Transcript
• DR BADAR UDDIN UMAR
DRUGS ACTING ON THE ANS
ANTICHOLINESTERASE POISONING ANTICHOLINERGIC DRUGS
LECTURE - 2
LEARNING OBJECTIVES:
At the end of this session the we shall be able to –• Discuss the clinical features and drug treatment
of organophosphorus poisoning• Explain the role of enzyme reactivators in
organophosphorus poisoning• List and explain the adverse effects and
contraindications of atropine• Discuss the aspects of pharmacokinetics, routes and
dosage of clinically important/ commonly used drugs
ORGANOPHOSPHORUS POISONING
• Poisoning with organophosphorus compounds (OPCs) may occur by –
• Accidental exposure during spraying insecticides or in industry
• Suicidal poisoning
• Homicidal poisoning (rare)
• War gas exposure
OPC POISONING
• Acetylcholine esterase enzymes (AChE) of the body will be destroyed
• Covalent phosphorus-enzyme bond
• Phosphorylation
• There will be massive (Acetylcholine) ACh accumulation in the body…….ACh toxicity
ORGANOPHOSPHORUS COMPOUNDS
• Organophosphates are pentavalent phosphorus compounds containing a labile group such as -
• Fluoride (in dyflos) or an
• Organic group (in parathion and ecothiopate)
• This group is released, leaving the serine hydroxyl group (-SH) of the enzyme phosphorylated
ORGANOPHOSPHORUS COMPOUNDS
• The inactive phosphorylated enzyme is usually very stable
• When phosphorylated by OPCs, AChE have no ability to hydrolyze ACh and
• Recovery of enzymatic activity depends on the synthesis of new enzyme molecules
• This may take weeks
• With ecothiopate, slow hydrolysis occurs over the course of a few days, so that their action is not strictly irreversible
ORGANOPHOSPHORUS COMPOUNDS
• Dyflos and parathion are volatile non-polar substances of very high lipid solubility
• Are rapidly absorbed through mucous membranes and even through unbroken skin and insect cuticles
• Due to this they can be used as war gases or insecticides
Organophosphate Insecticide Action.mp4
SIGNS AND SYMPTOMS OF OPC POISONING:
All s/s are due to ….excessive level of Ach in the body
Muscarinic actions will lead to-
Eye - Constricted pupils (Miosis), blurred vision, eye ache, conjunctival congestion, brow ache
Glands - Profuse Sweating, Salivation, Rhinorrhea & Lacrimation
GIT movement… Nausea, Vomiting, Diarrhea with abdominal cramps
S/S OF OPC POISONING CONT.….DUE TO MUSCARINIC ACTIONS…..
Genito urinary - Urgency for urination and spontaneous voiding and penile erection (in severe case)
Bronchospasm, bronchial secretion Difficulty in breathing
Pulse rate/ Bradycardia
Hypotension
Collapse
SIGNS AND SYMPTOMS OF OPC POISONING CONT.….
Nicotinic effects
• Fasciculation (early)
• Weakness (late)
• Paralysis
• Adrenomedullary discharge (sympathetic, early and transient)
CNS Effects
• Anxiety• Insomnia• Nightmares• Confusion• Tremors• Convulsions• Respiratory depression• Circulatory collapse
S/S OF OPC POISONING FOR EASY REMEMBERING:
DUMBBELLS…… stands for
• Diarrhea• Urgency for Urination • Miosis• Bradycardia • Bronchospasm • Emesis• Lacrimation • Laxation and • Salivation
MANAGEMENT OF OPC POISONING:
The therapy of organophosphate poisoning is known by the catchy acronym - AFLOP:
Atropine
Fluids
Oxygen
Pralidoxime
MANAGEMENT OF OPC POISONING:
General measures:
Termination of exposure by - Removal of clothes etc. that are contaminated
Washing the whole body
Gastric lavage
Cleaning the airways for easy respiration
Oxygen therapy and artificial respiration if needed
IV fluid for correction of dehydration and shock
IV Diazepam for convulsion
MANAGEMENT OF OPC POISONING:
Drugs used in OPC poisoning:
A) Atropine:
It is the antagonist of Ach
It will block the MR &
Will prevent the effects of Ach
MANAGEMENT OF OPC POISONING:
Dose of atropine:1-2 mg IM or IV immediatelyRepeated 5-15 min…..until signs of atropinization
Dryness of mouth Reversal of miosis (mydriasis) HR: above 70/min
MANAGEMENT OF OPC POISONING:
B) Enzyme reactivator / regenerator
Reactivate or regenerate AChE enzyme
So AChE will be free again and metabolize ACh
Oximes -
PAM (Pralidoxime) &
DAM (Diacetylmonoxime)
MANAGEMENT OF OPC POISONING:
Oximes The oxime group (=NOH) has a high affinity for
phosphorous atom
So, can hydrolyze the phosphorylated AChE enzyme
Should be given within 12 hrs. of poisoning, after that can’t be reversed (stabilized by ‘aging’)
AGING OF
ACETYLCHOLINESTERASE
LOSS OF AN ALKYL GROUP FROM PHOSPHORYLATED ACHE “AGES” THE ENZYME
AChE, phosphorylated and inhibited by DFP
“Aged” AChE
“AGING” OF PHOSPHORYLATED- ACHE
ADVERSE EFFECTS OF ATROPINE
ANTICHOLINERGIC DRUG
ADVERSE EFFECTS OF ATROPINE
• Dry mouth
• Blurred vision
• Tachycardia
• Constipation
• Urinary hesitancy and retention
• Atropine poisoning
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CONTRAINDICATIONS OF ATROPINE….
• Glaucoma
• Elderly males with enlarged prostate
• Paralytic ileus
• Ulcerative colitis
• Gastroesophageal reflux
• Tachycardia
• Cardiac insufficiency
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ATROPINE-LIKE DRUGS
• Atropine has got wide-spread effect• So, it produces many side-effects
• There are some Atropine-like synthetic drugs • which are used clinically for different conditions
Atropine-like synthetic drugs
• These drugs have got more effect in that specific purpose &
• has less side-effects than atropine
ATROPINE-LIKE SYNTHETIC DRUGS
• Atropine-like Mydriatic drugs
• Atropine-like antispasmodic drugs
• Atropine-like antiasthmatic drugs
• Atropine-like antiparkinsonic drugs
ATROPINE-LIKE MYDRIATICS:
• Homatropine
• Eucatropine
• Cyclopentolate
• Tropicamide
ATROPINE-LIKE MYDRIATICS:
• Atropine-like synthetic drug
• Duration of action: shorter than atropine
• Effect of atropine lasts for about 1 week
• Effects are like atropine but less side effects
ATROPINE-LIKE MYDRIATICS:
Used in eye for …..• Mydriasis for Funduscopic examination
• Accurate measurement of refractory error…. Specially for un-cooperative patients & young children (ciliary paralysis is required)
• Prevention of synechia (adhesion) formation in uveitis & iritis
ATROPINE-LIKE MYDRIATICS:
Homatropine
Duration : duration about 2-3 days
Cyclopentolate• Duration : duration about 1 day
Tropicamide• More shorter duration of action: 6 hrs.
ATROPINE-LIKE MYDRIATICS:
• Now-a-days, antimuscarinics are less used for opthalmoscopic examination if there is no need of long lasting effect
• Alpha-adrenergic stimulants (e.g., phenylephrine) are used for their short-lasting mydriatic effect, specially for funduscopic examination
ATROPINE-LIKE ANTISPASMODICS:
• Dicycloverine (Dicyclomine)• Oxybutynin
• Propantheline • Hyoscine butylbromide
ATROPINE-LIKE ANTISPASMODICS:
Dicycloverine (Dicyclomine)
• Tertiary amine• More lipid soluble• More absorbed• More CNS effect• Has some direct action on smooth muscle
ATROPINE-LIKE ANTISPASMODICS:
Propantheline
Hyoscine butylbromide
• Quaternary ammonium compound• Less lipid soluble• Less absorbed• Less CNS effect• More appropriate as GIT antispasmodics
ATROPINE-LIKE ANTISPASMODICS:
These are selective … less side-effects
Mainly used for….
• Traveler's diarrhea• Peptic ulcer disease• Spasmodic pain in GIT• IBS (irritable bowel syndrome)
ATROPINE-LIKE ANTIASTHMATIC:
• Ipratropium• Tiotropium (longer duration of action)
Selective effect in bronchus
• Used in bronchial asthma• Given by inhalation in bronchial Asthma
ATROPINE-LIKE ANTIPARKINSONIC DRUGS:
• Benztropine• Orphenadrine• Procyclidine
Selective effect in brain
• Decreases Ach effect in basal ganglia• Decreases tremor, rigidity in parkinsonism
LEARNING OUTCOMES:
• At the end of this session the students will be able to –• Discuss the clinical features and drug treatment of
insecticide (organophosphorus) poisoning• Explain the role of enzyme reactivators and the
importance of ‘aging’ in organophosphorus poisoning• List the adverse effects and contraindications of
atropine and explain the reasons of the same• Discuss the aspects of pharmacokinetics, routes and
dosage of clinically important/ commonly used drugs like atropine
Thank You
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