2 Cholinergic Transmission.ppt

Cholinergic Transmission Parasympathomimetics  Objectives By the end of this section you should be able to: Classify parasympathomimetics into directly and indirectly acting cholinergic agonists. Identify Acetylcholine and Pilocarpine as directly acting cholinergic ago...

Cholinergic Transmission Parasympathomimetics  Objectives By the end of this section you should be able to: Classify parasympathomimetics into directly and indirectly acting cholinergic agonists. Identify Acetylcholine and Pilocarpine as directly acting cholinergic agonists Explain why Acetylcholine is not therapeutically useful Correlate the actions of Pilocarpine to its therapeutic uses Differentiate between the action of directly and indirectly acting cholinergic agonists. Identify Neostigmine as an indirectly acting cholinergic agonist and correlate its actions to its therapeutic uses. List the adverse effects commonly observed with cholinergic agonists List the nursing implications related to use of parasympathomimetic drugs. The Cholinergic Neuron  ACh Receptors There are two main classes of acetylcholine receptors (AChR), 1.Nicotinic acetylcholine receptors (nAChR; N1, N2) 2.Muscarinic acetylcholine receptors (mAChR; M1, M2, M3). They are named for the ligands used to activate the receptors. Cholinergic Neurons and Receptors  Directly Acting Cholinergic Agonists These mimic the effect of ACh by binding directly to cholinoreceptors Examples: Acetylcholine Pilocarpine  1. Acetylcholine It has both nicotinic and muscarinic activity It is therapeutically of no importance because: a. It has a multiplicity of actions b. It is rapidly inactivated by cholinesterase enzyme  Actions of ACh Organ Effect Heart rate Blood pressure Salivary secretion GIT secretion and motility Bronchial secretion Tone of urinary bladder muscles Pupil sphincter muscle Ciliary muscle  2. Pilocarpine It has muscarinic activity applied in ophthalmology When applied topically to the cornea it leads to rapid miosis and contraction of the ciliary body. It is the DOC in emergency Pilocarpine lowering of IOP. Its use has hydrochloride 1% Ophthalmic been limited recently because: Solution  The action of pilocarpine lasts for about one day  The eye undergoes spasm of accommodation and vision is fixed at a particular distance making it impossible to focus  Adverse effects include some CNS disturbances and stimulation of profuse sweating and salivation. II. Indirectly Acting Cholinergic Agonists (Anticholinesterases)  Anticholinesterases e.g. Neostigmine (Prostigmine®), Edrophonium Uses: 1. To stimulate bladder and GIT 2. Myasthenia gravis  Myasthenia gravis "grave muscle weakness" A neuromuscular disease leading to fluctuating weakness and fatigability. It is an autoimmune disorders, caused by circulating antibodies that block acetylcholine receptors at the post- synaptic neuromuscular junction, inhibiting ACh.  Severe myasthenia (myasthenic crisis) may cause respiratory failure due to exhaustion of the respiratory muscles.  Diagnosis of MG Edrophonium test This test requires the intravenous administration of AChE inhibitor drugs that temporarily increases the levels of acetylcholine at the neuromuscular junction. Before In people with myasthenia gravis involving the eye muscles, edrophonium chloride will briefly relieve weakness Edrophonium OR Neostigmine After  Treatment of MG 1.Cholinesterase inhibitors to directly improve muscle function 2.Immunosuppressant drugs to reduce the autoimmune process. Some of the adverse effects observed with cholinergic drugs Cholinergic Transmission Parasympatholytics  Objectives By the end of this section you should be able to: Identify Atropine, Scopolamine and Ipratropium as cholinergic antagonists. Correlate the actions of Atropine and Ipratropium to their therapeutic uses. List the therapeutic applications of Scopolamine Discuss the actions and applications of Botox List the adverse effects observed while using parasympatholytics. List the nursing implications related to use of parasympathlytic drugs. Determine key points for patient and family education on parasympatholytics.  Cholinergic Antagonists Anti-muscarinic Agents: Examples: Atropine Scopolamine Ipratropium  1. Atropine Isolated from Atropa belladonna History Atropine extracts from the Egyptian henbane were used by Cleopatra in the last century B.C. to dilate her pupils, in the hope that she would appear more alluring. In the old days, women used the juice of the berries of Atropa belladonna to enlarge the pupils of their eyes, for cosmetic reasons "belladonna" is Italian for "beautiful lady". Actions: a. Eye: Mydriasis Unresponsiveness to light Cycloplegia In patients with glaucoma, increased IOP b. CVS: At low doses ------- BRADYCARDIA At high doses------ MODEST TACHYCARDIA  Therapeutic Applications a. Ophthalmic: c. Antisecretory; to block Mydriatic and respiratory secretions cycloplegic effect, used prior to surgery to measure refractive errors of the eye d. Antidote for overdose It may induce an attack of glaucoma in of cholinergic agonists susceptible individuals (e.g. poisoning by organophosphate insecticides and nerve b. Used in the gases. management of emergency bradycardia (as a drug in the emergency trolley)  Adverse Effects: Anticholinergic effects May cause confusion, restlessness and hallucinations such as: a.Dry mouth May exacerbate an attack of b.Tachycardia glaucoma in people with latent conditions 2. Hyoscine (Scopolamine) a.Used in High action prevention not treatment of on CNS motion sickness Scopderm ® Actions: Transderm Scop® –Anti-motion b. Used in sickness effect colics as an –Antispasmodic antispasmodi c to relieve absominal pain Buscopan ®  3. Ipratropium (Atrovent®) Blocks muscarinic receptors in the respiratory system leading to bronchodilation. Inhaled to treat asthma in patients unable to take adrenergic agonists.  Inhibition of ACh Botulinumrelease toxin (Botox®) Produced by Clostridium botulinum Used in conditions associated with increased muscle tone, including dystonia and spasticity Hyperhidrosis See this movie: http:// www.medindia.net/animation/botox.asp Pharmacology of Cholinergic Neurotransmission 1 Interference with synthesis Blockage of choline uptake 2 1 2 Release of 5 Neurotransmitter Botulinum toxin – prevents release of vesicles 3 4 3 3 Receptor Stimulation Pilocarpine 4 Receptor Blockade Atropine  Review on Cholinergic Transmission Can you state a therapeutic application for each drug Drug Therapeutic Application Pilocarpine Atropine Neostigmine Ipratropium Scopolamine Thank You 