PHARMACOLOGY PRESENTATION

10.Tuba Hasaan Qureshi 10692

1.Afshan Mushtaq 10597

2.Ammarah Shaikh 10604 3.Asra ALVI 10611

Syeda Kinza Mehmood 10682

Sualeha Batool Baig 10681

Group Members (No. 7)

6.Hira Akbar 10634

4.Erum Akhter 10617

7.Huma Ilyas 10635

5.Halima Sadia 10628

MANAGEMENT OF POISONED PATIENTS

Common Terms Used In Toxicology

Initial Management Of Poisoned Patients

MONITERING
Airway
Should be cleared of vomitus or any other obstruction & an oral airway or endotracheal tube inserted if needed.
The initial management of a patient with coma, seizures or otherwise altered mental status should follow the same approach regardless of poisoned involved. Attempting to make a specific toxicological diagnosis only delays the application of supportive measures

Circulation
Should be assed by continuos monitering of pulse rate, blood pressure, urinary output & evaluation of peripheral perfusion.

Breathing
Should be assessed by observation and if in doubt, by measuring arterial blood gases. Patients with respiratory insufficiency should be inttubated & mechanically ventilated.

History & Physical Examination

History: Oral Statement about the amount and even the type of drug ingested in toxic emergencies but it may be unreliable.

The Figure Shows Different Routes Of Administration Of Drug In Management Of Poisoned Pts
10% 6% 8% Ingestion Inhalation Dermal 76% Others

PHYSICAL EXAMINATION
Vital Signs Abdomen

Eyes

Mouth

Skin

Nervous System

Hypertension And Tachycardia Hypotension And Bradycardia Are Characteristic Feature Of Overdose With
Hypotension With Tachycardia Is Common With Rapid Respiration Are Typical With Hyperthermia May Be Associated With Hypothermia

Amphetamines, Cocaine And Anti Muscarinic Drugs

Ca Channel Blockers, Beta Blockers, Clonidine And Sedative Hypnotics.

TCAS ,Trazodone , Quetiapine , Vasodilators Ans Beta Agonist.

Salicylates, Carbon Mono Oxide

Sympathomimetics, Anti Cholinergics , Salicylates And Drug Producing Seizures Or Muscular Ragidity

CNS Depressants

The eyes are a valuable source of toxicologic information.

Miosis
Constriction of pupil is typical of opioids, clonidine, phenothiazines, and cholinesterase inhibitors

Mydriasis
Dilation of pupil is common with amphetamines , cocaine, LSD and atropine & other anti cholinergic drugs.

MOUTH: The mouth may show signs of burns due to corrosive substances or soot from smoke inhalation. Typical odours of alcohol, hydrocarbon,solvents ,or ammonia may be noted.poisoning due to cyanide can be recognized by some examiners.

SKIN The skin often appears flushed, hot and dry in poisoning with atropine and other antimuscuranics. Excessive sweating occurs in organophosphates, nicotine,and sympathomimitic drugs.

Abdominal examination may reveal ILEUS, which is typical of poisoning with Antimuscuranic, Opioids,and Sedative Drugs.
Abdominal cramping, and diarrhea are common in organophosphates,iron, arsenic theophylline.

Sualeha batool baig

Laboratory and imaging procedure

Arterial Blood Gas:

An arterial blood gas (ABG) test measures the acidity (pH) and the levels of oxygen and carbon dioxide in the blood from an artery. This test is used to check how well your lungs are able to move oxygen into the blood and remove carbon dioxide from the blood.

Electrolyte tests are typically conducted on blood plasma or serum, urine, and diarrheal fluids.

Measure the acid-base level in the blood of people who have heart failure, kidney failure,uncontrolled diabetes, sleep disord ers, severe infections, or after a drug overdose.

Electrolytes are positively and negatively charged molecules, called ions. The concentrations of these ions in the bloodstream remain fairly constant throughout the day in a healthy person. Changes in the concentration of one or more of these ions can occur during various acute and chronic disease states and can lead to serious consequences.

Sodium, potassium, chloride, and bicarbonate should be measured. The anion gap is then calculated by subtracting the measured anions from cations: anion gap = (Na+K) (HCo3+ Cl)

Drug that may induce an elevated anion gap metabolic acidosis include aspirin, metformin, methanol, ethylene glycol, isoniazid and Iron.

Examples of drug-induced anion gap acidosis:

TYPE OF ELEVATION OF THE ANION GAP

AGENTS

ORGANIC ACID METABOLITE

Methanol, ethylene glycol, diethylene glycol.

Cyanide,carbonmo noxide,ibuprofen,is oniazide,metformi n,salicylates,valproi c acid

LACTIC ACIDOSIS

Renal function tests :

Some toxins have direct nephrotoxic effects; in other cases, renal failure is due to shock or myoglobinuria. Blood uria nitrogen and creatinine levels should be measured and urine analysis performed. Elevated serum creatine kinase (CK) and myoglobin in the urine suggest muscle necrosis due to seizures or muscular rigidity. Oxylate crystals in the urine suggest ethylene glycol poisoning.

Serum osmolality:

The calculated serum osmolality is dependent mainly on the serum sodium and glucose and the blood urea nitrogen This calculated value is normally 280290mOsm/L.

The measured osmolality should not exceed the predicted by more than 10 mOsm/kg. A difference of more than 10 mOsm/kg is considered an osmolal gap. Causes for a serum osmolal gap include mannitol, ethanol, methanol, ethylene glycol and other compounds in very high concentration, usually small molecules and often toxins.

IMAGING FINDINGS:

A plane film of the abdomin may be useful because some tablets, particularly Iron and potassium may be radiopaque.Chest radiographs may reveal aspiration pneumonia, hydrocarbon pneumonia , or pulmonary edema. When head trauma is suspeted,a computed tomography(CT) scan is recommended.

TOXICOLOGY SCREENING TEST

A toxicology screen refers to various tests to determine the type and approximate amount of legal and illegal drugs a person has taken.

Toxicology screening is most often done using a blood or urine sample. However, it may be done soon after swallowing the medication.

This test is often done in emergency medical situations. It can be used to evaluate possible accidental or intentional overdose or poisoning. It may help determine the cause of acute drug toxicity, to monitor drug dependency, and to determine the presence of substances in the body for medical or legal purposes.

RISKS
Risks associated with having blood drawn are slight but may include:

Excessive bleeding Fainting or feeling lightheaded

Hematoma (blood accumulating under the skin)

Infection (a slight risk any time the skin is broken)

DECONTAMINATION

Decontamination procedures should be undertaken simultaneously with initial stabilization, diagnostic assessment, and laboratory evaluation. Decontamination involves removing toxins from the skin or gastrointestinal tract.

GI DECONTAMILNATION
Gastric lavage:

- Used with moderate to severe overdoses within an hour of ingestion.

-Lavage is contraindicated with ingestion of corrosives.

GI DECONTAMINATION CONTD..

Activated charcoal: Purported to be superior to lavage

- Used in toxic ingestions within an hour of the ingestion.

- Dosed as 1g/kg or 10:1 ratio of charcoal to poison

- Given as single dose or multiple dose.

GI DECONTAMINATION CONTD..
Cathartics:
- Given

with charcoal to enhance elimination

- Unproven efficacy when used alone. Whole bowel irrigation:

-Used for body stuffers/packers

Common toxic syndromes

Acetaminophen
Acetaminophen is one of the drugs commonly involved in suicide attempts and accidental poisonings. A highly toxic metabolite is produced in the liver.

Toxic dose (children)

More than 150-200mg/kg

Toxic dose(adult)

7gm

Initially,the patient is asymptomatic or has mild GI upset(nausea vomiting)

After 24-36hrs,evidence of liver injury appear,with elevated aminotransferase levels &hypoprothrombinemia.

In severe cases ,fulminant liver failure occur,leading to hepatic encephalopathy &death.renal failure

the antidote of acetaminophene is Nacetylcystein

Amphetamine & other stimulants

A major toxic effect of amphetamine in humans at higher doses,restlessnes,agitation,acute psychsis,seizures,hyperthermia,rhabdomylosis .hyperthermia can cause brain damage,hypotension ,coagulopathy & renal failure. There is no specific antidote.

ANTICHOLINERGIC AGENTS:
Examples of classes of medications with anticholinergic properties include: antihistamines (eg, diphenhydramine), tricyclic antidepressants (eg, amitriptyline), sleep aids (eg, doxylamine), cold preparations, scopolamine, and tainted illicit street drugs (eg, heroin "cut" with scopolamine). TREATMENT: Agitated patients may require sedation with a BDZ or an antipsychotic agents(haloperidol).The specific peripheral & central anticolinergic syndrome is physostigmine

Antidepressant
Tricyclics have a narrow therapeutic index. Ingestion of more than 1 gm of a tricyclic is considered potentially lethal. TREATMENT: Endotracheal intubation & assisted ventilation may be needed.intravenous fluid s are given for hypotension. Monoamine oxidase inhibitor (tranylcypramine,phenelzine)

Antipsychotic: Include phenothaizine &butyrophenones as well as newer atypical drugs. Some can cause QT prolongation. The potent dopamine D2
blocker are also associated with parkinsonian movement disorder.
TREATMENT: of antipsychotic overdose includes supportive care of the comatose patient, effective gastrointestinal decontamination with activated charcoal, intravenous fluids and ECG monitoring.

ORGANOPHOSPHATE AND CARBAMATE

MECHANISM OF TOXICITY:
Carbamate and Organophosphate insecticides are used Worldwide. They exert their toxicity through inhibition of acetylcholinesterase, with subsequent accumulation of excess acetylcholine.

CLINICAL FEATURES: Abdominal cramps,

diarrhea, excessive salivation, sweating, increased broncial secretions, agitation, confusion, and seizures.

TREATMENT: Caused by atropine and

pralidoxime. Atropine is an effective competitive inhibitor at muscuranic sitesbut not at nicotinic site while pralidoxime is active at both muscuranic and nicotinic sites.

Cyanide(CN) salts and hydrogen cyanide(HCN) are highly toxic chemicals used in chemical synthesis, as rodenticide or as a agent of suicide or homicide.
MECHANISM OF TOXICITY:
Cyanide binds readily to cytochrome oxidase, inhibiting oxygen utilize with in the cell and lead to cellular hypoxia and lactic acidosis.

SYMPTOMS:
symptoms of cyanide poisoning include shortness of breath, agitation, and tachycardia followed by seizures, coma, hypotension, and death.

TREATMENT:
It include rapid administration of activated charcoal or the conventional antidot kit include two forms of nitrite(amyl nitrite and sodium nitrite).

Digitalis and other cardic glycoside are found in many plants and in the skin of toads.
SYMPTOMS: Vomiting, TREATMENT:
It may occur as a result of acute over dose or from accumulation of digoxin in a patient with the renal insufficiency or from taken a drug that interferes with digoxin elimination. hyperkalemia, cardic rhythm disturbance including sinus bradycardia, AV block, atrial tachycardia with block, premature ventricular beats and other ventricular arrythmias.

The use of digoxin antibodies has revolutionized the treatment of digoxin toxicity. It is administered intravenously.

Over dosage with ethanol and sedative-hypnotic drugs( eg, benzodiazepines, barbiturates, -hydroxybutyrate [GHB], carisoprodol) occurs frequently because of their common availability and use.

SYMPTOMS:
Patient with ethanol and sedativehypnotic overdose may be euphoric and rowdy(drunk) or in the state of stupor or coma(dead drunk). Depression of protective airway reflexes may result in aspiration of gastric contents. Hypothermia may be present because of environmental exposure and depressed shivering.

TREATMENT: Treatment of
benzodiazepines overdose is to administered flumazenil, a benzodiazepines antagonist . However, it is not widely used as empiric therapy for drug overdose because it may precipitate seizures in patient who are addicted to benzodiazepines or who have ingested a convulsant drug . There are no antidot for ethanol, barbiturates, or most other sedative-hypnotics.

TOXIC AGENT MECHANISM EFFECTS OF ACTION

ETYLENE GLYCOL The major danger is due to sweet taste that attrack children and animal upon Upon ingestion, ethylene glycol is oxidized to glycolic acid which is, in turn, oxidized to oxalic acid, which is toxic Its toxic byproducts first affect the central nervous system, then the heart, and finally the kidneys. Ingestion of sufficient amounts can be fatal if untreated. ethylene glycol, may cause some alteration of mental status

TREATMENT

Fomepizole , an inhibitor of alcohol dehydrogenase that decrease concentration of toxic metabolites in blood and urine and to prevent renal injury,Ethanol ls also use as an antidote

TOXIC AGENT

MECHANISM OF EFFECTS ACTION

TREATMENT

METHANOL Methanol converted Characteristic

to formaldehyde via alcohol dehydrogenase and formaldehyde is converted to formic acid via aldehyde dehydrogenase . Formate is toxic ,inhibits mitochondrial cytochrome c oxidase, causing hypoxia visual disturbance plus coma seizures and acidosis

Fomepizol , inhibitor of alcohol dehydrogenase use for treatment of methanol poisoning.In case of severe poisoning hemodialysis used to eliminate both metanol and formate from the

TOXIC AGENT MECHANISM OF ACTION

EFFECTS
ACUTE IRON TOXICITY, i.e seen in chilrden Gastroenteritis with vomiting abdominal pain and bloody diarrhea followed by shock. severe metabolic acidosis coma and death. CHRONIC IRON TOXICITY,Also known hemochroatosis, organ failure and death

TREATMENT
Deferoxamine a potent iron chelating compound that promotes iron excreation in urine and feces,deferasirox is effective in protecting heart from iron overload,

IRON

Iron Replaces Other Vital Minerals Causing Enzyme Dysfunction. Iron oxide is formed when iron combines with several atoms of oxygen at once Due to its properties as an excellent oxygen transporter, iron tends to stimulate the growth of common bacteria. This leads directly to cancer, which is basically a parasite on the human body.

TOXIC AGENT

MECHANISM OF ACTION

EFFECTS

TREATMENT

LEAD

It cause inhibition of enzymatic function, interfere with oxidative phosphorylatio n alters cell signaling, changes in gene expression

CNS deficits ,peripheral neuropathy,ane mia,nephropath y,hypertention,r eproductive toxicity

The chelating agents used for treatment of lead poisoning are edetate disodium calcium, dimercaprol , which are injected, and succimer and dpenicillamine, which are administered orally.Chelation therapy is used in cases of acute lead poisoning

TOXIC AGENT

MECHANISM OF ACTION Mercury interacts with sulfhydryl groups ,inhibiting enzymes and altering cell membrane

EFFECTS

TREATMENT

MERCURY

ACUTE POISONING Chemical pneumonitis and non cardiogenic pulmonary edema CHRONIC POISONING Tremors, neuropsychiatric disturbance and gingivostomatiti s

Intramuscular dimercaprol(exposure to inorganic mercury salts), intravenous unithol,or oral succimer use in diminshing nephrotoxicity ,N acetyl lcysteine enhance body clearance of methylmercury may but if renal failure then hemodialysis or hemodiafiltration is done

TOXIC AGENT MECHANISM

OF ACTION

EFFECTS

TREATMENT

ARSENIC

Inhibits enzymes ,interfere with oxidative phosphorylatio n alter cell signaling,gene expression

On cvs shocks, arrythmias.CNS encephalopathy, peripheral neuropathy.Gastr oenteritis pancytopenia, c ancer

Dimercaprol and dimercaptosuccinic acid are chelating agents which cause the arsenic away from blood proteins Supplemental potassium decreases the risk of experiencing a life-threatening heart rhythm problem from arsenic trioxide

OXIC AGENT MECHANISM

OF ACTION

EFFECTS

TREATMENT

PIODS

Opioids bind to specific opioid receptors in the nervous system and other tissues. There are three principal classes of opioid receptors, , , , an overdose can leads to

Respiratory depression, Noncardiogenic pulmonary edema (NCPE), bradycardia, Seizures, Miosis, Hypothermia

Naloxone i.e antagonist at and receptor, Naltrezone

TOXIC AGENT MECHANISM

OF ACTION

EFFECTS

TREATMENT

THEOPHYLLINE

competitive Hypotention, nonselective trachycadia, phosphodiester seizures ase inhibitor and adenosine receptor antagonist

Propranolol or other beta blocker e.g esmolol are uesfull antidote phenobarbital is prefered over phenytoin for convulsion

Derived from a Greek word antididonai meaning given against. These are the substances which prevent or neutralize or counteract the action of poison.

MECHANICAL ANTIDOTES
They act by preventing absorption of poisons.

CHEMICAL ANTIDOTES
They counteract the action of poison by forming harmless compounds.

PHYSIOLOGICAL ANTIDOTES
They are the agents which on the tissue of the body and produce and produce symptoms exactly opposite to that of the poison.

SEROLOGICAL ANTIDOTES

ANTIDOTE

POISON

MECHANISM OF ACTION

COMMENTS

Acetylcysteine

Acetaminophen

The antidote acts as a glutathione substitute Must be given as binding to and early as possible inactivating the reactive i.e. within 8-10 metabolites produced hours of overdoses from acetaminophen.
Atropine is a muscarinic receptor antagonist. It works by blocking excess of acetylcholine to muscarinic receptors. Whereas pralidoxime is capable of restoring the cholinesterase activity at both nicotinic and muscarinic receptors. It must be given IV 1-2mg(0.05mg/kg for children) until symptoms of atropinism appear. Dose may be repeated every 1015 minutes.

Atropine Pralidoxime

Anticholinestrases; organophosphates, carbamates

ANTIDOTES

POISON
Membrane depressant cardio toxic drugs(TCAs, Qunidine etc)

MECHANISM OF ACTION
Sodium bicarbonate provides a rapid increase in extracellular sodium that helps overcome sodium channel blockade.

COMMENTS
1-2mEq/kg IV bolus usually reverses cardio toxic effects. Give cautiously in heart failure.

Bicarbonate, sodium

Calcium

Calcium binds with fluoride ions preventing further skin penetration of the acid. If given as Fluoride; Ca channel an antidote for Ca blockers channel blockers it maintains an adequate conc. Of ionized calcium thereby preventing cardiac dysrhythmias.

Start with 15mg/kg IV

ANTIDOTES

POISON

MECHANISM COMMENTS OF ACTION

It complexes the ferric ion of Iron to form a hexadentate complex, ferrioxamine which readily excretes into the urine. Give 15mg/kg/hr IV. 100mg of deferoxamine binds 8.5mg of iron.

Deferoxamine

Iron salts

Digoxin antibodies

Digoxin and related cardiac glycosides.

It binds with molecules of Digoxin or digitoxin. The Digoxin-antibody One vial binds 0.5mg complex is then of Digoxin. excreted renally in the urine and removed from the body.

ANTIDOTES

POISON

MECHANISM OF COMMENTS ACTION

Blocks the agonistic effect of the sympathetic neurotransmitters by competing for receptor binding sites. At lower doses they block beta-1 receptors only but begin to block beta-2 receptors as the dose increases. It has high affinity for alcohol dehydrogenase app. 100 folds greater than methanol and ethylene glycol thus blocking their conversion to their active metabolites and allowing elimination of the parent compound.

Esmolol

Theophylline, caffeine, metaproterenol

Infuse 2550g/kg/min IV

Ethanol

Methanol, Ethylene glycol

The therapy is initiated with 42g/70kg in adults.

ANTIDOTES

POISON

MECHANISM OF COMMENTS ACTION

Flumazenil antagonizes the actions of BDZ by competitively inhibiting the activity of GABA-BDZ receptor complex . It acts on cardiac cells to raise intracellular cAMP by the stimulation of the glucagon receptors. Adult dose is 0.2mg IV repeated as necessary up to a maximum of 3mg.ff

Flumazenil

Benzodiazepines

Glucagon

Beta Blockers

5-10 mg IV Bolus.

Nalaxone

Narcotic drugs, other Opioids derivatives

1-2mg initially by IV, A pure Opioids IM or subcutaneous antagonist. It prevents or injection. Larger reverses the effects of doses may be needed Opioids by direct to reverse the effects competition at mu,kappa of overdose with and sigma Opioids codeine or fentanyl receptor binding sites. derivatives.