Pharmacology Lecture 6 PDF

PHARMACOLOGY 1 DONE BY LECTURE 6 LAYAN BADER SARA AL-ASMAR EMAN AL-MALAKH  ‫اضية‬0‫حاضرة ا‬0‫مراجعة سريعة )هم نقاط ا‬ We talked about cholinergic agonists Which are divided into Direct drugs : they...

PHARMACOLOGY 1 DONE BY LECTURE 6 LAYAN BADER SARA AL-ASMAR EMAN AL-MALAKH  ‫اضية‬0‫حاضرة ا‬0‫مراجعة سريعة )هم نقاط ا‬ We talked about cholinergic agonists Which are divided into Direct drugs : they bind to either muscarinic or nicotinic receptors. (And we discussed muscarinic agonists ) Indirect drugs: they don’t do anything with the receptors. They just block the enzyme that breaks Ach ‫ في كل‬Ach ‫وبالتالي بزيد كمية‬ muscarinic ‫الجسم سواء عند‬ or nicotinic receptors  nicotinic drugs ‫ ورح نحكي عن ال‬direct drugs ‫ رح نكمل عن ال‬F‫ه‬ Drugs that are nicotinic agonists have very limited use ‫استخدامهم‬ ‫ قليل و محدود‬, why ? ‫ستقبل وحفزه‬0‫إذا أخدنا الدوا وارتبط ا‬ the autonomic nervous ‫ت بعيدة صعب‬S‫ستقب‬0‫أماكن ا‬ system with both its divisions(sympathetic and ‫يوصله الدوا‬ parasympathetic)will be also the drug has to have stimulated certain characteristics such as being very lipophilic , and very small in size ‫حتى‬ ‫ وممكن لو‬، ‫ت‬S‫ستقب‬0‫يوصل مواقع ا‬ nicotinic ‫طبيعة ال‬ ‫أخدنا من الدوا رح يلف الجسم‬ rapid ‫ انه بصيرلهم‬receptors ‫كامل وكمية قليلة الي توصل أو‬ ‫ كيف؟‬، desensitization ‫ممكن ما يوصل‬ V  " : ‫وضوع انه‬0‫ا‬ When nicotine binds to its receptor , sodium ion channels open , causing depolarization. (‫) بصير تحفيز‬ continuous administration ‫ ومع‬receptor ‫بعدها و بطبيعة ال‬ Desensitization will occur ‫ستقبل يتحسس وجود الدوا‬0‫و ببطل ا‬ ‫ا بناخدها غالبا بناخدها‬0 ‫ )نه ا)دوية‬، ‫عشان هيك ما بزبط ان الدوا‬ ‫ رح يكون في استجابه لكن بعد هيك ما‬p‫ فأول يوم أو يوم‬، ‫بشكل يومي‬ E ‫رح يفيد الدوا )نه بصير في‬ Desensitization of the receptor And that’s why, nicotine agonists aren’t produced But! There is a certain substance that’s used as a nicotine agonist ‫ادة عبارة عن مستخلص‬0‫ وهاي ا‬، ‫وجودة في الدخان‬0‫ ا‬tobacco ‫وهي مادة ال‬ ‫نباتي‬  There are nicotinic receptors in the brain but there is a dominant one called α4β2. When people smoke cigarettes, nicotine reaches the brain by the smoke that’s inhaled. Then it gets to the receptors and binds to them. Why people like to smoke or are addicted to it ? When nicotine receptors (α4β2) are stimulated , dopamine is released, which gives a feeling of alertness and pleasure. ‫ بسبب تأثيره مرة بدمن الشخص‬، " ‫ هو "ادمان سلوكي‬p‫دمان على النيكوت‬s‫ا‬ ‫عليه‬  But , how could nicotine be used to cease smoking?! We said when nicotine receptors are stimulated, dopamine is released, then after a while the receptors become desensitised. ‫ بالعادة ما يدخنون لفترات طويلة ورا بعض )نه بروح تأثير‬p‫دخن‬0‫ ا‬F‫ه‬ ‫ فبكون بينهم فترات وبالتالي بعد كل فترة برجع بصير في‬، p‫الدوبام‬ stimulation for the receptors continuous“ ‫ لفترات متواصلة‬nicotine p‫دخن‬0‫طيب لو أعطيت ا‬ “ nicotine administration ‫ )والي‬vape ‫( أو ال‬p‫ )لزقات النيكوت‬nicotine patches ‫متل ال‬ ‫ رح يصير في‬، p‫(أو حتى علكة النيكوت‬ ‫ج‬S‫ مفروض للع‬S‫هي أص‬ continuous nicotine in the blood Continuous stimulation of the receptors receptors ‫بصير لل‬ No release for Desensitization dopamine ‫ببطل الشخص يستمتع فيها‬ And eventually by time the person will stop smoking  · 5218159085. ~ L 92-015 nicotine JI from the Skin then it enters the blood.  > - an example of medications used to help stop smoking. S serious effects.  Inhibitors of Acetylcholinesterase Indirect acting cholinomimetics ‫ هاي ا)دوية ما بتميز إذا عنا‬، indirect ‫ نيجي )دوية ال‬F‫ه‬ muscarinic or nicotinic receptors that it block the enzyme that breaks‫دوية‬s‫والي بتعمله هاي ا‬ Ach ‫ الي‬Ach agonists ‫ زي تأثير ال‬organs‫تأثير هاي ا*دوية عال‬ ‫ت‬F‫ لكن زيادة عليهم انه في تأثير على العض‬، ‫حكينا عنهم قبل‬ Causes contraction in the muscles. paralysis in the muscle ‫و زيادة هاي ا*دوية بعمل‬ due to excessive contraction.  -(515-01- l ‫ بكون في‬cholinesterase inhibitors (indirect) ‫في ال‬ ‫مجموعات كيميائية معينة‬ carbamates Organophosphates quaternary ammonium =41Js (NH4 ) + b Jd1561 = /. which increases : +S ,/ the lipophilicity · 3j & II. S ·  ~ We have nicotine receptors in the CNS , so it will be stimulated too. But overstimulation of the brain causes a coma C ↳ - al jis y excessive alertness Causes Coma.  so direct ‫ مشابه لتأثير ال‬indirect ‫تأثير أدوية ال‬ Eyes → miosis will happen, so indirect drugs could be used to treat glaucoma Respiratory system → constriction GIT → increase in motility ‫ت‬9‫ عالعض‬indirect ‫كمان حكينا عن تأثير أدوية ال‬ At higher concentrations,desensitization of nicotine receptors in the neuromuscular junction will happen. Which then might cause paralysis or fasciculation  · 05e S If a high dose of atropine (or drags with the same action) is given, -atropine intoxication - we give indirect cholinomimetics such as physostigmine which increases Ach concentration.  Myasthenia gravis ‫ت‬S‫وهن العض‬: disease that causes muscle weakness ‫ ويعمل‬Ach ‫*نه بدل ما يرتبط‬، ‫ت‬F‫بصير في ارتخاء في العض‬ ‫ بتيجي بترتبط‬antibodies ‫ في‬،‫ت‬F‫ في العض‬contraction ‫رتباط‬T‫ بصير غير قادر على ا‬Ach ‫ فال‬، ‫بداله‬ leading to weakness, especially in muscles that control eye movement, facial expression, chewing, and swallowing. ‫طراف‬1‫و بعمل صعوبة في تحريك ا‬ ‫ج ؟‬9‫شو الع‬ pyridostigmine (or neostigmine ) ‫ج هاد ا@رض انه نعطي‬9‫ع‬ ‫ وبالتالي بزيد‬AchE(acetylcholinestrase) ‫هاي ا*دوية بتكسر ال‬ ‫ت فبنافس ال‬F‫ وبكون متوفر بكميات اكبر عند ا[ستقب‬.Ach‫تركيز‬ contraction of the ‫ وبرجع ال‬Ach ‫ وبرتبط ال‬antibodies muscles  has the same effect of muscarine receptor agonist +muscle contraction nicotine receptor agonist example: varenicline (chantix) sphincter muscle construction (miossis) eye ciliary muscle construction (accommodation to near vision) — treatment of glaucoma decrease the heart reat and contractility negative heart has both musicarinic and nicotinic effect dromotropy quaternary ammonium blood vessels vasodiation carbonated types bronchoconstriction are used in pesticides lung organophosphate parasympatomimmic drugs (muscarine agonist) effect bronchial gland secretion muscarine receptor stimulation (parasympatomimmic) increase molality nicotine receptor stimulation (ganglia +skeletal muscle) gi increase secretion effect it may cause paralysis if take in high conc relaxation of sphincter over stimulation cause coma stimulation CNS Cholinesterase-inhibitors (indirect ) cholinaregic agonist drugs cholimimmice drugs (direct) glands secretion edrophonium detrusor — contraction neostigmine urinary bladder examples trigonometry and sphincter — relaxation pyridostigmine nicotine physostigmine muscarine treatment of myasthenia gravis cholinmimmice alkaloids uses pilocarpine improve cognition for Alzheimer patients lobeline treated by atropine cholinaregic crisis types acetylcholine methacholine choline esters carbachol bethaechol NVD, urinary urgency, salivation , sweating, treatment:1) cholinaregic antagonist like atropine 2) toxicity vasodilation ,bronchial construction support respiratory and cv systems New topic Cholinoceptor-blocking drugs Here, the effects are exactly the opposite of the agonist effects. CNS: remember, M receptor agonists —> stimulation. Here, M receptor blockers cause a sedative (a kind of depression) effect. Eye: causes relaxation of the eye muscles, so it is contraindicated for glaucoma patients. We use it when we perform eye tests in the clinic to be able to see the retina through specialized tools. Bronchi: causes dilation, used for asthma and COPD patients. GIT: causes reduced activity, used for diarrhea patients. Genitourinary tract: decreases the urine outflow by relaxation of detrusor muscle, used for children that suffer from urinary incontinence at night. Glands: reduction of secretions in saliva, lacrimation, sweat, but has no effect on gastric acid secretions (ex: botulinum toxins are gland M receptor blockers that are used to treat excessive sweating disorder). It is contraindicated for patients that suffer from stomach ulcer that is a result of acid secretion  ‫ يعني تبع ا(غص بخليه‬،‫ تبع ا(غص بس الفرق هون با(لح‬scopolamine‫هاد هو نفسه ال‬ hydrophobic ‫ و(ا بدي استعمله لدوار الحركة بدي يوصل للدماغ ف بخليه‬hydrophilic These are uses of muscarinic antagonists: 1) Parkinson’s disease: they block acetylcholine receptors in the brain. 2) Motion sickness  ‫‪The only use of muscarinic antagonists in ophthalmologic disorders‬‬ ‫‪is to dilate the pupils for preparation to examine the retina‬‬ ‫‪Cyclopentolate: longer duration, where the blurry eye effect lasts‬‬ ‫‪for long (up to 2 days), and it is cheaper‬‬ ‫‪Tropicamide: shorter duration, where the blurry eye effect does not‬‬ ‫‪last for long (half a day maximum), but it is more expensive‬‬ ‫مرة اخدت أخوي الصغير عمره ‪ ٣‬سن‪ U‬على دكتور العيون عشان نفحصله عيونه راحو حطوله اول‬ ‫أشي قطرة بالع‪ U‬خلت البؤبؤ تبعه يتوسع وقالولي أخده واضل معاه ثلث ساعة نص ساعة وكل شوي‬ ‫يشيكو عالتوسع إذا صار و‪ ،g g‬وحتى أعطونا نظارات تمنع الضو انه يفوت كتير بعينه ‪d‬نه البؤبؤ عم‬ ‫بيتوسع كتير ف مضر انه يفوت كل هاد الضو مرة وحدة على عينه )طبعا ما رضي يلبسها(‬ ‫آخر أشي بس فحصوه بهاي ا‪g‬شي اللي بطلع ضو وشافو انه فيه توسع رجعو فوتوه عالعيادة‬ ‫وفحصوله نظره بهاي ا‪s‬له الكبيرة اللي ‪g‬زم يحط عليها ذقنه ويحطوله عيونه بعدسة‬ ‫وضله ‪d‬خر اليوم يا حرام ما بشوف ا‪d‬شياء القريبة وعيونه مغبشات بس شكلهم حاطينله قطرة من أم‬ ‫الغالية ‪d‬نه ما طول كتير وكان ا(ستشفى محترم يعني‬ ‫الحمد ‪ x‬با‪d‬خر طلع مابيحتاج يلبس نظارة‬ ‫فا(غزى من القصة انه هيك بيستعملو هاي القطرات وإنه هاد هو ا‪g‬ستعمال الوحيد ‪g‬لهم‬  Both are used as bronchodilators ‫طفال اللي عندهم سلس بولي‬d‫لع ج ا(ثانة العصبية اللي هو انه ا(ريض كل شوي بده يروح عالحمام أو ا‬ The disorder is caused by overstimulation of the urethra, so we use agents that decrease the stimulation. Used in the cholinergic crisis (overstimulation of muscarinic receptors), which can happen when: 1) the patient is exposed to a muscarine overdose (cholinergic poisoning) we treat them by giving atropine. 2) Patients that get intoxicated from mushrooms of Inocybe genus are also treated with atropine. It is toxic because it contains high amounts of muscarine. We treat them by giving muscarine blockers  Because sweating is blocked Toxicity from muscarine blockers can happen when: 1) the patient takes an overdose 2) it can happen with the people that eat grass and leaves excessively ‫كيف؟ بعرفش‬ It is contraindicated for elderly that suffer from glaucoma or benign prostate hyperplasia These drugs are contraindicated for elderly that suffer from glaucoma or benign prostate hyperplasia, because in males the inflation of the prostate will partially obstruct the urinary tract, so we cannot relax the urethral muscles as this will cause more pressure on the urinary tract (this will be explained in more detail later on)