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175 Cards in this Set
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Allergic Conjunctivitis Tx
Mast Cell Stabilizers |
Cromolyn - old generation
Olopatadine Azelastine Decreases Histamine release from Mast Cells Side Effects: eye irritation - can switch to different agents |
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Allergic Conjunctivitis Tx
Decongestants |
Pheniramine
Naphazoline Vasoconstrictors --> reduce redness |
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Allergic Conjunctivitis Tx
Corticosteroids |
Anti-inflammatory properties
Prevent the breakdown of phospholipids Work against Phospholipase A Less Arachidonic Acid, less Prostaglandins produced. |
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Allergic Conjunctivitis Tx
Pain Control |
Local Anesthetic - Tetracaine
NSAIDs Decreased the formation of Prostaglandins |
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Allergic Conjunctivitis Tx Overview
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Mast Cell Stabilizers
Decongestants Corticosteroids Pain Control |
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Bacterial Conjunctivitis Tx
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Origin: Contact Exposure/Poor Hygiene
*Sulfacetamide - solution *Gentamicin (Aminoglycoside) *Interchangeable Eye Drops v. Ointment Erythromycin - Eye Ointment Part of the routine tx in neonates Prevents Chlamydia - neonates --> asymptomatic in women Single BEST way to prevent blindness in child |
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Single BEST way to prevent blindness in child
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Erythromycin eye ointment as a neonate
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Viral Conjunctivitis Tx
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Trifluridine (Viroptic) - usually causes stinging irritation in the eye
Usually given w/NSAIDs Other medications Steroids (Prednisolone) Combinations Corticosteroids |
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Retinitis
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Immunocompromised Host
Cytomegalovirus (CMV) - opportunistic Pathogen --> Common in HIV+ pts receiving immunosuppressants for transplants --> Dx: Cotton Balls in Fundoscopic Exam Gancyclovir (Cytovene), IV or PO Implants - ophthalmologist Valgancyclovir - ABX - systemic tx |
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Glaucoma Tx
Old Gen Drugs |
Therapy geared toward decreasing intraocular pressure
Eye Drops - Commonly overdosed w/self-admin -Old gen: Pilocarpine: 3 strengths: to adjust tx --> NO longer first line Carbachol - Cholinergic |
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Glaucoma
New Gen Drugs Carbonic Anyhdrase Inhibitors |
New Gen Rx:
Work by decreasing intraocular volume (similar to diuretics) -Carbonic Anyhydrase Inhibitors: --> Acetazolamide - problem systemic effects --> increased change of metabolic acidosis --> Dorzolamide - generic, eye drop only |
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Glaucoma Tx:
Beta Blockers |
-Beta Blockers - pupillary dilation
-Timolol -Betaxolol |
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Glaucoma Tx:
Cholinergic Agents |
-Cholinergic Agents:
- Pilocarpine - Carbachol |
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Glaucoma Tx:
Alpha 2 Agonists |
Apraclonidine (Iopidine) - Patch (like Clonidine!)
Brimonidine (Alphagan) - PO No preference of one over the other Oral form - won't get the systemic effects of Apraclonidine |
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Glaucoma Tx:
Prostaglandins |
Reduce Intraocular Pressure
Latanoprost (Xalatan) Travoprost (Travatan) Interchangeable/both work well Vasodilation Effect |
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Otitis Tx:
Wax Build Up |
Triethanolamine polypeptide (Cerumenex)
+ Warm Water |
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Otitis Media Tx
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Oral ABX
Decongestants Pain Relief |
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Otitis Media Tx: ABX
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Gm + (Strep)
Gm - (H. infl) #1: Amox --> May pediatricians rx Aug (no need for Bacteroides/Staph coverage!) -Allergic: Pediazole --> Erythromycin/Sufasoxale |
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Allergic Rhinitis Tx Overview
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Anti-Histamines
CTSD's Cromolyn Sodium Ipratropium |
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Allergic Rhinitis Tx
Anti-histamines 1st Gen |
Sedating
Compete w/Histamine of H1 Receptor Less sneezing/itching/drying Work best w/seasonal AR, and those who need sleep --> great overnight SE: CNS, constipation, dry mouth, tacky, no urination Chlorpheniramine (Chlor Trimeton) - used more commonly w/AR Diphenhydramine (Benadryl) |
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Allergic Rhinitis Tx
Anti-histamines 2nd Gen |
Considered non-sedating
Not good overnight Competitively inhibit H1 receptor Loratadine (Claritin) Fexofenadine (Allegra) Cetirizine (Zyrtec) - * low sedating |
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Allergic Rhinitis Tx
Oral Decongestants |
Pseudoephedrine (Sudafed)
Increases NE in pre-synaptic terminal Vasoconstriction in nasal mucosa Decreased obstruction/bloodflow - Nasal passages open SE: HTN/Temp/HA/Nervous/Irritable/Tachycardia/palpitations/insomnia HTN: careful - rise in BP Don't assume pt has Chronic HTN; could be drug effect |
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Allergic Rhinitis Tx
Topical Decongestants |
Don't use > 3 days consecutively! - rhinitis medicaments
Phenylephrine - Neo-Synephrin Oxymetazoline - Afrin |
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RM
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Rhinitis Medicamentosa
Prolonged use of topical decongestants Induces rebound congestion upon withdrawal Leads to inflammatory hypertrophy of nasal mucosa, RM Caused by down regulation of alpha-adrenoreceptors --> less sensitive to endogenously released NE and exogenously applied vasoconstrictors Tx: wean over 7-10 days Reduce inflammation w/intranasal steroids |
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Allergic Rhinitis Tx
Intranasal Corticosteroids |
Most potent SINGLE med --> best job for tx of AR
Septal perforation = RARE Beclometasone (Vancenase) Fluticasone (Flonase) Mechanism: reduce inflammation suppress neutrophil chemotaxis mildly vasoconstrictive reduce intracellular edema Effect: reduce nasal blockage, pruritus, sneezing and rhinorrhea **VERY helpful for pt w/chronic allergic rhinitis who snores! |
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Allergic Rhinitis Tx
Cromolyn Sodoum |
Intranasal (Nasalcrom)
Mechanism: Mast cell stabilizing agent -->reduces Histamine and other mediators Effects: reduces nasal pruritus, sneezing, rhinorrhea, congestion Note: prophylactic use! Start before allergy season/Sx Disadvantage: short half life - dose every 4 hrs SE: locally, <10% of pts (sneezing, stining, burning irritation of nose) |
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Allergic Rhinitis Tx
Ipratropium |
Intranasal - Atrovent
Mechanism: Inhibits Muscarinic cholinergic receptors Effect: reduces watery rhinorrhea Note: limited to control of watery secretions --> effective at reducing both "cold air" and "gustatory" rhinitis SE: irritation/crusting/epistaxis |
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Allergic Rhinitis Tx
Saline |
Intranasal saline
ie: NaSal, SeaMist, Ocean, Ayr Effects: relief from crusting; soothing |
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Tx Options: AR
Anti-histamines + Decongestants |
Antihistamines +/- Decongestants
intermittent AR episodes antihistamines = first line tx (sneezing, pruritis, rhinorrhea) if nasal congestion a major sx, add an oral decongestant. combined tx with antihistamine/decongestant control sx better than with antihistamine alone. Ex: Allegra D (D=Decongestant) |
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Tx Options: AR
+ Nasal Steroids |
prolonged symptoms
add to antihistamine/decongestant regimen will reverse preexisting inflammation will prevent nasal priming |
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Recurrent Chronic Sinusitis (RCS
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sinus tenderness, facial pain with leaning forward, mucopurulent nasal d/c, halitosis, h/o perennial allergic rhinitis w/ recurrent sinus infections.
Perennial AR: “year-round” nasal congestion w/ clear d/c. |
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Tx of Recurrent Chronic Sinusitis
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Tx:
Sinusitis: oral Abx |
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Perennial AR
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Perennial AR: “year-round” nasal congestion w/ clear d/c.
AR: antihistamine, decongestant, nasal steroid, nasal saline, pt education (avoidance, modifying factors). Skin testing. Stop smoking. |
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Throat Infection
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Viral - Supportive Tx
Bacterial - usually Streptococcus - Tx: PCN G -Post-nasal drip --> secondary to AR Tx - Soreness: - Local Anesthetics - Phenol (Cepacol, Chloraseptic) --> spray/lozenges -Elderly: careful w/spray, may decrease gag reflex --> aspiration risk -Good Hydration |
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Current ONLY Oral Anticoagulant for Long-Term use
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Vitamin K Antagonist
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Heparin
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Mucopolysaccharides
Unfractionated (from pig mucosa or bovine lung) Low molecular weight Binds to antithrombin III and inactivates factors Xa, XIa, and XIIa Given IV or SQ (not IM) |
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Adverse Effects of Heparin
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Adverse effects:
Hemorrhage Thrombocytopenia (HIT) Paradoxical thrombosis Overdose: Protamine is a specific antidote Whole blood Fresh frozen plasma |
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LMWH
Types |
Low molecular weight heparin
Enoxaparin (Lovenox) Dalteparin (Fragmin) Ardeparin (Normiflo) Tinzaparin (Innohep) Decreased chances of HIT Fondaparinux (Arixtra) - heparinoid |
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Use of LMWH
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Use in DVT and PE treatment
May treat as an outpatient Fondaparinux 5-10 mg/day Do not use if CrCl < 30 ml/min Enoxaparin 1 mg/kg SQ q12h No monitoring of PTT needed Anti-factor X assay |
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Direct Thrombin Inhibitors
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Divalent
Hirudin Lepirudin (Refludan) Bivalirudin (Angiomax) Univalent Argatroban Dabigatran (Pradaxa) |
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Direct Divalent Thrombin Inhbitors
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Hirudin
Lepirudin (Refludan) Bivalirudin (Angiomax) |
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Direct Univalent Thrombin Inhibitors
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Argatroban
Dabigatran (Pradaxa) |
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Lepirudin (Refludan)
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Direct Divalent Thrombin Inhibitor
Derivative of hirudin Alternative to heparin Works in the presence of HIT Less monitoring Same precautions, ESPECIALLY withy renal dysfunction |
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Bivalirudin (Angiomax)
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Bivalent inhibitor of thrombin
IV Quick onset Short half-life |
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Argatroban
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Small molecule thrombin inhibitor
Used in patients with HIT |
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Oral Anticoagulation Targets
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Two Points in coagulation cascade:
Factor Xa (Apixaban, Rivaroxaban, Betrixaban) OR Thrombin (Dabigatran etexilate) |
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Oral DTI's
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Ximelagatran - withdrawn
Dabigatran (Pradaxa) |
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Argatroban
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Small molecule thrombin inhibitor
Used in patients with HIT |
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Dabigatran Pharmacokinetics
(ADME) |
A:
- Rapid Absorption - Bioavailability: 3-7% - relatively static under fast or fed conditions - Predictable; low variability D - Plasma concentration peaks within 1h (food: delays 2hrs) - Half life elimination: 12-17hr Vd: 50-70L M: - Metabolized by microcosmal carboxylesterases to active drug in liver. ---> Does not affect CYP activity E: -Urine (7% as unchanged drug), - Feces (86% of total dose) **RENAL EXCRETION: accounts for 80% of clearance |
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Dabigatran - Mechanism of Action and Drug/Food Effects
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Absorbed: Intestine
--> Microcosmal Carboxyesterase --> BIBR 1087/951 --> Dabigatran BIBR 953 --> Inhibits Free Thrombin --> Renal excretion Drug Interaction – P-glycoprotein inducer Rifampin - AVOID combination with dabigatran Drug-Food interactions Food has no affect on the bioavailability of dabigatran but delays the time to peak concentrations by 2h |
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Adverse Effects of Dabigatran
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Dyspepsia (11.3) [5.8]
Fatigue (6.6) [6.2] Dizziness (8.3) [9.4] Dyspnea (9.5) [9.7] Peripheral edema (7.9) [7.8] Diarrhea (6.5) [5.7] GI bleeding; MI; potential for accumulation in presence of renal dysfunction |
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Oral DTI's
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Ximelagatran - withdrawn
Dabigatran (Pradaxa) |
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Dabigatran:
Monitoring Parameters |
Activated Partial Thromboplastin Time (aPTT): values >2.5 time control may indicate over-anticoagulation
Ecarin Clotting Test (ECT) if available Thrombin Time (TT) CBC with differential Bleeding |
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Dabigatran - Mechanism of Action and Drug/Food Effects
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Absorbed: Intestine
--> Microcosmal Carboxyesterase --> BIBR 1087/951 --> Dabigatran BIBR 953 --> Inhibits Free Thrombin --> Renal excretion Drug Interaction – P-glycoprotein inducer Rifampin - AVOID combination with dabigatran Drug-Food interactions Food has no affect on the bioavailability of dabigatran but delays the time to peak concentrations by 2h |
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Dabigatran:
Prescription Info |
Dosing
Oral: 150mg twice daily Renal impairment: Clcr 15-30 mL/min : 75mg twice daily Clcr <15 mL/min: no recommendation Hepatic impairment: No adjustment required |
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Adverse Effects of Dabigatran
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Dyspepsia (11.3) [5.8]
Fatigue (6.6) [6.2] Dizziness (8.3) [9.4] Dyspnea (9.5) [9.7] Peripheral edema (7.9) [7.8] Diarrhea (6.5) [5.7] GI bleeding; MI; potential for accumulation in presence of renal dysfunction |
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Dabigatran
Clinical Trial: Dabigatran versus Warfarin in Patients with Atrial Fibrillation |
- Compare for prevention of stroke and systemic emboli
In patient with atrial fibrillation, dabigatran given at a dose of 110mg was associated with warfarin, as well as lower rates of major hemorrhage. Dabigatran administered at a dose of 150mg, as compared with warfarin , was associated with lower rates of stroke and systemic embolism but similar rates of major hemorrhage Dabigatran 110mg bid is as effective as warfarin and Dabigatran 150mg bid is superior to warfarin for the prevention of stroke in patient with atrial fibrillation |
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Downsides of Dabigatran
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Wide therapeutic window BUT poor drug compliance
2x daily dosing --> Nonadherence No specific antidote to reverse antithrobotic activity Risk Groups: - Renal/Hepatic impairment - Pts w/high bleeding risk |
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Dabigatran
Clinical Trial: Dabigatran versus Warfarin in Patients with Atrial Fibrillation |
- Compare for prevention of stroke and systemic emboli
In patient with atrial fibrillation, dabigatran given at a dose of 110mg was associated with warfarin, as well as lower rates of major hemorrhage. Dabigatran administered at a dose of 150mg, as compared with warfarin , was associated with lower rates of stroke and systemic embolism but similar rates of major hemorrhage Dabigatran 110mg bid is as effective as warfarin and Dabigatran 150mg bid is superior to warfarin for the prevention of stroke in patient with atrial fibrillation |
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Rivaroxaban
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Oral Direct Factor Xa Inhibitor
Predictable pharmacology High bioavailability Low risk of drug–drug interactions Fixed dose No requirement for monitoring |
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HTN
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Most patients asymptomatic
Cardiovascular morbidity & mortality risk directly correlated with BP; antihypertensive drug therapy reduces cardiovascular & mortality risk Persistent elevation of arterial blood pressure (BP) |
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Target-Organ Damage
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Brain: stroke, transient ischemic attack, dementia
Eyes: retinopathy Heart: left ventricular hypertrophy, angina Kidney: chronic kidney disease Peripheral Vasculature: peripheral arterial disease |
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Causes of secondary HTN
Rx |
Prescription drugs:
prednisone, fludrocortisone, triamcinolone amphetamines/anorexiants: phendimetrazine, phentermine, sibutramine antivascular endothelin growth factor agents estrogens: usually oral contraceptives calcineurin inhibitors: cyclosporine, tacrolimus decongestants: phenylpropanolamine & analogs erythropoiesis stimulating agents: erythropoietin, darbepoietin |
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Situational causes of secondary HTN
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β-blocker or centrally acting α-agonists
when abruptly discontinued β-blocker without α-blocker first when treating pheochromocytoma --> Reflex action |
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Food
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sodium
ethanol licorice |
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Mechanisms of HTN
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Increased cardiac output (CO):
increased preload: increased fluid volume excess sodium intake renal sodium retention venous constriction: excess RAAS stimulation sympathetic nervous system overactivity |
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Functional Vascular constriction
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Increased Peripheral Resistance
excess RAAS stimulation sympathetic nervous system overactivity genetic alterations of cell membranes endothelial-derived factors |
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Blood Pressure Determinants
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SVR and CO
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CO Determinants
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HR and SV
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Anemia Definition
and Mass Measurement |
Definition: Low oxygen carrying capacity in the blood due to low erythrocyte mass
Use Hct and Hb as surrogate markers for erythrocyte mass measurement (too difficult to measure) Hct is approx 3x Hb |
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Anemia P/E finding w/highest positive likelihood ratio
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conjunctival rim pallor
Note: Patient reported symptoms will vary greatly based on the rapidity of the change in Hct, medical co-morbidities and the cause of the anemia |
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Reticulocyte Count
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May be reported as the absolute count (determined by flow cytometry)
OR the reticulocyte count as a percentage of the total erythrocytes -->in this case you want to calculate the RETICULOCYTE INDEX (RI=reticulocyte% x pt’s Hct/45 x 0.5). |
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RI
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Reticulocyte Index
RI = reticulocyte% x pt's Hct/45 x .5 If low (RI<2), bone marrow hypoproliferation: production problems If normal (RI>2), bone marrow hyperproliferation: hemolytic anemia, acute blood loss |
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Microcytic
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(MCV<81): iron deficiency, thalassemia, sideroblastic anemia, anemia of chronic disease
First thing to check after a microcytic type found --> IDA |
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Sideroblastic Anemia
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Inability to incorporate iron into hemoglobin
Can be congenital or acquired (drugs – INH, chloramphenicol, EtOH, lead poisioning), Get “ringed sideroblasts” – mitochondria with lead deposits circling the nucleus of developing RBC in the bone marrow. |
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Normocytic Anemia
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(MCV 81-98): anemia of chronic disease, aplastic anemia, bone marrow infiltration, kidney disease, acute blood loss
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Macrocytic (MCV >98) Anemia
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alcohol, B12 deficiency, folate deficiency, myelodysplasia, drug toxicity, reticulocytosis, liver disease
MC ETOH abuse --> usually d/t B12/folate deficiency |
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Myelodysplasia
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Hematologic condition,
Abnl myeloid cell production (RBC, plt, PMNs, NOT lymphocytes), High risk of transformation into AML |
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Dx of Fe Deficiency Anemia
AND other characteristic lab results |
All patients with ferritin <15 are iron deficient (highly specific but not sensitive), values >100 essentially rule out iron deficiency.
Ferritin can be the most useful single test, though due to the fact that this is an acute phase reactant, only in patients without infection/inflammation Other characteristic iron study results are: elevated TIBC, low transferrin saturation and low serum iron level *Ferritin and Transferritin test - give same information |
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Sx of Fe Deficiency
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Atrophic glossitis
Angular chelitis koilonychia |
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Fe Deficient Anemia: TX
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Women: send for scope to determine cause first
Iron replacement can typically be given orally, ferrous sulfate or gluconate 325 mg, 1-3 times a day. (Start w/3x/day!!!) Ideally pts are treated with TID medication though this is rarely tolerated Sulfate salt is cheaper but generally less well tolerated Ferrous gluconate - iron salt --> causes iron to be better tolerated --> give to pts w/tolerance issues BUT less iron per mg compared to ferrous sulfate Ferrous Sulfate - rx w/more bang (Iron/mg) for your buck! SE: constipation; nausea |
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Causes of Poor iron absorption
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Noncompliance with meds!
W/food --> less Se/BUT less absorption Celiac sprue, IBD, concurrent Antacid/PPI (increase pH)/Calcium --> NO DAIRLY Iron chelates w/Ca/Mg --> no absorption Take w/OJ --> inc. absorption Hct will improve within a few wks of therapy. Pts should cont. tx for 6mo - 1 yr |
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Parenteral Iron
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Pts unable to tolerate enteral iron
OR Pt is severely deficient Iron dextran - IV Sodium ferric gluconate complex (Ferlisit) Iron sucrose * All 3 = equivalent dose/effect --> use cheapest! |
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Acute Iron toxicity
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Seen primarily in children
Whole bowel irrigation Deferoxamine Chelating agent - binds Iron in circulation --> renders it harmless |
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Hypoproliferative anemia
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MC ACD
Low reticulocyte count Typically normocytic, 25% = microcytic Labs: hi ferritin, lo serum iron, lo TIBC *Bone marrow stores: Fe nml *Testing not indicated May have mixed components w/IDA --> may raise TIBC |
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Etiology of Hypoproliferative anemias
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Multiple contributing factors!
Decreased transfer of iron to RBCs Decreased response to EPO Decreased EPO release Tx: underlying cause |
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ACD + Fe
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Low Serum Iron
Normal TIBC* (Unique) Low Transferrin Saturation Low to Normal Ferritin (like Fe def) Norm to hi Soluble Transferrin Receptor High ratio of soluble transferrin receptor to log ferritin |
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Macrocytic Anemia
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High MCV
MC = ETOH Also: Drug toxicity: zidovudine (AZT), hydroxyurea (leukemia rx) Hypothyroidism Liver DZ Myelodysplasia Be sure to assess reticulocyte count to eval for stress erythropoiesis (RI <2 = stress level response) Blood smear: for megaloblastic changes --> macro-ovalocytes and hypersegmented neutrophils *dysfunctional spleen/liver --> typically NON-megaloblastic |
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RI <2
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indicates stress level response
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Megaloblastic Macroctosis
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Blood smear: for megaloblastic changes
Blood smear: check for megaloblastic changes --> macro-ovalocytes and hypersegmented neutrophils (> 5 lobes) |
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Etiologies of Megaloblastic macrocytosis
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B12 deficiency,
folate deficiency, drugs that cause abnl DNA synthesis or folate metabolism, myelodysplastic syndromes |
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Non-megaloblastic macrocytosis
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Typical of liver DZ and hyposplenism
Smear: large target cells Acanthocytes Howell-Jolly bodies |
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Folate Deficiency (CAUSES/TX)
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Fruits and leafy veggies, grain
Causes include: alcohol due to both a decreased ability to absorb folate and, frequently, decreased intake of folate rich foods Malabsorption (celiac disease, IBD) Diseases/conditions associated with rapid cell turnover such as sickle cell disease, psoriasis, pregnancy Medications: trimethoprim, phenytoin, methotrexate Tx: Folic Acid supp, 1mg po qd ALWAYS check for concurrrent B12 def PRIOR to treating --> if not and present: anemia would improve; neuro Sxs progress r/o megaloblastic |
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Vitamin B12 deficiency
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Rarely d/t decreased dietary intake (large stores)
Typically d/t: Pernicious Anemia and IF deficiency Atrophic gastritis IBD PPIs, antacids (dec. stomach acid) --> B12 def can lead to: metabolic peripheral neuropathy neuropsych DZ (NOT seen in folate def) If B12 levels at lower limits of normal (200-300), consider checking methylmalonic acid AND homocysteine levels --> elevated w/B12 def |
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Vitamin B12 Dose
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PO 1000-2000 mcg po qd
IM 1000mcg IM qd x 7d, then awk x 4wks then qmont |
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Labs to order for Hemolytic anemia
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Retic count
peripheral smear --> will ddx causes of hemolysis Haptoglobin indirect bili and LDH |
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Extravascular Hemolytic Anemia
ETIOLOGIES |
Congenital Hb abnormalities:
Hemoglobinopathies Erythrocyte membrane abnormalities: hereditary spherocytosis Erythrocyte metabolic abnormalities: G6PD deficiency Auto-immune process: idiopathic underlying malignancy CVD lymphoproliferative d/o's medications (PCN, Cephs, NSAIDs) |
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G6PD Deficiency
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X-linked - decreased glutathione levels
MC form results in severe hemolysis w/meds (Primaquine, sulfa, dapsone), fava, infection Dx: enzyme activity testing May have false (-) in acute hemolysis, re-test at 2-3 mos Coombs test - direct antiglobulin + confirms dx of auto-immune hemolytic Tx w/short course systemic CTSD's -Transfusions - Consider at Hct < 25%, def at <21% in pts w/multiple medical problems -Also consider: on-going rapid blood loss highly symptomatic pts pt w/low Hct severe cardiovascular DZ -->Transfuse --> Expect Hct to increase 3% for ea. unit of blood |
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Anemia of Chronic Kidney DZ: Tx
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Hypoproliferative (low retic count)
Normocytic anemia --> Tx w/EPO therapy to stimulate production For EPO Therapy to be effective --> need adequate iron stores Ferritin >100 AND transferrin saturation > 20% Tx goal = Hb of 11-12 (Hct 33-36% Higher levels of Hb - assoc w/increased M/M (BB Warning on EPO preps) --> pt may FEEL better when Hb is higher --> RISKY BIZNESS |
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Tx of Chronic Kidney DZ
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Darbepoetin - Synthetic EPO
--> Longer lasting --> 1x/wk --> Expensive Epoetin ***Need adequate iron stores (more bang for your buck!) Even if indices don't show IDA --> better concurrent w/Fe |
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ESAs
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Erythropoiesis stimulating agents
-Epoeitin -Darbepoetin -Used in CKD (primary and secondary bone marrow d/o's) SE: HTN Thrombotic events Limits on use: Use if given drug that has myelosuppressive d/o's AIDs pts w/antiretroviral agents - anemia Chemo pts - immunosuppression |
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Thalassemia Trait
Initial Test |
Best first test if no Sxs/- FHx:
--> Hb electrophoresis --> CBC on siblings --> US for spleen size Check G6PD |
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Thalassemia Trait
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mild anemia with pronounced microcytosis (MCV <70)
Ethnicity: Mediterranean, Asian, African Pt are asymptomatic FamHx is often negative Dx thal trait: Hemoglobin electrophoresis |
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Thalassemia Intermedia
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Ineffective erythropoiesis,
more severe anemia, often require frequent transfusions, at risk of development of iron overload Iron deficiency anemia: usually more pronounced microcytic anemia than thal trait Microcytic, hypochromic RBC Target and teardrop cells |
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MC Etiologies by Gender
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Females: IDA
Males: ACD |
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Myeoloid Growth Factors
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Tx bone marrow deficiencies
--> autoimmune d/o's --> will help those w/chemo who got a drop in WBC count - infxn risk Recombinant Technology G-CSF (figrastim, Neupogen) GM-CSF (sargramostim, Leukine) G-CSF (filgrastim-PEG, Neulasta) Reduce duration of Neutropenia following chemo All 1x/d, EXCEPT filgrastim-PEG SE: arthralgia, myalgia, fever, malaise, capillary leak syndrome |
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G-CSF (filgrastim-PEG)
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Newest Myeloid GF
Difference - given 1x/wk by injection (NOT QD) More expensive Given to prevent neutropenia, and reduce the duration of neutropenia Decreases likelihood of infection Capillary leak syndrome |
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COPD Death Incidence Trends
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(age 25+)
Since 19080 increases in both genders; Male deaths more common than women |
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COPD:
Occupational exposure |
Long term exposure to:
inorganic dust organic dust chemicals - vapors, irritants, fumes |
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COPD Sxs
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Swollen airways; inflamed
Produce large amounts of mucus Cough + sputum on most days for at leat 3 mos period during 2 consecutive years wheezing lack libido recurrent respiratory infections fatigue weight loss |
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4 Components of COPD Management
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1) Assess and monitor disease
2) Reduce risk factors 3) Manage stable COPD -Eduction -Pharm -Non-Pharm 4) Manage exacerbations |
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EIB Tx in an athlete
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Can use Nedocromil OR Budesonide
--> Chronic asthmatics need to be on these --> can help w/recurrent EIB However most coaches/some pediatricians still have these pts take SABA, even if they're already on ICS. |
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Sinusitis Tx
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Augmentin
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Diagnostic Tests for COPD
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Spirometry or Full PFT
CXR Alpha 1 antitrypsin level and phenotype ABG Sputum gram stain/culture |
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Harmful Drugs for COPD
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Antihistamines --> dries secretons
--> cause sedation Cough Suppressants --> want to mobilize not suppress Sedatives Tranquilizers --> decrease ability to breath at proper rate --> breathe more shallowly --> increased infxn risk B-Blockers --> increased chance of bronchospasm --> Permanent damage to airway Narcotics --> decrease respirations |
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Pharmacotherapy for STABLE COPD
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Bronchodilators
(SABA, LABA, Anticholinergics (BIG ROLE in COPD!!!), Methylxanthines (Theo) and Corticosteroids Oral (pred) Inhaled (Flutic/Budesonide/Pulm) |
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Pharmacotherapy for STABLE COPD
BRONCHODILATORS |
Short-acting b2-agonist – Albuterol (Proventil)
Long-acting b2-agonist – Salmeterol (Serevent) and Formoterol (Foradil) Anticholinergics – Ipratropium (Atrovent)(BIG ROLE in COPD!!!), Tiotropium (Spiriva) Methylxanthines - Theophylline |
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Pharmacotherapy for STABLE COPD
Corticosteroids |
Oral – Prednisone
(Use in Asthma is better than in COPD ---> less effective) Inhaled – Fluticasone (Flovent), Budesonide (Pulmicort), Mometasone (Asmanex |
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GOLD Standard for COPD
Stage 0 |
Normal Post-bronchodilator FEV1 (% predicted)
Smoking cessation; Influenza vaccination |
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GOLD Standard for COPD
Stage 1 |
>80% Post-bronchodilator FEV1 (% predicted)
Smoking cessation; Influenza vaccination SABA prn |
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GOLD Standard for COPD
Stage 2 |
50-80% Post-bronchodilator FEV1 (% predicted)
Smoking cessation; Influenza vaccination SABA LABA + Ipratropium/Teotropium (regular tx w/1 or more Long-acting bronchodilators, including Tiotropium) Options: Wait to see response with JUST LABA or IAC, No/poor response - add the other +/- as needed Pulmonary rehabilitation |
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GOLD Standard for COPD
Stage 3 |
30-50% Post-bronchodilator FEV1 (% predicted)
Smoking cessation; Influenza vaccination SABA LABA + Ipratropium/Teotropium add ICS - esp if repeated exacerbation |
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GOLD Standard for COPD
Stage 4 |
<30% Post-bronchodilator FEV1 (% predicted)
Smoking cessation; Influenza vaccination SABA LABA + Ipratropium/Teotropium ICS End Stage --> Long term O2 therapy (LTOT) Consider Surgical options |
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COPD and how Bronchodilators works
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Reverse the increased bronchomotor tone
Relax the smooth muscle --> COPD --> permanent narrowing/damage of airways Reduce the hyperinflation --> drying effect Improve breathlessness Vagal cholinergic tone has more contribution for airway resistane --> Therefore Ipratropium works REALLY WELL!!! |
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COPD and Anticholinergics
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- - Cholinergic tone is the only reversible component of COPD
- Normal airway have small degree of vagal cholinergic tone (no perceptible effect d/t patent airways) - Airways narrowed in COPD --> vagal cholinergic tone has greater effect on airway resistance --> Anticholinergic drugs that act as muscarinic receptor antagonist ----> Will block the ACH-induced bronchoconstriction - Anticholinergics may reduce mucus hypersecretion ---> BUT no effect on Pulmonary vessels -----> Therefore don't cause a fall in PaO2 |
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Managing Stable COPD
--> systemic CTSD's? |
NEVER demonstrated to significantly impact mortality or exercise capacity
Slight improvements in symptom indices Significant side effects Rarely of benefit, generally of HARM to your patient Occasionally useful in a small subset failing other therapies AND with demonstrated bronchodilator response on PFT’s |
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Side effects of Corticosteroids w/COPD
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Hyperglycemia
Electrolyte imbalances GI - ulcerations Waking |
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COPD Exacerbations
Pathophys |
Chronic Inflammation + VIral Infxn (25%) + Bact Infxn (50%) + Air pollution (5%) + Unknown (20%)
---> = Acute Inflammation ---> = Exacerbation!!! |
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COPD Exacerbation
Definition Elements |
Worsening dyspnea
Increased sputum purulence Increase in sputum volume |
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COPD Exacerbation
Severity |
Elements: worsening dyspnea; increased sputum purulence; increased sputum volume
Severe - all 3 elements Moderate - 2 elements Mild - 1 element plus: URI in past 5 days Fever without apparent cause Increased wheezing or cough Increase (+20%) of respiratory rate or heart rate |
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Frequent Management Errors
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Inadequate teaching about how to use inhalers
--> Respiratory therapists can help Sub optimal dosing Inadequate monitoring Failure to advise patients to take medicine before exercising |
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Supplemental Oxygen Therapy and Fluid Intake
for COPD |
Supplemental oxygen therapy has been shown to prolong life and improve quality of life in hypoxic patients
--> Generally best w/stage 3/4 Increased fluid intake is not helpful unless the patient is dehydrated |
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Hospitalization and COPD
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Required if:
- Continue to deteriorate w/acute exacerbations despite therapy - co-morbid conditions - w/out home support - altered mentation - worsening hypoxemia and/or hypercapnia |
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Exercise/Nutrition for COPD
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- Weight control - Reduces heart strain and lung strain --> improves ability to carry oxygen to body
- Exercises to strengthen chest muscles --> improves breathing - Eat several small meals --> prevents reflux - Avoid gas-producing foods --> causes stomach swelling --> presses against diaphragm |
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New anti-inflammatory agents for COPD
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Matrix metalloproteinase inhibitors
Specific phosphodiesterase (PDE4) inhibitors Cilomilast (Ariflo) Rofumilast Piklanilast |
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New Txs for COPD
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Newer anti-inflammatory agents
-Matrix metalloproteinase inhibitors -Specific phosphodiesterase (PDE4) inhibitors Cilomilast (Ariflo) Rofumilast Piklanilast Anabolic steroids --> minor role in improved quality of life Repair agents --->Retinoic acid |
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Specific Phosphodiesterase (PDE4) Inhibitors
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Newer anti-inflammatory agents for COPD
- Currently being used; - also used to tx pulmonary HTN --> in clinical trial for COPD? Cilomilast (Ariflo) Rofumilast Piklanilast |
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Spirometry and COPD
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Useful and under-utilized!
Encourage patients to do at home |
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Thrombosis and Platelet Activation
Pathophysio |
BV wall injury
Rupture of atheromatous plaque Exposes circulating platelets to: ADP, TXA2, Epi, Thrombin, Collagen Tissue Factor ADP --> stim's Platelet aggregation Tissue Factor --> activates Extrinsic Pathway --> initiates Fibrin formation |
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Thrombosis and Platelet Activation
Pathophysio |
BV wall injury
Rupture of atheromatous plaque Exposes circulating platelets to: ADP, TXA2, Epi, Thrombin, Collagen Tissue Factor ADP --> stim's Platelet aggregation Tissue Factor --> activates Extrinsic Pathway --> initiates Fibrin formation |
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Main GOAL of Anticoagulation Therapy
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Prevent FURTHER growth of the clot
Clots left to themselves will grow Limited lifespan, will eventually disintegrate |
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Main GOAL of Anticoagulation Therapy
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Prevent FURTHER growth of the clot
Clots left to themselves will grow Limited lifespan, will eventually disintegrate |
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Heparin Mechanisms
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Mucopolysaccharides
Unfractionated from pig mucosa or bovine lung Low molecular weight = Enriched form Binds to antithrombin III and inactivates factors Xa, XIa, and XIIa Given IV to tx a clot SQ to prevent a clot NEVER IM --> too many BVs in muscle --> causes hematomas! Have to give a loading dose --> Anticoagulation/Inhibits Factors ASAP Monitor CBC: Catch drops in Hb Monitor Platelets: Observe for signs of bleeding --> risk of Heparin Induced Thrombocytopenia --> adjust dosage MC side effect = Hemorrhage |
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LMW Heparin
Types |
Enriched Heparin
Enoxaparin (Lovenox) Dalteparin (Fragmin) Ardeparin (Normiflo) Tinzaparin (Innohep) Fondaparinux (Arixtra) - heparinoid --> NOT a Heparin but acts like one --> the therapeutic dose does not cause HIT |
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Heparin Administration
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Given IV to tx a clot
SQ to prevent a clot NEVER IM --> too many BVs in muscle --> causes hematomas! Have to give a loading dose --> Anticoagulation/Inhibits Factors ASAP Monitor CBC: Catch drops in Hb Monitor Platelets: Observe for signs of bleeding --> risk of Heparin Induced Thrombocytopenia --> adjust dosage MC side effect = Hemorrhage |
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Heparin Mechanisms
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Mucopolysaccharides
Unfractionated from pig mucosa or bovine lung Low molecular weight = Enriched form Binds to antithrombin III and inactivates factors Xa, XIa, and XIIa Given IV to tx a clot SQ to prevent a clot NEVER IM --> too many BVs in muscle --> causes hematomas! Have to give a loading dose --> Anticoagulation/Inhibits Factors ASAP Monitor CBC: Catch drops in Hb Monitor Platelets: Observe for signs of bleeding --> risk of Heparin Induced Thrombocytopenia --> adjust dosage MC side effect = Hemorrhage |
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LMW Heparin
Types |
Enriched Heparin
Enoxaparin (Lovenox) Dalteparin (Fragmin) Ardeparin (Normiflo) Tinzaparin (Innohep) Fondaparinux (Arixtra) - heparinoid --> NOT a Heparin but acts like one --> the therapeutic dose does not cause HIT |
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Heparin Side Effects
and Antidotes |
Monitor CBC: Catch drops in Hb
Monitor Platelets: Observe for signs of bleeding --> risk of Heparin Induced Thrombocytopenia --> adjust dosage SE: MC side effect = Hemorrhage Paradoxical Thrombosis (RARE) --> New clot formation OVERDOSE: Antidotes: 1)Protamine --> Causes resistance to Heparin as an anticoagulant 2) Whole Blood and Fresh Frozen Plasma --> contain Clotting Factor --> If bleeding continues: Determine if HIT is cause of bleed - --> If so; STOP Heparin; give platelets, change agent --> If not: THEN tx w/Protamine |
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Heparin Administration
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Given IV to tx a clot
SQ to prevent a clot NEVER IM --> too many BVs in muscle --> causes hematomas! Have to give a loading dose --> Anticoagulation/Inhibits Factors ASAP Monitor CBC: Catch drops in Hb Monitor Platelets: Observe for signs of bleeding --> risk of Heparin Induced Thrombocytopenia --> adjust dosage MC side effect = Hemorrhage |
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Fondaparinux (Arixtra)
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heparinoid
--> chemically NOT a Heparin but acts like one --> the therapeutic dose does not cause HIT!!! Great alternative for LMWH in a patient who contracted HIT from Heparin therapy SE: 1 article claimed for it to cause HIT; but it's doses were way above therapeutic levels |
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Heparin Side Effects
and Antidotes |
Monitor CBC: Catch drops in Hb
Monitor Platelets: Observe for signs of bleeding --> risk of Heparin Induced Thrombocytopenia --> adjust dosage SE: MC side effect = Hemorrhage Paradoxical Thrombosis (RARE) --> New clot formation OVERDOSE: Antidotes: 1)Protamine --> Causes resistance to Heparin as an anticoagulant 2) Whole Blood and Fresh Frozen Plasma --> contain Clotting Factor --> If bleeding continues: Determine if HIT is cause of bleed - --> If so; STOP Heparin; give platelets, change agent --> If not: THEN tx w/Protamine |
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LMWH
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Decreased Chance of HIT
Not completely w/out risk: --> If got HIT on Hep; don't tx w/LMWH •Can be given therapeutic dose SQ --> Good for home therapy! Won't affect aPTT - don't monitor •lower risk for HIT – not completely lack of risk •if HIT on heparin --> dont place on LMWH → take it away all together INDICATIONS: DVT, PE --> Teach pts how to self-inject --> Don't need to hospitalize w/LMWH! CONTRAINDICATIONS: Renal Dysfx DON'T use if CrCl < 30 ml/min Exception: Enoxaparin: CAN use w/Renal Dysfx --> just adjust dose! If questionable dosage: Anti-F X Assay --> If increased activity; increase dose |
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Contraindications for LMWH
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Contraindications: Renal Dysfx
DON'T use if CrCl < 30 ml/min Exception: Enoxaparin: CAN use w/Renal Dysfx --> just adjust dose! |
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Fondaparinux (Arixtra)
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heparinoid
--> chemically NOT a Heparin but acts like one --> the therapeutic dose does not cause HIT!!! Great alternative for LMWH in a patient who contracted HIT from Heparin therapy SE: 1 article claimed for it to cause HIT; but it's doses were way above therapeutic levels |
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LMWH
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Decreased Chance of HIT
Not completely w/out risk: --> If got HIT on Hep; don't tx w/LMWH •Can be given therapeutic dose SQ --> Good for home therapy! Won't affect aPTT - don't monitor •lower risk for HIT – not completely lack of risk •if HIT on heparin --> dont place on LMWH → take it away all together INDICATIONS: DVT, PE --> Teach pts how to self-inject --> Don't need to hospitalize w/LMWH! CONTRAINDICATIONS: Renal Dysfx DON'T use if CrCl < 30 ml/min Exception: Enoxaparin: CAN use w/Renal Dysfx --> just adjust dose! If questionable dosage: Anti-F X Assay --> If increased activity; increase dose |
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Contraindications for LMWH
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Contraindications: Renal Dysfx
DON'T use if CrCl < 30 ml/min Exception: Enoxaparin: CAN use w/Renal Dysfx --> just adjust dose! |
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Divalent Direct Thrombin Inhibitors
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Hirudin
Lepirudin (refludan) - synthetic Bivalirudin (Angiomax) |
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Lepirudin
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Divalent Direct Thrombin Inhibitors
Derivative of hirudin - synthetic Alternative to heparin Works in the presence of HIT Less monitoring Same precautions |
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Bivalirudin
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Direct Divalent Thrombin Inhibitor
Bivalent inhibitor of thrombin IV Quick onset --> Short half-life --> can turn effect on rapidly |
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Univalent Direct Thrombin Inhibitors
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Argatroban, IV - used in pts w/HIT
Dabigatran, PO |
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Rivaroxaban
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Only drug in US that works directly against Factor X
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Darbigatran (Pradoxa)
Dose and Admin |
Univalent Direct Thrombin Inhibitor
Rapid Absorption, peaks 1 hr (2h w/food) Low variability Metabolized in liver to active form Doesn't affect CYP activity Difficult to monitor: if aPPT > 3.5 --> over-coagulation Liver Dysfx --> Don't need to adjust dose Renal Dysfx --> Adjust dose: potential for accumulation |
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Darbigatran Side Effects and Drug Interactions
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Only drug interation: Rifampin
(P-glycoprotein inducer) --> No antidote available! SE: dyspepsia, bleeding, fatigue, peripheral edema, diarrhea |
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DARBIGATRAN v. Warfarin
Clinical Trial |
110 mg - same outcomes
150mg - D - lower SE's/PE/Stroke; BUT similar rates of hemorrhage --> Remember if it's a better anticoagulant --> increased rates of hemorrhage So only use in pts who cannot tolerate Warfarin Big therapeutic window --> but low compliance (dyspepsia) |
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Rivaroxaban
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Specific, competitive, direct FXa inhibitor
Inhibits free and clot-associated FXa activity, and prothrombinase activity Inhibits thrombin generation via inhibition of FXa activity Prolongs time to thrombin generation High Bioavailability; low Rx interaction Inhibits peak thrombin generation Reduces the total amount of thrombin generated Does not require a cofactor No monitoring required --> Safe! Similar efficacy as Enoxaparin |
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Vitamin K Clotting Factors
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Require adequate Vita K stoarge for synthesis in liver
Need cofactor for oxidation --> carboxylation --> Oxidized Vitamin K --> recycles - Higher bleeding risk Ex: Warfarin |
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Warfarin Mechanism and Onset
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Mechanism: Antagonizes Vitamin K and depletes it's dependent coagulation factors (II, VII, IX, X, Prot C/S)
Onset: 1-2d; Monitor PT True anticoagulation 2-7d --> d/t F7 being depleted (1st) shortest half life of the vita k dpndnt factors --> Others still present and need to deplete |
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Warfarin General
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Antagonizes Vitamin K --> depletes Vita K dependent coagulation factors (II, VII, IX, X, Prot C/S)
Well Absorbed Highly Protein Bound Metabolized by liver **TERATOGEN!!** --> pregnant put on heparin instead |
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Warfarin Dosing Strategies
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Therapeutic goal: INR (varies)
Do not load doses --> may increase bleed! Start 1 day after initiating Heparin Periprocedural - restart after incision closure Onset of action: 1-2 days; "true" anticoagulation: 2-7 days Monitor PT --> elevated d/t F7 depletion (shortest half life) |
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Warfarin
Drug Interactions; Patient Ed and Side Effects |
1)Enzyme Inducers:
Cigarettes, Anti-Epileptics --> metabolize rx faster --> drug levels decrease Enzyme Inhibitors: 2) Anti-Emetics, Cimetidine - metabolizes slower --> increased [Warfarin] 3) Digoxin (Afib) --> displaces Warfarin from binding sites **DON'T give to pregnant women SE: bleeds (small bleed can tx w/Vita K), Thrombocytopenia --> signs of OD: bloody stool/urine, excess menstruation/bruising/epistaxis, oozing/bleeding from superficial injuries Patient Ed: Avoid Vitamin K containing foods NO Antacids! --> Decreased effect: spinach, organ meat, nutritional supplements --> communicate and adjust dosage |
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Antiplatelet Agents
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GP2b/3a inhibitors - bind receptors on platelets and inhibit aggregation or binding of ligands/fibrinogen
- Thienopyridines - Monoclonal Antibody - abciximab - Synthetic Peptides - MC used - Nonpeptide Inhibitors - Oral Agents - never made it to market |
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Thienopyridines
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Antiplatelet Agents
-Inhibit ADP-dependent activation of GP IIb/IIIa complex Tx of ACS, stroke prevention, post-stroke Ticlopidine (Ticlid) - hematologic SE's --> slow activity Clopidogrel (plavix) --> better than aspirin --> 6x MORE active than Ticlopidine; generic Prasugrel (effient) Ticagrelor (brilinta) |
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Anti-Thrombolytics
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Act on plasminogen to form Plasmin
Plasmin cleaves Fibrin --> dissolves clots Tx stroke (Alteplase)/MI, only small clots w/DVT MI: Great improvement if given in 3hrs from onset; must start ASAP w/Dx; must have w/in 30 min from arrival to dept Streptokinase Urokinase Anistreplase Alteplase Reteplase Tenecteplase |
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Alteplase (Activase, t-PA)
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Thrombolytic
Only one w/FDA approval for stroke Given over 90 mins |
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Reteplase (Retavase)
and Tenecteplase |
Thrombolytics
2 most frequently used, IV form R: 30 mins apart, 2 vials T: Single dose |
