antidotes and their MOA An antidote is a substance which can counteract a form of poisoning. The term ultimately derives from the Greek αντιδιδοναι antididonai, "given against"

1. Antidotes & their MOA
GROUP NO. 06
CLINICAL PHARMACY (TOXICOLOGY)

2. Flumazenil
ASRA HAMEED
12859

3. Flumazenil (GABA Modulators)
• Imidazobenzodiazepine derivative
• Antagonizes the actions of
benzodiazepines on the CNS
• Competitively inhibits the activity at the
benzodiazepine recognition site on the
GABA/benzodiazepine receptor complex

4. Benzodiazepine
Mechanism Of Action

5. symptoms of BZD overdose
• Central nervous system depression
• Ataxia
• Slurred speech
• Dizziness
• Confusion
• Drowsiness
• Blurred vision
• Unresponsiveness
• Anxiety
• Agitation
Severe symptoms include
coma and respiratory depression

6. Benzodiazepine Toxicity Differential
Diagnoses
• Acute Hypoglycemia
• Alcohol Toxicity
• Antidepressant Toxicity
• Encephalitis
• Hypernatremia (rise in serum sodium concentration by
decrease in total body water)
• Hyponatremia [abnormally low serum Sodium
(helps regulate the amount of water in and around cells)]
• Neuroleptic Agent Toxicity
• Sedative-Hypnotic Toxicity
• Stroke, Ischemic
• Toxicity, Antihistamine

7. Tests and procedures depend on the
presentation, as follows:
• Obtain a blood glucose level immediately if the
patient has an altered mental status
• Obtain an arterial blood gas (ABG) if respiratory
depression is present
• Obtain an electrocardiogram (ECG) to evaluate for
co-ingestants, particularly cyclic antidepressants
• Obtain a chest radiograph if respiratory compromise
is present
• Obtain a pregnancy test in women of childbearing
age

8. In patients with an intentional overdose,
measure the following:
• Serum electrolytes
• Glucose
• blood urea nitrogen (BUN)
• Creatinine clearance
• Ethanol
• Acetaminophen level

9. Approach Considerations
• As with any overdose, the first step is to
assess the patient's airway, breathing, and
circulation and to address these rapidly as
needed.
• The cornerstone of treatment in
benzodiazepine (BZD) overdoses is good
supportive care and monitoring.

10. activated charcoal
• Single-dose activated charcoal is not
routinely recommended, as the risks far
outweigh the benefit.
• BZD are very rarely fatal in overdoses,
and the altered mental status from BZD
overdose greatly increases the risk of
aspiration following oral charcoal dosing.

11. Flumazenil
• Flumazenil is a specific antidote for BZDs, but its use
in acute BZD overdose is controversial and its risks
usually outweigh any possible benefit.
• It should be considered only in isolated iatrogenic
BZD overdose in BZD-naive patients (e.g., during
conscious sedation on BZD-naive patient).
• In long-term BZD users, flumazenil may precipitate
withdrawal and seizures; in patients taking BZDs for
a medical condition, flumenazil may result in
exacerbation of the condition.

13. Flumazenil
• Common adverse events with flumazenil
include agitation and gastrointestinal
symptoms
• Serious adverse events include
supraventricular arrhythmia and convulsions

14. Vitamin C

16. Methemoglobinemia
• Hemoglobin within red blood cells attaches (binds) to
oxygen molecules in the lungs, which it carries through the
bloodstream, then releases in tissues throughout the body.
• Instead of normal hemoglobin, people with
methemoglobinemia, have an abnormal form called
methemoglobin, which is unable to efficiently deliver oxygen
to the body's tissues.
It promote the heme iron to
change from ferrous to ferric.
The ferric iron cannot bind
oxygen and causes cyanosis
and the brown appearance
of blood.
It promote the heme iron to
change from ferrous to ferric.
The ferric iron cannot bind
oxygen and causes cyanosis
and the brown appearance
of blood.

17. Cyanosis is a bluish discoloration, especially of the skin
and mucous membranes, due to excessive concentration
of deoxyhemoglobin in the blood caused by deoxygenation.

18. Treatment and
Patients with G6PD deficiency
• Methylene blue is the primary emergency treatment for
methemoglobinemia
• Methylene blue should not be administered to patients with
glucose 6-phosphate dehydrogenase (G6PD) deficiency,
• MB may not only be ineffective but it is also potentially
dangerous
• Pretreatment screening of G6PD deficiency is not usually
possible in emergency.
• If methylene blue is contraindicated, only moderate doses of
ascorbic acid
• Dose:300 to 1000 mg/day orally in divided doses

19. Repair the damaged hemoglobin

20. Glucagon
NEELAM SHARIF
12886

21. Beta Blockers and CCBs Overdose
 Some beta blockers may antagonize sodium channel
blockage QRS widens and some beta blockers cause
efflux blockade long QT
• Beta blockers overdose results in bradycardia and
hypotension
 CCBs prevent the opening of these voltage-gated
calcium channels (myocardial cells, smooth muscle
cells and β-islet cells of the pancreas) and reduce
calcium entry into cells during phase 2 of an action
potential.
 In an overdose situation, receptor selectivity is lost, and
effects not normally seen at therapeutic doses can
occur.

22. Mechanism of Action of Toxicity
a) Calcium enters open voltage-sensitive calcium channels to promote
the release of calcium from the sarcoplasmic reticulum. The
released calcium combines with troponin to cause muscle
contraction via actin and myosin fibers.
b) AC catalyzes the conversion of ATP to cAMP, which activates
protein kinase A (PKA), which promotes the opening of dormant
calcium channels, enhances release of calcium from the
sarcoplasmic reticulum, and facilitates release of calcium by
troponin during diastole.
c) Glucagon bypasses β-receptors and acts directly on Gs to
stimulate conversion of ATP to cAMP.
d) Amrinone inhibits PDE(Phosphodiestrase) to prevent the
degradation of cAMP.
e) Insulin promotes the uptake and use of carbohydrates as an
energy source.

23. Mechanism of action of toxicity

24. Specific features and Symptomsof
Beta Blockers Overdose

25. Specific Features and Symptoms Of
CCBs Overdose

26. Antidote Glucagon
• Glucagon is generally recognized as first-line therapy.
• Glucagon is a hormone secreted by the α2 cells of the
pancreatic islets of Langerhans..
• High-dose glucagon is recommended for cardiotoxicity
produced by β-blocker poisoning.

27. Mechanism of antidote glucagon

28. Glucose
(Dextrose 50%)
AMMARAH UROOJ
12852

29. MECHANISM OF INSULIN:

30. SYMPTOMS OF INSULIN TOXICITY:
High doses of insulin can lead to:
• dyselectrolytemia.
• Salt and water retention
• hyponatremia
• hypoglycemia
• hypokalemia
• dizziness and mild confusion
• anxiety or nervousness
• shakiness
• rapid heartbeat
• Hunger
• Irritability

31. EMERGENCY TREATMENT :
provide immediate attention to
patient before they lead to
dangerously low blood sugar.
People who have low blood sugar
levels are advised to consume 15
grams of a fast digesting
carbohydrate, such as glucose
tablets or a high-sugar food
immediately. High-glucose foods
include:
• raisins
• soda
• fruit juice
• honey
• candy

32. symptoms should improve within 15
minutes. If they don’t, or if a test shows
your levels are still low, repeat the above
steps until your blood sugar is above 70
mg/dL. If your symptoms still don’t
improve, seek medical help immediately.
Be sure to eat a meal after treating a low
blood sugar reaction.

33. MANAGEMENT OF
HYPOGLYCEMIA
Management includes the
following steps:
• Restoration of normal
plasma
glucose levels
• Prevention of relapse in
the
short term
• Prevention of recurrent
episodes
in the long term.

34. RESTORATION OF NORMAL PLASMA GLUCOSE
LEVEL:
In non-severe hypoglycemia, the oral consumption of
carbohydrates is usually adequate to restore plasma
glucose levels above the lower limit of the normal range.
Patients starting insulin for the treatment of their
diabetes should be taught to recognize the symptoms of
hypoglycemia and how to react in case of a
hypoglycemic event. Self-monitoring blood glucose
(SMBG) is strongly recommended for these patients If
hypoglycemia is suspected, a blood glucose
measurement using a portable glucose meter is
recommended in order to confirm low plasma glucose

35. Prevention of relapse in the
short term
Restoration of plasma glucose levels after an acute
hypoglycemic event usually follows quickly after the
administration of carbohydrates, either orally or
intravenously, or after a glucagon injection. It is very
important, however, to keep in mind that hypoglycemia
tends to relapse in some cases, this tendency depending
on the etiology of the initial decline in plasma glucose

36. Prevention of recurrent
episodes in the long term
• Recurrent hypoglycemia requires a thorough evaluation
of diabetes management A careful history is usually
adequate to identify hypoglycemia unawareness. In
other cases, careful follow-up with frequent SMBG or
even the use of a glucose sensor for continuous
subcutaneous glucose monitoring may be recommended

37. DEXTROSE 50% SOLUTION:
50% Dextrose Injection, USP
is a sterile, nonpyrogenic,
hypertonic solution of
dextrose in water for
injection for intravenous
injection as a fluid and
nutrient replenisher. Each
mL of fluid contains 0.5 g
dextrose, hydrous which
delivers 3.4 kcal/gram

38. Mechanism of Action:
• Provides immediate source of glucose for cellular metabolism. It provide
free water that pass through membrane pores both intracellular and
extracellular spaces.its smaller size allow the molecule to pass more freely
between compartment thus expanding both compatments simultaneously
Contraindications:
• 1. There are no absolute contraindications to the IV administration of dextrose
50% in the emergency setting.
2. Relative contraindication: Use with caution in patients with increasing
Intracranial pressure as the added glucose may worsen the cerebral edema.
•
Side Effects:
• 1. Patients may complain of warmth, pain or burning at the injection site.
2. Dextrose can cause severe neurologic symptoms (Wernicke's encephalopathy or
Korsakoff's psychosis) if patient is thiamine deficient.
•

39. Routes of Administration:
IV, IO.
Onset and Duration of Actions:
• Onset will be 30-60 seconds but duration depends upon
degree and cause of hypoglycemia.
Dosages:
• ADULT: 25 gm (50 ml solution preload) IVP/IO
May repeat once in 5 minutes
Over 2 years: 1 ml/kg slow IVP/IO of a 50% solution
(same solution as for the adult)
May repeat once in 5 minutes.
.

40. Thiamine
SABIHA GUL
131027

41. INTRODUCTION
• also known as vitamin B1,
• anti beriberi factor or antineuritic vitamin
• It is an important water-soluble vitamin
• is involved in carbohydrate, fat, amino acid,
glucose, and alcohol metabolism.
• is required as a coenzyme in enzymatic reactions
that involve the transfer of an aldehyde group.
• is essentially nontoxic
41

42. CHEMISTRY
• Thiamine contains a substituted pyrimidine ring
(dimethyl 6-amino pyrimidine) connected to a
substituted thiazole ring (Methyl hydroxy ethyl
thiazole) by means of Methylene bridge
42

43. 43
SYNTHESIS
Thiamine can be synthesized by plants and some microorganisms, but not
usually by animals.
Human beings require thiamine from diet, though small amounts may be
obtained from synthesis by intestinal bacteria.
Whole wheat flour, unpolished rice, beans, nuts and yeast are the good
sources of thiamine .
It is also present in liver, meat and eggs. The body can only store up to 30
mg of thiamine in its tissues

44. • It is present in large amounts in skeletal muscle, heart,
liver, kidney, and brain.
• It has a widespread distribution in foods, but there can
be a substantial loss of thiamine during cooking above
100°C (212°F).
• The half-life of thiamine is 9-18 days. It is excreted by
the kidney
44
OCCURRENCE

45. RECOMMENDED DAILY ALLOWANCE:
•Depends on calorie intake (0.5 mg/1000 cals )
• RDA is 1-1.5 mg/day
• Requirement increases with
• increased carbohydrate intake
•Pregnancy
• Lactation
• Smoking
• Alcoholism
•Prolonged antibiotic intake
•Serious or prolonged illness 45

46. METABOLISM
• Thiamine has a central role in energy-yielding metabolism, and
especially the metabolism of carbohydrates
• Thiamine pyrophosphate is an essential cofactor for enzymes that
catalyze the oxidative decarboxylation of α-keto acids to form an
acylated coenzyme A (acyl CoA).
• These include pyruvate dehydrogenase , α -keto glutarate
dehydrogenase and branched-chain α- keto acid dehydrogenase.
These three enzymes operate by a similar catalytic mechanism
46

47. THIAMINE AS AN ANTIDOTE
47
Thiamine use a antidote :
• Persons with alcoholism
•Ethylene Glycol Poisoning
•Wernicke–Korsakoff syndrome (WKS)

48. Wernicke–Korsakoff syndrome (WKS)
• Wernicke–Korsakoff syndrome (WKS) is the combined presence of Wernicke's
encephalopathy (WE) and Korsakoff's syndrome. Due to the close relationship
between these two disorders, people with both are usually diagnosed with WKS, as
a single syndrome.
• It is due to thiamine (vitamin B1) deficiency, which can cause a range of disorders
including beriberi, Wernicke's encephalopathy, and Korsakoff's psychosis.
SIGN AND SYMPTOMS
• These disorders may manifest together or separately. WKS is usually secondary
to alcohol abuse, It mainly causes
• vision changes,
• ataxia
• impaired memory.
48

49. CAUSES
• WKS is usually found in chronic alcoholics. Wernicke–Korsakoff syndrome
results from thiamine deficiency. It is generally agreed that Wernicke's
encephalopathy results from severe acute deficiency of thiamine (vitamin
B1)
Alcohol–thiamine interactions
Strong evidence suggests that ethanol interferes directly with thiamine uptake
in the gastrointestinal tract. Ethanol also disrupts thiamine storage in the
liver and the transformation of thiamine into its active form. The role of
alcohol consumption in the development of WKS has been experimentally
confirmed through studies in which rats were subjected to alcohol exposure
and lower levels thiamine through a low-thiamine diet
49

50. TREATMENT
• Thiamine administration should be initiated
immediately when the disease is suspected
• minimum dose of 500 mg of Thiamine
hydrochloride
• Such prompt administration of thiamine may
be a life-saving measure. Banana bags, a
bag of intravenous fluids containing vitamins
and minerals, is one means of treatment.
50

51. Persons with alcoholism
• It is well known that chronic alcoholics are at high risk for being deficient in vitamin B1
(thiamine), which is known to put the patient at an increased risk for Wernicke-
Korsakoff Syndrome, cerebellar degeneration, and cardiovascular dysfunction.
TREATMENT
• The current standard of treatment for such patients is to give them thiamine 100 mg
intravenously (IV) before administering glucose containing IV fluids and then to
continue this dose for several days.

52. Ethylene glycol poisoning
• It is a sweet kiler
• Ethylene glycol poisoning is caused by the ingestion of ethylene glycol the primary ingredient in
automotive antifreeze Ethylene glycol is a toxic, colorless, odorless, almost nonvolatile liquid with a
sweet taste that is sometimes accidentally consumed by children and animals due to its sweetness.
• symptoms of poisoning
• progress from signs similar to intoxication and vomiting to hyperventilation, metabolic acidosis
and cardiovascular dysfunction; and finally acute kidney failure
CAUSES
The major cause of toxicity is not the ethylene glycol itself but its metabolites,
mainly glycolic acid and oxalic acid.
LETHAL DOSE
Lethal dose is estimated as 1 -1.5 mls/kg or 100mls
52

53. TREATMENT
• Inhibit Absorption i.e Gastric lavage , syrup of ipecac and activated
charcoal
• „ Correct Acidosis i.e Bicarp drip
• „ Inhibition of Metabolism i.e
• Thiamine
• Fomepizole (4 -methylpyrazole)
• Ethanol „
• Pyridoxine
• „ Elimination of parent compound and the metabolites I,e remove
ethylene glycol and glycolate effectively
53

54. TREATMENT
THIAMINE : MOA
•–Prevents the formation of oxalic acid by
facilitating the conversion of glycoxylic acid to
alpha Hydroxy Beta ketoadipic acid.
•
DOSE
•100 mg IV q6 until ethylene glycol can no
longer be measured in the serum
54

55. Hydroxocobalamin
&
Sodium
Thiosulphate
NOSHEEN HAYAT
131018

56. CYANIDE POISONING
Cyanide poisoning occurs when a living
organism is exposed to a compound that
produces cyanide ions (CN−
) when
dissolved in water.

61. CYANIDE ANTIDOTES
Antidotes to cyanide include hydroxocobalamin
and sodium nitrite and sodium thiosulfate.
Sodium thiosulfate may be given in combination
with sodium nitrite or hydroxocobalamin, or may
be given alone. These agents are administered
intravenously.

66. Fomepizole
AISHA ABDULLAH
12850

67. Ethyiene glycol Toxicity & its
Mechanism of Toxicity

68. Stages of Ethylene Glycol
Intoxication
• Severe ethylene glycol poisoning may go
through three stages:
1)CNS depression
2) cardiopulmonary toxicity
3) renal toxicity

69. Stage 1
• At 4-12 hours after glycoaldehyde forms ,
these symptoms may appear:
• seizures
• coma
• cerebral edema (in some cases)
• gastrointestinal irritation (nausea and
vomiting)

70. Stage 2
• The following cardiorespiratory symptoms may appear 12-24 hours after ingestion
• tachycardia,
• tachypnea, and
• hypertension or hypotension.
• The following conditions may develop in this stage
• pulmonary edema,
• pneumonitis,
• congestive cardiac failure, and
• shock.
• Formation of oxalic acid may lead to deposition of calcium oxalate crystals in
• the meninges,
• blood vessel walls,
• lung, and
• myocardium.

71. Stage 3
• Kidney damage usually develops 24-72 hours after exposure.
Acidosis and acute renal failure may result from deposition of
calcium oxalate crystals in the kidneys.
• The following conditions characterize the third phase
• flank pain,
• costovertebral angle tenderness, and
• oliguric renal failure.

72. Diagnosis
• It is most reliably diagnosed by the measurement of the blood ethylene
glycol concentration. Ethylene glycol in biological fluids can be determined
by gas chromatography.
• Many hospital laboratories do not have the ability to perform this blood test
and in the absence of this test the diagnosis must be made based on the
clinical presentation of the patient.In this situation a helpful test to diagnose
poisoning is the measurement of the osmolal gap.
• Large anion gap acidosis is usually present during the initial stage of
poisoning. diagnosis of ethylene glycol poisoning should be considered in
any patient with a severe acidosis.
• Urine microscopy can reveal needle or envelope-shaped calcium oxalate
crystals in the urine which can suggest poisoning.

73. Treatment
• The most important initial treatment for ethylene glycol poisoning is
stabilizing the patient. As ethylene glycol is rapidly absorbed, gastric
decontamination is performed within 60 minutes of ingestion.
• Patients with significant poisoning often present in a critical condition. In this
situation stabilization of the patient including airway management with
intubation should be performed in preference to gastrointestinal
decontamination.Patients presenting with metabolic acidosis or seizures
require treatment with sodium bicarbonate and ticonvulsives such as a
benzodiazepine respectively.Sodium bicarbonate should be used cautiously
as it can worsen hypocalcemia by increasing the plasma protein binding of
calcium. If hypocalcemia occurs it can be treated with calcium replacement
although calcium supplementation can increase the precipitation of calcium
oxalate crystals leading to tissue damage.
• Intubation and respiratory support may be required in severely intoxicated
patients; patients with hypotension require treatment with intravenous fluids
and possibly vasopressors.[

74. Fomepizole & its MOA

75. Dosing
• The dosing and administrationof fomepizole is the same for children
and adults.
• Loading dose :15 mg/kg IV maximum of 1500 mg
• 12 hours later, give the 1st maintenance dose of 10 mg/kg IV.
Repeat every 12 hours
• Continue treatment until EG or methanol levels are below 20 mg/dl
and the patient is asymptomatic with normal pH.

76. Heparin
ZABAB KHAN
131066

77. • Ergotamine is a naturally occurring
ergot alkaloid
• Used for Preventing or treating
acute migraine headache
• Partial agonist or antagonist
activity against tryptaminergic,
dopaminergic and α-adrenergic
receptors
• Potent vasoconstrictor, analgesic,
Oxytocics

79. • Ergotamine doses of more than 15
mg/24 hours or more than 40 mg
over a few days are likely to cause
toxicity.
• Death has been reported in a 14-
month-old toddler after an acute
ingestion of 12 mg

80. • vasospastic effects
• nausea and vomiting
• impaired mental function
• confusion
• depression
• drowsiness
• rapid and weak pulse
• unconsciousness
• spasms of the limbs

82. • Reverses hyper-coagulable state by interacting
with anti-thrombin III to prevent local thrombosis
and ischemia.
• Heparin binds to antithrombin III (AT)
• The activated AT then
inactivates thrombin, factor Xa and other
proteases.
• The conformational change in AT on heparin-
binding mediates its inhibition of factor Xa.
• The formation of a complex between AT,
thrombin, and heparin results in the inactivation
of thrombin.

84. Vitamin K
ZABAB KHAN
131066

85.  Most widely prescribed anticoagulant (a drug
which reduces the risk of blood clots forming).
 decreases the clotting ability of the blood so
reduces the risk of blood clots forming
 Blood clots can be dangerous because they
can lead to serious life-threatening conditions
such as stroke.
 It is very effective at significantly reducing the
risk of stroke in people with atrial
fibrillation(AF)

86.  People taking warfarin need to have a
regular blood test called an international
normalised ratio (INR).
 INR measures the time it takes your blood
to clot.
 It is increased by taking warfarin, which, in
turn, increases the INR.
 Patients on warfarin, their target INR is 2.5
 If you’re not on warfarin your INR is around
1
 The lowest toxic dose in humans ranges
from 10 mg/kg to 15 mg/kg
 The probable lethal oral dose in humans is
believed to be between 50 and 500 mg/kg

92. o Red spots on your skin that look like a
rash
o Severe headache or dizziness
o Heavy bleeding after an injury
o Heavy bleeding during monthly period in
women
o You have severe stomach pain or you
vomit blood
o Pink, red, or dark brown urine
o Black or bloody bowel movements

93.  Vitamin K is a fat-soluble vitamin
 Vitamin K is known as the clotting vitamin,
because without it blood would not clot.
 Found in Green leafy vegetables, such as spinach
mustard greens, parsley and green leaf lettuce
 Vegetables such as broccoli, cauliflower, and
cabbage
 Fish, liver, meat, eggs, and cereals
 Vitamin K is also made by the bacteria in the lower
intestinal tract.
 Essential co-factor in the synthesis of blood
clotting factors ll, Vll, lX and X and proteins C and
S
 Antagonist of some oral anticoagulants (warfarin)

96. • Prothrombin time (PT) determinations (The
prothrombin test is sensitive to the levels of
three of the vitamin K–dependent clotting
factors (II, VII, and X)
• Rregular prothrombin level determinations are
recommended to determine responsiveness to
and need for additional vitamin K therapy .

97. • Allergic reactions,
• Blue color or flushing or redness of skin
• dizziness
• fast and/or weak heartbeat

98. Leucovorin
calcium
MISHA MEHMOOD

99. INDICATION
For the treatment of osteosarcoma (after high
dose methotrexate therapy). Used to diminish
the toxicity and counteract the effects of
impaired methotrexate elimination and of
inadvertent overdosages of folic acid
antagonists, and to treat megaloblastic anemias
due to folic acid deficiency.
• Also used in combination with 5-fluorouracil to
prolong survival in the palliative treatment of
patients with advanced colorectal cancer.

100. MOA OF FOLATE
ANATAGONIST

101. MECHANISM OF ACTION
LEUOCOVORIN
• As leucovorin is a derivative of folic acid, it can
be used to increase levels of folic acid under
conditions favoring folic acid inhibition (following
treatment of folic acid antagonists such as
methotrexate). Leucovorin enhances the activity
of fluorouracil by stabilizing the bond of the
active metabolite (5-FdUMP) to the enzyme
thymidylate synthetase.

103. Thank You
for
listening US