutic INR values o Evidence based dosing tools, patient Edu, follow up, and optimal patient communication: best patient outcomes o CYP 2C9 or VKORC1 gene variants: may require 2 to 4 weeks longer to reach target INR • Monitoring heparin adjustments: aPTT blood tests o Goal of therapy is 1.5 to 2.5 times the control o Platelet and Hct every 2 or 3 days o Thrombocytopenis: tends to occur about 4th day and resolves despite continued heparin therapy o Day 8: thrombocytopenia severe enough to require d/c med o After this time period: periodic testing of platelet and Hct and occult blood in stool o Low doses of SC heparin (5,000 U BID) do not require monitoring r/t does not prolong the aPTT • LMWH: same periodic monitoring of platelet and Hct: likelihood of thrombocytopenia is much less o Test for monitoring: anti factor Xa assay o aPTT may be prolonged: dopes not reliably reflect activity o Routine Xa not recommended: except in pregnant patients • ASA dose for antiplatelet therapy is low to moderate o Serum salicylate level is approximately 100 mcg/mL • Clopidogrel: safety profile similar to ASA, no routine monitoring • Ticlopidine: Severe neutropenia and thrombocytopenia have occurred o CBC, WBC with differential counts every 2 weeks, starting from the second week to the end of the third month of therapy o More frequent monitoring is necessary for patients whose absolute neutrophil counts consistently decline or are 30% lower than baseline o After the first 3 months: CBCs as needed for s/s of infection • Also know: Use of anticoagulants in pregnancy: • Enoxaparin is Pregnancy Category B. • Teratogenicity and fetal death have been reported as well for tinzaparin, although a clear cause-and-effect relationship was not established. • Fondaparinux is also listed as Pregnancy Category B but without adequate or well-controlled studies in pregnancy. • LMWHs do not cross the placenta and do not cause teratogenicity or fetal bleeding • The American College of Chest Physicians recommends LMWH as the first-line drug for women who require antithrombotic therapy during pregnancy: enoxaparin (Lovenox), dalteparin (Fragmin), and tinzaparin (Innohep) • The pharmacokinetics of LMWHs are altered during pregnancy. • LMWH passes in small amounts into breast milk but has low oral bioavailability and may be safely used during breastfeeding Thromboprophylaxis • Prevention and treatment of thromboembolism: o Warfarin is drug of choice for the prevention of venous thrombosis, systemic thrombosis, and pulmonary embolism • Prevention of embolic stroke in AFib: o Low risk for stroke: ASA 75 mg to 325 mg daily o Intermediate risk for stroke: oral anticoags ▪ Anticoags or a combination of ASA and clopidogrel o High risk for stroke: oral anticoags ▪ ACCP recommends: 150 mg of dabigatran BID rather than warfarin o For patients with paroxysmal AFib at high risk for stroke: warfarin target INR between 2 to 3 • Prevention of MI o Several protocols are effective in prevention of MI in patients with and w/o CAD ▪ Over 50 w/o symptomatic CVD: ASA 75 to 100 mg/day ▪ Established CAD (1 year post ACS, with prior revascularization, coronary stenoses greater than 50% by angiogram, and/or evidence for cardiac ischemia on Dx testing): ASA 75 to 100 mg/day or clopidogrel (75 mg/day) ▪ Patients with ACS who have undergone PCI with or w/o stent placement: dual therapy: 90 mg ticagrelor BID plus ASA 75 to 100 mg/day • ACCP: recommends use of ticagrelor over clopidogrel in PCI o Patient who have experienced an MI: anticlot therapy ▪ STEMI: fibrinolytics then ongoing therapy after hospital d/c o Post-AMI TX: o Anterior AMI w/ r/f LV thrombus who do not get a stent: warfarin (INR target 2 to 3) and ASA 75- 100 mg/day o Patients with an acute MI who have a bare metal stent: triple therapy ▪ Warfarin (INR target 2-3), ASA low dose, and 75 mg daily clopidogrel for a month after stent placement ▪ Then warfarin and one antiplatelet drug for months 2 and 3 ▪ After 3 months: d/c warfarin and replaced with dual antiplatelet therapy (90 mg ticagrelor BID plus ASA 75 to 100 mg/day for up to 12 months o Patients with DM: ASA 75 to 162 mg/day o Vorapaxar: approved for reduction of thrombotic CV events in patients with Hx of MI or with PAD ▪ Patient takes one 2.08 mg tablet daily in addition to ASA or clopidogrel • Prevention of Post-Operative Thromboembolism o J Co requires that all hospital have a formal active strategy to prevent venous thrombosis o LMWH, low dose heparin, or fondaparinux ▪ Moderate-risk major general surgery, higher risk patients who are having a major procedure for CA, major vascular surgery, major gynecological surgery, major urological procedures, bariatric surgery, thoracic surgery, and many orthopedic surgeries o Length of Tx: determined by the type of surgery, ranging from a single dose to 10 days for most orthopedic procedures, to 28 days in high risk patients, patients undergoing major gynecological surgery, and patients having major surgery for CA o Hip or knee replacement: Apixaban 2.5 mg BID • The ACCP recommends the use of LMWH, low-dose heparin, or fondaparinux as thromboprophylaxis in the following surgical procedures: moderate-risk major general surgery, higher-risk patients who are having a major procedure for cancer, major vascular surgery, major gynecological surgery, major urological procedures, bariatric surgery, thoracic surgery, and many orthopedic surgeries • LMWH should not be used for thromboprophylaxis in patients with mechanical prosthetic heart valves, especially pregnant women, as prosthetic heart valve thrombosis may occur. Population needed warfarin starting dose adjustment: Older than 75 years • Multiple comorbid conditions • Poor nutrition (low albumin) • Elevated INR when off warfarin • Elevated liver function tests • Changing thyroid status INR target goals o Prevention of DVT, PE, or systemic embolism: 2-3 o Prevention of embolic stoke in patient with AFib: 2-3 o Patients with St. Jude Medical bileaflet PHV: 2-3 o Patients with tilting disk valves and bileaflet PHV ion aortic position: 2.5-3.5 o Patients with CarboMedics bileaflet valve or Medtronic Hall tilting disk PHV: 2-3 o Patients with MHV and high risk (atrial thrombus, AFib, hypercoagulable state, and low EF): 2.5-3.5 o Patients with caged ball or caged disk PHV: 2.5 to 3.5 o Patients with bioprosthetic valve in mitral position: 2-3 o Patients with bioprosthetic vale in aortic position: 2-3 Anticoagulant preferred for patients at high risk for stroke with atrial fibrillation: • High risk for stroke: oral anticoags o ACCP recommends: 150 mg of dabigatran BID rather than warfarin • For patients with paroxysmal AFib at high risk for stroke: warfarin target INR between 2 to 3 o than 80, less than 60 kg, or crt 1.5 dose at 2.5 mg BID Drugs which decrease anticoagulant medication effectiveness: o Heparin: NTG decreases effect of heparin o Warfarin: oral contraceptives, barbiturates, carbamazepine, chlordiazepoxide, cholestyramine, dicloxacillin, griseofulvin, nafcillin, rifampin, flu vaccine, foods high in vitamin K, large amounts of avocado, soy milk, ginseng o Clopidogrel: phenytoin, tolbutamide, tamoxifen, torsemide, Fluvastatin, NSAIDS Chapter 19: Drugs Affecting the Immune System • Know the pharmacodynamics, pharmacotherapeutics clinical use, drug interactions and adverse drug reactions for: Immunizations Immunizations • Frequently encountered in primary care: Prevent the spread of infectious diseases • Single best technique for preventing infectious disease Attenuated Vaccines Influenza Live, Attenuated Influenza Vaccine • Pharmacodynamics o LAIV: included strains dependent upon predicted circulating influenza strains • Pharmacotherapeutics o Contraindicated: o Egg or egg product hypersensitivity, asthma, reactive airway disease, or other chronic d/o of the pulmonary or CV systems o Persons with underlying medical conditions: DM, renal dysfunction, and hemoglobinopathies o Known or suspected immunodeficiency diseases or immunosuppressive therapy ▪ Patients who are immune compromised or with HIV should not be vaccinated with LAIV o Do not administer to those with Guillain-Barre syndrome o Preg Cat C: should not be vaccinated with LAIV o Contraindicated: children under 2 y/o r/t increased incidence of RAD and asthma o Contraindicated in children or adolescents receiving ASA or other salicylates r/t Reye syndrome • ADRs o Usually well tolerated: mild and transient ADRs o Adults: reported resp symptoms: runny nose or nasal congestion, HA, sore throat, cough, and muscle aches o No serious ADRs have been reported in children older than 2 or adults • Drug Interactions o Wait 48 hrs after stopping antivirals to receiving LAIV o May be concurrently administered with MMR and varicella o May be given with any of the inactivated vaccines ▪ May be given with inactivated or live vaccines on the same day if not separate vaccines by 4 weeks • Clinical Use and Dosing o Children and adults aged 9 through 49: 0.2 mL LAIV o Children 5 to 8: w/o prior flu immunization: two doses (0.2 mL each) separated by 4 weeks o Children 8 years and younger who have previously received two doses in the same year need only one day annually o Intranasally: half of drug in each nostril • Monitoring and Patient Education o Lab monitoring not necessary o Live virus: stay away from close contact with immunocompromised persons for 7 days after admin o Report serious or moderate reactions: difficulty breathing, wheezing, hives, swelling, unusual weakness, and temp 38.9C or higher Measles, Mumps, and Rubella Vaccine (MMR) ▪ Pharmacodynamics o Stimulates the immune system to produce antibodies by inducing a subclinical infection with attenuated virus particles o Subclinical infection is not contagious o The antibodies are capable of virus neutralization by complement activation, induction of cell mediated immunity , and opsonization o M-R-Vax II: commonly used combo vaccine also ProQuad ▪ Pharmacotherapeutics o The virus has been detected 1 to 4 weeks in the pharynx or nose after vaccine administration: does not appear to cause virus transmission o Relatively few true contraindications o Previous anaphylactic reaction to the MMR, neomycin, or gelatin ▪ Hx of contact dermatitis to neomycin is not a contraindication o Not recommended for immunocompromised patients ▪ Do not give to patients who are severely immunocompromised r/t CA, leukemia, or lymphomas or on immunosuppressive drug therapy (high dose steroids or radiation) o May be given to close contacts of immune suppressed patients (health care workers) o Deferred if a patient has moderate or severe febrile illness ▪ Minor illnesses with or w/o fever (diarrhea, URI, or OM) are not contraindications o Patients who receive blood products should wait 3 months before getting the MMR o MMR should be given at least 2 weeks before immune globulin (IG) ▪ Those who receive IG should wait 3 to 11 months o Do not give to pregnant women or women who may become pregnant within 3 months ▪ r/t congenital rubella syndrome in the infant o Safely given to children of all given ▪ May not be immunogenic in infants under 12 months ▪ If given under age 12 months, revaccinate at 12 to 15 months, and a third dose at 4 to 6 y/o ▪ ADRs o Children: fever 7 to 12 days after vaccination, lasts 1 to 2 days otherwise asymptomatic o May cause transient maculopapular rash 7 to 10 days o May cause febrile seizure: highest risk at 6 to 14 days o Thrombocytopenia: rare and may occur within 2 month, generally benign and transient o Injection site pain, redness and swelling, muscle or joint aches, and dizziness or light headedness ▪ Drug Interactions o Do not give to patients receiving immunosuppressants (high dose corticosteroid, interferon, and antineoplastic drugs) r/t insufficient response to immunization o MMR may be inactivated by IG: give 14 to 30 days before or 3 months after o Delay PPD for 4 to 6 weeks after MMR: temporary decrease in tuberculin skin sensitivity o MMR and varicella: compatible if done the same day (different needles, separate sites) ▪ If not given the same day: separate by 1 month o MMRV (ProQuad): measles, mumps, rubella, and varicella in children 12 months to 12 y/o ▪ First dose separate MMR and varicella vaccines r/t risk of febrile seizures with MMRV o MMR can be given with LAIV on the same day, if not 4 weeks ▪ Clinical Use and Dosing o Routinely given SC at 12 to 15 months with repeat dose at age 4 to 6 y/o o Second dose: may be given as soon as 4 weeks after the first dose o Indicated ruing an epidemic or before international travel o CDC recommends second dose as MMRV o Adults: born in 1957 or later who are at least 18 should receive at least one dose of MMR if no serological proof of immunity or documentation of a dose given on or after the patient’s first birthday o High risk groups: students entering college, military, and international travelers, healthcare workers: two doses o Adults born before 1957 are considered immune but documentation of immunity is important ▪ Monitoring and Patient Education o Labs not needed o Rubella titer: to determine immunity o All patients or the parents/guardians: required by law to receive Vaccine Information Statements that are developed by the CDC o Provide adequate information to the patient before immunization should be made o Fever up to 103 7 to 12 days after admin o Patient may experience rash, malaise, or sore throat Measles, Mumps, Rubella, and Varicella Vaccine o Pharmacodynamics o Similar to MMR o MMRV (ProQuad): live attenuated virus, produces a subclinical infection o Creates active immunity to measles, mumps, rubella, and varicella o Pharmacotherapeutics o Same as for MMR: Hx of anaphylactic reaction to neomycin or gelatin or any other component of the vaccine ▪ Immediate Tx for anaphylaxis reaction should be available when administering MMRV o Contraindication: primary or acquired immunodeficiency (HIV/ADIS and patients with blood dyscrasias, leukemia, lymphomas, or other malignant neoplasms affecting the bone marrow or lymphatic system o Preg Cat C: do not administer, avoid pregnancy for at least 3 months o Untreated TB or febrile illness with temp greater than 101.3, deferred until well o Use with caution in patient with Hx of cerebral injury, seizures, or other conditions in which physiological stress due to fever should be avoided r/t increased risk of fever and febrile seizures with MMRV o Avoid for 3 months after blood transfusion or IG admin o ADRs o Similar to MMR o More likely to develop fever and rash o Injection site pain, erythema, and swelling o Drug Interactions o Same as MMR: immunosuppressants, IG, tuberculin skin tests, and salicylates o Clinical Use and Dosing o Given SC at 12 to 15 months o First dose may be given any time before age 12 o Three months should elapse before second dose of MMRV o MMRV: can be given 1 month after MMR o Patient Education o Talk with parents about increases risk of fever and febrile seizures with the combo vaccine Oral Poliovirus Vaccine (No longer used in the US but used in other countries) o Pharmacodynamics o Stimulates immune system to produce anti-poliovirus antibodies: Sabin poliovirus types 1, 2, and 3 o Live attenuated virus enters small intestine: replicates in villous epithelial cells o Specialized epithelial cells transport the viral antigens to the B cells and macrophages: produce antibodies in 1 to 2 weeks o Live attenuated poliovirus lingers in GI for 4 to 6 weeks o Two doses of PPV are needed for intestinal immunity ▪ Three doses for lifelong immunity o Pharmacotherapeutics o Contraindication: anaphylactic reaction to any previous dose of OPV o Do not use with neomycin or streptomycin hypersensitivity o Delay with moderate or severe febrile illness or severe resp infection o Contraindicated: viral GI infection, ongoing diarrhea, or vomiting o Immunocompromised patients may develop poliomyelitis from live poliovirus o Contraindicated: CA, leukemia, lymphoma, radiation therapy, immunodeficiency (HIV or AIDS) or drugs that effect immunity ▪ Use IVP in immune compromised patients and household members are immune compromised o Pregnancy Cat: C o ADRs o Low incidence of paralytic poliomyelitis (those who receive it and household contacts) o Most likely to occur after the first dose o Household members are exposed r/t virus shedding in feces o Drug Interactions o Do not administer to patients receiving immunosuppressants, r/t insufficient response to immunization ▪ Use IPV in these patients o MMR, MMRV, hep B, DTP, DTaP, influenza, and HIB may be given with OPV o Avoid concurrent administration with cholera vaccine, parenteral typhoid vaccine, or plague vaccine r/t increased ADRs o IG may be given with OPV o Clinical Use and Dosing o IPV is first choice for immunization o OPV: use only for special circumstances: mass vaccination campaigns to control outbreaks or in unvaccinated children who will be traveling in less than 4 weeks to endemic or epidemic areas Rotavirus Vaccine o Pharmacodynamics o Leading cause of gastroenteritis in infants and young children worldwide o RotaTeq live oral vaccine: contains five strains (Gi, G2, G3 or G4, P7) o Rotarix: G1, G3, G4, and G9 o Both vaccines are live vaccines that replicate in the small intestine and induce active immunity o Pharmacotherapeutics o Do not administer: ▪ Infants who are or may be potentially immunocompromised (including infants with blood dyscrasias, leukemia, lymphoma, or other malignant neoplasms, infants on immunosuppressive therapy) ▪ Infants with primary and acquired immunodeficiency states (HIV/AIDS) ▪ Infants who have received blood transfusion or blood products in the past 42 days o Delay vaccine with febrile illness except when withholding the vaccine creates greater risk to the patient o Minor URI with low grade fever (under 100.5) not a reason to withhold o Do not administer with acute gastroenteritis until it improves o Rotavirus may shed in stools: prudent to use caution if in contact with those with malignancies or otherwise immune compromised and contacts on immunosuppressive therapy o Hx of intussusception is a contraindication r/t increased risk of intussusception following the first dose o ADRs o ARF intussusception o RotaTeq: GI ADRs: vomiting, diarrhea o Rotarix: slight incidence of vomiting in the week after admin o Drug Interactions o Can be administered concurrently with DTaP, IPV, HIB, HBV, and pneumococcal conjugate vaccine o Clinical Use and Dosing o RotaTeq: series of three ready to use oral liquid doses ▪ 6 to 12 weeks first dose, second and third doses in 4 to 10 week intervals o Rotarix: two dose schedule of 1 mL/dose given at 2 to 4 months o May be given between 6 to 24 weeks, give the two doses 4 weeks apart o No considerations for blood products or IG Varicella Virus Vaccine o Pharmacodynamics o Varivax: live vaccine, produces IgG antibody humoral immune response to VZV o Also have cell mediated immune response: activation of CD41 helper T cells and CD 81 T lymphocytes o Efficacy is measured by protection against disease and protection against severe disease ▪ One dose: 94% over 10 years ▪ Two doses: 98% effective against any disease and 96% effective against household exposure o Vaccination appears to prevent serious illness even in those who do not seroconvert ▪ Post vaccination cases are mild, and recovery is quicker o Pharmacotherapeutics o Contraindicated: neomycin or gelatin hypersensitivity o Delay vaccine if moderate or severe illness present with or w/o fever o Immune compromised individuals: ARF development of varicella from use of live virus o Contraindicated: CA, leukemia, lymphoma, radiation therapy, and immunodeficiency, symptomatic HIV o Contraindicated: drugs that affect the immune system ▪ Those on low dose systemic steroids (asthma) if less than 2 mg/kg or less than 20 mg/day of prednisone and not otherwise immune compromised o May be given to a patient if an immune compromised person in the household o If a rash develops: avoid contact with immune compromised people for the duration of the rash o Avoid in pregnancy: Category C o Avoid pregnancy for 1 to 3 months o ADRs o Children and adults: fever, injection site reaction, and a vesicular rash o Adults and adolescents: two injections and have similar ADRs ▪ Fever, injection site reaction, generalized vesicular rash o Drug Interactions o Do not give to those taking immunosuppressants: r/t insufficient immunization o Avoid use during IG therapy, do not use for 3 to 11 months o Check for need to revaccinate if taken close together o MMR and varicella are compatible: given the same day, separate by 1 month if not o Can be given simultaneously with DTaP, DT, Td, HIB, IPV, OPV, PCV13, or HBV o Avoid ASA for 6 weeks after vaccination r/t Reye syndrome o Clinical Use and Dosing o Vaccinate at 12 to 15 months: all healthy children ▪ Second dose at 4 to 6 y/o (before kindergarten) ▪ Separate first and second dose by at least 3 months o Healthy adolescents age 13 and older w/o Hx of infection who have not been vaccinated: two doses 4 to 8 weeks apart o If a child is accidentally administered zoster vaccine (Zostavax) instead of varicella vaccine (Varivax): should be counted as a valid vaccine and reported to VAERS whether ADRs occur ▪ Child will still require two doses of varicella vaccine o Adults: w/o immunity should receive the vaccine ▪ Adults at high risk of exposure: live with children, live or work in an environment in which transmission is likely (teachers, healthcare workers, day care workers) or could occur (college dorm, correctional institution, military) or immune compromised household member ▪ Nonpregnant women of childbearing age, and international travelers o Adults should receive two doses: 4 to 8 weeks apart o Patient Education o ARF fever, injection site reaction, or vesicular rash Zoster Vaccine o Pharmacodynamics o Shingles is a localized and painful cutaneous eruption caused by reactivation of VZV o Latent in neuronal cell bodies and when reactivated causes shingles o Zoster vaccine (Zostavax): live attenuated VZV o Reduces risk of shingles by 50% and 66% effective in preventing post herpetic neuralgia o Reduces severity of zoster o Approved for adults aged 50 years and older o Most effective in patients aged 60 to 69 and least effective in those over age 80 o Pharmacotherapeutics o Contraindicated: Hx of anaphylactic reaction to neomycin, gelatin, or vaccine components o Do not give to those with primary immunodeficiency states o Do not give to those with leukemia, lymphoma, CA of the bone marrow or lymphatic system or AIDS r/t development of disseminated disease o Do not take while actively receiving high dose corticosteroids (prednisone), wait a month after stopping o Not approved for women of childbearing age and should not be used in pregnancy o Do not give to those with active TB or acute illness, or with fever o ADRs o Injection site pain/tenderness, erythema, swelling, and pruritis; HA o Drug Interactions o Stop antiviral drugs (acyclovir, famciclovir, and valacyclovir) 24 hours before vaccine admin o Do not use antiviral for at least 14 days after vaccination o Can be given before, after, or at the same time as blood products or antibody containing products o Stop long term/high dose prednisone for 1 month before vaccination o Short term or low dose may be vaccinated o Methotrexate low doses, azathioprine, or 6 mercaptopurine for Tx of RA, psoriasis, polymyositis, sarcoidosis, or IBD may be vaccinated with zoster vaccine o Clinical Use and Dosing o A single dose of zoster vaccine is recommended for all adults aged 60 years or older o SC tissue of deltoid o Can be given with Hx of herpes zoster o Can be given with Td, Tdap, and pneumococcal o Separate zoster vaccine and other live virus vaccines by 4 weeks o Zoster vaccine is not recommended for those who received the varicella vaccine o Patients with chronic medical conditions (CRF, DM, RA, and chronic pulmonary disease) may be vaccinated o Defer in severe illness or with fever o Can be given in minor acute illness w/o fever (URI) o Immunosuppressed: greater morbidity and mortality from herpes zoster o Give at least 14 days prior to immune suppressive therapy o Avoid for at least 24 months after stem cell transplant o Avoid antiviral meds for 14 days after vaccination o If a child is accidentally given zoster vaccine: valid vaccine, report to VAERS o If an adult is given varicella vaccine: not a valid dose and the zoster vaccine is given the same day o If not the same day 28 days later Oral Typhoid Vaccine Pharmacodynamics o Used to increase resistance to enteric fever caused by Salmonella typhi o Spread by ingesting water contaminated by feces from infected persons o Risk is greatest in travelers to South Asian, East and Southeast Asia, Africa, Caribbean, and Central and South America o OTV (Vivotif Berna): live attenuated vaccine Ty21a o Ingested and works in the small intestine to synthesize a lipopolysaccharide that evokes a protective immune response o 50 to 80% effective in preventing typhoid fever o Efficacy of protective immunity: dependent upon the size of the bacterial inoculum consumed Pharmacotherapeutics o Contraindication: hypersensitivity to typhoid vaccine o Do not give to immune compromised patients o Do not given during acute febrile illness or acute GI illness o Preg Cat C: if vaccine is needed use inactivated vaccine o Not recommended for children younger than 6 y/o: use inactivated vaccine in young children ADRs o Infrequent and transient and resolve with intervention o ABD pain, diarrhea, vomiting, fever, HA, and rash have been reported Drug Interactions o Mefloquine (Lariam) (antimalaria drug): can inhibit the growth of the live Ty21a strain: given either 24 hours before or after mefloquine o Immunosuppressants: insufficient response to the vaccine o OTV: do not given while receiving sulfonamides and ABX r/t prevention of sufficient degree of multiplication to induce a protective immune response Clinical Use and Dosing o Used for primary immunization against S. typhi in the following o Travelers to areas of increased risk o Household contact with a documented typhoid fever carrier o Lab workers o In patients over 6 y/o: dose is one capsule on alternative days for a total of four doses o Take 1 hour before meals (empty stomach) with a glass of cold water o Swallow whole o All four doses must be taken at least 1 week prior to travel Yellow Fever Vaccine Pharmacodynamics o Viral illness spread by some species of mosquitoes in Central and South America and in tropical regions of Africa o Endemic in sub Saharan African and tropical South America o Produces a hemorrhagic fever and is fatal in 20 to 50% of severe cases o All travelers should use personal protective measures to avoid mosquito bites o Vaccination is recommended for travel to endemic areas o Refer to current CDC guidelines for endemic areas because they can change o Certification of vaccination may be required to travel into some areas o Yellow fever vaccine (YF-Vax): live attenuated virus that is prepared by culturing the 17D strain virus in a living chick embryo Pharmacotherapeutics o Avoid in patient with Hx of egg hypersensitivity or sensitivity to chicken protein or gelatin o Contraindicated in immune compromised o Use with caution in HIV patients o Contraindicated: thymus d/o that affects immune function o Defer vaccination for 8 weeks following blood or plasma transfusion o Pregnancy Category C: use only if exposure risk is high o Contraindicated: infants younger than 6 months r/t increased r/f vaccine associated neurological disease o Use with caution in infants aged 6 to 8 months o Rare cases of encephalitis have occurred in infants at this age o Use with caution: aged 60 years and older r/t increased r/f serious ADRs after vaccination ADRs o Fever or malaise (7 to 14 days after vax) o Myalgia or HA o Anaphylaxis has occurred: keep epi on hand when given the vaccine o Very rare reaction: yellow fever vaccine associated viscerotropic disease: fever and multiple organ failure o Higher among those 60 and older o Case fatality ration is 53% o Yellow fever vaccine associated neurological disease: conglomerate of clinical syndromes including meningoencephalitis, GBS, encephalomyelitis, bulbar palsy, and Bell’s palsy o Adverse neuro outcomes are usually seen among infants as encephalitis but may occur at any age Drug Interactions o Concurrent vaccination with HAV, HBV, meningococcal vaccine, typhoid fever vaccine, DTaP, Tdap and measles vaccines is ok o Immunosuppressants: insufficient response to the yellow fever vaccine Clinical Use and Dosing o Immunization against yellow fever is recommended for all people over age 9 months who are living in or traveling to endemic areas o Dose is a single 0.5 mL dose given SC o Should be repeated every 10 years Bacillus Calmette-Guerin Vaccine Pharmacodynamics o BCG lowers the risk of serious complications of primary TB in children o Not widely used in the US but used in countries where TB is endemic o BCG stimulates natural infection with My tuberculosis and results in a T cell medicated immune reaction and immunity against TB but with variable degrees of protection o The protective effect of BCG used in children against military and meningeal TB is about 80% o It is less effective in adults Pharmacotherapeutics o Do not use in Active TB o PPD skin testing should be performed on all patients over 2 months of age o Contraindicated in CA, leukemia, lymphoma, radiation therapy, and immunodeficiency o Patients with symptomatic or asymptomatic HIV should not receive BCG o Drugs that affect the immune system: contraindicated o Take precautions to avoid accidental exposure to BCG solutions during preparation and administration because this is a live attenuated virus o Pregnancy Cat C: CDC does not recommend use ADRs o Normal reaction: skin lesions that appear within 10 to 14 days after the multiple puncture disc application o The lesions consist of small red papules at the site of admin o Papules reach max diameter (3 mm) after 4 to 6 weeks and then scale away and slowly subside o Lymphadenopathy: may occur in a regional lymph node and resolves spontaneously o Osteomyelitis: rare o BCG induced osteomyelitis: affects the epiphyses of the long bones and can occur from 4 months to 2 years after administration o Lupoid like skin reactions: Tx with INH for 3 months o Disseminated BCG infection and death are very rare and usually occurs in patients with impaired immune systems Drug Interactions o Anti-TB agents (RIF, INH, streptomycin) and immunosuppressives: interfere with development of an appropriate immune response o BCG: will cause PPD skin tests to give false positive readings for up to 10 years, after 10 years: a positive PPD usually indicates infection with M. Tuberculosis Clinical Use and Dosing o In the US: given only in very special circumstances: unavoidable risk of exposure to M. tuberculosis and failure of other methods of prevention and control of TB o Should be considered for infants and children who reside in settings in which the likelihood of TB transmission and subsequent infection is high provided no other measures can be implemented (removing children from the source of infection) o May be considered for health care workers who are employed in settings in which the likelihood of transmission and subsequent infection with TB strains resistant to INH and RIF is high o BCG: given to healthy infants from birth to 2 months w/o TB skin testing o After that, BCG is given only to children with negative Mantoux skin tests o Must be administered exactly as manufacturer suggests o Vaccine is dropped onto clean, dry skin over the deltoid muscle and spread over the area to be punctured, using the edge of the multipuncture disc o The prongs of the disc are coated with the virus by lightly dipping them into the spread vaccine o The prongs of the disc are pressing into the skin and held for 5 to 10 seconds o After the disc is removed: vaccine is respread to fill all the puncture areas o Additional vaccine may be applied to ensure a wet vaccine site o Keep the area dry for 24 hours, no dressing is required o The person administering: take precautions against coming into contact with the live virus o Educate not to touch the site r/t live virus o Keep clean until local reaction has resolved Inactivated Vaccines Diphtheria, Tetanus, and Pertussis Vaccine Pharmacodynamics o Various combinations of diphtheria, tetanus, and pertussis vaccines: basic pharmacodynamics are the same o Diphtheria toxoid: induces the production of antibodies against the exotoxin excreted by Corynebacterium diphtheria o Complete immunization (four doses, then boosters every 10 years) reduces incidence by 95% o Immunized persons who develop diphtheria have milder illness o Infection with C. diphtheria does not confer immunity: those previously infected should vax o Tetanus toxoid: contains antigens that induce the production of antibodies against the exotoxin excreted by Clostridium tetani o Duration of immunity: 10 years o Natural immunity to C. tetani does not occur in the US and patients with previous C. tetani infection should be vaccinated o Pertussis vaccine: inactivated pertussis antigens o Acellular pertussis vaccine contains one or more immunogens derived from Bordetella pertussis and unlike whole cell vaccine contains little or no endotoxin o Antibodies produced against B. pertussis Pharmacotherapeutics o In the US: DTaP be used for primary immunization of infants and children o DTaP contraindication: immediate anaphylactic reaction with a pervious dose o Encephalopathy w/in 7 days of a previous dose, unexplained by another cause: do not use ▪ In this case DT should be substituted for DTaP o Patients with unstable, progressive, neurological problems: defer until neuro status clarified o Precautions: previous temp of 105 or higher within 48 hours after a dose, Hx of continuous crying (more than 3 hours) within 48 hours of a dose, convulsions within 3 days of a previous dose, and collapse or shock like state (hypotonic-hyporesponsive episode) within 48 hours of a dose o Precautions: seizures 3 days or less after a previous dose of DTaP, persistent or inconsolable crying lasting more than 3 hours within 48 hours of a pervious dose, GBS less than 6 weeks after a previous dose of tetanus toxoid containing vaccine, or moderate or severe acute illness with or w/o fever o DTaP: may be given to immunocompromised patients or patients on immune suppressive drugs: immune response may be less than optimal o HIV infected patients may be immunized o Patients with minor acute or febrile illness may be immunized ▪ Delay in cases of moderate or severe illness, with or w/o fever o Infants born prematurely should begin series based on their DOB: first vaccine at 2 months o Pregnant women, including pregnant adolescents, receive a booster of Tdap with each pregnancy ideally between 27 and 36 weeks gestation: passive pertussis immunity, gives 2 to 3 months of protection o Td and Tdap are Pregnancy Cat C: but have been used extensively worldwide in pregnant women o DT contraindications: patients older than age 7, who should be given Td or Tdap, as appropriate o DT and Td: hypersensitivity to any component of the vaccine and moderate to severe illness, with or w/o fever: do not postpone for minor illnesses o Tdap contraindications: GBS 6 weeks or sooner after previous use of tetanus toxoid containing vaccine, previous arthus reaction after receiving tetanus or diphtheria vaccine, or a progressive neurological d/o o Tdap and Td should be deferred with moderate or severe illness, with or w/o fever ADRs o Injection site reactions of mild to moderate pain, erythema, swelling, and induration for a few days o Transient low grad fever, chills, malaise, generalized aches and pain, and HA may occur o Fever was common after DPT and less common after DTaP o Drowsiness, fretfulness, and GI upset may occur o Tdap: most frequent ADR pain at injection site o Seizures may occur and are more likely in children with a Hx of seizures: less common now that DPT is no longer used in the US o Seizures may be r/t fever: antipyretic prophylaxis after DTaP admin every 4 to 6 hrs Drug Interactions o Decreased immunological response: radiation, antineoplastic agents, or immune suppressive agents o DTaP, DT, Tdap, or Td may be coadministered with HBV, HIB, meningococcal, influenza, hep A, and pneumococcal vaccines o Do not co administer: cholera vaccine, typhoid vaccine, or plague vaccine r/t accentuated ADRs Clinical Use and Dosing o DTaP: routinely given at 2, 4, 6, and 15 to 18 months and 4 to 6 years old o Tdap: recommended at age 11 to 12 y/o o Patients should receive a booster dose of Td or Tdap Q 10 years o “Cocooning”: Parents, siblings, grandparents, childcare providers, and health care personnel who care for infants younger than 12 months receive Tdap vaccine to protect the infant against pertussis Haemophilus B Conjugate Vaccine Pharmacodynamics o HIB conjugate vaccine: consist of the HIB capsular polysaccharide covalently linked to another antigen to increase immunogenicity o Stimulates the immune system to produce antibodies that destroy the capsule: making the organism vulnerable to antibody and cell mediated immunity o Unconjugated capsule polysaccharide vaccines cause B cell stimulation only o Conjugation: T cell stimulation occurs as well o HIB conjugate vaccine comes singly and in combo with other vaccines (HBV/HIB, DTaP/HIB, DTaP/IPV/HIB, meningococcal/HIB Pharmacotherapeutics o Anaphylactic reaction to the vaccine or any component is contraindicated o Moderate to severe illness with or w/o fever may be reason to delay vaccination o Minor illness is not a reason to delay admin o HIB should only be given to children under the age of 6 ADRs o Pain, redness, and swelling at the injection site Drug Interactions o No known interactions Clinical Use and Dosing o Dosing depends on the vaccine used o The first dose can be given at 6 weeks but no earlier Inactivated Poliovirus Vaccine Pharmacodynamics o Parenteral noninfectious suspension of three types of inactivated poliovirus o All US poliovirus vaccines as inactivated polio: reduce risk of vaccine associated polio Pharmacotherapeutics o Hx of immediate hypersensitivity reaction after receiving IPV is a contraindication o Neomycin, streptomycin, or polymyxin B hypersensitivity should not receive the vaccine o IPV is preferred over OPV in immune suppressed patients however a protective immune response is not guaranteed o IPV can be administered to patients with HIV o IPV may be given in pregnancy: Category C o Can be used in infants as young as 6 weeks old ADRs o Injection site reaction o Systemic reactions are infrequent Drug Interactions o Immune response to IPV may be diminished by immunosuppressant medications o Revaccinate 3 months after d/c immunosuppressants o Can be coadministered with all other childhood vaccines Clinical Use and Dosing o Primary series of IPV is four doses given at 2, 4, and 6 to 18 months and 4 to 6 years o Four weeks between doses one and two and 2 to 3 o Minimal interval between dose three and four is 6 months Hepatitis B Virus Vaccine Pharmacodynamics o HBV is produced by recombinant DNA from common baker’s yeast that is genetically modified to synthesize HbsAg o Active immunization with HBV stimulates the immune system to produce anti-hepatitis B surface antigen antibodies Pharmacotherapeutics o Contraindication: hypersensitivity to yeast or other components of the vaccine o Moderate or severe illness with or w/o fever is a contraindication to HBV o Patients with renal disease requiring hemodialysis or patients with immunosuppression may require larger doses to achieve adequate serum levels of anti HBs o Pregnancy Cat C: CDC has stated that pregnancy is not a contraindication ADRs o Injection site reactions o Systemic complaints: fatigue, weakness, malaise, fever, HA, NVD, and pharyngitis o Serum sickness has occurred days to weeks after admin o Alopecia: a very rare side effect Drug Interactions o Immunosuppressants and antineoplastic agents may require larger doses or additional doses Clinical Use and Dosing o Vaccination with HBV is recommended for all ages particularly those at high risk of contracting hep B o IV drug users, infants born to mothers who are HbsAg positive, hemodialysis patients, sexually active people with multiple partners, incarcerated people, international travelers, household contacts of hep B carriers, and sexual contacts of hep B carriers o Patients getting tattoos, share razors, toothbrushes, or body piercing jewelry are also at risk o Healthcare workers, day care workers, and other people exposed to body fluids are at risk o Patients with DM are at increased risk and it is recommended they receive the HBV series o Universal vaccination of all infants as a comprehensive strategy to control hep B o Current childhood immunization: three dose HBV series to newborns or at age 11 to 12 o The series can be started at any age o Schedule for vaccinating infants: first dose at birth or before age 2 months, second dose at age 1 to 4 months, dose 3 at 6 to 18 months o The series can be completed in as little as four months o Series is never restarted: no matter how long since the previous dose Hepatitis A Virus Vaccine Pharmacodynamics • HAV vaccine is used to confer immunity to hep A in people at risk of contracting the disease • Stimulation of specific antibodies takes place w/o producing disease symptoms • Antibody titers after HAV are lower than those resulting from Hep A infection • Antibody titer of 20 mIU/mL is protective • Two products available: both have a two dose schedule Pharmacotherapeutics • Contraindication: Hx of severe reaction to HAV • Contraindication: Moderate or severe illness, w/ or w/o fever • Can be given to immunosuppressed but may have lower antibody titers • Pregnancy Category C: CDC has stated that HAV may be given in pregnancy if indicated and poses no risk to the fetus • Safety and effectiveness in children under 12 months have not been established ADRs • Soreness at the injection site, HA, malaise Drug Interactions • Decreased immunological response while taking immunosuppressants or antineoplastic agents Clinical Use and Dosing • Pre-exposure protection from hep A in adults and children • Recommended that all children begin HAV series at 12 months • Those at increased risk: o Traveling or working in endemic regions, over 12 months (S. America, Africa, Greenland, and Asia) o Men who have sex with men o Illegal drug users o Occupational risk for infection (research lab) o People with clotting factor d/os o People with chronic liver disease o Household members and close personal contact of internationally adopted children from endemic countries (start first dose as soon as the adoption planning process begins: at least 2 weeks before arrival • Two products available: HAVrix and VAQTA also combo products (HAV and HBV) • HAVrix: Two dose schedule 6 to 12 months apart • VAQTA: Adults 6 months apart, children 6 to 18 months apart • IM into deltoid: adults and children 3 y/o and older o Vastus lateralis: 12 months to 36 months old o Injection into gluteal region results in suboptimal response • Those with impaired immunity may require additional doses to obtain adequate response o Post immunization testing for those that are immune compromised, not for healthy adults r/t high seroconversion rates in both children and adults Human Papillomavirus Vaccine Pharmacodynamics • HPV causes cervical CA: HPV-16 and HPV 18 cause neoplasia • Two vaccines: o Gardisil (quadrivalent HPV recombinant vaccine for types 6, 11, 16, and 18) o Gardisil 9 (types 16, 18, 31, 33, 45, 52, and 58 Pharmacotherapeu