PHARMACOLOGY PRESENTATION

Group Members

(No. 7)

1.Afshan Mushtaq 10597

2.Ammarah Shaikh 10604

3.Asra ALVI 10611

4.Erum Akhter 10617

5.Halima Sadia 10628

6.Hira Akbar 10634

7.Huma Ilyas 10635

Sualeha Batool Baig 10681

Syeda Kinza Mehmood

10682

10.Tuba Hasaan Qureshi 10692

MANAGEMENT OF POISONED PATIENTS

Toxicology is the branch of pharmacology

that encompasses the deleterious

effects of chemical and

physical agents on biologic

system.

Toxicokinetics denotes the absorption, distribution,

excreation and metaboloism of toxic agents.

Toxicodynamics is used to denote the

injurious effect of these

substance on vital functions.

Toxidromeis a syndrome caused by a

dangerous level of toxin accumulate in the body. It is a

term used to describe a

constellation of symptoms caused

by a drug overdose.

Common Terms Used In Toxicology

Initial Management Of Poisoned Patients

AirwayShould be cleared of vomitus or any other

obstruction & an oral airway or endotracheal tube inserted if needed.

CirculationShould be assed by continuos monitering of pulse rate, blood pressure, urinary output

& evaluation of peripheral perfusion.

BreathingShould be assessed by observation and if in doubt, by measuring arterial blood gases.

Patients with respiratory insufficiency should be inttubated & mechanically

ventilated.

MONITERING

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

History & Physical Examination

History:Oral Statement about the amount and even the type

of drug ingested in toxic emergencies but it may be

unreliable.

76%

8%

6%10%

IngestionInhalationDermalOthers

The Figure Shows Different Routes Of Administration Of Drug In Management Of

Poisoned Pt’s

PHYSICAL EXAMINATIONVital Signs

Eyes Mouth

Skin

Abdomen

Nervous System

VITAL SIGNS:Careful evaluation of vital signs (blood pressure, Pulse, respiration,and temperature)is

essential in all Toxicologic emergencies.

Hypertension And Tachycardia Amphetamines, Cocaine And Anti Muscarinic Drugs

Hypotension And Bradycardia Are Characteristic Feature Of Overdose

With

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

Hypotension With Tachycardia Is Common With

TCA’S ,Trazodone , Quetiapine , Vasodilators Ans Beta Agonist.

Rapid Respiration Are Typical With Salicylates, Carbon Mono Oxide

Hyperthermia May Be Associated With

Sympathomimetics, Anti Cholinergics , Salicylates And Drug

Producing Seizures Or Muscular Ragidity

Hypothermia 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.

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

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

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.

TYPE OF ELEVATION OF

THE ANION GAP

ORGANIC ACID METABOLITE

LACTIC ACIDOSIS

AGENTS

Methanol, ethylene glycol, diethylene

glycol.

Cyanide,carbonmonoxide,ibuprofen,isoniazide,metformin,s

alicylates,valproic acid

Examples of drug-induced anion gap 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 nitrogenThis calculated value is normally 280-290mOsm/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.

RISKSRisks associated with

having blood drawn are slight but may include:

Excessive bleeding

Fainting or feeling light-headed

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 N-

acetylcystein

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.

CHOLINESTERASE INHIBITOR

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).

CYANIDE

Digitalis and other cardic glycoside are found in many plants and in the skin of toads.

MECHANISM OF TOXICITY: 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.

SYMPTOMS: Vomiting, hyperkalemia, cardic rhythm disturbance including sinus bradycardia, AV block, atrial tachycardia with block, premature ventricular beats and other ventricular arrythmias.

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

DIGOXIN:

Over dosage with ethanol and sedative-hypnotic drugs( eg, benzodiazepines, barbiturates, γ-hydroxybutyrate [GHB], carisoprodol)

occurs frequently because of their common availability and use.

SYMPTOMS: Patient with ethanol and sedative-hypnotic 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.

ETHANOL & SEDATIVE-HYPNOTIC DRUGS

TOXIC AGENT MECHANISM OF ACTION

EFFECTS TREATMENT

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

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 ACTION

EFFECTS TREATMENT

METHANOL Methanol converted 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

Characteristic 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 blood.ethanol is also use

TOXIC AGENT MECHANISM OF ACTION

EFFECTS TREATMENT

IRON Iron Replaces Other Vital Minerals Causing Enzyme Dysfunction.Iron oxide is formed when iron combines with several atoms of oxygen at onceDue 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.

ACUTE IRON TOXICITY, i.e seen in chilrdenGastroenteritis 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

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

TOXIC AGENT MECHANISM OF ACTION

EFFECTS TREATMENT

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

CNS deficits ,peripheral neuropathy,anemia,nephropathy,hypertention,reproductive toxicity

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

TOXIC AGENT MECHANISM OF ACTION

EFFECTS TREATMENT

MERCURY Mercury interacts with sulfhydryl groups ,inhibiting enzymes and altering cell membrane

ACUTE POISONINGChemical pneumonitis and non cardiogenic pulmonary edemaCHRONIC POISONINGTremors, neuropsychiatric disturbance and gingivostomatitis

Intramuscular dimercaprol(exposure to inorganic mercury salts), intravenous unithol,or oral succimer use in diminshing nephrotoxicity ,N acetyl l–cysteine 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 phosphorylation alter cell signaling,gene expression

On cvs shocks, arrythmias.CNS encephalopathy, peripheral neuropathy.Gastroenteritis 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

TOXIC AGENT MECHANISM OF ACTION

EFFECTS TREATMENT

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

Respiratory depression, Non-cardiogenic pulmonary edema (NCPE), bradycardia, Seizures, Miosis, Hypothermia

Naloxone i.e antagonist at μ and κ receptor, Naltrezone

TOXIC AGENT MECHANISM OF ACTION

EFFECTS TREATMENT

THEOPHYLLINE competitive nonselective phosphodiesterase inhibitor and adenosine receptor antagonist

Hypotention, trachycadia, seizures

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.

ANTIDOTES

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

CLASSIFICATION OF ANTIDOTES

ANTIDOTE POISON MECHANISM OF ACTION COMMENTS

Acetylcysteine Acetaminophen

The antidote acts as a glutathione substitute

binding to and inactivating the reactive metabolites produced from acetaminophen.

Must be given as early as possible i.e. within 8-10

hours of overdoses

AtropinePralidoxime

Anticholinestrases; organophosphates,

carbamates

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 10-

15 minutes.

SOME COMMON ANTIDOTES

ANTIDOTES POISON MECHANISM OF ACTION COMMENTS

Bicarbonate, sodium

Membrane depressant cardio toxic drugs(TCAs,

Qunidine etc)

Sodium bicarbonate provides a rapid

increase in extracellular sodium that helps overcome sodium channel blockade.

1-2mEq/kg IV bolus usually reverses

cardio toxic effects. Give cautiously in

heart failure.

Calcium Fluoride; Ca channel blockers

Calcium binds with fluoride ions preventing further skin penetration of the acid. If given as

an antidote for Ca channel blockers it

maintains an adequate conc. Of ionized calcium

thereby preventing cardiac dysrhythmias.

Start with 15mg/kg IV

SOME COMMON ANTIDOTES

ANTIDOTES POISON MECHANISM OF ACTION COMMENTS

Deferoxamine Iron salts

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.

Digoxin antibodies Digoxin and related cardiac glycosides.

It binds with molecules of Digoxin

or digitoxin. The Digoxin-antibody complex is then

excreted renally in the urine and

removed from the body.

One vial binds 0.5mg of Digoxin.

SOME COMMON ANTIDOTES

ANTIDOTES POISON MECHANISM OF ACTION COMMENTS

EsmololTheophylline,

caffeine, metaproterenol

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.

Infuse 25-50µg/kg/min IV

Ethanol Methanol, Ethylene glycol

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.

The therapy is initiated with

42g/70kg in adults.

SOME COMMON ANTIDOTES

ANTIDOTES POISON MECHANISM OF ACTION COMMENTS

Flumazenil Benzodiazepines

Flumazenil antagonizes the actions of BDZ by

competitively inhibiting the activity of GABA-BDZ

receptor complex .

Adult dose is 0.2mg IV repeated as

necessary up to a maximum of 3mg.ff

Glucagon Beta BlockersIt acts on cardiac cells to raise intracellular cAMP by the stimulation of the

glucagon receptors. 5-10 mg IV Bolus.

NalaxoneNarcotic drugs, other Opioids

derivatives

A pure Opioids antagonist. It prevents or

reverses the effects of Opioids by direct

competition at mu,kappa and sigma Opioids

receptor binding sites.

1-2mg initially by IV, IM or subcutaneous

injection. Larger doses may be needed to reverse the effects

of overdose with codeine or fentanyl

derivatives.

SOME COMMON ANTIDOTES