Organophosphorus compounds are widely used as pesticides and chemical weapons. They work by inhibiting acetylcholinesterase, leading to accumulation of acetylcholine and overstimulation of nicotinic and muscarinic receptors. Clinical features include excessive secretions, nausea, vomiting, diarrhea, weakness and respiratory failure. Treatment involves decontamination, atropine to block muscarinic effects, pralidoxime to reactivate acetylcholinesterase, and supportive care. Prognosis depends on prompt diagnosis and treatment, with mortality risks highest within 24 hours from respiratory or cardiac failure.
Toxicology on aluminium phosphide, the characteristics, fatal dose,fatal period, sign and symptoms, postmortem appearance and medicolegal importance are discussed.
Acute kidney injury (AKI) is a potentially life-threatening
syndrome that occurs primarily in hospitalized patients
and frequently complicates the course of critically ill
patient.
Acute Kidney Injury is is (abrupt) reduction in kidney functions as evidence by changed in laboratory values; serum creatinine, blood urea nitrogen(BUN)and urine output
Rodenticide Poisoning + Rat Killer paste poisoning managementVasif Mayan
Rodenticide paste poisoning
Case Study
Clinical features
Management
Investigations
Treatment guidelines
pathogenesis
N acetyl cysteine
Coumarins
other rodenticides
Dr. Sachin Verma is a young, diligent and dynamic physician. He did his graduation from IGMC Shimla and MD in Internal Medicine from GSVM Medical College Kanpur. Then he did his Fellowship in Intensive Care Medicine (FICM) from Apollo Hospital Delhi. He has done fellowship in infectious diseases by Infectious Disease Society of America (IDSA). He has also done FCCS course and is certified Advance Cardiac Life support (ACLS) and Basic Life Support (BLS) provider by American Heart Association. He has also done a course in Cardiology by American College of Cardiology and a course in Diabetology by International Diabetes Centre. He specializes in the management of Infections, Multiorgan Dysfunctions and Critically ill patients and has many publications and presentations in various national conferences under his belt. He is currently working in NABH Approved Ivy super-specialty Hospital Mohali as Consultant Intensivists and Physician.
Toxicology on aluminium phosphide, the characteristics, fatal dose,fatal period, sign and symptoms, postmortem appearance and medicolegal importance are discussed.
Acute kidney injury (AKI) is a potentially life-threatening
syndrome that occurs primarily in hospitalized patients
and frequently complicates the course of critically ill
patient.
Acute Kidney Injury is is (abrupt) reduction in kidney functions as evidence by changed in laboratory values; serum creatinine, blood urea nitrogen(BUN)and urine output
Rodenticide Poisoning + Rat Killer paste poisoning managementVasif Mayan
Rodenticide paste poisoning
Case Study
Clinical features
Management
Investigations
Treatment guidelines
pathogenesis
N acetyl cysteine
Coumarins
other rodenticides
Dr. Sachin Verma is a young, diligent and dynamic physician. He did his graduation from IGMC Shimla and MD in Internal Medicine from GSVM Medical College Kanpur. Then he did his Fellowship in Intensive Care Medicine (FICM) from Apollo Hospital Delhi. He has done fellowship in infectious diseases by Infectious Disease Society of America (IDSA). He has also done FCCS course and is certified Advance Cardiac Life support (ACLS) and Basic Life Support (BLS) provider by American Heart Association. He has also done a course in Cardiology by American College of Cardiology and a course in Diabetology by International Diabetes Centre. He specializes in the management of Infections, Multiorgan Dysfunctions and Critically ill patients and has many publications and presentations in various national conferences under his belt. He is currently working in NABH Approved Ivy super-specialty Hospital Mohali as Consultant Intensivists and Physician.
organo phosphorus poisning(op) is a common type of poisning due to consumption of highly toxic organophosphorus usually available in agriculture pesticides and herbicides. it may lead to high toxic effects when consumed for the suicide purpose.
Keynote Presentation given to medical staff of the West Africa Rescue Association affiliated with International SOS, on management of organophosphate poisoning.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
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Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
3. INTRODUCTION
Organophosphorus compounds are chemical agents
in wide-spread use throughout the world, mainly in
agriculture.
They are also used as nerve agents in chemical warfare
(e.g. Sarin gas), and as therapeutic agents, such as
ecothiopate used in the treatment of glaucoma.
They comprise the ester, amide or thiol derivatives of
phosphoric acid and are most commonly used as
pesticides in commercial agriculture, field sprays
and as household chemicals.
4. There are no rules and regulations governing the
purchase of these products, and they are therefore
readily available “over the counter”, despite them
being a major cause of morbidity and mortality.
Exposure to organophosphates in an attempt to
commit suicide is a key problem, particularly in the
developing countries, and is a more common cause
of poisoning than the chronic exposure
experienced by farmers or sprayers in contact with
pesticides.
5. CLASSIFICATION
There are more than a hundred organophosphorus compounds
in common use. These are classified according to their toxicity
and clinical use:
1. Highly toxic organophosphates: (e.g. tetra-ethyl
pyrophosphates, parathion). These are mainly used as
agricultural insecticides.
2. Intermediately toxic organophosphates: (e.g.
coumaphos, clorpyrifos, trichlorfon). These are used as animal
insecticides.
3. Low toxicity: (e.g. diazinon, malathion, dichlorvos). These
are used for household application and as field sprays.
7. Exposure
Home Exposure Occupational Exposure Other Exposure
Accidental ingestion Farms & Farm worker Dietary exposure-
Pesticide residues on
crops
Lawn and garden use Pesticide applicator Leaching from soils to
ground water
Insect control Manufacture Community exposure
Food supply Mixing and handling Airborne drift from
commercial
app
Water supply Landscapers Contaminated
drinking water
9. Pharmacokinetics
o Most organophosphates are highly lipid soluble
compounds and are well absorbed from intact skin,
oral mucous membranes, conjunctiva and the
gastrointestinal and respiratory tracts.
o They are rapidly redistributed to all body tissues.
o The highest concentrations are found in the liver and
kidneys.
10. .
This high lipid solubility means that they easily cross
the blood/brain barrier and therefore produce potent
effects on the CNS.
Metabolism occurs principally by oxidation in the liver
with conjugation and esterase hydrolysis producing a
half-life of minutes - hours.
11. .
The oxidative metabolites of malathion and
parathion (malaoxon and paraoxon) are active forms
and are subsequently hydrolyzed into inactive
metabolites.
Elimination of organophosphorus compounds and
its metabolites occur mainly via urine, bile and
faeces
12. mechanism of action
OP Inactivate Acetyl Cholinesterase (Ach E).
Establishment Of A Covalent Bond With AchE.
Ach E Is An Enzyme That Degrades The
Neurotransmitter Acetylcholine (Ach) Into Choline
And Acetic Acid.
Ach Is Found In CNS & PNS, Neuromuscular
Junctions, And Red Blood Cells (RBCS).
Once Ach E - Inactivated, Ach Accumulates
Throughout The Nervous System →
Overstimulation Of Muscarinic And Nicotinic
Receptors.
13. Once an organophosphate binds to AChE, the enzyme can undergo
one of the following:
• Endogenous hydrolysis of the phosphorylated enzyme by
esterases or paraoxonases
• Reactivation by a strong nucleophile such as pralidoxime (2-
PAM)
• Irreversible binding and permanent enzyme inactivation (aging)
The onset and severity of symptoms depend on the specific
compound, amount, route of exposure, and rate of metabolic
degradation
14. Clinical features of Organophosphorus Poisoning
Following exposure to organophosphorus compounds, the
toxic features are usually obvious within 30 minutes to 3
hours.
This may be delayed in some cases depending on the rate
and amount of systemic absorption.
The majority of patients give a history of intentional or
accidental ingestion of organophosphorus compounds.
Toxicity is produced by the rapid absorption of the
compound through the gastrointestinal, respiratory tracts
and skin.
15. Cont…
The clinical symptoms and signs are non-specific and will
depend on the specific agent, the quantity and the route of
entry.
Some patients present with vomiting, diarrhoea and
abdominal pain, whilst others may be unconscious on arrival
at the hospital. A high index of suspicion is therefore needed to
make an early diagnosis.
The clinical features can be broadly classified as secondary to
the
(a) muscarinic effects
(b) nicotinic effects and
(c) central receptor stimulation.
16. Cont…
Early cases present predominantly with
parasympathetic over-activity, and a characteristic
garlic smell.
The end result may be a multi-system manifestation
involving the gastrointestinal, respiratory,
cardiovascular and nervous systems, as well as
involvement of skeletal muscle, other organs and
metabolic effects such as hypo- or hyperglycemia.
Most fatalities occur within 24 hours and those who
recover usually do so within 10 days.
18. Who classification for severity
MILD MODERATE SEVERE
Serum/rbc cholinesterase
level 2-8 u/l
0.8-2 u/l <0.8 u/l
Walks and talks
Abd pain nausea vomit
headache
Salivation sweating
Talks with soft voice
Cannot walk
Fasiculations present
Miosis restlessness
anxiety
Coma convulsions
profuse bronchial
secretions
19. Cardiac manifestations
The commonest cardiac manifestations following
poisoning are hypotension (with warm, dilated
peripheries), and bradycardia. Patients seldom present
with tachycardia and hypertension due to predominant
nicotinic receptor stimulation.
Cardiac manifestations are often the cause of serious
complications and fatality.
Electrocardiographic manifestations include prolonged Q-
Tc intervals, elevation of the ST segment, inverted T waves
and a prolonged PR interval. There may also be rhythm
abnormalities such as sinus bradycardia , ventricular extra-
systoles, ventricular tachycardia and fibrillation.
20. .
Ludomirsky et al described three phases of cardiac
toxicity following organophosphate poisoning:
Phase I: A brief period of increased sympathetic
tone
Phase II: A prolonged period of parasympathetic
activity including AV node blockade
Phase III: Q-T prolongation followed by torsade
de pointes, ventricular tachycardia and
ventricular fibrillation
21. Respiratory manifestations
Respiratory manifestations of acute
organophosphorus poisoning include
bronchorrhoea, rhinorrhoea, bronchospasm and
laryngeal spasm.
This is due to the action of the organophosphate on
muscarinic receptors.
The integrity of the airway may be compromised by
excessive secretions.
22. .
The nicotinic effects lead to weakness and
subsequent paralysis of respiratory and
oropharyngeal muscles.
This increases the likelihood of both airway
obstruction and aspiration of gastric contents.
Finally, central neurological depression may lead to
respiratory arrest
23. .
Three different types of paralysis are recognized
based largely on the time of occurrence and their
differing pathophysiology:
Type I paralysis or acute paralysis
Type II paralysis or Intermediate syndrome
Type III paralysis or Organophosphate- induced
delayed polyneuropathy
Neurological manifestations
24. Type I paralysis or acute paralysis
is seen during the initial cholinergic phase.
This is when large numbers of both muscarinic and
nicotinic receptors are occupied by acetylcholine,
leading to persistent depolarization at the
neuromuscular junction.
Clinical features include muscle fasciculation,
cramps, twitching and weakness.
At this stage the patient may require ventilatory
support due to the weakness of the respiratory
muscles leading to respiratory depression and arrest.
25. Type II Paralysis/Intermediate syndrome
The intermediate syndrome is a distinct clinical entity that
occurs 24 to 96 hours after the ingestion of an OP compound.
Approximately 10-40% of patients treated for acute poisoning
develop this illness.
The onset of the IMS is often rapid, with progression of muscle
weakness from the:
ocular muscles
neck muscle (the patient cannot raise their head from the
pillow)
proximal limbs
respiratory muscles (intercostals and diaphragm) over the
course of 24 hours.
26. Clinical feature
clinical manifestations of IMS typically occur within 24 to 96
hours, and affect conscious patients without fasciculation or
other cholinergic signs.
Marked weakness of neck flexion and varying degree of
proximal limb muscle weakness, manifesting as weakness of
shoulder abduction and hip flexion, are the constant clinical
features.
Respiratory insufficiency is common and frequently draws
medical attention to the onset of the syndrome.
Other possible manifestations are involvement of muscles
innervated by motor cranial nerves and decreased deep
tendon reflexes.
Sensory impairment is not a clinical manifestation of
IMS.
27. Type III paralysis or organophosphate- induced
delayed polyneuropathy. (OPIDP)
is a sensory-motor distal axonopathy that usually
occurs after ingestion of large doses of an
organophosphorus compound.
The neuropathy presents as weakness and ataxia
following a latent period of 2-4 weeks.
Initial stimulation causes excitatory fasciculation,
which then progresses to an inhibitory paralysis. The
cardinal symptoms are distal weakness of the hands
and feet.
28. .
This is often preceded by calf pain, and in some
cases, parasthesia of the distal part of the limbs.
Delayed CNS signs include tremor, anxiety and
coma.
29. MANAGEMENT
DIAGNOSIS
Diagnosis of OP poisoning based on the H/O
exposure to OP compounds, characteristics
manifestation of toxicitiy and improvement of sign
and symptoms after administration of atropine.
Garlic-like smell is an added clinical sign especially if
the patient has ingested sulphur containing OP
compound.
This may be aided by insisting the patient attendant
to search for a possible poison container in the
vicinity of the patient.
30. Contd.
Cholinesterase (ChE) estimations (plasma butyryl
cholinesterase and red cell AChE) are the only useful
biochemical tool for confirming exposure to OP.
Clinical severity graded on the basis of the
pseudocholinesterase level :-
Mild - 20-50% enzyme activity.
Moderate 10-20% enzyme activity.
Severe <10% enzyme activity.
• Though the enzyme activity does not correlate well
with clinical severity.
31. Contd.
Plasma Butyrylcholinestrase Red cell acetylcholinestrase
Easily assayed Difficult to assay
Doesn’t correlate well with neuronal
activity .
Correlate well with neuronal activity
30% activity – normal muscle function
< 10% activity – grossly deranged
muscle function.
Response to antidotal therapy is less Increased activity after
pralidoxime therapy.
Levels altered in malnutrition, chronic
illness, chronic liver disease and
infection.
Levels altered in hemoglobinopathies
and thalassemia.
32. Contd.
Analytical identification of OP compound in gastric
aspirate or in the body fluids gives the clue that
patient has been exposed to OP compound.
However in doubtful cases and especially if
laboratory facilities are not available, 1 mg atropine
can be given intravenously. If this does not
produce marked anticholinergic
manifestations, anticholinesterase poisoning
should be strongly suspected.
33. Treatment
Decontamination and Supportive therapy
Blockade of Muscarinic activity with ATROPINE.
Reversal of cholinesterase inhibition with OXIME.
Correction of Metabolic abnormalities
Prevention of infection.
Management of complication.
34. Decontamination and Supportive therapy
Comatose or vomiting patients should be kept in left
lateral, preferably head down position with neck
extension to reduce the risk of aspiration.
Patent airway should be secured with placement of
airway or with endotracheal intubation especially if
the patient is unconscious or having seizure.
Frequent suctioning is essential as excessive
oropharyngeal and respiratory secretions may
occlude the airway.
Need for oxygen therapy can be assessed by frequent
assessment of arterial oxygen saturation.
35. Contd.
All clothing, hair accessories are to be removed and placed
in appropriate waste bags. The person is to be washed
with copious amount of water and soap.
Skin folds and underside of fingernails and long hairs
require particular attention. Ocular decontamination is to
be carried out by washing eyes with water/normal saline.
The health care workers need protection through personnel
protecting equipments. Rubber Gloves and gowns are
recommended as these compounds are known to penetrate
latex /vinyl gloves.
36. Contd
Gastric lavage
should be considered in patients presenting within 1-2 hours of
ingestion of poison.
Risks of gastric lavage include aspiration, hypoxia, and laryngeal
spasm.
reduced with proper management of airway.
Activated charcoal
reduce the poison load by adsorbing it.
Its efficacy has not been conclusively proven in humans.
single to multiple dose activated charcoal is routinely used in clinical
practice.(25gm 2 hourly).
AVOID cathartics and induced emesis.
37.
38. Blockade of muscarinic activity with atropine
Specific antidote for muscarinic effects, no effect on
nicotinic symptoms.
It reverses life threatening features that can result in
death :
central respiratory depression
bronchospasm, excessive bronchosecretion
severe bradycardia, and hypotension.
Current guidelines recommend the use of incremental
dose regimen to attain target end points, followed by
setting up an infusion to maintain these end-points.
Bolus dose regimen (2-5 mg atropine every 10-15 min)
found inferior to standard regimen.
Continous infusion regimen ( 1 mg/min till full
atropinisation) can be used in resource poor setting.
39. Contd.
Target end-points for Atropine therapy :
Heart rate >80/ min.
Dilated pupils.
Dry axillae.
Systolic blood pressure >80 mm Hg.
Clear chest on auscultation with resolution of bronchorrhea (absence of
wheeze and crepts).
• Recommended dose is an initial iv bolus of 1.8-3mg with
subsequent doses doubled every 5 minutes if there is no response
or repeat same dose until atropinization is achieved.
• Maintenance dose: 20% of initial atropinizing dose per hour for
first 48 hours and gradually taper over 5 -10 days, continuously
monitoring the adequacy of therapy.
40. Contd.
Look for atropine TOXICITY
Agitation, confusion, hyperthermia, urinary retention and severe
tachycardia.
can precipitate ischaemic events in patients with underlying coronary
artery disease.
Over atropinisation may necessitate discontinuation of
the atropine infusion, followed by frequent observation.
When they settle down the infusion is to be started at 70-
80 % of the previous rate.
Anticholinergic agent glycopyrrolate along with atropine
can be used in order to limit the central stimulation
produced by atropine.
41. Contd.
Since glycopyrrolate does not enter CNS initial
muscarinic signs like coma or drowsiness will not
respond.
It’s use is recommended
when there is copious secretion as an adjunct to atropine
when features of atropine toxicity like delirium etc are confused with
CNS effects of poison
when atropine is not available.
Dose : 7.5 mg of glycopyrolate in 200ml of saline is started as
infusion and is titrated to the desired effects of dry mucus membranes.
42. Reversal of cholinesterase inhibition by OXIMES.
Oximes work by reactivating acetylcholinesterase that
has been bound to the OP molecule.
Pralidoxime
most frequently used oxime worldwide
Nucleophilic agent
other members include obidoxime and trimedoxime and experimental
HI 6 and HLO 7.
The therapeutic window for oximes is limited by the time taken for
‘ageing’ of the enzyme-OP complex, because ‘aged’ enzyme can no
longer be reactivated by oximes.
Mechanism of action :
Oximes get attached to the free anionic site of the enzyme ChE. The
oxime end then reacts with the phosphorus atom of OP attached at the
esteratic site of the enzyme. This oxime phosphate so formed
diffuses away leaving the enzyme intact (Reactivated ChE).
43. Contd.
Dose :
WHO recommends pralidoxime dose of 30 mg/kg bolus iv over 20-
30 min followed by continuous infusion of 8mg/kg/hour Infusion
continued until recovery : 12 hrs after atropine has been stopped and
BChE noted to increase.
Largest oximes trial recommends 2gm loading dose followed by
500mg/hr maximum for 7 days .
Side effects : Dizziness, headache, blurred vision, and
diplopia, are common side effects of oxime therapy.
Formation of stable phosphoryl oximes – high anticholinesterase
activity.
Rapid administration may lead to tachycardia, laryngospasm,
muscle spasm, and transient neuromuscular blockade.
44. Treatment of complication
Cardiovascular complication :
Muscarinic receptor stimulation cause bradycardia and hypotension
usually responds to atropine. Severe hypotension might benefit from
vasopressors. The value of vasopressors versus higher doses of
atropine is not yet clear.
While nicotinic receptor stimulation cause sinus tachycardia and
hypertension.
ECG changes: Prolonged QTc interval, ST segment elevation, low
amplitude T waves, extrasystole and prolonged PR interval.
Respiratory complication :
Regular and close observation in initial course will guide when to
ventilate. Regular suctioning and high flow oxygen should be given
to all patients with respiratory distress. Further, ABG should be
done to guide the therapy.
45. Contd.
Indication of ventilator support :
I. Respiratory Gas Tensions
i Direct Indices
Arterial Oxygen Tension < 50 mm Hg on room air
Arterial Co2 Tension > 50 mm Hg in the absence of metabolic alkalosis
ii Derived Indices
P a o2/ Fio2 < 250 mm of Hg
PA-aOo2 ( Pulmonary arterial-alveolar O2 gradient) > 350 mm of Hg
II. Clinical - Respiratory Rate (RR)> 35 breaths/min
III. Mechanical Indices
Vital capacity < 15 ml/kg.
Maximum inspiratory force <- 25 cm of H2O.
46. Contd.
CNS complication :
Patients poisoned with organophosphorus frequently develop agitated
delirium.
The cause is complex, with contributions from the pesticide itself,
atropine toxicity, hypoxia, alcohol ingested with the poison, and medical
complications.
Diazepam is first-line therapy for seizures; however, seizures are
uncommon in well oxygenated patients with pesticide poisoning.
Seizures seem to be more common with organophosphorus nerve agents
(such as soman and tabun).
Animal studies suggest that diazepam reduces neural damage and
prevents respiratory failure and death, but studies in humans are few.
Gacyclidine : anti-glutamatergic compound, inh. Seizure caused by nerve
gas poison.
Dose : 10 mg IV slowly which can be repeated up to 30-40 mg/24
hrs.
47. Supportive treatment
Antibiotic prophylaxis :-
Broad spectrum antibiotics
risk of infection due to frequent and multiple interventions.
Hydrocarbon Aspiration :-
ingestion of liquid concentrates of OP, hydrocarbon solvent
aspiration causes chemical pneumonitis.
These cases are to be managed as a case of Acute Respiratory
Distress Syndrome.
Furosemide :- It is recommended if pulmonary oedema
persists, even after full atropinisation.
48. Magnesium sulphate :-
blocks ligand-gated calcium channels, resulting in reduced
acetylcholine release from pre-synaptic terminals, thus
improving function at neuromuscular junctions, and reduced CNS
overstimulation mediated via NMDA receptor activation.
I/V MgSo4 (4gm) on first day shown to decrease hospitalization
period and improve outcome.
Clonidine :-
alpha2-adrenergic receptor agonist.
reduces acetylcholine synthesis and release from presynaptic
terminals.
Animal studies show benefit of clonidine treatment, especially in
combination with atropine, but effects in human beings are
unknown.
Dose : 0.15-.30 mg i/v bolus f/b 0.5 mg over 24hr.
49. Sodium bicarbonate :-
Increases in blood pH (up to 7·45–7·55) have been reported to improve
outcome in animals through an unknown mechanism.
Useful in nerve gas poisoning.
Dose : 5 meq/kg over 1 hour f/b 5-6 meq/kg/day.
The roles of FFP, haemodialysis and haemofiltration are
not yet clear.
a recent non-randomised controlled study in China suggested a benefit
of haemofiltration after poisoning with dichlorvos, which has poor
solubility in fat, and therefore should have a relatively small volume of
distribution.
A systematic review of these therapies in organophosphorus poisoning is
underway, but randomised controlled trials will be needed to establish
good evidence-based treatment guidelines.
50. A better approach than use of butylcholinesterase
might be to give recombinant bacterial
phosphotriesterases or hydrolases.
These proteins break down organophosphorus pesticides
enzymatically and protect animals from pesticide poisoning.
Future clinical development of such enzymes could reduce blood
concentrations of organophosphorus, allowing optimum activity of
other treatments.
51.
52. Mechanism of INTERMEDIATE SX
IMS is well recognized as a disorder of the neuromuscular
junction; however, its exact underlying mechanisms are not
clearly defined.
Senanayake and Karalliedde in their first report of IMS
suggested that the syndrome might be caused by pathologic
change in the postsynaptic end-plate region of striated
muscles.
Proposed mechanism of IMS are:
Downregulation or desensitization of postsyneptic Ach Receptors.
Prolonged Ach esterase inhibition.
Failure of postsyneptic Ach release.
Oxidative stress related myopathy.
Muscle necrosis.
53. Treatment of IMS
Treatment of IMS is mainly supportive and there are
no specific antidotes available for this devastating
syndrome.
With supportive therapy, recovery from IMS occurs 5–18 days after
the onset of weakness.
Regression of toxic signs among patients who survived IMS followed
a distinct pattern. Muscle power first resumed in cranial
nerve-innervated muscles, followed by respiratory
muscles, proximal muscles, and neck flexors.
54. Organophosphate induced delayed
polyneuropathy (OPIDN )
Occurs 1-3 weeks after acute exposure.
Usually present with symptoms of cramping muscle pain followed by
numbness and paraesthesia in distal upper and lower limb.
Can cause foot drop, wrist drop, muscle wasting and deformity such as
clawing of the hands.
Physical examination :
Symmetrical flaccid weakness of the distal muscle
Variable sensory loss
Dominant hand affected more
Tendon reflex are lost or reduced ; absent ankle reflex being a
constant feature
55. Pathophysiology of OPIDN
Neuropathy inducing OP compounds cause inhibition of
carboxylesterase i.e. NTE (neuropathy target esterase).
Inhibition should be irreversible and significant.
degeneration of distal regions of large, long myelinated axons as the
primary lesion, which progresses to Wallerian-like degeneration of
affected fiber regions.
Inhibition of NTE is necessary antecedent to OPIDN but
precise relationship has not been defined till now.
Physiological function of NTE is not known.
Dichlorovos and nerve agent are not associated with
OPIDN.
56. Treatment
Recovery from OPIDN is incomplete and may be limited to the hands
and feets, although substantial functional recovery after 1-2 years may
occur in younger patient.
Currently no drug is approved for treatment of OPIDN.
Following drugs are under trial :
Phenylmethylsulfonyl fluoride (PMSF)- serine protease inhibitor.
Corticosteroid and vitamin
Calcium channel blocker
Ganglioside mixture
57. Mortality
Worldwide Mortality 3-25%.
Mortality Rates Depend On The
Type Of Compound Used,
Amount Ingested,
General Health Of The Patient,
Delay In Discovery And Transport,
Insufficient Respiratory Management,
Delay In Intubation, And
Failure In Weaning Off Ventilatory Support.
Editor's Notes
. Clinical effects are manifested via activation of the autonomic and central nervous systems and at nicotinic receptors on skeletal muscle.
.[3
Complications include severe bronchorrhea, seizures, weakness, and neuropathy. Respiratory failure is the most common cause of death