Mechanism of toxicity,signs and symptoms,diagnostic tests,antidote and its mode of action.safety profile for the antidote

1. TOXICITY FOR
• Methotrexate
• Iphosphamide,
• Lithium carbonate
EDITED
BY MR MOMPATI LETSWELETSE
(CPhT) SECOND YEAR STUDENT

2. METHOTREXATE:MECHANISM OF
POISONING
• MTX inhibits dihydrofolate reductase, an
enzyme that reduces folic acid to
tetrahydrofolic acid. This inhibition interferes
with DNA synthesis and cell reproduction.

3. SYMPTOMS OF METHOTREXATE
POISONING
• GIT disturbance
• Bone marrow depression
• Intestinal peforation
• Mouth sores/ulcers
• Stomatitis(inflammation of the mucous membrane of
the mouth.)
• fatigue

4. TESTS
• Regular blood tests
• Liver biopsies

5. LEUCOVORIN:ANTIDOTE
• Large doses of oral folic acid might inhibit
absorption of methotrexate. For large acute
ingestions there is no reason to prefer folic
acid over activated charcoal.

6. SAFETY PROFILE
• LEUCOVORIN
-Given at high dose of (60mg/day)
-Must be taken with capecitabine at a dose of
1004mg/m2/day
-Take a one week rest after taking leucovorin

7. IFOSFAMIDE: MECHANISM OF
POISONING
• Many vitro studies suggest that the
metabolite chloroacetaldehyde is directly toxic
to tubular CELLS
• Energy depletion by mitochondrial damage

8. SIGNS AND SYMPTOMS
• Nephrotoxicity and neurotoxicity
• Chest pain
• Shortness of breadth
• Urinating frequently
• Unusual tiredness
• Black stools

9. TESTS
• Complete blood count
• Urine test
• Kidney function

10. MESNA;ANTIDOTE
• Ifosfamide is metabolized to products that cause
hemorrhagic cystitis(is the sudden onset of hematuria
combined with bladder pain and irritative bladder
symptoms. Hematuria is blood in the urine.).In the
kidney mesna disulfide to the free thiol
compund,mesna which reacts chemically with
the urotoxic ifosfamide metabolites resulting in
their detoxification.
• Treatment of MTX toxicity includes the
administration of activated charcoal in the event
of a recent, oral overdose.

11. SAFETY PROFILE
• ifosfamide/mesna should be carefully
monitored in patients receiving phenobarbital.

12. LITHIUM CARBONATE:MECHANISM OF
POISONING
• Li being a metal mimic another monocavalent
cation in the body. Li by mimicking sodium is
able to permeate the fast voltage-sensitive
channels present in excitable tissues
• Unlike Na it is not effectively removed from
the intracellular compartment by Na/k Atpase
and tend to accumulate High conce of Li
displace K leading to partial depolarization of
the membrane.

13. SIGNS AND SYMPTOMS
• Convulsions
• renal failure
• Blurred vision
• GIT disturbance
• Blurred vision
• Ringing in the ears

14. TESTS
• Lab tests i.e.
• Kidney function
• Thyroid function
• Lithium and calcium blood levels

15. LITHIUM CARBONATE(antidote)
• No specific antidote for lithium poisoning is
known
• Early symptoms of lithium toxicity can usually
be treated by reduction or cessation of dosage
of the drug and resumption of the treatment
at a lower dose after 24 to 48 hours. In severe
cases of lithium poisoning, the first and
foremost goal of treatment consists of
elimination of this ion from the patient.