Scribd Logo
Upload

Welcome to Scribd!

  • 9 views

    Toxicology 6

    Uploaded by

    vkm8r5n7h6
    The document discusses over-the-counter decongestants and NSAIDs, including their mechanisms of action, toxicity features, and treatment. Decongestants work by constricting blood vessels in the nose while their toxicity can cause effects like hypertension, seizures, and psychosis. Acetaminophen is the most common drug involved in overdose and its toxicity results from a reactive metabolite that binds to liver cells, causing liver damage.

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd

    Toxicology 6

    Uploaded by

    vkm8r5n7h6
    9 views6 pages
    The document discusses over-the-counter decongestants and NSAIDs, including their mechanisms of action, toxicity features, and treatment. Decongestants work by constricting blood vessels in the nose while their toxicity can cause effects like hypertension, seizures, and psychosis. Acetaminophen is the most common drug involved in overdose and its toxicity results from a reactive metabolite that binds to liver cells, causing liver damage.

    Original Title

    Toxicology 6✅

    Copyright

    © © All Rights Reserved

    Available Formats

    PDF, TXT or read online from Scribd

    Did you find this document useful?

    Is this content inappropriate?

    The document discusses over-the-counter decongestants and NSAIDs, including their mechanisms of action, toxicity features, and treatment. Decongestants work by constricting blood vessels in the nose while their toxicity can cause effects like hypertension, seizures, and psychosis. Acetaminophen is the most common drug involved in overdose and its toxicity results from a reactive metabolite that binds to liver cells, causing liver damage.

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    9 views6 pages

    Toxicology 6

    Uploaded by

    vkm8r5n7h6
    The document discusses over-the-counter decongestants and NSAIDs, including their mechanisms of action, toxicity features, and treatment. Decongestants work by constricting blood vessels in the nose while their toxicity can cause effects like hypertension, seizures, and psychosis. Acetaminophen is the most common drug involved in overdose and its toxicity results from a reactive metabolite that binds to liver cells, causing liver damage.

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    of 6

    Over the counter drugs

    Decongestants & NSAIDs

     Dr. Mohammed Fareed

     Decongestants

    Decongestants reduce nasal congestion by stimulating the alpha-adrenergic


    receptor sites on vascular smooth muscles which causes the dilated arterioles
    to constrict and thereby reduce the blood flow to engorged nasal vascular
    beds.

    Pseudoephedrine is the d-isomer of ephedrine and has only 25% of the


    adrenergic receptor activity of ephedrine.

    Both ephedrine and pseudoephedrine are stimulants of alpha as well as beta


    adrenergic receptors, Phenylpropanolamine is devoid of beta-adrenergic
    receptor activity.

    In fact in 2000, discontinuation of phenylpropanolamine (PPA) from all


    pharmaceutical products and has issued a public health warning concerning
    the risk of haemorrhagic stroke associated with phenylpropanolamine use,
    particularly among women.

    The dose of PPA used for appetite suppression is greater than the dose used
    in cough and cold preparations.

    compounds such as :

    naphazoline, oxymetazoline, tetrahydrozoline, and xylometazoline, which


    are powerful alpha2- adrenergic receptor stimulants.

     Clinical Toxic Features

    1. Toxicity usually manifests as CNS stimulation, hypertension, and


    tachycardia (bradycardia with phenylpropanolamine).

    Headache is common. Serious manifestations include seizures,


    dysrhythmias, cerebral haemorrhage, and psychosis.

    1
    2. Imidazoline decongestants (such as xylometazoline or oxymetazoline)
    cause CNS depression, hypotension, bradycardia, and respiratory depression.

    Imidazolines may also be used in combination with other sympathomimetics

    (e.g. phenylephrine or ephedrine), in which case, hypertension may be seen.

    Miosis may be present. Mydriasis has also occurred.

    4. Chronic overuse may result in reactive vasodilation of the nasal mucosa.

    Acute psychosis and hypertension have been reported with chronic abuse.

    Signs and symptoms of phenylpropanolamine overdose:

    phenylpropanolamine has a propensity to cause significant hypertension, and


    may result in reflex bradycardia, extensive myocardial ischaemia, cerebral
    haemorrhage, or renal toxicity. Tachycardia can also occur.

    Psychiatric disturbances, particularly in children, have been reported after


    ingestion of phenylpropanolamine.

     Treatment

    Because of hypertension, drowsiness and coma, emesis is not indicated even


    when nasal decongestants have been ingested.

    Activated charcoal and gastric lavage are also not routinely recommended,
    though they may be of value in phenylpropanolamine ingestions.

    Monitor serum creatine phosphokinase and renal function in severely


    symptomatic patients, and those with prolonged seizures or coma.

    1. Seizures, agitation, and psychosis should be treated with IV diazepam.


    Refractory cases should be managed with barbiturates or neuromuscular
    blocking agents.

    Monitor for respiratory depression, hypotension, arrhythmias

    2. Severe symptomatic palpitations, tremor, and associated anxiety may


    respond to propranolol, particularly in patients with combination overdose of
    phenylpropanolamine and other sympathomimetic agents.
    2
    However, propranolol may worsen hypertension in patients with single-
    ingredient phenylpropanolamine overdose.

    3. Persistent or highly elevated hypertension should be treated with


    nitroprusside or nifedipine.

    Nitroglycerin and phentolamine are possible alternatives.

    4. Hypotension can be managed with isotonic fluids,Trendelenberg position,


    and dopamine infusions.

    5. Dysrhythmias usually respond to standard doses of lignocaine or


    bretylium. Propranolol can also be used.

    Dialysis may be beneficial in phenylpropanolamine overdose.

     NON-STEROIDAL ANTI-INFLAMMATORY DRUGS

     ACETAMINOPHEN (N-ACETYL-PARAAMINOPHENOL,
    PARACETAMOL)

    INCIDENCE

    Poisoning cases with APAP exceed those of all other agents in this category
    (fivetimes greater incidence than with aspirin). It is the most common drug
    involved in overdose, registering approximately 60% of all analgesic
    exposures, and the second most common cause of liver failure in the U.S.

     METABOLISM AND MECHANISM OF TOXICITY

    Hepatic glucuronide and sulfate conjugation (Reactions 1 and 2,) produce


    the inactive corresponding conjugates, which account for 95% of
    metabolism and elimination in urine.

    In addition, at therapeutic acute doses, the remaining 5% of the product is


    detoxified and eliminated in the minor cytochrome P450 oxidase pathway
    (Reaction 3). The result is the production of the reactive intermediate, N-
    acetyl-p-benzoquinoneimine (NAPQI) metabolite.

    Further conjugation by cellular glutathione results in the production of


    mercapturic acid and cysteine conjugates (Reaction 4).
    3
    With chronic use or with large doses, the glucuronide and sulfate
    conjugation metabolic routes (1 and 2) are saturated, and more importantly,
    glutathione stores are depleted (4).

    This leaves the cytochrome P450 oxidase pathway (Reaction 3) to


    accumulate toxic NAPQI metabolite. Binding of NAPQI to hepatocyte
    membranes and sulfhydril proteins accounts for the hepatotoxic sequelae.

    (Binding of NAPQI to hepatocyte membranes and sulfhydril proteins


    accounts for the hepatotoxic sequelae).

    (Binding of NAPQI to hepatocyte membranes and sulfhydril proteins


    accounts for the hepatotoxic sequelae).

    4
     SIGNS AND SYMPTOMS OF ACUTE TOXICITY (Note :Only
    arrow column wanted) :

     CLINICAL MANAGEMENT OF ACUTE OVERDOSE

    Activated charcoal is beneficial if administered to an individual who


    presents within 1 to 2 h postingestion.

    At 8 h postingestion, activated charcoal, emetics, or gastric lavage are not


    necessary.

    N-acetylcysteine (NAC) is the antidote for acetaminophen

    poisoning. In its conversion to cysteine, NAC restores glutathione reserves


    by providing sulfhydril donors for the eventual detoxification of NAPQI.

    In addition, NAC increases sulfate conjugation, thereby preventing excess


    NAPQI production.

    NAC also acts as an antioxidant, enhancing oxygen utilization; this effect


    may be of benefit in patients with fulminant hepatic failure.

    Currently, the protocol is 140 mg/kg oral loading dose followed by 17 doses
    of 70 mg/kg every 4 h, for a total of 1330 mg/kg over 72 h.

    5
    The dose is continuous over the 72 h until the acetaminophen assay reveals a
    nontoxic level.

     ACETYL SALICYLIC ACID

     CLINICAL MANAGEMENT OF TOXICITY

    Activated charcoal and cathartics are recommended to effectively bind


    salicylates and to prevent intestinal obstruction due to concretions,
    respectively.

    Sodium bicarbonate administration enhances ASA elimination by


    alkalinizing the urine while simultaneously reversing metabolic acidosis.

    Other supportive measures include correcting the dehydration, maintaining


    kidney function (forcing fluids),rectifying electrolyte imbalance (especially
    potassium for hypokalemia that may result from bicarbonate infusion), and
    instituting supportive measures for hyperthermia, seizure control, and
    pulmonary edema. … END

    You might also like