2024 BUC Lect 11 Pharmacovig.... [Autosaved] 3.pptx

Drug information

1. Pharmacovigilance Medicine Safety All medicines are safe! ( ) Approved medicines are safe!( ) No medicine is safe!( ) No medicine is without risk! ( ) Pharmaco = medicine © Vigilare = to watch Def .: It is the science related to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem through post-marketing research (2-5 years) .

2. Pharmacovigilance Learning from History Thalidomide Disaster Tranquillizer launched -1957 First reports of birth defects – 1959 13 reports of birth defects – 1961 Withdrawn shortly afterward 10000 infants affected by Phocomelia. No teratogenicity detected during clinical trials and prior to launch.

3. Why do we need pharmacovigilance ? Reason 1: Insufficient evidence of complete safety • Animal experiments • Clinical trials prior to marketing Reason 2: Dying from a disease may be inevitable, dying from a medicine is unacceptable (WHO,2005) Reason 3: ADR are expensive Limitations of clinical trials 1. Number of patients is limited: ~ 3000 2. Narrow population: Specific age and weight 3. Narrow indications: only those having the specific disease studied 4. Short duration: often no longer than a few weeks or months.

4. Economic impact of ADRs • The estimated annual cost of drug-related morbidity and mortality resulting from non-optimized medication therapy was $528.4 billion in 2016. (Watanabe JH, McInnis T, Hirsch JD. Cost of Prescription Drug-Related Morbidity and Mortality. Ann Pharmacother . 2018 Sep;52(9):829-837. doi : 10.1177/1060028018765159. Epub 2018 Mar 26. PMID: 29577766 .) • The cost to the country of ADRs may exceed the cost of the medications themselves. • 30-60 % of ADRs may be preventable.

5. Objectives To improve patient and public care and safety . To contribute to the ( Risk Benefit Analysis ) the assessment of benefit, harm, effectiveness, and risk of drugs To promote the effective communication with health professionals (Egyptian Drug Authority) and the public ( Hot line 15301, https:// www.edaegypt .gov.eg ) of EPVC

6. Serious adr . When the patient outcome is: 1. Death 2. Life-threatening 3. Hospitalization 4. Disability - or permanent change, impairment, damage or disruption in the patient's body function/structure, physical activities or quality of life 5. Congenital abnormalities 6. Requires intervention to prevent permanent damage

7. Adverse events happen due to : Poor quality product Suboptimal Drug Use Unidentified Factors Signal: The reported information (Phase IV CLINICAL TRIAL) regarding a possible causal relationship between a drug and adverse events ( Oscala ). Signal detection is an essential element of pharmacovigilance Ex (NIZORAL tablet) & LF tests and GCP.

8. Poor quality product ex.: Product contamination Poor packaging Questionable stability Labeling concerns Suboptimal Drug Use Medication errors : Medication errors result in ADEs. A higher dose has higher chances of developing an ADE . A lower dose decreases the clinical effectiveness Drug interactions : Drug interactions are not necessarily clinically significant, and sometimes result in beneficial outcomes 3. Unidentified Factors Adverse drug events could also happen due to idiosyncratic factors that cannot be explained by the current pharmacological logic

9. Side effect : Unintended effect occurring at a normal dose related to the pharmacological properties and it is dose related. Adverse event: Medical occurrence temporally associated with the use of a medicinal product, but not necessarily causally related to this product , may be a complication of the disease itself . Adverse reaction : A response to a drug that is noxious , dangerous and un expect ed, at normal doses .

10. ADR classification Type A reactions — Augmented pharmacologic effects Dose-related & Predictable from drug pharmacology Common & Normally reversible May be manageable with dose adjustment Example: bleeding with warfarin Type B reactions — Bizarre effects Not dose-related, Unpredictable & Uncommon May be serious/irreversible Indicative that drug needs to be stopped Example: anaphylaxis with penicillin Type C reactions — Chronic..... Repeated drug use Type D reactions — Delayed …. Take time to develop Carcinogenesis, teratogenesis Type E reactions – End of treatment … Withdrawal , rebound phenomena etc. Type F – Failure … Treatment did not work — therapeutic failure Vaccines Type G – Genetic reactions

11. 16 Characteristics of good pharmacovigilance systems: Easy to use (reporting forms offline and also online communication ) Allows reporting by patients and healthcare providers Well-structured reports to facilitate analysis Standardized procedures and definitions Allows analysis of product class level (e.g., erythropoietin) and on an individual product level Efficient communication practices Training of healthcare professionals

12. 17 The WHO’s International Drug Monitoring Program VigiFlow is software for signal reporting. It helps, especially, nonindustrialized countries with limited technical resources to report adverse reactions VigiAccess is an open access database to see the signal reports globally VigiLyze is a signal detection and management system that can use national, regional or global data as the starting point for quantitative signal detection Signal: The reported information (Phase IV CLINICAL TRIAL) regarding a possible causal relationship between a drug and adverse events ( Oscala ). Signal detection is an essential element of pharmacovigilance Ex (NIZORAL tablet) & LF tests and GCP.

13. Anaphylactic Shock Definition Any acute onset of hypotension or bronchospasm or upper airway obstruction where anaphylaxis is considered possible, with or without typical skin features (urticarial rash or erythema/flushing , and/or angioedema ). Mechanism of onset Most cases of anaphylaxis are IgE mediated . Following previous exposure to an antigen, IgE antibodies are released into the circulation. These antibodies bind to glycoprotein receptors on tissue mast cells or blood-borne basophils , thereby sensitizing them and triggering the release of chemical mediators.

14. symptoms Mild or moderate reactions (may not always occur before anaphylaxis): Swelling of lips, face, eyes. Tingling mouth. Abdominal pain, vomiting. Anaphylaxis – Indicated by any one of the following signs: Difficult or noisy breathing Swelling of tongue Swelling throat Difficulty talking or hoarse voice. Wheeze or persistent cough which is usually sudden Persistent dizziness or collapse Pale and floppy (young children ) Anaphylaxis triggers and reaction times Common triggers are foods, insect stings and drugs ( medications ). Less common triggers include latex, tick bites, exercise (with or without food), cold temperatures, radiocontrast agents, immunisation (rare) and unidentified (idiopathic). Anaphylaxis time: within one to two hours of ingestion in food allergy. Anaphylaxis to stings and injected medications (including radiocontrast agents and vaccines) usually occurs within 5-30 minutes but may be delayed. Anaphylaxis to oral medications can also occur but is less common than to injected medications.

15. Immediate actions for anaphylaxis 1. Phone ambulance - 123 to transport patient to the nearest hospital. 2. Remove allergen (if still present). 3. LAY PERSON FLAT - do NOT allow them to stand or walk • If unconscious or pregnant, place in recovery position - on left side if pregnant • If breathing is difficult allow them to sit with legs outstretched • Hold young children flat, not upright 4. GIVE ADRENALINE INJECTION - Give intramuscular injection (IMI) adrenaline into outer mid-thigh without delay . Adrenaline (epinephrine) is the first line treatment for anaphylaxis Further adrenaline may be given if no response after 5 minutes . (IF IN DOUBT GIVE ADRENALINE) 5. Give oxygen (if available). 6. Transfer person to hospital As soon as possible . Adrenaline administration and dosages Adrenaline is the first line treatment for anaphylaxis and acts to reduce airway mucosal oedema induce bronchodilation induce vasoconstriction increase strength of cardiac contraction. Give INTRAMUSCULAR INJECTION (IMI) OF ADRENALINE into outer mid-thigh (0.0 1 mg per kg up to 0.5mg per dose) without delay using an adrenaline autoinjector if available OR adrenaline ampoule and syringe, as shown in the table below: 

16. Adrenaline administration and dosages Adrenaline ampoule contain 1mg adrenaline per 1mL

17. Note , antihistamines and steroids should never be relied upon alone as first-line therapy ??? USE OF ANTIHISTAMINES There is (conflicting data) with regard to the use of antihistamines in anaphylaxis. as the concentration of histamine is so great that, by the time anaphylaxis is diagnosed, it is too late for a competitive blocker to be of value. Antihistamines do not actually prevent mediator release. mediators other than histamine are of equal biological importance . H2 receptor blockers should theoretically worsen cardiac function. However Several authors have reported the successful use of H2 receptor blockers in refractory anaphylactic shock. However, until their role in shock is further established, H2 receptor blockers are not the drugs of first choice. USE OF STEROIDS The role of steroids is also uncertain, as there is little evidence for any therapeutic benefit in anaphylactic shock. Even if given intravenously, they may take up to 4-6 h to be maximally effective. Theoretical beneficial effects include an increase in tissue responsiveness to beta-adrenergic agonists, prevention of neutrophil and platelet aggregation, and inhibition of inflammatory mediator synthesis.

18. Management of anaphylaxis in pregnancy and children pregnant women Management of anaphylaxis in pregnant women is the same as for non-pregnant women. Prompt administration of adrenaline (IM adrenaline 0.01mg per kg up to 0.5mg per dose) should not be withheld due to a fear of causing reduced placental perfusion. The left lateral position is recommended. children Infants with anaphylaxis may retain pallor despite 2-3 doses of adrenaline, and this can resolve without further doses. More than 2-3 doses of adrenaline in infants may cause hypertension and tachycardia (Monitor blood pressure). The correct way to hold an infant is flat .