(From Dr. Nardell’s ANS Physiology Handout, by Brian Buschman)
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All antimuscarinic drugs are competitive antagonists to muscarinic receptors. Atropine and scopolamine block all classes of muscarinic receptors but synthetic antimuscarinics may be specific. Tertiary antimuscarinics (including atropine and scopolamine) only block muscarinic receptors. Quaternary ammonium compounds may block both muscarinic and nicotinic receptors.
The key drugs in this class are atropine and scopolamine as well as the M1-selective blocker pirenzepine.
If we first look at atropine we can see that it first effects the heart and glands of the face (lacrimal, salivary and sweat). As the dose gets higher it will also inhibit the sphincter of the iris and then the ciliary muscle. At an even higher dose it can effect the viscera and the CNS (it can be used to treat Parkinson’s).
1) Low dose – mild vagal stimulation (bradycardia), fatigue, depression of vestibular function, reduction in Parkinsonian tremor. Slight depression of systems that is more prominent with scopolamine then atropine which makes scopolamine a good motion sickness drug.
2) High dose – amnesia, malaise, restlessness, delirium. CNS depression as it’s just not working.
1) At low doses it decreases heart rate due to it’s CNS effects.
2) At high doses it causes tachycardia because of loss of vagal reflex and because of loss of decreased BP due to decreased TPR (see vascular effects). It also causes increased conduction, increases refractoriness and increases contractibility.
1) Low doses only work to antagonize choline esters.
2) High doses cause dilation of cutaneous vasculature (atropine makes you turn red).
Effects are all the opposite of the expected parasympathetic responses. Bronchiodilation, relaxation of the bladder and such.
Pirenzepine being an M1 selective only functions to reduce HCl output from parietal cells.
Sympathetic response. Decreases lacrimation. Relaxation of ciliary muscle which can block the canals of Schlemm which causes glaucoma.
Decreases sweat glands, turn it red and body temperature rises. The most serious toxic atropine effect in infants is hyperthermia.
These are the opposite of the DUM BELS. It’s known as “Mad as a hatter, blind as a bat, read as a beat, dry as a bone, bloated as a toad and hot as hell.”
Toxicity that results is death is usually by respiratory failure. It can be diagnosed with physostigmine (AChE inhibitor). If the symptoms do not go away in this high ACh environment then it must be from failure of the receptors such as with atropine toxicity.
Oral bioavailabilities vary. Tertiary amines enter all tissues but quaternary drugs do not enter the CNS. The ones that block both nicotinic and muscarinics do not do that in the CNS just in the ganglia. Only the muscarinic blockers enter then CNS. Atropine and scopolamine have slightly longer T½ then some of the other drugs.
Atropine is used all over the place
Scopolamine is used for motion sickness and sedation
Homatropine is used ophthalmologicly to cause mydriasis
Cyclopentolate is used ophthalmologicly to cause mydriasis
Tropicamide is used ophthalmologicly to cause mydriasis
Pirenzepine is the selective M1 blocker for GI and GU
Benzatropine helps treat Parkinson’s
Ipratropium is the quaternary amine we need to know that helps treat asthma. It is not as effective as b2 agonists like albuterol but has fewer adverse effects.
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