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HIGH ALERT MEDICATION MANAGEMENT High Alert Medication (HAM) bear a heightened risk of causing significant patient harm due to error in storage, prescribing, dispensing, administration and use. INTRODUCTION High Alert Medications (HAM) are associated with a significant risk of harm. Mishaps wi...

HIGH ALERT MEDICATION MANAGEMENT High Alert Medication (HAM) bear a heightened risk of causing significant patient harm due to error in storage, prescribing, dispensing, administration and use. INTRODUCTION High Alert Medications (HAM) are associated with a significant risk of harm. Mishaps with high alert medication in comparison with others may or may not be more common but the consequences following medication errors can be serious to patients. Factors like inherent risk of using HAM, vulnerable patient groups (pregnant women, paediatric patients, geriatric patients, cancer patients etc.), healthcare setting (e.g. outpatient vs inpatient settings), organizational culture, high-risk clinical scenarios (e.g. emergency and anesthesia settings) etc. could impose difficulties for healthcare professionals in ensuring patient safety while delivering health services. Accordingly, a holistic approach towards addressing medication safety is required keeping in view all the interlinked components. As per international practices, the list of HAM in healthcare settings varies depending on the patient population treated and medicines required. DRAP has notified a tailored high-risk/high alert medication list, on the basis of medicines being used in Pakistan and internationally reported cases related to HAM. HAM, as a whole, warrant special safeguards during the process of healthcare to reduce the risk of unnecessary patient harm associated with AEs/ADRs such as preventable medication errors. Safe use of HAM is widely dependent on / influenced by the following four factors: i. Education and involvement of patients and the public ii. Knowledge, skills and safe practices by healthcare professionals iii. Safe handling and use of Medicines iv. System design and infrastructure to support safe medication use  DEFINITION AND ACRONYMS ADR “Adverse Drug Reaction” means response to drug or therapeutic goods which is noxious and unintended that occurs at doses normally used for the prophylaxis, diagnosis or therapy of disease or for the restoration, correction or modification of physiological function. A response in thiscontext means that a causal relationship between a therapeuticgood and an adverse event is at least a reasonable possibility. An adverse reaction, in contrast to an adverse event, is characterised by the fact that a causal relationship between a therapeutic good and an occurrence is suspected. AE “Adverse Event” means any untoward medical occurrence in a patient or clinical investigation subject administered a drug or therapeutic good and which does not necessarily have a causal relationship with this treatment. High Alert drugs that bear a heightened risk of causing significant patient Medication (HAM) harm when they are used in error. Although mistakes may or may not be more common with these drugs, the consequences of an error are more devastating to patients. Institute of Safe Medication Practices (ISMP) LASA Look alike Sound Alike Medication Error Means any preventable event that may cause or lead to inappropriate medication use or patient harm while the medication is in the control of the healthcare professional, patient or consumer PV “Pharmacovigilance” means the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other therapeutic good related problems. Serious ADRs or AEs means an untoward medical occurrence that at any dose results in patient death, is life-threatening, requires inpatient hospitalization or results in prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect or is judged to be a medically important event or reaction  HIGH ALERT MEDICATIONS Medication errors are significant and often preventable healthcare problems. Although many medication errors may not cause grave harm to patients but risk associated with some drugs is higher than others. Errors in the administration of such drugs can have catastrophic clinical outcomes in patients. Medications having a very narrow margin of safety require heightened vigilance, as these can cause severe patient harm when implicated in an Adverse Event. An error associated with the use of these drugs can result in significant patient injury and special precautions must be employed with their overall management. Due to this potential of risk, these drugs are identified as High Alert Medications. HIGH ALERT MEDICATION MANAGEMENT & SAFE USE General Principles Safety must be ensured at all stages and steps of handling and dealing with high alert medication. Following are some basic principles for awareness of the healthcare professionals: A list of high alert medications (HAM) identified from the master list and used within the facility 1. The list is displayed in prominent areas e.g. in nursing units, physician rooms, procedure rooms, medication storage areas (within or outside pharmacy) and is also freely accessible through the organization’s intranet/webpage. 2. HAMs and LASA drugs should be labeled as HIGH ALERT MEDICATIONs, LASA respectively as a reminder for healthcare professionals to remain vigilant in the management of the same. Be extra careful with drugs that are Look-Alike/Sound-Alike in addition to being one of the high alert medications as well. 3. Medications identified as high alert or LASA should be targeted for specific error prevention strategies. 4. HAMs and LASA are required to be stored, prescribed, dispensed, administered and monitored using practices that ensure safety for the patient discouraging operational shortcuts and reckless behaviour. 5. HAM and LASA must be counterchecked (preferably by a second independent healthcare professional) when prepared, at the time of dispensing and before administration to the patients. 6. The right to prescribe certain HAMs should be defined by the organization e.g. chemotherapeutic drugs can be prescribed by an oncologist/hematologist and thrombolytics by Cardiologist or Neurologist Only etc. 7. The appropriateness of each order is reviewed by a pharmacist before dispensing / administering. 8. Minimize or eliminate medication order transcription (by Nursing or other staff). Original physician order should be accessible to pharmacists for review. (Tips: use electronic physician order entry system or send duplicate/scanned copy of original order to pharmacy) 9. Use of electronic/computerized system for prescribing, dispensing and Administration Clinical decision support in computerized order entry systems 10. Barcode assisted medication administration 11. Use of drug libraries in smart infusion/syringe pumps 12. Standardized labels 13. Isolated and controlled storage of certain HAMs 14. Dispensing of diluted, ready-to-administer premixed parenteral HAMs by pharmacy 15. Use of Oral Syringe for liquid (oral) medication administration 16. Medication reconciliation at a patient’s admission, transition of care and discharge etc. 17. Monitor and report Adverse Drug Reactions (ADRs), Adverse Events (ADEs), near miss and medication errors related to HAMs. Take appropriate steps to prevent recurrence in future. Healthcare Professionals and staff should be encouraged to report errors without the fear of repercussion or penalty. 18. Organizations must promote the culture of safety and accountability Storage: 1. Drugs should be stored and transported in conditions appropriate to maintain their efficacy and stability i.e. controlled conditions of (temperature, humidity and light etc.) 2. Controlled drugs (e.g. narcotics) should kept under lock and key for authorized access only. 3. Other HAMs should also be in authorized access and be protected from loss or theft across the healthcare facility 4. Drugs should be stored and used as per First Expire First Out (FEFO) principle 5. Lot (batch #) and expiry of drug should remain visible and traceable to ensure effective drug recall 6. Use cautionary label on packs and storage shelves, bins of high-alert medications and LASA drugs. 7. HAMs and LASA should be kept separately in labeled containers as indicated in monographs for each category 8. Avoid look-alike and sound-alike medications from being stored in close proximity. 9. Drugs intended for a specific route of administration must be stored in a conspicuous manner for differentiation e.g. Oral medicines separate from intravenous Intravenous separate from epidural or intramuscular inj. Sustained-release or depot forms must be stored separately from immediate-release forms Topical drugs from oral and parenteral etc. Each type must be labeled properly on bin/shelf to alert the staff e.g. “Not for IV use” or “Epidural Use only” etc. 10. Use TALL-man lettering to emphasize differences in medication names (e.g. DOPAmine and DOBUTamine) as indicated in the monographs 11. Limit the nursing unit’s floor stock medication to standard requirement, reducing /restricting the quantity and availability of multiple strengths or dosage forms. 12. Medicines should be identified and checked with generic name in addition to their brand names while storing, picking for dispensing/administration or placing back any unused items. 13. Drugs which are not needed (hold/discontinued) should not be stored with those due for administration 14. When new stock is received or unused drugs are returned, caution must be exercised to put them back in the right place (in their designated shelf or bin). Placement in the wrong place can result in medication error when the next dispensing takes place. 15. All equipment used in monitoring and/or maintenance of storage conditions for medicines (e.g. thermos- hygrometers, dehumidifiers, data loggers etc.) must be properly validated, calibrated and on periodic preventive maintenance (PPM). 16. Follow the 6 rights of safe drug administration: Right patient, Right drug, Right dose, Right time, Right route, Right documentation in charts 17. Always compare drug in hand against drug name, strength and route mentioned in physician’s order before administration 18. In case of any ambiguity, the prescriber should be contacted for clarification before administering the medicines 19. In case of any changes in orders, effective and immediate communication and documentation should be assured 20. The practice of double checking or second person verification for dose, route, dilution etc. can eliminate chances of errors 21. One patient’s drugs (either new or leftover) should not be used for another patient 22. Unlabeled drugs or those for which information on the contents, strength, expiry dilution etc. is not known should never be used. Any unlabeled and unidentified syringes should be immediately discarded in a safe manner / as per SOPs, if found in patient care area 23. If a drug is to be prepared before administration, the preparation, calculation and dilution etc. should be completed in a clean, safe, clutter free area with minimum-to-no distractions The drug should be properly labelled if administration is at a later time If a multi-dose vial is used for drug preparation, it should be marked with date-of-opening, dilution concentration and the personnel’s name & designation. Such vials should be discarded immediately on expiry date 24. Majority of serious administration errors occur due to administration of drug by the wrong route. Always verify the drug in hand and the source of invasive line before administration. Common errors include: Connecting oral medicines contained in syringe (or enteral feed bags) with Intravenous (IV) cannula Epidural or intrathecal medications given via IV route (and vice versa) 25. Verbal orders should not be given / taken for HAMs unless it’s for an emergency/life threatening situation, or during a procedure  High Alert Medication List Notified by the National Pharmacovigilance Centre, DRAP. S# Class/Category Drugs * 1. Adrenergic agonists IV form of Epinephrine, Phenylephrine, Norepinephrine etc. 2. Adrenergic antagonists IV form of Metoprolol, Labetalol 3. Anaesthetic agents General, Inhaled and IV form of drugs like Propofol, Ketamine, Isoflurane and Sevoflurane etc. 4. Antiarrhythmics IV form of Lidocaine and Amiodarone etc. 5. Antithrombotic agents Anticoagulants: Warfarin, low molecular weight heparin (Enoxaparin),Unfractionated heparin Direct oral anticoagulants and factor Xa inhibitors: Rivaroxaban, Fondaparinux Apixaban etc. Thrombolytics: Alteplase and Streptokinase. 6. Anti-infective Amphotericin, Vancomycin, Aminoglycosides. 7. Cardioplegic agents Both commercial products and compounded within hospitals 8. Chemotherapeutic agents All parenteral and oral chemo 9. Dextrose Hypertonic Dextrose water 20% and above for parenteral use 20%and above 10. Dialysis solutions Both hemodialysis and peritoneal dialysis solutions 11. Epidural and Intrathecal Bupivacaine, Ropivacaine 12. Hypoglycemics Oral form of Glimepiride, Glibenclamide, Glipizide etc. agents,sulfonylurea 13. Inotropic drugs IV form of Digoxin and Milrinone 14. Insulins All Insulins 15. IV electrolytes Undiluted Potassium Chloride for Inj, concentrate and injections of Magnesium Sulphate, Potassium Phosphate, IV form of Hypertonicsaline. 16. Liposomal forms of drugs E.g. Liposomal Doxorubicin vs conventional Doxorubicin HCl 17. Look alike and sound Each patient care facility to review and develop their own look alikedrugs alike(similar appearance) and sound alike (that sound similar or are read like) drugs pairs list based on their incident/ error data. 18. Moderate sedation agents IV form of Dexmedetomidine, Midazolam etc. 19. Moderate and minimal Oral form of Chloral Hydrate, Midazolam, parenteral form of sedation agents for Ketamine etc. children 20. Neuromuscular blocking Succinylcholine, Rocuronium, Atracurium, Cis-Atracurium etc. agents 21. Opioids All opioids including oral (liquid concentrate, immediate and sustained release formulations), Parenteral and transdermal form. 22. Parenteral Nutrition Both commercial products and compounded within hospitals 23. Others IV form of Oxytocin, Vasopressin, and Promethazine. Look-alike and Sound alike drugs Look-Alike Sound-Alike (LASA) medications involve medications that are visually similar in physical appearance or packaging (see pictures below) and names of medications that have spelling similarities and/or similar phonetics or Read-Alike effect. Therefore, LASA drugs are sometimes also referred to as LASARA drugs. For example: Digoxin Dobutamine Epinephrine Lasix Thyroxin Dopamine Norepinephrine Losec Angised Filgrastim Vincristine Lamisil Ansaid Peg-Filgrastim Vinblastine Lamnet  High Alert Medications List (HAMs) Dosage No. Class Sub Class Generic Brand Form Dobutine, Dobuject Dobutamine Injection Dalpam, Dopa Inj, Dopacin, Direct Dopamine Injection Inopan, Acting Adrenergic Agents 1. Epinephrine Injection Adrenaline Agonists Norepinephrine Injection Noradrin, Norephed Phenylephrine Injection Synephrine Terbutaline Injection Britanyl, Direct and Indirect Acting (mixed Ephedrine Injection Efed, Ephedrine, Sedaphrine acting) Agents Adrenergic Labetalol Injection Labetalol 2. Beta Blockers Antagonists Metoprolol Injection Merol, General Isoflurane Injection Forane Anesthetics: Inhaled Sevoflurane Liquid Sevorane Thiopental Injection Pentothal Sodium, Thioptone Etomidate Infusion Etomidate Lipuro Anesthetic 3. Katafast, Ketacil, Ketajin, Agents General Ketamine Injection Ketanaar, Ketasol, Anesthetics: Intravenous Fentanyl Injection Fentra Profol Lipuro, Propofol Propofol Infusion Epocain, L-Caine, Licain, Lignocaine AD, Lignocaine, Injection Xylocaine with Adrenaline, Xylocaine, Class I (Na+ Lidocaine Channel Blocker) A-fenac Plus, Artecid Plus, Injection Articure, Astefenac Plus, Inj Difam + Plus, Dilaram-L Diclofena 4. Antiarrhythmic c Sodium Class II (Beta Adrenoreceptor Metoprolol Injection Merol, Metoprolol Blocker)  Class III (K+ Amiodarone Injection Cordarone Channel Blocker) Other Antiarrhythmic Digoxin Injection Lanoxin Drugs Antithrombotic Apixaban Tablet Apiban, Apixaget agents / Enoxaparin Injection Clexane 5. Anticoagulants Anticoagulants Fondaparinux Injection Arixtra / Thrombolytic Heparin Injection Heparin Arixa, Nabaxo, Oxaban, Revoban, , Rivaban, Rivaclot, Rivarox, , Rivaroxaban Tablet Rivaxo, Rivfaas, , Valoxaban, Xarelto, Warfarin Tablet Hemolyte, Warfin Diclair-ST, Durakinase, Eskinase, Thrombolyti Streptokinase Injection Streptase c Agents Urokinase Injection Urofix Vancocin, Vancomycin, Vancorin, Cell Wall Inhibitor Vancomycin Injection Amikacin Injection Amicin, Amifate, Amikacin, Aminoglycosides Amkay, Amkeen, Grasil Gentacil, Gentamycin, Genta, 6. Anti-Infective Gentamicin Injection Genticyn, Nebcin, Obramycin, Tobcin, Tocin Tobramycin Injection Amphotericin B Anti-fungal Injection Anfotericina FADA Lipid Complex Ampule, Dextrose (2 brands), Glucosteril, 7. Dextrose hypertonic 20% and above Dextrose 25% Infusion Medisol, Mini, Pladex-25, Sterifluid, Diamicron Tablet Hypoglycemic Glicazide Tablet + 8. Agents Glimin Metformin Sulfonylurea Glimepiride Tablet Getryl,  Tablet + Amaryl M, Getformin, Metformin Tablet + Fantasmic, Piozer G , Zoliget Pioglitazone Tablet Gleezid, Glipase, Minidiab Glipizide Tablet + Minidiab AF Metformin Daonil, Tablet Glibenclamide (glyburide) Tablet + Glimet, Glucomet, Metformin Novonorm Metiglinides Repaglinide Tablet Abocain, Bucane, Bupicain, Epidural and Neuraxial Bupivicaine Injection Sensocain 9. Intrathecal Local Anesthetics Ropivacaine Injection Ropicain Injection Lanoxin Digoxin Liquid Doxin 10. Inotropic Medicine Tablet Digitek, Lanoxin Milrinone Injection Milron Rapid Acting Insulin Aspart Injection Novorapid Insulin Glulisine Injection Apidra Insulin Lispro Injection Humalog Lispro Short Acting Actarapid HM, Humulin-R, Innogen- Regular Insulin Injection R, Insuget Regular Injection + Insulin Insulin Novomix Aspart Aspart Protamine Injection + Insulin Intermediate Insulin Humalog Mix 11. Insulin Lispro Acting Lispro Protamine Humulin-N, Innogen-N, Insuget-N, Injection Insulatard HM, Insuman Basal Isophane Insulin / Injection + NPH Insulin Humulin 70/30, Innogen M30, Regular Insuget 70/30, Mixtard 30 HM Insulin Insulin Detemir Injection Levemir Long Acting Insulin Glargine Injection Basagine, Lantus, Toujeo Injeciton + Ultra-long Acting Insulin Degludec Insuli Ryzodeg n Aspart  IV Electrolytes / Concentrated Potassium 12. Injection Mini KCL, Potassium Chloride Electrolytes for IV Use Chloride Magnesium Injection Magnesium Sulfate Sulfate Liposomal forms of drugs / Lipid Amphotericin 13. Based Drugs and their conventional Injection Anfotericina FADA BLipid counterparts Complex Chloral Hydrate Syrup Cedate, Chloral Hydrate Dexmedetomidine Injection Precidex Moderate Sedation Agents, Dormicum, Hypozam, 14 Moderate and minimal sedation Injection Noctrum, DMZ agents for children Midazolam Tablet Dormicum, Tracrium Atracurium Injection Cisatracurium Injection Cis-Curon 15 Neuromuscular Blocking Agents Rocuronium Injection Roconium, Trocuronium B-Metho, S-Choline Succinylcholine Injection ,Suxaium, Suxamin, Suxathon, Suxinium Oxytocin (2 brands), Syntomax, 16 Oxytocin Injection 17 Promethazine Injection Etosil, Phenerzine, Promethazine Trexol, Methotrexate, Injection , Unitrexate, 18 Methotrexate Trexol, Blutrexate, Cytotrexate, Tablet Methotrexate, Pharmatrexate, Unitrexate ANEMIA Dr. Muhammad Junaid Hassan Sharif  BACKGROUND Anemia is the most common blood disorder worldwide. It is a decrease in hemoglobin (Hgb) and hematocrit (Hct) concentrations below the normal range for age and gender. Hgb is an iron-rich protein found in red blood cells (RBCs). Its main purpose is to carry oxygen from the lungs to the tissues. RBCs are formed in the bone marrow, where they take up Hgb and iron before being released into the circulation as immature RBCs, known as reticulocytes. After 1 - 2 days, the reticulocytes mature into erythrocytes, which have a lifespan of about 120 days. Erythrocytes are removed from circulation by macrophages, mainly in the spleen. 2 Anemia can occur due to 1. Impaired RBC production, 2. Increased RBC destruction (hemolysis) 3. Blood loss. A decrease in Hgb or RBC volume results in decreased oxygen carrying capacity of the blood. Anemia can result from 1. Nutritional deficiencies (e.g., iron, folate, vitamin B12) 2. Complication of another medical disorder, such as chronic kidney disease (CKD) 3. Malignancy. 3  SYMPTOMS OF ANEMIA Most patients with mild or early-stage anemia are asymptomatic. If anemia becomes severe and/or prolonged, the lack of oxygen in the blood can lead to classic symptoms of Fatigue, Weakness, Shortness of breath, Exercise intolerance, Headache, Dizziness, Anorexia and/or Pallor. 4  SYMPTOMS OF ANEMIA If sudden blood loss occurs, the patient can experience acute symptoms, such as Chest pain, Fainting, Palpitations Tachycardia. Patients with iron deficiency anemia can develop Glossitis (an inflamed, sore tongue), Koilonychias (thin, concave, spoon-shaped nails) Pica (craving and eating non-foods such as chalk or clay) 5  Patients with vitamin B12 (cobalamin) deficiency can present with neurologic symptoms, including Peripheral neuropathies, Visual disturbances and/or Psychiatric symptoms. A decreased oxygen supply can cause ischemic damage to many organs. In chronic anemia, the heart tries to compensate for low oxygen levels by pumping faster (tachycardia). This can increase the mass of the ventricular wall (hypertrophy) and lead to heart failure. 6 Common Lab tests in anemia  TYPES OF ANEMIA The type and cause of anemia cannot be determined based on signs and symptoms alone. The mean corpuscular volume (MCV), which reflects the size or average volume of RBCs, can help determine the type of anemia and the possible underlying cause. A low MCV means that RBCs are smaller than normal (microcytic) and a high MCV means that RBCs are larger than normal (macrocytic). These findings correlate with different causes of anemia. Certain genetic conditions can cause anemia due to dysfunctional RBCs. 8 9 Iron studies further evaluate microcytic anemia; they include Serum iron (bound to transferrin), Serum ferritin (iron stores), Transferrin saturation (amount of transferrin binding sites occupied by iron) Total iron binding capacity (amount of transferrin binding sites available to bind iron or unbound sites). Vitamin B12 and folate levels further evaluate macrocytic anemia. Vitamin B12 is required for enzyme reactions involving methyl malonic acid and homocysteine, making these tests potentially useful in confirming a diagnosis. Reticulocyte counts are a measure of RBC production, which is usually impaired in anemia. 10 1-IRON DEFICIENCY ANEMIA 11  IRON DEFICIENCY ANEMIA Dietary iron is available in two forms: 1. Heme iron (found in meat and seafood) 2. Non-heme iron (found in nuts, beans, vegetables and fortified grains, such as cereals). Heme iron is more readily absorbed which is affected by gastric pH and other foods. Meat, seafood, poultry and ascorbic acid increase the absorption of non-heme iron, while foods that contain phytate and polyphenols (e.g., grains, beans, cereals and legumes) can decrease non-heme iron absorption. This is particularly important for patients who follow a vegetarian diet, since they are more likely to consume foods with a less absorbable form of iron along with foods that decrease the absorption of iron. 12  Vegetarians may require iron supplementation, even if dietary intake of iron seems adequate. Preventative measures can be used for some of the at-risk patient populations. For example, women who use hormonal contraception may experience less bleeding during menstrual periods and their risk of developing iron deficiency may be lower. The CDC recommends low-dose iron supplementation (30 mg/day) for all pregnant women, beginning at the first prenatal visit; this is usually provided in the prenatal vitamin. Larger doses of iron are required if iron deficiency anemia (IDA) is diagnosed in pregnancy. 13 Causes of Iron Deficiency 14  DIAGNOSIS AND TREATMENT LABORATORY FINDINGS ↓ Hgb, MCV< 80 fL,↓ RBC production (low reticulocyte count) ↓ serum iron, ferritin and TSAT ↑ TIBC TREATMENT:ORAL IRON THERAPY Recommended dose:100 - 200 mg elemental iron per day* Take iron on an empty stomach** Avoid H2RAs and PPIs; separate from antacids Sustained- release or enteric-coated formulations cause less Gl irritation but are not recommended for initial therapy 15  Continued.. GOALS ↑ in serum Hgb by 1g/dL every 2-3 weeks: Continue treatment for 3-6 months after anemia has resolved until iron stores return to normal. 16  Oral Iron Drug Brand DOSE Ferrous sulfate Fefol Vit (GSK) 325 mg (65 mg elemental iron) PO Daily to TID Ferrous fumarate Tri-Hemic 600 324 mg (106 mg elemental (Pfizer) iron) PO daily to TID Ferrous gluconate Sangobion 324 mg (38 mg elemental iron) (MERCK) PO daily to TID Carbonyl iron ------------- 90 mg (90 mg elemental iron) PO daily or as directed Polysaccharide Rubifer, (AGP) 150 mg PO daily iron complex. Ferosoft FA (Hilton) 17  Oral Iron Oral iron supplementation can adequately treat most patients with IDA; Parenteral iron therapy is typically reserved due to a higher risk of side effects, cost and burden of administration. Contraindications Hemochromatosis, hemolytic anemia, hemosiderosis Side Effects Constipation (dose-related), dark and tarry stools, nausea, stomach upset Monitoring Hgb, iron studies, RBC indices, reticulocyte count 18 Oral Iron Drug Interactions Antacids, H2RAs and PPIs ↓ iron absorption by ↑ gastric pH. Patients should take iron 2 hours before or 4 hours after taking antacids. Iron is a polyvalent cation that can ↓ the absorption of other drugs by binding with them in the GI tract to form non absorbable complexes. Quinolone and tetracycline antibiotics (less of a concern with doxycycline and minocycline): take iron two hours before or 4 -8 hours after these agents. Bisphosphonates: take iron 60 minutes after oral ibandronate or 30 minutes after alendronate/risedronate. Cefdinir, levothyroxine, levodopa and methyldopa -separate from iron by 2 - 4 hours. Vitamin C ↑ the absorption of iron. 19 Oral Iron Patient Counseling This medication is used to treat a condition called anemia. It needs to be taken for a few months for your symptoms to improve. Take this medication on an empty stomach. If stomach upset occurs, it can be taken with food, but avoid cereals, tea, coffee, eggs, milk and high fiber products, as these decrease iron absorption. Iron can cause dark stools, which is expected. If you develop constipation, your healthcare provider can recommend a stool softener (e.g., docusate sodium). 20 2-Parenteral Iron Provides elemental iron and avoids the issues with iron absorption. These factors make it more effective and result in faster increases in Hgb levels. The total dose needed to replenish iron stores (e.g.,1,000 mg) can be provided in a single infusion, if desired. Due to the risk of more severe adverse reactions, as well as the cost of therapy, IV iron administration is typically restricted to the following patients: CKD on hemodialysis (most common use of IV iron). CKD receiving erythropoiesis-stimulating agents (ESAs). 21  Unable to tolerate oral iron or failure of oral therapy (e.g., IBD, celiac disease, certain gastric bypass procedures, achlorhydria and bacterial overgrowth syndromes such as H. pylori). Losing iron too fast for oral replacement. As an alternative when blood transfusions are not accepted by the patient (e.g.for religious reasons). 22  Intravenous (Parenteral) Iron Therapy Drug Brand Side effects Iron sucrose Venofer Muscle aches Flushing Ferumoxytol Faraheme Hypotension Hypertension Iron dextran complex INFeD Tachycardia Chest pain Peripheral edema Sodium ferric Ferrlecit gluconate Ferric carboxymaltose Injectafer Ferric pyrophosphate Triferic citrate 23  Intravenous (Parenteral) Iron Therapy Side effects All parenteral iron products carry a risk for hypersensitivity reactions (including anaphylaxis) Monitoring Hgb, iron studies, reticulocyte count, vital signs, signs and symptoms of anaphylaxis Give by slow IV injection or infusion decrease the risk of hypotension All agents are stable in NS; Feraheme is stable in NS or D5W 24 2-Macrocytic Anemia 25  MACROCYTIC ANEMIA Macrocytic anemia is caused by vitamin B12 or folate deficiency, or both. Pernicious anemia, the most common cause of vitamin B12 deficiency, occurs due to a lack of intrinsic factor, which is required for adequate vitamin B12 absorption in the small intestine. Other causes of macrocytic anemia include alcoholism, poor nutrition, gastrointestinal disorders (e.g., Crohns disease, celiac disease) and pregnancy. The long-term use (> 2 years) of metformin, H2RAs or PPIs can decrease the absorption of vitamin B12. 26  Vitamin B12 deficiency can result in serious neurologic dysfunction, including cognitive impairment and peripheral neuropathies. Folic acid deficiency does not result in neurologic symptoms; it causes ulcerations of the tongue and oral mucosa, and changes to skin, hair and fingernail pigmentation. Vitamin B12 is required for enzyme reactions involving methyl malonic acid and homocysteine, they accumulate when vitamin B12 is deficient. Homocysteine levels can also be elevated in folate deficiency. 27  DIAGNOSIS OF MACROCYTIC ANEMIA In addition to low Hgb and high MCV, reticulocyte counts and serum levels of vitamin B12 and/or folate will be low. Since vitamin B12 is required for enzyme reactions involving methylmalonic acid and homocysteine, they accumulate when vitamin B12 is deficient. Homocysteine levels can also be elevated in folate deficiency 28  TREATMENT OF MACROCYTIC ANEMIA The initial treatment of vitamin B12 deficiency typically involves vitamin B12 injections, to bypass absorption barriers, followed by oral supplements, if appropriate. Vitamin B12 injections are recommended first line for anyone with a severe deficiency or neurological symptoms. Drug Brand Cyanocobalamin, vitamin B12 Neurobion (Merck), IM or deep S/C: 1000 mcg Lysovit Syrup (Pfizer), daily/weekly/monthly depending on severity Iberet-folic (Abbott) Oral/sublingual:1,000-2,000 mcg daily Folic acid, folate, vitamin 0.4-1mg daily 29 Contraindications Allergy to cobalt or vitamin B12 (an intradermal test dose is recommended for any patient suspected of vitamin B12 sensitivity prior to intranasal or injectable administration) Side effects Pain with injection rash, polycythemia vera, pulmonary edema (all rare) Monitoring Hgb, hct, vitamin b12,reticulocyte count Side effects Bronchospasm, flushing, rash, pruritus, malaise (all rare) Monitoring Hgb, Hct, folate, reticulocyte count 30  Vitamin B12 and Folic Acid Drug Interactions Chloramphenicol can ↓ the efficacy of vitamin B12. Colchicine can ↓ the absorption of vitamin B12. The efficacy of raltitrexed (a chemotherapeutic agent) can be ↓ by folic acid; avoid combination. Folic acid can ↓ the serum concentration of fosphenytoin, phenytoin, primidone and phenobarbital. Green tea and sulfasalazine may ↓ the serum concentration of folic acid. 31 NORMOCYTIC ANEMIA 32  A-ANEMIA OF CHRONIC KIDNEY DISEASE Primarily due to a deficiency in erythropoietin (EPO), a hormone produced by the kidneys that stimulates the bone marrow to produce RBCs. Iron therapy and erythropoiesis-stimulating agents (ESAs) are the treatments for anemia of CKD. IV iron is first-line for hemodialysis (HD) patients. Non-HD CKD patients with anemia can be treated with oral iron supplements. The KDIGO guidelines (Kidney Disease Outcomes Quality Initiative) recommend iron therapy in both if TSAT is < 30% and ferritin levels are < 500 ng/mL. 33  The KDOQI guidelines recommend iron therapy if TSAT is < 20% (non-HD and HD patients) and ferritin levels are < 100 ng/mL in non- HD patients and < 200 ng/mL in HD patients. These criteria are important when using ESAs. ESAs help maintain Hgb levels and reduce the need for blood transfusions, but they are ineffective if iron stores are low. 34 35 Contraindications Uncontrolled hypertension, pure red cell aplasia (PRCA) that begins after treatment. Epoetin alfa: multi dose vials contraindicated in neonates, infants, pregnancy and lactation Side Effects Arthralgia/bone pain, fever, headache, pruritus/rash, N/V, cough, dyspnea, edema, injection site pain, dizziness Monitoring Hgb, Hct, TSAT, serum ferritin, BP 36  ESA Patient Counseling This medication is used to treat a condition called anemia and help reduce the need for a blood transfusion. This medication can increase your risk of life-threatening conditions, including heart attack, heart failure, stroke or blood clots. Seek emergency medical help if you have symptoms such as: Chest pain, Shortness of breath, Leg pain (with or without swelling), Cool or pale arm or leg, Sudden confusion, Trouble speaking, Numbness or weakness on one side of your body (e.g., face, arm or leg), Trouble seeing or loss of consciousness. 37  ESA Patient Counseling For people with cancer: this medication can make your tumor grow faster This medication can cause high blood pressure, seizures or serious allergic reactions. Stop the medication and contact your healthcare provider right away if you have any of these symptoms. This medication comes in a single dose vial and must be drawn up into a syringe. 38 Instructions for use include : Do not shake the vial or syringe; this will ruin the medication and it will not work. Do not use the medication if it has changed color or has any particles in it. Recommended sites for injection into the skin include the outer areas of the upper arms, the abdomen (except for two inches around the navel), the front of the middle thighs and the upper outer area of the buttocks. Rotate injections sites. Throw away used needles. 39  B-APLASTIC ANEMIA Occurs when the bone marrow fails to make enough RBCs, WBCs and platelets. It can be caused by drugs, infectious diseases, hereditary conditions or autoimmune disorders. In many cases, the cause is unknown. Patients with AA are at risk for life-threatening infections or bleeding. Treatment can include immunosuppressants, blood transfusions or a stem cell transplant. Eltrombopag, a thrombopoietin nonpeptide agonist, increases platelet counts and is approved for the treatment of severe aplastic anemia in patients who are unresponsive to immunosuppressive therapy. 40  C-HEMOLYTIC ANEMIA Develops when RBCs are destroyed and removed from the bloodstream before their normal lifespan of 120 days. This type of anemia can be acquired (e.g., drug- induced or associated with an immune disorder) or inherited. There is more than one mechanisms of drug-induced hemolytic anemia, but most often the medication binds to the RBC surface and triggers the development of antibodies that attack the RBC. The direct Coombs test is used to detect antibodies that are stuck to the surface. Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked inherited disorder that most commonly affects persons of African, Asian, Mediterranean, or Middle Eastern descent. 41  The G6PD enzyme protects RBCs from harmful substances. Without sufficient levels of the enzyme, RBCs hemolyze 24 - 72 hours after exposure to oxidative stress. Infections, certain foods, severe stress, and certain drugs are factors that can increase the risk of hemolysis. Most individuals do not need treatment but should be instructed to avoid certain high-risk medications, foods or other known triggers. 42 THANKS 43  Management of Poisonings: The Pharmacist’s Role How to identify and diagnose poisonings in an emergency care setting 1  Learning Objectives After this presentation you should be able to: Know which substances are commonly involved in poisonings Understand how poisoning cases are diagnosed and identify common toxidromes Understand the management options available to treat poisonings, including categories of antidotes 2  Introduction A poison is defined as “a substance that is capable of causing the illness or death of a living organism when introduced or absorbed”, which introduces the question: Is a medicine a poison? 3  Introduction As outlined in the Poisons Act 2018 (1972) and Medicines Act 1968 UK “any chemical substance (natural or synthetic) capable of producing psychological and physiological effects is a drug” “any chemical substance (natural or synthetic) capable of causing illness and even death when ingested or absorbed” 4  Introduction There is no National Poisons Information Service/Centre in Pakistan Most common cause of poisoning reported in literature includes; 1. Accidental episodes, 2. Medication errors, 3. Self-harm 4. Drug misuse. Whereas the primary exposure route of poisoning is ingestion followed by inhalation. 5  Introduction It is important for pharmacists to be familiar with the treatment for, and clinical management of, common poisoning/overdose. Pharmacists can support patients by Providing advice, Maintaining availability of antidotes, Appropriate dosing Monitoring and involvement with long term care. 6  Introduction When poisonings are accidental or as a result of a medication error, pharmacists should be involved in; Counselling and Education of both healthcare professionals and patients Discussing Appropriate Use Supporting deprescribing, where appropriate, if polypharmacy- related 7  Diagnosis When patients present with suspected poisoning, it is important to determine which toxidrome the patient is experiencing Helps in identifying the patient’s onward management and care Particularly important when ❖The patient is unable to offer information on substance(s) taken if unconscious ❖Unwilling to disclose what has been taken. 8  Diagnosis A toxidrome can be defined as “ a collection of findings that are evident either from physical examination of the patient or from ancillary testing, caused by drug overdose, withdrawal or exposure to a toxin” Toxidromes are a collection of symptoms and physical manifestations that allow classification of the pharmacodynamic property of the toxin or drug, the causative agent can be narrowed down, and appropriate management selected 9  Diagnosis There are seven toxidromes that are categorized as either excitatory or inhibitory; 1. Sympathomimetic, 2. Anticholinergic, 3. Hallucinogenic, 4. Serotonin syndrome (serotonin toxicity), 5. Opioid, 6. Sedative-hypnotic 7. Cholinergic 10 Excitatory and inhibitory toxidromes according to signs, symptoms and manifestations 11 Excitatory and inhibitory toxidromes according to signs, symptoms and manifestations 12 13 14 15 16 17  Diagnosis The initial assessment, history and clinical examination of the patient is absolutely crucial. Resources available from the scene may be able to provide valuable information and history of the patient 1. Family members, 2. Carers, 3. Passers-by 4. Paramedics. 18  Risk factors for overdose and poisoning Age — children aged < 5 years are at highest risk from poisonings; Unemployment, social isolation, low socio-economic status; Chronic physical or mental illness; History of frequent or repeated use of medications for pain relief; Certain professions (e.g. doctors); Prior planning/precautions taken/suicide note; Institutionalization (e.g. prison); Substance abuse (e.g. drugs, alcohol) 19  Diagnosis Once resources have been exhausted and history completed, a clinical examination is needed using the ABCDEF assessment Airway, Breathing, Circulation, Disability, Exposure, Formulate plan 20 21 22 Formulate Plan 23 First inspection and immediate impression 24 First inspection and immediate impression If the patient appears The patient’s if the patient is unconscious or has alertness should be awake, ask them how collapsed, shake checked they are. them and ask if they are OK If response is normal, If they speak only in Failure of the patient they have a patent short sentences, they to respond is a clear airway, are breathing may have breathing marker of critical and have brain problems illness. perfusion. 25  First inspection and immediate impression As much as possible information from the ambulance handover: Was there anything of relevance found at the scene (e.g. empty medication packets, alcohol, drug paraphernalia, etc)? Is this the only casualty or are there others, if multiple? Were any antidotes, such as naloxone, given by ambulance crews at the scene, and did these have a clinical effect? 26 ABCDEF Approach 27  A: Airway, anticipatory monitoring and oxygen Patients who are talking coherently are unlikely to have an immediate airway problem, but careful reassessment is necessary as effects of poisons can be delayed. Patients who are experiencing poisoning are at high risk of vomiting and aspiration. Those with a decreased conscious level, owing to medical illness or non-physical trauma, who do not meet the criteria for the initiation of rescue breathing or chest compressions (CPR), should be managed in the recovery position. 28  A: Airway, anticipatory monitoring and oxygen Anyone with a decreased conscious level is at risk of an unsafe airway. Airway support from an appropriately trained airway competent clinician (i.e. anaesthetist) may be indicated in those with a Glasgow Coma Scale (GCS) score of less than 8 29 30  B: Breathing and adequacy of ventilation Abnormal respiratory rate (breaths per minute) may indicate what type of drug has been ingested as part of a clinical toxidrome; for example, low respiratory rate can be caused by opiate toxicity. Arterial blood gas measurements are often needed to assess adequacy of ventilation and acid base status, even if the patient is fully conscious. 31  C: Circulatory assessment and cannula A 12-lead electrocardiogram is mandatory and essential to assess Heart rate, Arrhythmias, QRS duration QTc prolongation. In many cases, continuous 3-lead heart monitoring is recommended early in management of poisonings. 32  D: Disability (neurology) Poisoned patients are at risk of altered consciousness, confusion and convulsions. Consciousness levels should be checked using the GCS. The patient’s pupils should be monitored, as they may help identify the substance ingested (e.g. pin-point pupils in opiate overdose, dilated pupils in tricyclic antidepressant overdose). 33  E: Exposure/environment/‘everything else Associated evidence of drug use should be thoroughly checked if the cause of suspected poisoning is uncertain (e.g. patches, ‘track marks’, injuries). When patients are confused or comatose, it is easy to miss injuries. Capillary blood glucose should be checked regularly, particularly in cases of excess alcohol and insulin/oral hypoglycaemic agent ingestion to monitor blood glucose levels. 34  E: Exposure/environment/‘everything else In females of child-bearing age, accurate pregnancy status should be ascertained to ensure that any treatments offered take into account pregnancy status and any potential risks to an unborn child. A bedside pregnancy test, with consent, should be performed. Any unexpected or expected positive results should prompt swift referral to an appropriate specialist (midwife or obstetrician) and their involvement in the patient’s care 35  F: Formulate a plan — find and fix When the poison is not known, toxidromes can help aid substance identification. The drug may remain unknown, but recognition and initiation of treatment based on the toxidrome can be lifesaving. Once the ABCDEF approach has been completed and management of identified toxidrome has started, it is important to recognize the need for further assessment of the patient, as focus on the poisoning/overdose can result in other issues being missed. 36 Early or delayed clinical manifestations which could be missed if further assessment of the patient is not completed 37  Management of Poisonings: Management How to manage poisonings in an emergency care setting 1 Management 2  Management Of Poisoned Patient INITIAL MANAGEMENT (DRSABCD approach) Airway is cleared ( remove vomitus) Monitor adequacy of breathing (ventilator) Circulation should be assessed (pulse rate, BP, urinary output) If altered mental status ( dextrose I/V 25g (50mL) adults & 0.5g/Kg (2mL/kg of 25% dextrose) in children regularly If alcoholic or malnourished patient administer thiamine 100mg I/M or I/V If narcotic toxicity, then administer narcotic antagonist i.e. Naloxone 0.4-2mg I/V 3  Physical Examination ▪ Vital signs (BP, pulse rate, respiratory rate, temperature) ▪ Eyes ( is miosis then drugs suspected maybe narcotics, clonidine, etc & if mydriasis then drugs may be cocaine, LSD atropine, etc & then finally nystagmus a characteristic of phenytoin, barbiturates) ▪ Mouth ( burns due to corrosive substances, alcoholic smell, cyanide poisoning recognized by the odor of bitter almonds, etc) 4  Physical Examination Skin (burns in acid accidents, excessive sweating in case of organophosphate poisoning, etc) Abdomen ( hyperactive bowel sound or abnormal diarrhea in organophosphate, iron toxicity) Nervous system (nystagmus, muscular rigidity, comma, etc) 5  Lab & Imaging Procedures ❖ABGs (Arterial blood gases) ( conditions like hypercapnia i.e., increased concentration of CO2 in body, Aspiration pneumonia ❖Electrolytes ( most important of them are 4 i.e., sodium, potassium, chloride & bicarbonate and anion gap is measured (Na + K) – (Cl + HCO3) normal range 12-16 mEq/Lit 6  Lab & Imaging Procedures ▪ RFTs ( BUN levels, Creatine kinase levels ) ▪ ECG (QRS complex if above 0.1 sec it indicates abnormal ECG,QT segment elevation) ▪ X-ray findings & CT scan (chest x-ray reveals aspiration pneumonia, & head trauma is evaluated by CT scan) 7  Management Once the toxidrome has been identified or the causative agent found, an antidote or management of clinical symptoms can commence. 8  DECONTAMINATION Skin decontamination ❖Retain clothes for examination, ❖Washing vigorously with soap GI decontamination ❖Four methods for GI contamination 1. Emesis 2. Gastric lavage 3. Activated Charcoal 4. Catharsis 9 1-EMESIS ▪ IPECAC syrup ▪ Adult (30mL) 6-12 age (10-15 mL) repeat after every 15 min only 2 times. ▪ Contraindicated in following conditions i.e. Zero gag reflex, mucosa ulcerated, airway not cleared, unconscious, seizures. ▪ Ipecac fluid extract is avoided because it is 14 times more potent & cardio toxic 10  2-Gastric lavage Gastric lavage involves the placement of a naso-/orogastric tube into the stomach, through which small amounts of water or saline are administered and removed through a siphoning action. This is repeated until returning fluids do not show any further gastric contents. The procedure can cause vomiting; therefore, a suction device must be present to stop aspiration of gastric contents. This procedure is now rarely undertaken owing to risk of inducing vomiting and possible aspiration of vomitus. Consider if the patient presents within one hour of ingestion of a potentially lethal dose/toxin, such as arsenic, to minimize further absorption of ingested toxin. 11 2-GASTRIC LAVAGE ▪ 0.9% normal saline solution used at body temperature ▪ If not at body temperature, it can cause hyperthermia ▪ 10-12 washes 120-300mL / wash i.e. total 1.5-4 liters ▪ Airways are protected then carried out. 12  3-Activated Charcoal The use of activated charcoal is still debated in the management of poisonings. In general, a single dose of activated charcoal should be given to most patients who present within one hour of ingestion, although it is important to acknowledge that many patients will often not present within this time frame Additionally, activated charcoal does not work on all causative agents; for example, it has little value in lithium overdose as there is negligible absorption If patients are not fully alert, senior advice should be sought before administration and airway protection ensured owing to the serious risk of aspiration. 13  3-ACTIVATED CHARCOAL ❖In certain situations, with delayed gastric emptying (e.g. carbamazepine or tricyclics overdose), multiple doses of activated charcoal over time should be considered ❖Strong adsorption ❖10:1 ratio repeated dose of charcoal to dose of toxin ❖50g in 1 glass water administer either orally or with a gastric tube ❖Effective in phenobarbitone and theophylline toxicity ❖Does not bind iron, lithium or potassium ❖Not useful in poisoning of corrosive materials 14 4-CATHARSIS ❖objective is to remove toxin from GI & reduce absorption ❖Sodium sulfate 10% 150-200mL ,1-2mL per kg child( contraindicated if heart problem) ❖Magnesium sulfate 10% 250-350 mL 1-2mL per kg) child ( contraindicated if renal impairment ❖Sorbitol 70% 100-150mL child dose ( 1-2mL per kg) ❖Milk of magnesia (15-80mL) adult (0.1-0.2 mL/kg) child dose ❖Magnesium Citrate 10% adult dose 250-350mL child dose 1-2 mL/kg 15  Methods of Enhancing Elimination of Toxins Renal elimination ❖Medication to stimulate urination or defecation may be given to try to flush the excess drug out of the body faster. Forced alkaline diuresis ❖Infusion of large amount of Normal Saline+NaHCO3 ❖Used to eliminate acidic drug that mainly excreted by the kidney eg salicylates ❖Serious fluid and electrolytes disturbance may occur ❖Need expert monitoring 16 PERITONIAL DIALYSIS ❖Simple and available but in efficient in removing most of the drugs ❖Chances of peritoneal infection HEMODIALYSIS/HEMOPERFUSION ❖Blood is pumped from the patient via a venous catheter through a column of adsorbent and re circulated in the patient ❖Remove high molecular weight toxins efficiently ❖Rate limiting step is the affinity of adsorbent for the drug and rate of blood flow through the cartridge ❖Does not improve fluid and electrolyte balance. 17  Hemodialysis Certain circumstances may trigger consideration of dialysis (e.g. refractory severe acidosis, digoxin overdose, lithium overdose) to help either correct electrolyte derangement, clear a drug or metabolites, or support kidneys if in acute renal failure. 18 19  Antidotes Category A: antidotes that should be immediately available in the emergency department or any area where poisoned patients are initially treated, such as acetylcysteine for paracetamol overdose/poisoning; Category B: need to be available within one hour of patient identification/presentation, such as fomepizole for use in ethylene glycol poisoning; Category C: held supra-regionally and must always be discussed with toxicologist, such as pralidoxime chloride for organophosphorus insecticides poisoning. 20  Antidotes It should be noted that not all medicines used to manage patients with suspected overdose or poisoning are listed, but should still be readily available; for example, insulin, benzodiazepines, glyceryl trinitrate and magnesium. 21 22 23 24 Patient journey after initial emergency department management 25  Patient journey after initial emergency department management People who have deliberately self-poisoned should have a psychosocial assessment of their needs and risks by a specialist mental health professional while they are in hospital. People who have a serious psychiatric disorder and/or are at high risk of suicide are generally admitted for the treatment of the psychiatric disorder. 26  Children and young people aged under 16 years who have deliberately self-poisoned should be admitted overnight on a pediatric ward and assessed the next day by an appropriately experienced healthcare professional. Young people aged 16–17 years do not always need to be admitted overnight. If the patient is to be admitted to critical care, the level of critical care involvement needs to be considered. There are two levels: Level 2 — single organ dysfunction (1 nurse: 2 patients) i.e. non- invasive ventilation or blood pressure support; Level 3 — multi-organ dysfunction (1 nurse: 1 patient) i.e. intubated patients or patients requiring continuous venous-venous hemodialysis. 27  The transfer destination within the hospital may depend on the nature of the presentation. The patient may even require transfer to a tertiary centre for more specialist care (extracorporeal membrane oxygenation (ECMO) or neuro/cardiac units). Transfers tend to be coordinated regionally, typically via dedicated transfer teams, unless it is an emergency. 28  Summary of points for pharmacy professionals to consider when treating patients who have been poisoned Remain calm and be systematic in your thought process; use a structured plan: First inspection and immediate impression; Escalate concerns early — early treatment will be beneficial for each patient and reduce further morbidity/mortality risk; Have a team de-brief if you can and talk through what went well and what did not go so well to identify improvement possibilities. 29