Atropine

Pharmacokinetics

Because it is a tertiary amine co, atropine is relatively lipid soluble and readily crosses membrane barriers. The drug is well distributed into the CNS and other organs.

The duration of action of normal doses is 4-8 hours except in the eye, where effects last for 72 hours longer  

Pharmacological Effects

The peripheral actions of muscarinic blockers are mostly predictable effects derived from cholinoceptor blockade .

Clinical Uses

The muscarinic blockers have several useful therapeutic applications in the central nervous system, eye, bronchi, gut, and the urinary bladder.   Cardiovascular:RR no specifity to the heart

• Bradycardias and heart block

• Treatment of bradycardia caused by excessive beta-blockers

• Treatment of reflex bradycardia caused by alpha stimulants e.g. noradrenaline   Neurological:

• Motion Sickness: scopolamine is a standard therapy for motion sickness; this drug is one of the most effective agents available for this condition. - A transdermal patch formulation is available.

• Treatment of parkinsonism: benztropine, biperiden, and trihexyphenidyle are representative of several antimuscarinic agents used in parkinsonism.

Eye (Local drops); parasympathetic system predominately on eye

• Fundus examination: Antimuscarinic drugs (Substitutes are better) are used to dilate the pupil and to paralyze accommodation.
• To counteract the effect of miotics
• Iritis and iridocyclitis: Alternatively with miotics to cut recent mild adhesions between the iris and anterior surface of the lens.

  Bronchi: SELECTIVE Muscarinic on respiratory system without presentation of other side effects Ipratropium is a quaternary antimuscarinic agent used by inhalation to reduce bronchoconstriction in asthma and chronic obstructive pulmonary disease (COPD). Although not as effective as beta gonists, ipratropium is less likely to cause cardiac arrhythmias. It has very few antimuscarinic effects outside the lungs because it is poorly absorbed and rapidly metabolized.

Gastrointestinal:

• To relieve spasm in the G.I.T (intestinal colic, spastic colon and biliary colic)
• Muscarinic blockers can also be used to reduce cramping and hypermotility in transient diarrheas.

Bladder:

• symptomatic treatment Cystitis: Glycopyrrolate, and similar agents may be used to reduce urgency in mild cystitis and to reduce bladder spasms following urologic surgery.
• Nocturnal enuresis: emepronium could be used for treatment of nocturnal enuresis and urinary incontinence;
• To releive ureteric spasm in renal colics
• Urinary incontinence; espicially in old female patients

In Pre-Anaesthetic Medication

Atropine is given half an hour before the administration of the general anaesthetic to produce the following:

• Decrease salivary and bronchial secretion:

  • This prevents or minimizes the possibility of inhalation of the salivary secretions preventing the postoperative lung infection.

  • The inhibition of the mucus secretion in the bronchial tree prevents the possibility of blockage of a main bronchus, which could lead to lung collapse.

• Atropine protects the heart from excessive vagal tone, which sometimes occur at the beginning of the first plane of the surgical stage of anesthesia (Stage III).

• Counteracts the inhibitory effect of morphine and the anaesthetic on the respiratory center.

Side Effects

Mild side effects may develop after the use of therapeutic doses for example:

• Dryness of the mouth.
• Skin flushing:
• Children are more susceptible to develop coetaneous V.D which makes the child flushed and this is usually accompanied by slight elevation of body temperature (Due to reduction of sweating) especially in hot environments.
• Retention of urine especially in patients with enlarged prostate.
• Acute attack of glaucoma in patients who have or susceptible to glaucoma.
• • Glaucoma (contraindicated)

Atropine toxicity; Physostigminetreatment

A traditional mnemonic for atropine toxicity is “Dry as a bone, red as a beet, mad as a hatter “. This description reflects both predictable antimuscarinic effects and some unpredictable actions.

In young children Blockade of thermoregulatory sweating may result in hyperthermia or “ atropine fever”. This is the most dangerous effect of the antimuscarinic drugs and is potentially lethal in infants. - infant has no manifestation of infection, with dry mouth, fever due blockage of sweating.   In adults

• Dryness of secretions:
• The condition is described by “dry as a bone “ because sweating, salivation, and lacrimation are all significantly reduced or stopped in the elderly.
• Acute angle – closure glaucoma may occur
• Urinary retention is possible.
• Constipation.
• Blurred vision is common adverse effects in all age groups.
• Full dilatation of the pupil and lost light reflex.  

Treatment of Toxicity (symptomatic)

• Control of environmental temperature and application of cold baths and sponges.
• Cathetrization if necessary.
• Protection of the respiratory system.
• Avoidance of over treatment of convulsions by barbiturates.
• Physostigmine may be used to counteract the CNS effects. Can we use nesostigmine????

The lethal dose in adults is more than 0.5 gm of atropine and more than 0.2 -0.3 gm of scopolamine.