ZAPORIZHIA STATE MEDICAL UNIVERSITY

PHARMACOLOGY DEPARTMENT

LECTURE 10

Adverse Drugs Reactions.

Principles of Treatment
of Acute Poisoning with Drugs
Requirements of the WHO for medicines

Effectiveness

Safety
Availability for a patient
 Adverse Drugs Reaction (ADR) -

any response to drug that is noxious and

unintended and that occurs at doses used in
man for the prophylaxis, diagnosis or
therapy of disease or for modification of
physiological function (WHO).

It excludes ADRs due to Drug Overdose (Poisoning),

Drug Abuse and Therapeutical Errors.
 STATISTICS
Mortality from Adverse Effects (AEs) of Drugs
(excluding medical errors and malusage)
takes the 5 place after:
Cardiovascular diseases
Cancer
Respiratory organs diseases
Traumas
AEs as the reason for hospitalization: 4,2 6%
Frequency of AEs in hospitalized patients: 5-35%
The drug administration may result
in the development of:

Side effects
Untoward effects
Toxic effects
Allergic and idiosyncratic effects
 Adverse Drugs Reaction (ADR)

1) Quantitative Intolerance (Type A )

2) Qualitative Intolerance (Type B)
a) Idiosyncrasy (Genetic / Unknown
mechanism)
b) Allergy (Immunological):
Types I, II, III and IV
Oxygen, Naloxone, Glucose, and Thiamine
should be administered for those patients
found with Altered Mental Status.

Physical and chemical restraints

Tranquilizers or Neuroleptics
should be used for agitated patients.
Gastric decontamination includes gastric
emptying, adsorption of the toxin in the
gut, and irrigation of the bowel.
Activated charcoal (1 g/kg) should be
administered to bind any remaining toxin.
Saline cathartics (MgSO4) given 30 min
after activated charcoal to reduce transit
time through the GIT.
 Agents for General Management

I. EMETICS.
1. Act directly on Chemoreceptor Trigger Zone:
Apomorphine hydrochloride amp 1% - 1 ml
SC 0.2-0.5 ml
2. Act reflexly on CTZ:
Ipecacuanha
 II. Adsorbents: Activated charcoal

III. Alkalinizing Agents:

Correction of metabolic acidosis
Restore acid-base balance

Sodium bicarbonate (4% - 50 ml) -

=> Alkalizes Urine interfering with
the Renal Tubular Reabsorption of Organic Acids
(Aspirin, Phenobarbital) and their excretion

Trisamine (Trimethamine - 3.66%-250 ml) -

a systemic Na+ free alkalinizer
 FORCED DIURESIS
1.Water load:
5% Glucose
Polyglucin
Neohemodes 1.0-1.5 L
2. Fast Introduction of a Power Diuretic:
Furosemide 1%-6-8 ml IV or
Mannitol 15-20% - 200-400 ml IV infusion

3.Substitutional Infusion of Electrolyte Solutions:

Ringer-Locke solution 200-400 ml I
 HEAVY METAL POISONING

Metal Antagonists:
Trilon B (EDTA)
Pentacin
Tetacinum-Calcium (CaNa2 EDTA)
Penicillamine
Deferoxamine

=> form non-toxic water soluble compounds

with Bivalent and Trivalent Metals,
which are fast excreted from organism
 Unithiol and Natrii Tiosulfate -
contain active SH-groups, which are bound with
Thiol Poisons in blood and tissues and are forming
non-toxic complexes, excreted with urine.
Poisons inactivation restores and activates function
of enzymatic system in organism.

Deferoxamine chelates iron by binding Fe3+

to the 3 Hydroxamic Groups of the molecule
 Adrenaline
BP, Venous Pressure, heartbeating,
severe anxiety, nausea and vomiting, respiratory
distress, large pupils, expressed paleness and
coldness of skin, pulmonary edema, renal failure,
metabolic acidosis.
Treatment: symptomatic and supportive measures
as Adrenaline is rapidly inactivated in the body.
-Adrenoblockers Phentolamine and Tropaphene
for hypertension;
-blocker Anapriline for arrhythmias.
 Noradrenaline
BP, photophobia, retrosteranal or pharyngeal
pain, intense sweating, vomiting,
cerebral hemorrhage, convulsions,
cardiac arrhythmias.
Treatment:
Atropine sulfate for reflex bradycardia,
Phentolamine for exravasation,
Anapriline for arrhythmias.
Mesatone (Phenylephrine)
palpitation, BP, ventricular extrasystoles and
other cardiac arrhythmias, myocardial infarction,
excitability.
Treatment:
-adrenoblockers: Phentolamine
-blocker Anapriline for arrhythmias
 Nitroglycerine
Vasodilation and Methemoglobinemia:
BP, Intracranial Pressure with Confusion,
throbbing headache, palpitations, visual
disturbances, flushing of the skin, sweating (with
skin later becoming cold and cyanotic),
bloody diarrhea, initial hyperpnea, dyspnea,
bradycardia, heart block, fever, paralysis, tissue
hypoxia (from methemoglobinemia) - cyanosis,
and metabolic acidosis, coma, clonic seizures and
circulatory collapse.
Death may result from circulatory collapse or
asphyxia.
Antidotes:
Glucose 5%-500ml +Ascorbinic acid 5%-10-15 ml,
Methylene blue (1% - 7-10 ml) or
Chromosmon -1% Methylene Blue in 5%Glucose
Symptomatic treatemnt:
Sodium hydrocarbonate, Trisamine,
Sulfocamphocaine (10% 3-4 ml), Mesatone,
Noradrenaline hydrotartrate 0.2% 1 ml
in Glucose 5% 500 ml IV infusion
 Aminazine (Chlorpromazine)
CNS depression: deep sleep, coma, BP and t,
abnormal involuntary muscle movements, agitation,
seizures, arrhythmias
Treatment: IV fluids,
Adrenaline is not given !!!
Strophanthine 0.025%1 ml in 20 ml 0.9% NaCl IV;
Prednisolone, Hydrocortisone
Seizures are treated with parenteral
Diasepam or GOBA;
Arrhythmias with Difenin;
Extrapyramidal reactions -
with Biperidine or Dimedrole (Diphenhytdramine)
 Clozapine [non-typical Neuroleptic]
Drowsiness, Sedation, Delirium, Coma, BP, HR,
hypersalivation, Respiratory Depression, Seizures.
Treatment:
Hypotension is treated with IV fluids,
Strophanthine 0.025% 1 ml in 20 ml 0.9% NaCl IV,
Prednisolone or Hydrocortisone.
Avoid Adrenaline and derivatives!!!

Seizures are treated with Diazepam or GOBA;

Arrhythmias with Difenin;
Extrapyramidal reactions with Biperidine or
parenteral Dimedrole (Diphenhytdramine)
 Butadione (Phenylbutazone)
GIT discomfort, Oliguria, Hematuria, Acute
Renal Failure, Seizures, Enhanced
Excitability, Collapse, Hyperthermia,
Hemorrhagic Purpura.
Treatment : Gastric Lavage, Activated
charcoal via nasogastric tube,
Symptomatic and Supportive measures
(respiratory support and correction of fluid
and Electrolyte Imbalances).
Antidotes:
 Atropine
Dose (g) General Symptoms

0.0005 HR, Dry Mouth, Photophobia, Thirst,

Eye Dryness, Conjunctivitis
0.001 HR, Increased Intraocular Pressure,
Mydriasis, Constipation
0.003
t , Restlessness, Ataxia, Disorientation, Urine
0

Retention, Abdominal Distention

0.007 Blurred Vision, Depression of all secretion's kinds,
Confusion
0.008 Agitation, Motional Discoordination,
Maximal Mydriasis

0.01 Apathy, Hallucination, Delirium, Unconsciousness

Treatment:
Antidotes Physostigmine 0.1%-1 ml or
Proserine (Neostigmine) 0.05%-1 ml SC,
General supportive measures
gastric lavage with 0.01% KMnO4 - 10-15 L
Activated charcoal via nasogastric tube.
For discontinuance of psychomotor excitability
Aminazine (2.5% 2 ml) or Diazepam (0.5% 2 ml).
Forced diuresis: equally 1.5 L of Isotonic Solution
and 5% Glucose, then Lazix 1% 8-12 ml IV
 Pachycarpine hydrobromide
Dizziness, blurred vision, BP, HR,
decreased bronchial secretion, dyspnea,
muscular fibrillation, Cardiovascular Collapse,
Respiration Center Paralysis.
Treatment:
Proserine or Galanthamine,
Vitamine B1
Ephedrine, Adrenaline, Noradrenaline,
Cordiamin
Dobutamine
Strophanthine
 PHOS (Anticholinesterases of Irreversible Action)
Tremor, syncope, miosis, blurred vision,
bronchospasm, increased bronchial secretions,
excessive sweating, muscle weakness, cramps,
paralysis, restlessness or agitation, bradycardia,
hypotension, arrhythmias, diarrhea, nausea,
vomiting, abdominal pain, excessive salivation,
lacrimation, urinary incontinence.
Treatment:
Atropine 0.1% 2-5 ml IV
Cholinestrase Reactivators
Alloxime or Dipyroxime or Isonitrozine,
Forced diuresis, Caffeine 10% - 2 ml;
Ethanol 40% 50-100 ml.
 Propranolol (Anapriline)
BP, HR, Heart Failure, Bronchospasm, AV block,
Intermittent Claudication, Marble Paleness,
Extremity Coldness,
nausea, vomiting, diarrhea, abdominal cramping,
cardiovascular collapse.

Treat bradycardia with Atropine, Ephedrine, Isadrine.

Cardiac failure - with Strophanthine and Furosemide
Hypotension - with Dobutamine, Dopamine, Adrenaline
Treat bronchospasm with Euphylline.
 Digitoxine
GIT, CNS and Cardiac Reactions: anorexia, nausea,
vomiting, diarrhea, fatigue, muscle weakness,
agitation, hallucination, arrhythmias (AV block,
ventricular extrasystoles); hypotension;
Yellow-Green halos around visual images,
blurred vision, light flashes, photophobia, diplopia,
K+ and Ca2+
Antidotes :
Atropine, KCl, Panangin,
Trilone B, Unithiole ,
MgSO4, Cholestyramine ,
Phenytoin (Diphenine) or Lidocaine,
Novocainamide - for Ventricular arrhythmias that
do not respond to the above treatments.
 Morphine
Respiratory Depression, CNS Depression,
Miosis (pin-point pupils), BP, HR, to, Shock,
Apnea, Cardiopulmonary arrest, Circulatory Collapse,
Pulmonary Edema, Convulsions; skin is bluish and
cold, face is pale, Urine retention, bladder overflowed.
Treatment:
Narcotic Antagonist Naloxone 0.04% 1 ml;
Gastric lavage with 0.01% KMnO4 or 0.2% Tannin;
Cordiamin 1-2 ml SC or IV,
Caffeine 10% - 2 ml
Strophantine 0.05% - 0.5 ml,
Forced diuresis is effective
 Phenobarbital
unsteady gait, slurred speech, sustained
nystagmus, somnolence, mental confusion,
respiratory depression, pulmonary edema, areflexia,
and coma, jaundice, BP, HR, to, oliguria.
Treatment: Bemegrid, Cordiamin, Caffeine,
Sulphocamphocaine
Narcotic antagonist Naloxone
Vitamine B1 , B6 and B12 for treatment hypoxic
damage of the brain.
Detox therapy includes forced diuresis
with osmotic diuretics Mannitol with following
alkalinization of urine
 Clopheline (Clonidine) [2-agonist]
BP, HR, to, CNS and, respiratory depression,
apnea, seizures, lethargy, irritability.
Treatment:
Gastric lavage, activated charcoal.
Vasopressors Mesatone, Norepinephrine,
1 AM Dobutamine
Analeptics Cordiamin, Caffeine
 Novocaine
Convulsions, Respiratory depression, BP, HR,
AV conduction delay, AV block,
Ventricular fibrillation, cyanosis, oliguria,
confusion and lethargy, coma, collapse.
Treatment: Respiratory and CV support.
Diazepam or GOBA to treat any convulsions.
Vasopressors including Norepinephrine
 Ethanol.
Blood Alcohol Clinical Effect
Concentration (g/L)
0.5-1 Sedation, subjective high,
increased reaction time
1-2 Impaired Motor Function,
Slurred speech, Ataxia
2-3 Emesis, Stupor

3-4 Coma

>5 Respiratory depression, death

 ANTISHOCK THERAPY:
Plasma substitutes: Polyglucine,
Neohemodese,
Rheopolyglucine
Glucose 5% - 400 ml,
NaCl 0.9%-400 ml
Cardio-vascular agents:
Dopamine, Dobuamine
Cordiamine, Ephedrine, Strophanthine
Vasopressors: Mesatone and Norepinephrine
Glucocorticoids: Prednisolone 60-100 mg
Hydrocortisone 125 mg
 Heparin
Antidote: Protamine sulfate 1% 5 ml IV or IM.
Acidum Aminocapronicum 5% 100 ml PO or IV
Calcium Chloride or Calcium Gluconate
Prednisolone or Hydrocortisone,
Vitamins C and P.
Neodicumarine
Antidote: Vicasole (vitamine K) 1%-1 ml,
Fresh Frozen Plasma or Whole Blood
 Dimedrole (Diphenhydramine)
Drowsiness, seizures, coma, respiratory depression,
Anticholinergic symptoms - dry mouth, flushed skin,
fixed and dilated pupils, and GIT symptoms

Treat hypotension with cardio-vascular agents:

Dobutamine, Strophanthine, and control seizures
with Diazepam. Do not give stimulants.
 Sulfadimesine
Dizziness, Drowsiness, Headache, Anorexia,
Nausea, vomiting, Hemolytic Anemia,
agranulocytosis, dermatitis, acidosis, sensitivity
reactions, jaundice

Treatment: gastric lavage, forced diuresis.

Transfusion of Fresh Frozen Plasma or Whole
Blood, Folic acid to rescue bone marrow.
 Isoniazid
nausea, vomiting, slurred speech, blurred vision,
visual hallucinations, CNS depression from stupor to
coma, with respiratory distress, seizures
Treatment: gastric lavage,
control seizures with Diazepam,
Pyridoxine (Vitamine B6)
initial dose 1-4 g (20-80 ml 5% Pyridoxine) IV,
followed by 1 g every 30 min thereafter, until the
entire dose is given.
 Quinine
Ringing in ears, tinnitus, vertigo, fever, rash,
Cardiovascular effects: BP, HR, AV
block,
GI distress: diarrhea, nausea, vomiting;
Blindness, apprehension, confusion,
seizures.
Treatment: gastric lavage,
Fluid and electrolyte replacement,
stabilization of BP and renal function.
 Co-trimoxazole
Clinical manifestation: mental depression,
drowsiness, anorexia, jaundice, confusion,
headache, nausea, vomiting, diarrhea, facial
swelling, slight elevations in liver function test
results, bone marrow depression.

Treatment: emesis or gastric lavage, correction of

acidosis, forced oral fluid, and IV fluids.
Transfusion of appropriate blood products in severe
hematologic toxicity;
Folic acid is used to rescue bone marrow.
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