TOXICITY FOR

• ASPIRIN AND OTHER SALICYLATES• CARBON MONOXIDE• THEOPHYLLINE

EDITED BY MR MOMPATI LETSWELETSE(CPhT) SECOND YEAR STUDENT

ASPIRIN AND OTHER SALICYLATES

MECHANISM OF TOXICITY

• Salicylates impair cellular respiration by uncoupling oxidative phosphorylation. They stimulate respiratory centers in the medulla, causing primary respiratory alkalosis.

• Salicylates simultaneously and independently cause primary metabolic acidosis

• Salicylates alter platelet function and may also prolong the prothrombin time.

SIGNS AND SYMPTOMS– Altered mental status (coma)– Sweating– Because fluid overload can result in pulmonary edema, – Increased vital signs (HTN, inc RR, inc T)– hyperventilation resulting from direct respiratory center

stimulation– Irritable – Serious dehydrationmay occur from hyperventilation,

vomiting, and fever.

DIAGNOSIS

Serum salicylate level– Every 2-4 hours until clearly decreasing

• Then q 4-6 until <30 mg/dLBedside tests

– Trinder’s reagent – 10% ferric chloride– Ames phenistix

chest x-rayprothrombin timeserum creatinine

MECHANISM OF TOXICITY

• There is no specific antidote for salicylates

• Sodium bicarbonate is often used to increase the excretion of the Salicylates .Treat metabolic acidosis with intravenous sodium bicarbonate

• Activated charcoal• Hemodialysis if severe

MECHANISM OF TOXICITY• Drugs which are weak acids (e.g. salicylates) exist

in a state of equilibrium between their ionised and un-ionised form

• By increasing the systemic pH with sodium bicarbonate more of the salicylate is trapped in its ionized form in the extra-cellular fluid resulting in enhanced renal excretion.

• Therefore sodium bicarbonate should be administered to correct any acidosis (arterial pH should not rise above 7.6) and to alkalinise the urine (optimum pH 7.5-8.5)

SAFETY PROFILE• It is very difficult to produce an alkaline pH if

the patient is hypokalaemic as hydrogen ions tend to be excreted with the bicarbonate instead of potassium. Therefore the potassium should be kept at the upper end of normal

CARBON MONOXIDE

Carbon monoxide (CO) is a deadly, colorless, odorless, poisonous gas. It is produced by the incomplete

burning of various fuels, including coal, wood, charcoal, oil, kerosene,

propane, and natural gas.

MECHANISM OF TOXICITY

• CO combines with oxygen binding sites on hemoglobin

• CO has higher affinity for hemoglobin than Oxygen.• It forms carboxyhemoglobin (Carboxyhemoglobin

is a stable complex of carbon monoxide and hemoglobin that forms in red blood cells upon contact with carbon monoxide. Large quantities of CO hinders the ability of Hb to deliver oxygen to the body. which cannot transport oxygen). Thus decreasing the transfer of oxygen to tissues.

MOT Cont…

• second mechanism -CO also has a high affinity for myoglobin(a red protein containing haem, which carries and stores oxygen in muscle cells) and effects on the mitocondrial A respiratory enzyme chain which is responsible for effective tissue utilization of oxygen. After acute CO poisoning the organs most sensitive to hypoxia(deficiency in the amount of oxygen reaching the tissues.) will be most affected; i.e. the brain and the heart

SIGNS AND SYMPTOMS

• Mental confusion• Shortness of breath due to oxygen depletion• Loss of muscular coordination due to low energy• Loss of consciousness• Coma• Shock• respiratory failure• Ultimately death

DIAGNOSIS

• Obtain history of potential CO exposuree.g. being exposed to a residential fire• Measuring the levels of CO in the blood by measuring

the amount of carboxyhemoglobin compared to the amount of hemoglobin in the blood. A CO-oximeter is used determine carboxyhemoglobin levels.

• Measuring the concentration of CO in exhaled sample(ppm) by using a device called Breath CO monitor., the CO concentration correlates with the levels of carboxyhemoglobin.

TREATMENT/ANTIDOTE

• Administration of 100% oxygen.• Provide 100% oxygen by tight-fitting mask

or via endotracheal tubeOxygen increases the removal of CO from hemoglobin in turn providing the body with normal levels of oxygen.

SAFETY PROFILE(ANTIDOTE)

• Oxygen is a flammable gas therefore should be handled accordingly.Keep backup tanks on hand.Secure extra tubing and cords so that you don't trip over them

THEOPHYLLINE

MECHANISM OF TOXICITY

is an antagonist of adenosine receptors, and it inhibits phosphodiesterase at high levels, increasing intracellular cyclic adenosine monophosphate (cAMP)

SIGNS AND SYMPTOMS

• cardiotoxicity:cardiac dysrhythmias, supraventricular tachycardia, atrial fibrillation and flutter, ventricular tachycardia, refractory hypotension.

• metabolic abnormalities:hypokalaemia (severe, refractory), hypophosphataemia, hypomagnaesemia, hyperglycaemia, metabolic acidosis (lactate), respiratory alkalosis.

DIAGNOSIS

• Serum theophylline levels are essential for diagnosis and determination of emergency treatment

• electrolytes, glucose, BUN, creatinine, hepatic function tests, and ECG monitoring.

antidote

• ACTIVATED CHARCOAL

MECHANISM OF ACTION

• It binds to the poison to prevent stomach and intestinal absorption. Binding is reversible so a cathartic such as sorbitol may be added as well.

• It is important to aggresively control nausea and vomiting in order to perform MDAC treatment. It is also important that the patient is able to protect his/her airway in order to prevent aspiration of activated charcoal which can be detrimental.

• Haemoperfusion is effective in theophylline overdose, and is the elimination procedure of choice

• Haemoperfusion is effective in theophylline overdose,

• and is the elimination procedure of choice

SAFETY PROFILE

• Activated charcoal is safe for most adults when used short-term. Side effects of activated charcoal include constipation and black stools. Most serious, but rare side effects are a slowing or blockage of the intestinal tract, regurgitation into the lungs, and dehydration.