toxicology of cardioactive & cyanogenic glycosides

1. Toxicology of cardioactive &
cyanogenic glycosides
Nabeela jabeen
Mphil pharmacognosy

2. Cardio active glycosides
• Digoxin is commonly used for the treatment of atrial fibrillation,
especially with co-existing congestive heart failure.
• Cardiac glycosides, including digoxin, inhibit the sodium-potassium-
ATPase.

3. Cont…
• The increased intracellular sodium ultimately results in increased
intracellular calcium and increased inotropy.
• The excessive intracellular calcium can result in delayed after-
depolarizations, which may result in premature contractions and
dysrhythmias.

4. Digoxin toxicity
• Acute toxicity is more likely to result in a younger individual following
an acute overdose.
• Nausea,
• vomiting,
• hyperkalemia,
• dysrhythmias are common.

5. • Chronic digoxin toxicity frequently occurs in the elderly as a result of
• decreased clearance of digoxin,
• due to either declining renal function or
• drug-drug interactions.
• Symptoms
• Nausea, malaise, and weakness are common findings in chronic digoxin
toxicity.

6. Key management points
• the key points in management are as follows:
• 1) assessment and stabilization of the airway, breathing, and circulation.
• 2) determine if there are any indications for giving digoxin immune fab
fragments.
• 3) administer an appropriate dose of fab fragments as indicated.

7. Emergency Management
• Certainly any patient with an unprotected airway should have
advanced airway measures, including endotracheal intubation,
performed.
• If hyperkalemia or life-threatening dysrhythmias are present, the
patient should receive digoxin immune Fab fragments.

8. Management points not to be missed
 Obtain a serum potassium concentration.
Obtain a 12-lead electrocardiogram.
 Monitor for signs of end-organ hypoperfusion, including adequacy of
mentation and renal perfusion.
 Administer digoxin immune Fab fragments as indicated.

9. Diagnosis
• The diagnosis of digoxin toxicity is primarily a clinical diagnosis based
on symptoms, as well as the electrocardiogram and potassium.
• Digoxin levels can be obtained, but should not be the sole basis for
determining digoxin toxicity.

10. Cont..
• Because of the narrow therapeutic index of digoxin, patients can be
digoxin toxic with therapeutic digoxin concentrations.
• Furthermore, an elevated digoxin concentration does not translate to
digoxin toxicity.

11. Normal lab values
• A therapeutic serum digoxin concentration should be 0.8-2.0 ng/mL.

Normal serum potassium concentration should be 3.5-5 mEq/L.

12. Specific Treatment
• The first priority in treatment is ensuring the patient has an adequate
airway and breathing.
• Patients who are bradycardic can receive atropine 0.5 mg IV, although
any response is likely to be transient and minimal.

13. Toxicology of cyanogenic glycosides
• The major edible plants in which cyanogenic glycosides occur are
almonds, sorghum, cassava, lima beans, stone fruits and bamboo
shoots.
• A cyanogenic food of particular economic importance is cassava
(Manihot esculenta)

14. • Cassava is by far the most important cyanogenic food crop for
humans and is an important source of dietary energy in tropical
regions.
• The predominant cyanoglycoside in cassava is linamarin.
• It is present in leaves and tubers, both of which are eaten.
• Linamarin is also present in beans of the lima or butter type.

15. • Amygdalin is the cyanogenic glycoside responsible for the toxicity of
the seeds of many species of Rosaceae, such as bitter almonds,
peaches and apricots.
• Sweet almonds are low in amygdalin as a result of breeding
processes.
• Their use in marzipan is common but the preparation procedure
should eliminate most of the cyanide.

16. • Potential toxicity of cyanoglycosides arises from enzymatic
degradation to produce hydrogen cyanide, resulting in acute cyanide
poisoning.
• The enzyme responsible (β- glucosidase) may arise from the plant
material or from gut microflora.

17. • Clinical symptoms of acute cyanide poisoning include
• rapid respiration,
• drop in blood pressure,
• rapid pulse, headache, dizziness, vomiting, diarrhoea, mental
confusion, stupor, blue discolouration of the skin due to lack of
oxygen (cyanosis), twitching and convulsions.

18. Toxicology of cyanogenic glycosides
• Cyanogenic glycosides are chemical compounds contained in foods
that release hydrogen cyanide when chewed or digested.
• The act of chewing or digestion leads to hydrolysis of the substances,
causing cyanide to be released
• Cyanogenic glycosides are common in certain families such as the
Fabaceae, Rosaceae, Leguminosae, Linaceae, and Compositae

19. Source of cyanogenic glycosides
• Edible parts of plants, such as
• apples, apricots,
• cherries, peaches,
• plums, quinces,
• particularly in the seed of such fruits.

20. • Also found in almonds, stone fruit, pome fruit, cassava, bamboo
shoots, linseed/flaxseed, lima beans, coco yam, chick peas,
cashews, and kirsch

21. • cyanogenic glycosides include some food ingredients with flavoring
properties such as ground almonds powder or paste, marzipan,
stone fruit, and alcoholic drinks made from stone fruits.
• These foods therefore represent potential sources of hydrogen
cyanide

22. Toxicity is depend upon…
• Release of hydrogen cyanide.
• Cyanide toxicity can occur in animal including humans at doses
between 0.5 and 3.5 mg HCN per kilogram body weight.
• Children are particularly at risk because of their smaller body size

23. Symptoms
• vomiting,
• stomach ache,
• diarrhea,
• convulsion,
• in severe cases death

24. Cyanide detoxification in human
• Cyanide is detoxified in the body by the enzyme rhodanase with the
help of sulfur‐containing amino acids to thiocyanate, which is
excreted in the urine.
• However, the detoxication mechanism of cyanide in the human
body can only cope with low level of cyanide generated from
consumption of small amount of cyanogenic plants.

25. Imidazole alkaloids
• 80% imidazole is corrosive to skin
• Cause eye irritation
• Effect RBCs

26. Pyrrolizidine alkaloids.
• cause irreversible hepatic damage; toxicity signs are a consequence of
impaired liver function.
• PA,s intoxication leads to pulmonary damage as a primary effect;
hepatic effects are less prominent.

27. Tropane alkaloids
• Toxicity from plants containing tropane alkaloids manifests as classic
anticholinergic poisoning.
• Symptoms usually occur 30-60 minutes after ingestion and may
continue for 24-48 hours because tropane alkaloids delay gastric
emptying and absorption.

28. • Scopolamine, acting as an antagonist at both peripheral and central
muscarinic receptors, is thought to be the primary compound
responsible for the toxic effects of these plants.
• Tropane alkaloids are found in all parts of the plants, with highest
concentrations in roots and seeds.

29. • As little as one-half teaspoon of Datura seed, equivalent to 0.1 mg of
atropine per seed, has caused death from cardiopulmonary arrest.
• The usual route of ingestion is as a tea, although ingesting seeds or
other plant parts and smoking dried leaves also are common.