Home Page – Toxic substances

 FOXGLOVE

Brief introduction

Foxglove is an attractive, tall, biennial plant that grows in acidic soils. It is native to Europe, North Africa and Central Asia. Its trumpet-like (glove) flowers bloom in the spring and have purple, pink, cream, white, yellow or rose color.

Scientific name: Digitalis

Family: Plantaginaceae (5)

Order: Lamiales

Kingdom: Plantae

Botanical name: Digitalis purpurea

Other names

• Digitalis
• Fairy’s Gloves
• Witches’ Fingers
• Fairy Thimbles

Foxglove is a tall attractive plant with various colors. Image source here

Brief History

• Known since 1000AD.
• Cultivated in England since 1400’s in England
• First recorded as fox glove in the year 1542 by Leonhard Fuchs
• Grown in American gardens since 1700’s.
• Known and value as heart stimulant since 1700
• Discovered by British Dr. William Withering in 1785 for the treatment of heart conditions (1).

Detailed history here

Mechanism of action

Foxglove works by increasing sodium (Na) ions in intracellular space through inhibition of sodium potassium ATPase thereby leading to decrease in gradient across cell membrane. The intracellular increase in Na cause accumulation of intracellular calcium (Ca) by exchanging Na for Ca through Na-Ca exchange system. This means Na are pump out of the cell (extracellular) while Ca goes into the cell (Intracellular). This cytoplasmic Ca accumulation improves heart contraction. Ca is normally stored in the sarcoplasm and chronic heart failure patient lack a functional sarcoplasm, so they depend on the Na- Ca exchange system to supply the Ca needed for heart contraction. This means that Na in the cytoplasm must increase to cause Ca accumulation for heart contraction. So Foxglove is given to heart patient to cause this increase in Na. Increase in contraction then leads to Increase stroke volume, because foxglove cause increase in cardiac output.

Cardiac Output=Stroke Volume x Heart Rate).

Diagram representation of mechanism of action of Foxglove. Image source here

Image source here

Uses

As poisonous as it is, it is still very useful. It is used as digoxin  in medicine, which is a cardiac glycoside, isolated from the foxglove plant – Digitalis purpurea. Digitalin is the drug gotten from foxglove plants. The Food and Drug Administration approved it for heart failure treatment in 1998.

– It is a positive inotrope: increase cardiac contraction.

– It is an anti arrhythmic used to control heart rate.

–  It is used for congestive heart failure treatment in relieving associated fluid retention (edema).

Toxicity

All parts of the plant are toxic!

Toxicity results from overdose of digitalis in foxgloves.

Chronic toxicity is more common than acute intoxication (4).

Sources of Toxicity

– Accidental ingestion of any part of the plant

– Intentional ingestion to cause self-harm

– Animals and children are attracted by the beautiful color

Poisonous Ingredient in Foxglove

• Deslanoside
• Digitoxin
• Digitalis glycoside

Symptoms of Toxicity

• nausea
• vomiting
• diarrhea
• faint
• dizziness
• disorientation
• blurred vision

image source here

Diagnosis

• clinical history
• combination of signs and symptoms
• radiological studies – chest xrays
• laboratory tests – high serum concentration of digoxin, urine test

Treatment (2,3)

• First aid treatment
  • Call 911
  • Call poison control
  • Remove residue by cleaning the mouth with cloth
  • Do not induce vomiting except directed by medical professionals
• Medical treatment
  • Gastric lavage to remove it from the stomach
  • breathing support if needed
  • activated charcoal to prevent it substance from being absorbed by the body
  • laxatives to eliminate it from the body
  • Intravenous fluids if needed
• Advanced treatment
  • KCl
  • Antidote – Digibind
  • Lidocaine
  • Atropine

image source here

Prognosis

Depends on

• Age of patient
• Time of presentation
• Symptoms last for 1 to 3 days
• Mortality increased with heart block or arrhythmia
• Death is 1-5%

REFERENCES

1. William Withering, An Account of the Foxglove and some of its Medical Uses(Birmingham, England: M. Swinney, 1785).
2. Graeme KA. Toxic plant ingestions. In: Auerbach PS, Cushing TA, Harris NS, eds. Auerbach’s Wilderness Medicine. 7th ed. Philadelphia, PA: Elsevier; 2017:chap 65.
3. Lim CS, Aks SE. Plants, mushrooms, and herbal medications. In: Walls RM, Hockberger RS, Gausche-Hill M, eds. Rosen’s Emergency Medicine: Concepts and Clinical Practice. 9th ed. Philadelphia, PA: Elsevier; 2018:chap 158.
4. Gurel E, Karvar S, Yucesan B, Eker I, Sameeullah M. An Overview of Cardenolides in Digitalis – More Than a Cardiotonic Compound. Curr. Pharm. Des. 2017;23(34):5104-5114.
5. Olmstead, R. G.; dePamphilis, C. W.; Wolfe, A. D.; Young, N. D.; Elisons, W. J. & Reeves P. A. (2001). “Disintegration of the Scrophulariaceae”. American Journal of Botany. American Journal of Botany, Vol. 88, No. 2. 88 (2): 348–361.

Brief Introduction

Ethylene glycol is an organic industrial compound that is produced from ethylene (ethene) through the reaction of ethylene oxide (intermediate) with water. It is regarded as alcohol with two -OH groups i.e diol. It is clear, colorless with sweet taste and viscous at room temperature.

Ethylene glycol is clear and odorless. Image source here

History 

Detailed history here

First discovered in 1859 by Charles-Adolphe Wurtz – A french chemist.

Used as a coolant and to make explosives during World War 1

Industrial production started in 1937

Introduced as aircraft engines coolant, replacing water.

Other Names

• 1,2-dihydroxyethane
• monoethylene glycol 
• 1,2-ethanediol
• IUPAC name: ethane-1,2-diol

Properties

Routes of Exposure

   Systemic toxicity– Only through ingestion.

   Non-systemic toxicity –

1. Through inhalation: can cause eye and respiratory tract irritation
2. Through the skin: poorly absorbed through skin
3. Eye exposure: can cause local adverse health effects

Sources of exposure

• Air: spray (aerosol), vapor, or mist.
• Water: water contamination.
• Food: food contaminants
• Agricultural: If released as a liquid spray (aerosol) or mist, it can contaminate agricultural products. If released as a vapor, it is unlikely to contaminate agricultural products.

Uses: 2 major uses

1. Industrial Use

 Use for producing

– polyester fiber used for clothes, upholstery, carpet, and pillows.

– polyethylene terephthalate (PET)- plastic resin found in beverage (soda, water, juice).

– fiberglass used for jet skis, bathtubs and bowling balls.

– ink for ballpoint pens; increase ink viscosity.

– heat transfer fluids such as industrial coolants for gas compressors, heating, ventilating, air-conditioning systems, ice skating rinks.

– used in the natural gas industry to remove water vapor from natural gas before further processing.

Image source here

2. Transportation Use

– antifreeze: to help keep a car’s engine from overheating and  from freezing in the winter.

– component of deicing solutions used in a variety of transportation applications, including cars, boats and aircraft, as well as on airport runways during the cold winter months.

– used in hydraulic brake fluid product

Image source here.

Mechanism of action

Toxicity occur mostly by ingestion because of its sweet taste. After ingestion, it is absorbed by the stomach and intestines and remain in the body for many days. Its by product- calcium oxalates stay in the body longer (2). It is oxidized to glycoaldehyde and then to glycolic acid and this is then converted to glyoxylic acid. The glyoxylic acid is then converted to oxalic acid and glycine. Once in the system, it first affect the central nervous system, then heart, and lastly affect the kidneys. Glycolic acid is the major cause of metabolic acid (3) while oxalic acid does not cause metabolic acidosis but are deposited in many tissues as calcium oxalate crystals (4).

 Image source here

 

Symptoms of toxicity (1)

Signs of ethylene glycol toxicity manifests in 3 stages

Stage 1 (30mins – 2hrs)

• Neurological signs
• Gastrointestinal signs
• Signs similar to alcohol toxicity (6)

Stage 2 (12 -24hrs)

• Alcohol signs resolve
• Internal organ damage (6)
• Cardiovascular (heart failure)
• pulmonary damage
• Low blood calcium concentration

Stage3 (12-72hrs)

• man (24-72hrs), cats (12-24hrs), dog (36-72hrs)
• kidney failure
• Gastrointestinal damage

Diagnosis

•  In urine – Calcium oxalate

calcium oxalate in ethylene glycol poisoning  image source here

• In blood- Acidosis, high osmol gap, high anion gap, hypocalcemia

Image source here

Confirmatory diagnosis – blood glycolic acid or ethylene glycol concentrations but this is not readily available (5).

Treatment

• Fomepizole- preferred antidote

Image source here                                                                               

Image source  here 

• Ethanol if no fomepizole
  

  source here

• Hemodialysis in the case of renal failure (7)

Prevention

• Clean up any antifreeze spill immediately using cat litter, sand or other absorbent materials.
• Check automotive for leaks.
• Store antifreeze away from pets and children.
• Keep pets and small children away from the area when draining the car radiator.
• Dispose used antifreeze only by taking to a service station.
• For antifreeze is placed in toilets, ensure the lid is down and the door closed.

References

1. Kruse, JA (October 2012). “Methanol and ethylene glycol intoxication”. Critical Care Clinics. 28 (4): 661-711. doi:1016/j.ccc.2012.07.002. PMID22998995
2. Davis DP, Bramwell KJ, Hamilton RS, Williams SR. Ethylene glycol poisoning: case report of arecord-high level and a review. J Emerg Med. 1997;15:653–67.
3. Jacobsen D, McMartin KE. Antidotes formethanol and ethylene glycol poisoning. J ToxicolClinToxicol. 1997;35:127–43.
4. Barceloux DG, Krenzelok EP, Olson K, Watson W. American Academy of Clinical Toxicologypractice guidelines on the treatment of ethyleneglycol poisoning. Ad Hoc Committee. J ToxicolClinToxicol. 1999;37:537–60.
5. Church AS, Witting MD. Laboratory testing inethanol, methanol, ethylene glycol, and iso-propanol toxicities. J Emerg Med. 1997;15:687–92.
6. Antifreeze Poisoning in Dogs & Cats (Ethylene Glycol Poisoning)”Archived 2014-09-12 at the Wayback Machine, Pet Poison Helpline, accessed Sept. 11, 2014.
7. Barceloux DG et al. American Academy of Clinical Toxicology practice guidelines on the treatment of ethylene glycol poisoning. J Toxicol Clin Toxicol 1999;37:537-60

LEAD (Pb)

 

Brief Introduction

Symbol Pb. It is an extremely toxic metal even at a very low exposure.  Lead is a natural occurring element  with atomic number 82- highest atomic number of any stable element

History

• It has been in existence since 3000 B.C
• one of the first metals discovered by humans
• a statue found in turkey is still the oldest known lead-containing object from 6,500 B.C
• Egyptians used lead to glaze pottery between 3,000 and 4,000 B.C. 
• The Babylonians and the Assyrians used it to construct buildings
• used by ancient Romans to make water pipes
• used by ancient Chinese as a stimulant and to make coins 4,000 yrs ago
• early warriors used it to make bullets
• more detail here

Ancient Rome pot made of lead image source here

   Ancient Rome coin made of lead image source here

     Properties

• heavy and dense than materials.
• soft and malleable
• relatively low melting point 621.5 °F
• high density
• high resistance to corrosion
• pure lead is silver color with tint of blue
• it changes to dull gray color on exposure to air
• non biodegradable so persist in the environment

Picture of lead with its characteristic silver color with hint of blue. source here

Toxicity (1,2,3)

• Highly poisonous
• Affects most organs and systems in the body (1)
• At airborne levels of 100 mg/m³, it is dangerous to life and health (2)
• When ingested it is absorbed into the bloodstream(3)
• Lead is a neurotoxin that accumulates in soft tissues and bones

Mechanism of toxicity (4,5,7)

• Binds to the sulfhydry (SH) groups found on many enzymes, thereby interfering with the functions of the enzymes (4)
• Mimick and displace other metals which act as cofactors in many enzymatic reactions (5)
• cross the blood-brain barrier and interacts with calcium
• It degrades the myelin  sheaths of neurons, reduces their numbers, interferes with neurotransmission  routes, and decreases neuronal growth (4)
• It impaired heme synthesis by preventing incorporation of iron into protoporphyrin IX , leading to microcytic anemia (7)
• More detail here.

image source here

 

 Effect on various body system

image source here

• Nervous system
  • the number one target for lead
  • fetus and children prominently vulnerable
  • encephalopathy (degeneration of brain)  

symptoms-loss of memory, muscular tremor, fatigue, hallucination, headache

• Hematopoietic System
  • prevent  hemoglobin synthesis
  • reduces life span of circulating red blood cells
  • causes anemia  (8) .
• Renal Effects
  • Renal dysfunction occurs at high levels  >60 μg/dL (10)
  • Nephropathy
• Cardiovascular Effects
  • hypertension is seen in humans and animals
• Reproductive Health Effects
  • at blood concentrations > 40 μg/dl        
  • Men
    • decrease in sperm count, sperm volume, sperm motility
    • reduced libido
    • abnormal spermatogenesis
    • abnormal prostatic function
    • change in  testosterone level
  • Women (10)
    • more susceptible to infertility
    • premature membrane rupture
    • miscarriage
    • premature delivery
    • pre-eclampsia
    • pregnancy hypertension (6).
• Effect on Bone
  • Bone is the primary site where lead is stored in the body  (9)   

picture shows various organ affected by lead source here

Routes of Absorption: 3 major routes

Skin route

– major source especially for those that work with organic lead compounds.

– rate of absorption through the skin is lower for  inorganic lead (11)

Inhalation

– second major source of exposure

– dust

– almost all inhaled lead is absorbed into the body

– smokers;  from smoke from the cigarette                                                                                                                                                                                             

 Ingestion

– food or water contamination

– lead-based paint is the major source for children

– old toys, furniture, crafts

Major sources of lead toxicity. image source here

Prevention

• irreversible once organ toxicity effects has occurred
• Prevention preferred over treatment
• Prohibiting industries dealing with lead close to habitable areas
• Screening children for early medical intervention
• Nutrition – mineral elements, flavonoids, vitamins, garlic

Treatment- prevention is better than cure!!!

Give dose of calcium and iron

Acute cases-  use disodium calcium

chronic- administer  succimer and dimercaprol

Conclusion

Lead is highly toxic even at a very low dose.

Image source here

References

1. United States Food and Drug Administration (2015). Q3D Elemental Impurities Guidance for Industry (PDF) (Report). United States Department of Health and Human Services. p. 41. Retrieved 15 February 2017
2. National Institute for Occupational Safety and Health. “NIOSH Pocket Guide to Chemical Hazards — Lead”. www.cdc.gov. Retrieved 18 November 2016.
3. Occupational Safety and Health Administration. “Substance data sheet for occupational exposure to lead”. www.osha.gov. Archived from the original on 16 March 2018. Retrieved 1 July 2017.
4. Rudolph, A. M.; Rudolph, C. D.; Hostetter, M. K.; et al. (2003). “Lead”. Rudolph’s Pediatrics (21st ed.). McGraw-Hill Professional. p. 369. ISBN 978-0-8385-8285-5.
5. Dart, R. C.; Hurlbut, K. M.; Boyer-Hassen, L. V. (2004). “Lead”. In Dart, R. C. (ed.). Medical Toxicology (3rd ed.). Lippincott Williams & Wilkins. p. 1426. ISBN 978-0-7817-2845-4.
6. Flora G, Gupta D, Tiwari A. Toxicity of lead: A review with recent updates. Interdiscip Toxicol. 2012;5(2):47-58. doi:10.2478/v10102-012-0009-2
7. Cohen, A. R.; Trotzky, M. S.; Pincus, D. (1981). “Reassessment of the Microcytic Anemia of Lead Poisoning”. Pediatrics. 67 (6): 904–906. PMID 7232054.
8. Guidotti,T.L.,McNamara,J’.,Moses,M.S.,2008.The interpretation of trace element analysis in body fluids. Indian J Med Res.;128:524–532.
9. Renner R. Exposure on tap: Drinking water as an overlooked source of lead. Environ Health Perspect. 2010;118:A68–A74. [PMC free article] [PubMed] [Google Scholar]
10.  Grant LD. Environmental Toxicants. John Wiley & Sons, Inc.; 2008. Lead and compounds; pp. 757–809. [Google Scholar]
11. Wani, A. L.; Ara, A.; Usman, J. A. (2015). “Lead toxicity: A review”. Interdisciplinary Toxicology. 8 (2): 55–64. doi:10.1515/intox-2015-0009. PMC 4961898. PMID 27486361.

 

 

Avermectins

Introduction

Avermectins are naturally occurring, potent, macrolide drugs used to treat both intra and extra intestinal parasites and are also used in the treatment of insect pest infestation but lack significant antibacterial or antifungal activities (6). They are broadly considered as blocker of neurotransmitters due to their antiparasitic and anthelmintic activities.

Brief History (1, 2, 4, 5)

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