Clinical Toxicology PDF

PhLE MODULE 4 – PHARMACOLOGY CLINICAL TOXICOLOGY TRANS BY MLVGA, RPh COMMON...

PhLE MODULE 4 – PHARMACOLOGY CLINICAL TOXICOLOGY TRANS BY MLVGA, RPh COMMON MAJOR PATHOPHYSIOLOGIC MECHANISMS INTRODUCTION Causes nerve excitability → CNS Stimulation seizures → brain damage TOXICOLOGY Loss of airway protective reflexes CNS Depression and respiratory drive → respiratory depression Study of poison, its mechanism of action, Diarrhea and its management Urination Study of adverse effects / events of Parasympathomimetic Miosis, muscle fasciculations Bronchoconstriction, bradycardia physical / chemical agents in humans, Effects (DUMBBELS) Emesis other organisms, and environment Lacrimation Salivation, sweating POISONS Mydriasis Agitation Sympathomimetic Has deleterious effects; may cause Effects (MATHS) Tachycardia Hypertension physical injuries or death Seizure, sweating Sola dosis facit venenum – the dose makes Heart: Cardiac arrhythmias the poison Vasculature: Cardiovascular Effects ‣ Vasodilation → hypotension Toxin – natural source ‣ Vasoconstriction → hypertension Toxicants – man-made / artificial source Respiratory Effects Aspiration → bronchospasm Interference with O2 transport and Cellular Hypoxia Side Effects – related to therapy utilization Muscle breakdown with Musculoskeletal Adverse Effects – deleterious / toxic effects myoglobinuria → renal failure, Effects lactic acidosis, hyperkalemia ✓ Immune-mediated: hypersensitivity rxn ✓ Receptor-related: idiosyncrasy, tolerance, RISK ASSESSMENT or desensitization ✓ Others: teratogenicity Estimate potential effect on human health and FDA PREGNANCY CATEGORIES environmental significance of various types of CATEGORY HUMANS ANIMALS chemical exposure A (-) (-) No human studies (-) Hazard – ability of a chemical agent to cause injury B (-) (+) in a given situation or setting C No human studies (+) D (+) Benefit > Risk Risk – expected frequency of the occurrence of an E/X (+) Risk > Benefit undesirable effect arising from exposure to a chemical or physical agent TERATOGENIC DRUGS ACEi Renal dysgenesis AREAS OF TOXICOLOGY Fetal alcohol syndrome ✓ Facial anomalies 1. Mechanistic – mechanism of toxicity Alcohol ✓ Growth retardation ✓ Neuro-developmental 2. Descriptive – direct toxicity testing defects Carbamazepine Neural tube defect 3. Regulatory – decision making process using Clear cell cervical carcinoma of the Diethylstilbestrol information from: mechanistic and descriptive vagina or cervix Lithium Ebstein’s Anomaly (assess safety or if a substance possess a risk) Methimazole Aplasia cutis Phenytoin Fetal hydantoin syndrome SPECIALIZED AREAS OF TOXICOLOGY Retinoids Heart and brain abnormalities 8th cranial nerve (vestibulocochlear) 1. Clinical Toxicology Streptomycin damage Tetracycline Teeth discoloration, bone problems Study of adverse effects in humans caused Thalidomide Phocomelia, amelia by incidental/accidental overdose Valproic Acid Spina bifida / neural tube defect Nasal hypoplasia / fetal warfarin Mechanistic + descriptive toxicology Warfarin syndrome 1 | PhLE Module 4 – MLVGA, RPh  PhLE MODULE 4 – PHARMACOLOGY CLINICAL TOXICOLOGY TRANS BY MLVGA, RPh 2. Environmental Toxicology 2. According to Duration Deals with the harmful effects of chemicals Acute – ↑ dose in short period of time (< to the environment / organisms 24 hours) Regulatory + descriptive toxicology Subacute – less than 1 month Chronic – ↓ dose in longer period of time 3. Forensic Toxicology (> 3 months) Medicolegal aspects of poisoning Subchronic – duration is 1-3 months Mechanistic + regulatory 3. According to Onset TOXICOKINETICS Immediate – seen after single administration ABSORPTION Delayed – seen after a lapse of time Parameters: BIOAVAILABILITY (F) – rate 4. Reversible vs Irreversible and extent of absorption; extent / fraction of drug that enters systemic circulation Reversible – reversed by administration of Affected by: the antidote o Physical Properties – lipid soluble Irreversible – permanent damage, = ↑ extent; water soluble = ↓ carcinogenic, and teratogenic effects extent FACTORS THAT INFLUENCE EFFECTS OF POISON o Gastric Emptying Rate – ↓ GER = ↓ absorption ROUTE o Health of GIT Oral o First pass effect – hepatic o Most common or important metabolic o ↑A = lipid soluble DISTRIBUTION o ↓GER = delay absorption (ex. anticholinergic) Parameter: VOLUME OF DISTRIBUTION Dermal (Vd) o lipid soluble = ↑ damage Affected by: Protein binding – ↑ PB = ↓ o ↑ absorption – (ex. phenol) VD Inhalation – gases/particle < 0.5μm; 𝑑𝑜𝑠𝑒 systemic or local effect 𝑉𝑑 = IV 𝑝𝑙𝑎𝑠𝑚𝑎 𝑐𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛 IM METABOLISM AND EXCRETION Rectal Parameter: CLEARANCE – rate by which a Concentration – ↑ conc = ↑ toxicity known volume of plasma is cleared by drug Affected by: Liver and kidney function – PATIENT-RELATED FACTOR specially in pediatric and geriatric px Age (Pediatric) POISONS Child Inutero ✓ 1-2 weeks – conception / EFFECTS OF POISONS implantation; abortion ✓ 3-8 weeks – embryogenesis 1. According to Extent / Location period; morphologic change (ex. Local – Ex. Phenol ACEi) Remote – Ex. Paraquat → Pulmonary ✓ > 8 weeks – minor physiologic fibrosis changes Systemic – Ex. Metabolic acidosis Examples: 2 | PhLE Module 4 – MLVGA, RPh  PhLE MODULE 4 – PHARMACOLOGY CLINICAL TOXICOLOGY TRANS BY MLVGA, RPh ✓ Tetracycline – teeth discoloration PRIMARY SURVEY and bone problems AIRWAY ✓ ACEi – renal dysgenesis ✓ Diethylstilbestrol (DES) – uterine Should be cleared of any obstruction or / cervical cancer to daughter any vomitus ✓ Thalidomide – phocomelia → Optimize airway position limb deformities Place the neck and head in “sniffing” Age (Geriatric) – ↓ liver/kidney function; ↓ muscle position mass; ↑ fat deposition Apply the jaw-thrust maneuver Place the patient in a head-down, left- Tolerance / Tachyphylaxis – increase dose sided position to get same effect (Ex. Nitrates, Morphine) CAUTION: Do not perform neck ✓ Dispositional Tolerance – ↓ amt manipulation if neck injury is suspected of chemical agent reaching the Management: circulation ✓ Remove any obstruction ✓ Desensitization – ↓ response of ✓ Administer / provide artificial receptors to an agent airway via insertion of oral airway Idiosyncrasy and Pharmacogenetics or insertion of endotracheal tube ✓ G6PD Deficiency – triggers: sulfa drugs, antimalarials, analgesics, BREATHING acetanilide, antibiotics (nalidixic Assess O2 saturation – using pulse acid), INH, nitrofurantoin oximeter NORMAL: 95-100% O2 RR: 12-21 breathes/min ABG: For determination of acidosis / alkalosis; NORMAL: 7.40-7.45 Management: ✓ Pseudocholinesterase Deficiency ✓ O2 supplementation if O2 sat is – ex. Succinylcholine → malignant 90/60 mmHg INGESTION ✓ Pulse rate: 65-100 bpm Management: 1. Lavage ✓ For HTN: ▪ Give 200mL PNSS IV Passage of tube via mouth or nose down bolus to consume 1L to stomach followed by sequential ▪ Check breath sounds administration of warm saline solution and ✓ Pulseless / bradycardic: removal of small volume of liquids ▪ Start chest compression Used for massive ingestion ▪ Initial: 30 comp/min Contraindications: o Unconscious patients DEPRESSED MENTAL STATUS o Ingestion of corrosive substances o Ingestion of SR and enteric- Assessment: coated tablets ✓ Check for responsiveness (tap / sternal rub) 2. Dilution / Neutralization – CI in alkali and acids ✓ Check for capillary blood glucose; NORMAL: 70-200 g/dL 3. Emesis (Syrup of Ipecac / Apomorphine) – toxin Differential Diagnosis: does not cause rapid onset coma / convulsion → ✓ Hypoglycemia – Mgt. Dextrose aspiration 50/50 Contraindications (4C’s) ✓ Alcohol intoxication – Mgt. Vit B1 100mg IV (for the prevention of ✓ Children