Therapeutics Problems

DR.SUKANTA SEN
Professor
Dept. of Pharmacology
 Clinical features of organophosphorus
pesticide poisoning
Features due to overstimulation of muscarinic
acetylcholine receptors in the parasympathetic system
• Bronchospasm
• Bronchorrhoea
• Miosis
• Lachrymation
• Urination
• Diarrhoea
• Hypotension
• Bradycardia
• Vomiting
• Salivation
• Features due to overstimulation of nicotinic
acetylcholine receptors in the sympathetic
system
• Tachycardia
• Mydriasis
• Hypertension
• Sweating
• Features due to overstimulation of nicotinic
and muscarinic acetylcholine receptors in the
CNS
• Confusion
• Agitation
• Coma
• Respiratory failure
• Features due to overstimulation of nicotinic
acetylcholine receptors at the neuromuscular
junction
• Muscle weakness
• Paralysis
• Fasciculations
• Diagnosis of organophosphorus poisoning should

ideally be confirmed with an assay to measure

butyrylcholinesterase activity in plasma (or

acetylcholinesterase in whole blood).

• However, the results of such assays are rarely

available in time to affect clinical decision making.

• Check airway, breathing, and circulation. Place patient in the
left lateral position, preferably with head lower than the feet, to
reduce risk of aspiration of stomach contents.

• Provide high flow oxygen, if available.

• Intubate the patient if their airway or breathing is compromised

• Obtain intravenous access and give 1–3 mg of atropine as a

bolus, depending on severity.

• Set up an infusion of 0・9% normal saline; aim to keep the

SBP above 80 mm Hg and urine output above 0・5 mL/kg/h
• Record pulse rate, blood pressure, pupil size, presence of
sweat, and auscultatory findings at time of first atropine dose

• Give pralidoxime chloride 2g (or obidoxime 250 mg)

intravenously over 20–30 min into a second cannula; follow
with an infusion of pralidoxime 0・5–1 g/h (or obidoxime 30
mg/hr) in 0・9% normal saline.
• 5 min after giving atropine, check pulse, blood pressure,
pupil size, sweat, and chest sounds.
• If no improvement has taken place, give double the original
dose of atropine
• Continue to review every 5 min; give doubling doses of
atropine if response is still absent.
• Once parameters have begun to improve, cease dose
doubling. Similar or .smaller doses can be used
• Give atropine boluses until the heart rate is more than 80 beats
per minute, the SBP is more than 80 mm Hg, and the chest is
clear (appreciating that atropine will not clear focal areas of
aspiration).

• Sweating stops in most cases.

• A tachycardia is not a contraindication to atropine since it can

be caused by many factors.

• The pupils will commonly dilate; however, this sign is not a

useful endpoint for initial atropine treatment because a delay
exists before maximum effect.

• However, very dilated pupils are an indicator of atropine

toxicity
• Once the patient is stable, start an infusion of atropine giving every
hour about 10–20% of the total dose needed to stabilise the patient.

• Check the patient often to see if too much or too little atropine is being
given.

• If too little is given, cholinergic features will re-emerge after some

time.

• If too much is given, patients will become agitated and pyrexial, and
develop absent bowel sounds and urinary retention.

• If this happens, stop the infusion and wait 30–60 min for these features
to settle before starting again at a lower infusion rate

• Continue the oxime infusion until atropine has not been needed for
12–24 h and the patient has been extubated.
Acute AC:
• Immediate medical therapy in acute AC consists of commencing IOP-
lowering eye medications such as topical β-blocker, α2-agonist and even
prostaglandin analogues as soon as possible.

• Once the IOP is sufficiently reduced to allow iris reperfusion,

pilocarpine is instilled to induce miosis in an attempt to widen the anterior
chamber angles and reestablish aqueous outflow.
• (Pilocarpine should, however, be avoided in cases where it may
exacerbate pupil block, such as in pseudoexfoliation, phacomorphic
glaucoma and aqueous misdirection, i.e., where AC is secondary to lens-
induced or retro-lenticular mechanisms.)
• In addition, intravenous or oral acetazolamide 5–10 mg/kg
[alternatives: hyperosmotic agents, e.g., intravenous 20% mannitol
1–2 g/kg, oral 50% glycerol 1–1.5 g/kg (contraindicated in
diabetics), oral isosorbide 1.5–2.0 g/kg] is often useful in helping
to lower the IOP and hastening resolution of corneal edema so that
a laser peripheral iridotomy can be definitively done.

• Acetazolamide should be given as a stat dose of 500 mg IV

followed by 500 mg PO.

• Topical steroids help to reduce intraocular inflammation, while

analgesics and anti-emetics help make the patient more
comfortable, until laser peripheral iridotomy is done.
• Inflammation is an important part of the pathophysiology and
presenting symptomology. Topical steroids decrease the
inflammatory reaction and reduce optic nerve damage.

• The current recommendation is for 1-2 doses of topical

steroids.

• Placing the patient in the supine position may aid in comfort

and reduce IOP. It is also believed that, while supine, the lens
falls away from the iris decreasing pupillary block.
• After the initial intervention, the patient should be reassessed.
• Reassessment includes evaluating IOP, evaluating adjunct
drops, and considering the need for further intervention, such as
osmotic agents and immediate iridotomy.
• Approximately 1 hour after beginning treatment,
pilocarpine, a miotic that leads to opening of the angle, should
be administered every 15 minutes for 2 doses.
• In the initial attack, the elevated pressure in the anterior
chamber causes a pressure-induced ischemic paralysis of the
iris. At this time, pilocarpine would be ineffective.
• During the second evaluation, the initial agents have decreased
the elevated IOP and hopefully have reduced the ischemic
paralysis so pilocarpine becomes beneficial in relieving
pupillary block.
• No standard rate of reduction for IOP exists; however, Choong
et el identified a satisfactory reduction as IOP less than 35 mm
Hg or a reduction greater than 25% of presenting IOP.

• If the IOP is not reduced 30 minutes after the second dose of

pilocarpine, an osmotic agent must be considered.

• An oral agent like glycerol can be administered in non-diabetics.

In diabetics, oral isosorbide is used to avoid the risk of
hyperglycemia associated with glycerol.

• Patients who are unable to tolerate oral intake or do not experience

a decrease in IOP despite oral therapy are candidates for IV
mannitol.
• Hyperosmotic agents are useful for several reasons.

• They reduce vitreous volume, which, in turn, decreases IOP.

• The decreased IOP reverses iris ischemia and improves its

responsiveness to pilocarpine and other drugs.

• Osmotic agents cause an osmotic diuresis and total body fluid

reduction.

• They should not be administered in cardiovascular and renal

patients.

• Choong et el demonstrated that 44% of patients required the

addition of an osmotic agent to decrease IOP. Repeat doses may be
necessary if no effect is seen and if tolerated by the patient.