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TOXICOLOGY – LEC

Prelims Notes

CANCER CHEMOTHERAPY

 Cancer – refers to a heterogeneous group of diseases caused by an impairment of normal


functioning of genes, which leads to genetic damage.
 Metastasis – uncontrolled growth and ability to evade local tissue

Carcinogenesis

 the mechanism of how many cancers occur is thought to be a multistage, multi-factorial


process that involves both genetic and environmental factors.
a. Initiation – exposure of normal cells to a carcinogen, producing genetic damage to a
cell
b. Promotion – the environment becomes altered to allow preferential growth of
mutated cells over normal cells. The mutated cells become cancerous
c. Progression – increased proliferation of cancer cells allows for invasion into local
tissue and metastasis.

Types of Cancer

1. Benign tumor – are generally slow growing, resemble normal cells, localized, and are not
harmful.
2. Malignant tumor – often proliferate more rapidly, have an atypical appearance, invade and
destroy surrounding tissues, and are harmful if left untreated.
 CATEGORY (according to location of tumor growth)
a. Solid tumors:
 Carcinomas are tumors of epithelial cells. (breast, lungs, kidney,
liver, colon, brain, prostate)
 Sarcomas include tumors of connective tissues (blood, bone, fats,
muscles, ligaments)
b. Hematological malignancies:
 Lymphomas are tumors of the lymphatic system and include
Hodgkin and non-Hodgkin lymphomas.
 Leukemia are tumors of blood- forming elements and is classified as
acute or chronic; myeloid or lymphoid

The Cell Cycle and Specific CT Agents

1. M phase, or mitosis, is the phase in which the cell divides into two daughter cells.
 multiplication and cell division
 Vinca Alkaloids - synthesized in Periwinkle or chichirica– Catharanthus roseus
 Taxanes or taxol– synthesized in Pacific Yew Tree – Taxus brevifolia or Taxus
baccata (bark)
2. G1 phase, or postmitotic gap, is when RNA and the proteins required for the specialized
functions of the cell are synthesized in preparation for DNA synthesis.
 Synthesis of important proteins responsible for DNA replication
 Asparaginase and Prednisone
3. S phase is the phase in which DNA synthesis and replication occurs.
 DNA replication
 antimetaboliteS
4. G2 phase, or the premitotic or postsynthetic gap, is the phase in which RNA and the
enzymes topoisomerase I and II are produced to prepare for duplication of the cell.
 formation of Topoisomerase I and II (aka DNA gyrase) – responsible for DNA
splicing
 Bleomycin and Etoposide
5. G0 phase, or resting phase, is the phase in which the cell is not committed to division. Cells
in this phase are generally not sensitive to chemotherapy. Some of these cells may re-enter
the actively dividing cell cycle. In a process called recruitment, some chemotherapy
regimens are designed to enhance this reentry by killing a large number of actively dividing
cells.
 not sensitive to CT agents
 resting phase
 determinant whether the cells become cancerous

Tumor Markers – are natural cells inside the body the increases their concentration when you
have a specific type of cancer

1. Carcino-embryonic Antigen (CEA): colorectal cancer Male breast cancer –possible


2. α-feto protein: hepatocellular cancer Female prostate cancer – not possible
3. Prostate Specific Antigen (PSA)

Major Causes of Carcinogenesis

1. Genetic
 Primitive Neuro Ectodermal Tumors; expected LE is 25yo
2. Lifestyle – smoking and drinking alcohol, fatty foods
3. Environment and Occupational
 Benzopyrene and aromatic substances
4. Medications
 Immunosuppresants (Cyclosporine and GCs)
5. Viruses
 EBV (Epstein Barr Virus)
 HPV (Human Papilloma Virus) – cervical and ovarian cancer
 HBV (Hepatitis B Virus) – liver CA
Treatment

1. Specific CT Agents – can target specific cell cycle sites; safer


 Phase-specific agents are most active against cells that are in a specific phase of the
cell cycle. These agents are most effective against tumors with a high growth
fraction.
2. Non-Specific Agents – do not target a specific phase; independent of the cell cycle
 Phase-nonspecific agents are effective while cells are in the active cycle but do not
require that the cell be in a particular phase. Independent of the cell cycle. Dose-
dependent agents. Examples are alkylating agents and antitumor antibiotics.
 Cell cycle–nonspecific agents are effective in all phases, including G0. Examples
are Carmustine and Lomustine. Radiation therapy is also considered cell cycle
nonspecific.

Objectives of Chemotherapy

1. Remission induction – maximize cell killing


2. Consolidation – eradication of any undetectable cancer cells; lowering to 103 concentration
3. Maintenance – given the lower dose to maintain or prolong remission

Chemotherapy dosing:

 Body Mass Index (BMI)


 Body Surface Area (BSA)
 Area Under the Curve (AUC)

DRUGS

1. Antitumor Antibiotic (Specific CTA)


a. Bleomycin
 MOA: targets G2 phase; causes DNA fragmentation
 USES: Hodgkin’s and non-Hodgkin lymphoma
 AE: pulmonary toxicity (1-2% of patients); higher risk of ARDS
2. Antimetabolites (Specific CTA)
 MOA: targets S phase; DNA or RNA synthesis inhibitor
a. Methotrexate (antagonist)
 Folic Acid analog
 Acute lymphoblastic leukemia
 Used also in RA; rescue drug for ectopic pregnancy
 ANTIDOTE: Folinic Acid (Leucovorin)
b. 5-Fluorouracil (Prodrug) Adjuvant – uses 1-2
 Pyrimidine analog CT agents
 Breast and GI carcinomas, skin cancer Neo-adjuvant – uses
c. Mecaptopurine (Prodrug) all possible agents
 Purine analog
 Acute leukemia in children
3. Epipodophyllotoxins – derived from Mayapple or Mandrake root extract – Podophyllum
peltatum
 MOA: blockage of DNA cell division by damaging strands
a. Etoposide
 USES: small cell and non-small cell lung CA and Hodgkin lymphoma
b. Tenoposide
 USES: Acute lymphoblastic leukemia
4. Taxanes or taxol – derived from Pacific Yew Tree or European Yew – Taxus brevifolia or
baccata
 MOA: mitotic spindle poison
a. Paclitaxel
 USES: Kaposi’s sarcoma
 AE: Sensory neuropathy
b. Docetaxel
 USES: second line therapy in advance or refractory solid tumors
 AE: neurotoxicity
5. Alkylating Agents (Non-Specific CTA)
 MOA: transfers an alkyl group to the DNA causing cell death
 Classifications:
1) Bis (chloroethyl) amines or Nitrogen mustards – first used in WWII
a. Cyclophosphamide
 Toxicity: hemorrhagic cystitis → bladder cancer
 Antidote: Mesna® (Sodium methyl sulfonate)
b. Methchloroethamine
 USES: Hodgkin lymphoma
c. Chlorambucil
d. Melphalan
2) Nitrosoureas
a. Carmustine
b. Lomustine
c. Streptozocin
 USES: pancreatic cancer
3) Aziridines
a. Thiotepa
 USES: ovarian, bladder, breast CA
b. Triethyleneamine
4) Alkyl sulfonates
a. Busulfan
 USES: chronic granulocytic leukemia
6. Anthracyclines
 Antibiotics isolated from Streptomyces
 MOA: prevent DNA and RNA replication and promote free radicals, thus cell
destruction
 AE: cardiotoxicity; Acute – conduction problems, myocarditis, and pericarditis;
Chronic – CHF, dilated cardiomyopathy
a. Daunorubucin
 USES: acute lymphocytic and granulocytic leukemia and wide range
of solid tumors
b. Doxorubicin
 USES: metastatic adenocarcinoma and thyroid carcinoma, bladder
and lung cancer.
7. Antitumor Antibiotics (Non-Specific CTA) – derived from Streptomyces
 MOA: inhibits DNA/RNA synthesis
a. Dactinomycin
 USES: pediatric tumors such as Wilm’s tumor (nephtoblastoma) and
Ewing’s sarcoma (bone and soft tissue tumor)
 AE: GI, alopecia, myelosuppresion
b. Mitomycin
 USES: squamous cell cancers; rectal and anal CA
 AE: myelosuppression
8. Platinum Analogs
 Inorganic metal complex
 MOA: Thought to have cytotoxic effects similar to alkylating agents
a. Cisplatin
 USES: broad range of solid tumors
 AE: Nephrotoxicity, ototoxicity, peripheral sensory neuropathy
b. Carboplatin (2nd gen) – more expensive
 USES: same as Cisplatin
 AE: less nephrotoxic, myelosuppression
TOXICOLOGY – LEC
Prelims Notes

SUMMARY OF CHEMOTHERAPEUTIC AGENTS 14. Nelarabine


15. Permetrexed
I. ALKYLATING AGENTS 16. Pentostatin
1. Altretamine (hexamethylmelamine) 17. Thioguanine
2. Busulfan
3. Carmustine IV. MITOTIC INHIBITORS
4. Chlorambucil 1. Docetaxel
5. Carboplatin 2. Ixabepilone
6. Cisplatin 3. Paclitaxel
7. Cyclophosphamide 4. Vinblastine
8. Dacarbazine 5. Vincristine
9. Estramustine 6. Vinorelbine
10. Ifosfamide
11. Lomustine V. TOPOISOMERASE INHIBITORS
12. Mechlorethamine
13. Oxaliplatin 1. Etoposide
14. Procarbazine 2. Irinotecan
15. Streptozocin 3. Teniposide
16. Temozolomide 4. Topotecan
17. Thiotepa
VI. ENZYMES
II. ANTITUMOR ANTIBIOTICS 1. Asparaginase
1. Bleomycin 2. Pegaspargase
2. Dactinomycin
3. Daunorubicin VII. PROTEIN TYROSINE KINASE INHIBITORS
4. Doxorubicin 1. Dasatinib (Sprycel)
5. Epirubicin 2. Erlotinib (Tarceva)
6. Idarubicin 3. Imatinib mesylate (Gleevec)
7. Mitomycin C 4. Lapatinib (Tykerb)
8. Mitoxantrone 5. Nilotinib (Tasigna)
9. Valrubicin 6. Sorafenib (Nexavar)
7. Sunitinib (Sutent)
III. ANTIMETABOLITES
1. Azacytidine VIII. mTOR KINASE INHIBITORS
2. Capecitabine 1. Temsirolimus
3. Cladribine
4. Clofarabine IX. MISCELLANEOUS
5. Cytarabine 1. Arsenic trioxide
6. Decitabine 2. Bexarotene (Targretin)
7. Fludarabine 3. Bortezomib (Velcade)
8. Floxuridine 4. Isotrenitoin (13-cis retinoic acid,
9. Fluorouracil Accutane)
10. Gemcitabine 5. Tretinoin (all-trans-retinoic acid, ATRA;
11. Hydroxyurea Vesanoid)
12. Mercaptopurine 6. Lenalidomide
13. Methotrexate 7. Thalidomide
DIAGNOSIS OF POISONING

A poisoning case can present to a doctor or hospital in any one of a number of ways:

1. Fulminant
 Produced by a massive dose
 Death occurs very rapidly
 Ex. Ingestion of muriatic acid, ingestion of
2. Acute
 Produced by a single dose or several small doses taken in a short period.
 Onset of symptoms is abrupt
 Ex. One large dose of APAP
3. Chronic
 Produced by small doses taken over a long period
 Onset is insidious
 Ex. Arsenic poisoning
4. Subacute
 Characterized by a mixture of features of acute and chronic poisoning

 For unconscious patients, these are the following non-specific features: (General
Symptoms)
a. Impairment of consciousness
b. Respiratory/Cardiovascular depression
 either tachycardia or bradycardia
c. Dehydration due to vomiting/diarrhea
 esp. those with drug addiction
d. Hypothermia
e. Convulsions
f. Cardiac arrhythmias

 Some valuable clues to narrow down the differential diagnosis (PURPOSE: narrowing down
of diagnosis):
a. Ocular clues – several drugs/poison affect the pupils of the eyes (miosis or
mydriasis)
b. Olfactory clues – some poisons have distinctive odors which may be perceived in the
vicinity of a poisoned patient, esp. in the breath.
c. Dermal clues – some poisons have characteristic dermal manifestations in acute
toxicity.
d. Oral clues – careful examination of the mouth
Different Toxic Syndromes

1. Anticholinergic Syndrome
 CAUSES:
a. Antihistamines h. Antispasmodics
b. Antiparkinsonian i. Skeletal muscle relaxants
drugs j. Plants [Datura – stramonium
c. Atropine (Jimson or Jamestown weed,
d. Scopolamine devils snare) & metel (devils
e. Amantadine trumpet)]
f. Antipsychotic drugs k. Fungi (Amanita muscaria -
g. Antidepressants muscarine)

 SYMPTOMATOLOGY:
1) Delirium with mumbling speech
2) Tachycardia
3) Dry hot skin
4) Mydriasis
5) Myoclonus
6) Urine retention
7) Decreased bowel sounds
8) Convulsions and arrhythmias (severe cases)

2. Cholinergic Syndrome
 CAUSES:
a. Organophosphate
b. Carbamates
c. Parasympathomimetic drugs (AChE Inhibitors)
d. Some mushrooms
 SYMPTOMATOLOGY:
1) Confusion 7) Sweating
2) CNS depression 8) Fasciculations
3) Salivation 9) Seizures
4) Lacrimation 10) Miosis
5) Urinary and fecal 11) Pulmonary edema
incontinence 12) Tachy/Bradycardia
6) Vomiting

3. Sympathomimetic Syndrome
 CAUSES:
a. Cocaine
b. Amphetamines
c. Upper respiratory decongestants (PPA, Ephedrine, and Pseudoephedrine)
 SYMPTOMATOLOGY:
1) Paranoia 6) Sweating
2) Delusions 7) Mydriasis
3) Tachycardia 8) Seiures
4) HTN 9) Arrhythmias
5) Hyperpyrexia

4. Sedative Syndrome
 CAUSES:
a. Opiates (morphine, f. Meprobamate
fentanyl, codeine, g. Ethchlorvynol
heroin) h. Gluthethimide
b. Barbiturates i. Clonidine (off-label use: ADHD
c. BZDs due to sedation – has
d. Ethanol Peripheral: anti-HTN and
e. Methaqualone Central: anxiolytic)

 SYMPTOMATOLOGY:
1) Miosis
2) Hypotension (respiratory depression in use of Opiates and BZDs)
3) Bradycardia
4) Hypothermia
5) CNS depression
6) Hyporeflexia
7) Coma
8) Convulsions (rare)

Sympathetic Syndrome

 ALICE IN WONDERLAND SYNDROME SIDE EFFECTS OF SEDATION


Red as beet: FLUSHING
Drowsiness and Dizziness
Mad as hatter: PARANOIA HA and Sore throat
Blind as bat: CYCLOPLEGIA, MYDRIASIS Reduced HR and BP changes
Dry as bone: DECREASED SECRETIONS Delirium and memory loss
Hot as hare: HYPERPYREXIA N&V and aspiration
 MATHS Confusion, restlessness, and agitation
Prolonged recovery and trouble
Mydriasis sleeping
Agitation
Tachycardia
Hyperthermia/HTN
Seizures/Sweating
DRUGS/POISON PRODUCING PUPILLARY CHANGES
MIOSIS MYDRIASIS NYSTAGMUS

Barbiturates Alcohol Alcohol


BZDs Amphetamines Barbiturates
Caffeine Antihistamine Carbamazepine
Carbamates CO Phencyclidine
Carbolic Acid (Phenol) Cocaine Phenytoin
Clonidine Cyanide
Methyldopa Datura (Atropine)
Nicotine Ephedrine
Opiates
Organophosphate
Parasympathomimetics

TOXIC OPHTHALMOLOGICAL MANIFESTATIONS


FEATURE CAUSE
1. Diplopia Barbiturates
Cannabis
Ethanol
Opiates
Phenytoin
Tetracycline
Vitamin A
2. Blurred Vision Alcohol
Anticholinergics
Botulism
Ethanol
Lithium
MAOIs
Methanol
3. Altered Color Perception Cannabis
CO
Digitalis
HCs
Ibuprofen
Nalidixic Acid
Thioridazine
4. Corneal Deposits Chloroquine
Vitamin D
5. Oculogyric Crisis Phenothiazines
Butyrophenones
Metoclopramide
6. Optic Neuritis Chloroquine
Digitalis
Disulfiram
Ergot
Heavy Metals
Methanol
Penicillamine
Quinine
Ethambutol
DIAGNOSTIC ODOURS
ODORS SUBSTANCES
1. Acetone (apple-like) Chloroform
Ethanol
Isopropranol
Lacquer
2. Acrid (pear-like) Chloral hydrate
Paraldehyde
3. Bitter almond Cyanide
4. Burnt rope Marijuana (Cannabis)
5. Coal gas CO
6. Disinfectant (hospital odor) Phenol
Creosote
7. Garlicky Arsenic
Dimethylsulfoxide
Organophosphate
Phosphorus
Selenium
Tellurium
Thallium
8. Mothballs Camphor
Naphthalene
9. Musty (Fishy) Aluminum phosphide
Zinc phosphide
10. Rotten egg Carbon disulfide
Disulfiram
HS2
Mercaptans
NAC
11. Shoe polish Nitrobenzene
12. Vinegar Acetic Acid
13. Wintergreen (Gaultheria procumbens) Methyl salicylate

DERMAL MANIFESTATION OF POISONING


ACUTE CHRONIC
POISON/DRUG FEATURE POISON/DRUG FEATURE
Datura Dry, hot skin Heroin Needle marks
Atropine Barbiturates
Morphine
Phencyclidine (angel’s dust)
Organophosphates Profuse sweating Bromides Acne, brown color
Salicylates Iodides
Arsenic Coaltar products
LSD Phenytoin
CO Cherry pink color Arsenic Rain drop pigmentation,
hyperkeratosis, dermatitis
Cyanide Brick red color Chlorinated HCs Eczematous dermatitis
Barbiturates Blisters Chloroquine Dark pigmentation
CO Busulfan
Imipramine Clofazimine
Methadone Phenothiazines
Nitrazepam Phenytoin
Warfarin Petechiae Bromides Erythema nodosum
Purpuric spots Iodides
Penicillin
Salicylates
Tetracycline
Clonidine Flushing
Ergot
Niacin (MOA: oxidation)
Sympathomimetics
Theophylline

DRUG-INDUCED ORAL MANIFESTATIONS


FEATURE DRUG/POISON
1. Glossitis Trimethoprim-sulfamethoxazole
Diclofenac
Naproxen
Metronidazole
Amoxicillin
Erythromycin
Piroxicam
2. Stomatitis Cytotoxic drugs
Penicillamine
Gold salts
Gentian violet dye
3. Sialadenitis Phenylbutazone
Isoproterenol
Nitrofurantoin
Iodine
4. Parotitis Methyldopa
Clonidine
Phenyl/oxyphenbutazone
Thioridazine
5. Gingival hyperplasia Phenytoin
Sodium valproate
Phenobarbitone
Nefedipine
Diltiazem
Verapamil
6. Pigmentation Cisplatin
Oral contraceptives
Antimalarials
7. Dental discoloration Fluorides
Tetracyclines
Chlorhexidine
Iron tonic syrups
8. Dental caries Cough and vitamin syrups
Antibiotic suspensions
9. Xerostomia Antipsychotics
TCA
Antihistamines
Anticholinergics
Anticonvulsants
Narcotics
Diuretics
Centrally acting anti-HTN
10. Sialorrhea Parasympathomimetics
Iodides

General Management of Poisoning

Ways to manage a poisoned patient

1. Stabilizations
 The initial survey should always be directed at the assessment and correction of life-
threatening problems, if present. Attention must be paid to the airway, breathing,
circulation, and depression of the CNS.
2. Evaluation
 As far as treatment is concerned, the emphasis should be on basic supportive
measures
3. Decontamination
 This is with reference to skin/eye decontamination, gut evacuation and
administration of activated charcoal
4. Poison Elimination
 Depending on the situation, this can be accomplished by different methods
5. Antidote Administration
 Unfortunately, antidotes are available for less than 5% of poisonings
6. Nursing and Psychiatric Care
 General nursing care is especially important in comatose patients and those who
have been incapacitated by the poison. Psychiatric intervention is frequently
essential in suicidal overdose.

AIRWAY BREATHING and CIRCULATION

 Symptoms of airway obstruction includes:


a. Dyspnea
b. Air hunger
c. Hoarseness
 Signs comprise
 Stridor
 Intercostal and substernal retractions
 Cyanosis
 Sweating
 Tachypnea
 Some drug may exacerbate asthma, those drugs includes: Penicillins, NSAIDs, sulfonamides.
Drugs that stimulate respiratory center: cocaine, amphetamine, salicylates.
 Several drugs produce changes in pulse rate and blood pressure, while others induce
cardiac arrhythmias and heart block (AV block)

Poisoning – without knowledge


Overdose – with knowledge (MJ – propofol + midazolam)

TOXIC RESPIRATORY DEPRESSION


FAILURE OF RESPIRATORY CENTER FAILURE OF RESPIRATORY MUSCLES
Antidepressants Neuromuscular blocking agents
Antipsychotics Nicotine
Ethanol Organophosphates
Opiates Shellfish poisoning
Sedatives Snake bite (Cobra)
Strychnine (Strychnos nux vomica)

AGENTS CAUSING NON-CARDIOGENIC PULMONARY EDEMA


Amphetamines NSAIDs
Anticoagulants Opiates (especially heroin)
Aspirated oil, talc Oxygen toxicity
Beta-blockers Radiation
Calcium Channel Blockers Salicylates
CO Sulfonamides
Cocaine Thiazide diuretics
Cytotoxic and immunosuppressive drugs TCA
Irritant gases

DRUGS ASSOCIATED WITH DISTURBANCES IN PULSE RATE AND BLOOD PRESSURE


Tachycardia & Normotension Antihistamines
Caffeine
Cannabis
Lomotil (Atropine & Diphenoxylate)
Thyroxine
Tachycardia & Hypotension CO
Cyanide
Phenothiazines
Theophylline
Tachycardia & Hypertension Amphetamines
Cocaine
Phencyclidine
PPA
Bradycardia & Hypotension Clonidine
Levodopa
MAOIs
Organophosphates
Opiates
TCAs
Bradycardia & Hypertension PPA

DRUG/TOXIN INDUCED ARRYTHMIAS


SINUS BRADYCARDIA or A-V BLOCK SINUS TACHYCARDIA
α-adrenergic drugs Amphetamines
β-blockers Anticholinergics
Carbamates Antihistamines
Cardiac glycosides CO
Organophosphates Phencyclidine
Cyclic antidepressents Phenothiazines
Theophylline
Cyclic antidepressants

Depression
 This is generally defined as an unarousable lack of awareness with a rating of <8 on the
Glasgow Coma Scale
 Before proceeding to an elaborate exercise in diagnosis however, it may be desirable to first
ascertain for sure that the patient is really comatose and not just pretending (psychogenic
or hysterical coma). This is often encountered in suicide gesture in contrast to attempted
suicide.

GRADING THE SEVERITY OF CNS INTOXICATION


DEPRESSANTS STIMULANTS
GRADE FEATURES GRADE FEATURES
0 Asleep, but can be aroused
1 Semicomatose, withdraws 1 Restlessness, irritability,
from painful stimuli, insomnia, tremor,
reflexes intact hyperflexia, sweating,
mydriasis
2 Comatose, does not 2 Confusion, HTN, tachypnea,
withdraw from painful tachycardia, extrasystoles
stimuli, reflexes intact
3 Comatose, most reflexes 3 Delirium, mania,
lost, no depression of CVS arrhythmia, hyperpyrexia
or respiration
4 Comatose, reflexes absent, 4 Convulsions, coma, and
respiratory and circulatory circulatory collapse
failure

GLASGOW COMA SCALE (Scottland)

Featured observed Score

1. Eye Opening
a. Spontaneous E4
b. To speech 3
c. To pain 2
d. Nil 1
2. Best Motor Response
a. Obeys M6
b. Localises 5
c. Flexes (withdrawal) 4
d. Flexes abnormally (decorticate rigidity) 3
e. Extends (decerebrate rigidity) 2
f. Nil 1
3. Best Verbal Response
a. Oriented V5
b. Confused conversation 4
c. Inappropriate words 3
d. Incomprehensible sounds 2
e. Nil 1
 Generally, brain injury is classified as:
 Severe – GCS ≤8
 Moderate – GCS 9-12
 Minor – GCS ≥13

Respiratory Insufficiency

 First establish an open airway


 Remove dentures
 Use the chin lift and jaw thrust, to clear the airway by the tongue falling back
 Remove saliva, vomitus, blood, etc. from the oral cavity by suction or finger-sweep method
 Place the patient in a semi-prone (lateral) position.
 If required, insert an endotracheal tube.
 If ventilation is not adequate, begin artificial respiration with Ambu bag
 Increase O2 saturation
Circulatory Failure

 Correct academia, if present


 Elevate foot end of the bed (Trendelenburg position)
 Increase the BP and volume
 Administer vasopressors like DA and NE
 DA = 800mcg/mL
 NE = 16mcg/mL
 200mL NSS to correct hemodynamic factors (↑BV and ↑HR circulation)

Cardiac Arrhythmia

 Obtain an ECG, institute continuous cardiac monitoring and administer oxygen.


 Evaluate for hypoxia, acidosis, and electrolyte disturbance (increase in K+)
 Lignocaine and amiodarone are generally first line agents for stable monomorphic
ventricular tachycardia, particularly in patients with underlying impaired cardiac function
 ALTERNATIVES: Sotalol and Atropine – used to correct bradycardia
 Classification of Anti-Arrhythmias

CNS Depression

 Generally uses COMA COCKTAIL (for differential diagnosis)


a. DEXTROSE – 100mL/50% solution; to correct hypoglycemia
b. OXYGEN – 100% (hyperbaric oxygen); to correct respiratory depression
c. NALOXONE – 2mg; if toxicant is an opioid
d. THIAMINE – 100mg; for alcohol toxicity
 Even if a particular case was not due to any of these causes, administration of these
antidotes was considered relatively harmless

Hypothermia
 Rewarming: water bath (115 deg F) until temp is 92 deg F
 Rectal and esophageal thermometers
 There is a need to correct underlying problems: Hypotension (failed circulation) and
Hypoventilation (↓O2)
 Drugs that produces hypothermia:
1. Alcohols 6. Hypoglycemics
2. Antidepressants 7. Opiates
3. Barbiturates 8. Phenothiazine
4. BZDs 9. Sedative-hypnotics
5. CO
Hyperthermia

 Oral temperature above 102 deg F is referred to as hyperthermia. If it exceeds 106 deg F
(which is very rare), there is imminent danger of encephalopathy.
 In a few individuals there is a genetic susceptibility to hyperthermia, especially on exposure
to skeletal muscle relaxants, inhalation anaesthetics, and even local anaesthetics—
malignant hyperthermia. (Genetically determined; lahat ng tao pwede magkaron ng MH)
 This should be distinguished from neuroleptic malignant syndrome (not genetically
determined), which is also characterized by high fever apart from other neurological signs,
but is the result of adverse reaction to phenothiazines and antipsychotic or neuroleptic
drugs, and has no genetic basis.

AGENTS THAT INDUCE HYPERTHERMIA


Muscular Hyperactivity Amphetamines
Antidepressants
Cocaine
MAOIs
Phencyclidine
Strychnine
Withdrawal (alcohol/opiates)
Increased Metabolic Rate Dinitrophenol
Salicylates
Thyroid Hormones
Impaired thermoregulation Anticholinergics
Antihistamines
Antipsychotics
Ephedrine
PPA
Phenothiazines

 Treatment:
 Remove all clothes, and pack the neck and groin with ice.
 Immersion in cold water bath (77oF) is very effective but dangerous in the elderly and in
heart patients.
 Stop cooling measures when core temperature falls below 102 deg F, and nurse the patient
in bed in a cool room.
 Administration of Dantrolene may be benefcial in some cases.
 Do not use antipyretic drugs like paracetamol. They are ineffective

Convulsions (Seizures)

 Treatment:
 Administer O2 by nasal cannula or mask.
 BZDs (Diazepam or Lorazepam) → Phenytoin → Phenobarbitone

Movement Disorders

DRUG-INDUCED MOVEMENT DISORDERS


DRUG DISORDERS
Amoxapine Parkinsonism
Amphetamines Hyperkinetic movements
Antihistamine Orofacial dystonia
Myoclonic jerking
Butyrophenones Parkinsonism
Orofacial dystonia
Opisthotonus
Trismus
Caffeine Myoclonic jerking
Carbamazepine Orofacial dystonia
CO Parkinsonism
MAOIs Rigidity
Opisthotonus
Nicotine Flaccid fasciculations
Organophosphates Flaccid Fasciculations
Pethidine Tremor
Muscle jerking
Phencyclidine Generalized rigidity
Trismus
Orofacial dystonia
Twitching
Phenothiazines Orofacial and other dystonias
Phenytoin Choreoatetosis
Strychnine Rigidity
Opisthotonus
Trismus
TCAs Twitching
Myoclonic jerking

DECONTAMINATION

Eye

 If at home: running water, use non-germicidal soap.


 If in ambulance: basin + water

Skin

 Agricultural and industrial substances that are absorbed intradermally:


 Phenol
 pesticides
 aromatic compounds
 To lower down absorption, use COSS.
 Cold water
 O
 Strip off the patient
 Saline solution
Phenolic burns Polyethylene
Phosphorus Copper sulfate
Hydrofluoric acid Calcium gluconate
Coal or tar Mineral oil or petrolatum

Gut
1. Emesis
 Syrup of Ipecac (Cephalis ipecacuanha/acuminata) during 60s and 70s
 MOA: stimulation of Chemoreceptor Trigger Zone (CTZ)
 INDICATION: Conscious and alert poisoned patient who has ingested a
poison not more than 4 to 6 hours earlier.
 Has three main substances:
 Cephaline
 Emetine - responsible for emesis
 Psychotrine – responsible for psychosis
 DOSE: 30mL (adult) and 15mL (child)
 CI:
 Pregnant
 Infants <1yo
 Heart disease
 Patients intoxicated with Digitalis
 Convulsion
 Patient with mental problems
 AE:
 aspiration pneumonia
 cardiotoxicity
 Mallory Weiss tears (resembles stomach ulceration); due to
protracted vomiting
 Not used today due to no assurance of effectivity and has many
contraindication
 Other Emetics
 Apomorphine [SQ]
 MOA: targets CTZ
 DOSE: 6mg (adults) and 1-2mg (child)
 CI: respiratory depression (TCA, BZDs, Barbiturates)
2. Gastric Lavage
 1-2hrs after ingestion
 CI: acid ingestion, coma, sharp substances
3. Catharsis
 CATEGORIES:
a. Saline – MOA: osmotic retention→defacation (ex. D-sorbitol – agent of choice
for catharsis)
 MgSO4
 Mg citrate
 NaSO4
b. Saccharide
 CI: recent bowel surgery, corrosives and electrolyte imbalance
4. Activated charcoal
 MOA: adsorption
 DOSE: 1g/1000m2 of SA or 1g/kg
 AE: pulmonary aspiration, unpleasant taste, & vomiting
5. Whole bowel irrigation
 Using NGT in the stomach that contains solutions like PEG-Electrolyte Lavage
Solution (ELS), specifically PEG-3500
 USES: Cocaine ingestion

Other Decontamination Techniques

1. Hemodialysis
2. Hemoperfusion
3. Peritoneal Dialysis
4. Hemofiltration
5. Plasmapheresis
6. Plasma perfusion
7. Cardiopulmonary Bypass