cholinergic drugs _abhijit.pptx

A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed

1. CHOLINERGIC DRUGS Cholinergic drugs are: Drugs that stimulate the parasympathetic system Also called parasympathomimetics – they mimic the effects of the PSNS neurotransmitter Cholinergic agents copy the action of acetylcholine ( ACh ) – a neurotransmitter released from nerve endings that bind on the receptors of cell membranes of organs, tissues, and glands

2. Acetylcholine ( ACh ) an ester of choline , is the neurotransmitter of the parasympathetic system . The nerves that synthesize, store and release ACh are called ‘cholinergic.’

3. There are two types of cholinergic drugs: direct-acting and indirect-acting . Direct-Acting Cholinergic Drugs Bind to cholinergic receptors on specific effector organs, stimulating the organ in a similar way as ACh They are synthetic derivatives of choline Have widespread systemic effects including cardiac muscle, smooth muscle, exocrine glands, and the eye

4. Indirect-Acting Cholinergic Drugs Inhibit the enzyme ‘ acetylcholinesterase ,’ resulting in more ACh available at the receptors These drugs have the added cholinergic effect of improved skeletal muscle tone and strength Indirect-acting cholinergic drugs for Alzheimer’s disease are widely distributed, including to the central nervous system, thus improving cholinergic neurotransmission in the brain

5. Cholinergic drugs may be classified as: IRREVERSIBLE Organophosphorus compounds.

6. ACTIONS OF ACETYLCHOLINE Acetylcholine is taken as the prototype of parasympathomimetic drugs. Muscarinic Actions Muscarinic actions resemble the actions of the alkaloid muscarine found in some mushrooms These actions result from the stimulation of the muscarinic receptors by acetylcholine.

7. Heart The action of ACh is similar to that of vagal stimulation. It depresses the SA node and thereby reduces the heart rate and force of contraction. In larger doses, AV conduction is depressed. Blood vessels ACh relaxes the vascular smooth muscles and dilates the blood vessels of the skin and mucous membrane. The BP falls due to a fall in total peripheral resistance.

8. 3. Smooth muscle ACh increases the tone of all other (non-vascular) smooth muscles. Gastrointestinal tract–tone and peristalsis is enhanced, sphincters are relaxed, resulting in rapid forward propulsion of intestinal contents. Urinary bladder – detrusor contracts and trigonal sphincter relaxes–promotes voiding of urine. Bronchial smooth muscle –contracts resulting in bronchospasm .

9. 4. Secretory glands Acetylcholine enhances the secretions of all glands; salivary, lacrimal , nasopharyngeal, tracheobronchial , gastric and intestinal secretions are increased. Sweating is also increased. Enhanced bronchial secretions and bronchospasm result in severe dyspnoea .

10. 5. Eye Acetylchetine brings about constriction of pupil ( miosis ) by contracting the circular muscles of the iris Stimulation of muscarinic receptors present in the sphincter pupillae results in miosis . Drainage of aqueous humor is facilitated and intraocular pressure falls. Ciliary muscle contracts resulting in spasm of accommodation.

11. Adverse effects Too much cholinergic medication can result in overstimulation of the parasympathetic nervous system, causing unwanted side effects. The acronym  SLUDGE-M  will help us remember the adverse effects of cholinergic drugs. S Salivation L Lacrimation U Urination D Defecation G Gastroenteritis E Emesis M Miosis

12. Other Adverse Effects of Cholinergic Drugs ↓ HR and BP Conduction abnormalities – AV block and cardiac arrest Headache, dizziness, convulsions ↑ bronchial secretions, bronchospasms Overdosing can cause life-threatening problems Antidote for cholinergics is the anticholinergic drug atropine

13. Nicotinic Actions These effects resemble the actions of the alkaloid nicotine and are brought about by stimulation of the nicotinic receptors by acetylcholine.

14. NMJ Acetylcholine brings about contraction of skeletal muscles by stimulating NM receptors present in the neuromuscular junction . Large doses cause persistent depolarisation of skeletal muscles resulting in paralysis. 2. Autonomic ganglia Acetylcholine stimulates the sympathetic and parasympathetic ganglia and the adrenal medulla.

15. 3. CNS Acetylcholine is a neurotransmitter at several sites in the CNS. The important actions of acetylcholine are summarised in Table Actions of acetylcholine CVS ↓HR ↓BP Non-vascular contraction, ↑gut peristalsis, promotes urine voiding Smooth muscle bronchospasm Glands ↑secretion Eye miosis , spasm of accommodation, ↓IOP NMJ muscle contraction Ganglia stimulation

16. Uses Acetylcholine is destroyed in the gut when given orally. On intravenous administration, it is rapidly metabolised by pseudocholinesterases in the plasma and by true cholinesterase at the site of action. Therefore it is not used therapeutically except occasionally as 1% eyedrops to produce miosis during some eye surgeries.

17. Esters of choline are effective orally; carbachol and bethanechol are resistant to both cholinesterases and have a longer duration of action. Their muscarinic actions are prominent with a sustained effect on g.i . smooth muscles and urinary bladder. Methacholine is rarely used. Carbachol is used in glaucoma.

18. Bethanechol may be used in hypotonia of bladder and g.i . smooth muscles and in some cases of postoperative paralytic ileus and urinary retention; It may also be used in xerostomia as an alternative to pilocarpine .

19. Adverse effects include diarrhoea , flushing, salivation, sweating, bradycardia , hypotension, syncope and bronchospasm .

20. CHOLINOMIMETIC ALKALOIDS Pilocarpine is an alkaloid obtained from the leaves of Pilocarpus microphyllus . Like ACh it stimulates cholinergic receptors, but its muscarinic actions are prominent.

21. Its actions on the eye are important–when applied to the eye it causes miosis , spasm of accommodation and a fall in intraocular tension. It also increases sweat (diaphoretic) and salivary secretions ( sialogogue ).

22. Adverse effects When used as eyedrops , burning sensation and painful spasm of accommodation, browache and corneal edema can occur. Long term use can cause retinal detachment.

23. Uses 1. Pilocarpine is used in glaucoma (see below). Pilocarpine ocusert is available and can deliver pilocarpine constantly for 7 days. 2. Pilocarpine is also used alternately with mydriatics like homatropine to break the adhesions between the iris and the lens. 3. It is used to counter dryness of mouth that is seen following radiation of head and neck.

24. Glaucoma Glaucoma is an eye disease characterised by increased intraocular pressure. Aqueous humor is secreted by the ciliary body and it drains through the canal of Schlemn . Rise in intraocular pressure (above 30 mm of Hg) can damage the optic nerve.

25. If untreated, irreversible damage can occur - optic nerve degenerates leading to permanent blindness. Glaucoma is one of the common causes of blindness. Hypertension, myopia and family history of glaucoma are risk factors.

26. Glaucoma is of two types : 1. Acute congestive/narrow angle/closed angle glaucoma—in this, iris blocks the drainage of aqueous humor at the canal of Schlemn leading to increased intraocular pressure. It needs immediate treatment. 2 . Chronic simple/wide angle/open angle glucoma – onset is slow; needs long term treatment. Surgery is the preferred option .

27. Two categories of drugs may be used in the treatment of glaucoma. They are - 1. Drugs that decrease the formation of aqueous humor – Timolol , betaxolol , levobunolol , carteolol , apraclonidine , brimonidine , dipivefrine , adrenaline, acetazolamide , dorzolamide . 2. Drugs that increase the drainage of aqueous humor- Carbachol , pilocarpine , physostigmine , echothiophate , latanoprost .

28. Drugs used in glaucoma are summarised Drugs Adverse effects Comments β blockers Timolol , betaxolol , carteolol , levobunolol Conjunctival irritation, redness and discomfort first line drugs • No miosis -hence no headache or browache Cholinergics • Pilocarpine , carbachol Corneal edema, spasm of accommodation, browache , myopia Used with β blockers Physostigmine , echothiophate Browache , cataract, retinal detachment

29. Drugs Adverse effects Comments Adrenergic agonists Dipivefrine , adrenaline Conjunctival redness, photosensitivity, allergic reactions 2nd line drugs—may be combined with β blockers α2 adrenergic agonists Apraclonidine , brimonidine Conjunctival redness, photosensitivity Higher topical activity than clonidine Carbonic anhydrase inhibitors Acetazolamide , methazolamide , dorzolamide Hypokalaemia , anorexia, drowsiness 2nd line drugs—given orally; slow release acetazolamide is better tolerated; topical dorzolamide is now available - has fewer side effects

30. ANTICHOLINESTERASES Anticholinesterases ( antiChEs ) or cholinesterase inhibitors are drugs which inhibit the enzyme cholinesterase. As their structure resembles that of ACh , they bind to acetylcholinesterases and inactivate them. Acetylcholine Cholinesterase Choline + Acetic acid

31. Thus ACh is not hydrolysed and it accumulates. The actions of all these drugs are due to this accumulated ACh . Hence the actions are similar to cholinergic agonists. The structure of AChE contains an anionic site and an esteratic site

32. Acetylcholine and reversible anticholinesterases bind to both anionic and esteratic sites of the acetylcholinesterase ( AChE ) enzyme. Edrophonium binds only the anionic site and is short acting as the binding is rapidly reversible. OP compounds bind only esteratic site but exception is echothiophate which binds both anionic and esteratic sites

33. Reversible anticholinesterases except edrophonium bind to both anionic and esteratic sites. Edrophonium binds only to anionic site and the binding is quickly reversible—hence it is very short acting. Organophosphates (OP) bind only to the esteratic site but the enzyme is phosphorylated (by covalent bonds) and the binding is stable. With some OPs the binding takes many days to be reversed while with others it is not fully reversible at all.

34. Specific Cholinergic Drugs 1. Direct-acting Bethanechol ( Urecholine ) – ↑ the tone and motility of the bladder and GI tract (should cause urination within 60 min in a pt with urinary retention). Pilocarpine ( Pilocar ) – used to constrict pupils, which ↓ intraocular pressure (glaucoma).

35. 2. Indirect-acting Neostigmine ( Prostigmin ) – given for the diagnosis and treatment of myasthenia gravis—it causes skeletal muscle contractions. Donepezil (Aricept) – used to treat mild-moderate Alzheimer’s disease—it ↑ ACh in the brain and helps ↑ or maintain memory or learning capabilities (it manages the symptoms, but is not a cure).

36. Contraindications to using cholinergic drugs Asthma Hyperthyroidism Peptic ulcer Coronary artery disease Cholinergic drugs can exacerbate these conditions and should be avoided.

37. Nursing Considerations for Cholinergic Agonists Here are important nursing considerations when administering cholinergic agonists: Nursing Assessment These are the important things the  nurse  should include in conducting  assessment , history taking, and examination: Assess for contraindications or cautions (e.g. history of allergy to drug, GI obstruction, pregnancy or lactation status, etc.) to avoid adverse effects.

38. Establish baseline physical assessment to monitor for any potential adverse effects. Assess orientation, affect, reflexes to monitor CNS drug effects. Assess vital signs, especially pulse and  blood  pressure to monitor for possible excess stimulation of the cardiac system. Assess abdomen, auscultating for bowel sounds and palpating for distention. Monitor  intake and output , noting any complaints of urinary urgency to monitor for drug effects on the  urinary system .

39. Administer oral drug on empty stomach to decrease nausea and vomiting. If drug is given intravenously, administer slowly to avoid severe cholinergic effects. Monitor patient response closely (e.g.,  blood pressure , ECG, urine output) to arrange to adjust dose accordingly to ensure the most benefit. Maintain a cholinergic-blocking drug on standby such as  atropine  to use as an antidote for excessive doses of cholinergic drugs

40. Discontinue drug if excessive salivation, diarrhea, emesis, or frequent urination becomes a problem to decrease the risk of severe adverse reactions. Provide safety precautions if the patient reports poor visual acuity in dim light to prevent  injury . Provide comfort measures (e.g., quiet room, support and relaxation measures) to help patient cope with drug effects. Provide patient education about drug effects and warning signs to report to enhance knowledge about drug therapy and promote compliance.