Lecture 7 Pharmacology 1 PDF

PHARMACOLOGY 1 DONE BY LECTURE 7 LAYAN BADER SARA AL-ASMAR EMAN AL-MALAKH  Adrenoceptor Agonists & Sympathomimetic Drugs In this lecture we will learn about adrenergic neurotransmission, what are the chemical neurotransmitters that stimulate the transmit o...

PHARMACOLOGY 1 DONE BY LECTURE 7 LAYAN BADER SARA AL-ASMAR EMAN AL-MALAKH  Adrenoceptor Agonists & Sympathomimetic Drugs In this lecture we will learn about adrenergic neurotransmission, what are the chemical neurotransmitters that stimulate the transmit of signals through the adrenergic neurons, what are the receptors for these neurotransmitters, and what are there effects on the organs and on the systems. Remember: the adrenergic nerve signaling is in the sympathetic pathway in the body. So, the drugs that act positively on these locations are called “sympathomimitics” or “adrenergic agonists”. Preganglionic neuron: Cell body is in the CNS, and the connective dendrites are in the ganglia Postganglionic neuron: Cell body is in the ganglia and the connective dendrites are in the effected organ ‫خضر‬$‫كتوب با‬+‫ اليوم رح نركز عا‬.‫حاضرات اللي قبل وهاد الك>م اللي هون كله إعادة‬+‫هاد الس>يد حكينا با‬ The adrenergic neurotransmission connects between the ganglia and the effector organ. Th receptors are located on the postsynaptic neuron on the effector organ. Note: this figure shows the peripheral nervous system only. Don’t forget that there are adrenergic receptors in the CNS as well. The neurotransmitters in the adrenergic transmission are called the “catecholamines”. They are composed of a catechol and an amine group. They include: adrenaline (epinephrine), noradrenaline (norepinephrine), isoprenaline (isoprotenol), dopamine, and much more chemical neurotransmitters. When the nerve impulse reaches to the adrenergic neurons, all the chemical neurotransmitters will get released. However, the dominant neurotransmitter is norepinephrine. The MAO and the COMT enzymes break down the NE to dopamine and tyrosine, then they get stored in the vessels, ready to get resynthesized when we need them again. The alpha and beta receptors that are the binding site of adrenergic neurotransmitters (mentioned in the previous figure) are G-protein coupled receptors. They are transmembrane receptors that penetrate the organ’s cell membrane 7 times —> we call it “7-transmembrane G-protein coupled receptor”. Remember, also muscarine receptors are G-protein coupled. When the catecholamines bind to the receptors on the effector organ, they may have a stimulant or an inhibitor effect. This is because they are a type of G-protein coupled receptors. Remember, we have 2 kinds of receptors for the adrenergic neurotransmission: alpha and beta. Each of them has several subtypes that differ in effect. How does the neurotransmitters bind to the receptors? The important types of catecholamines in this lecture are isoprotenol, epinephrine, and norepinephrine. All of them bind to both alpha and beta receptors. However, they differ in affinity of binding to each receptor. Alpha adrenoceptors bind the best with epinephrine (high affinity). They bind with lower affinity to norepinephrine (intermediate affinity), and bind the lowest to isoprotenol (low affinity) Beta adrenoceptors bind the best with isoprotenol (high affinity). They bind with lower affinity to epinephrine(intermediate affinity), and bind the lowest to norepinephrine (low affinity) Remember, epinephrine has the highest affinity to all alpha receptors. It has equal affinity towards alpha1 and alpha2 receptors. Autoreceptors are the cells that secrete a neurotransmitter and contain a receptor sensitive to this neurotransmitter at the same time. ‫بنرجعلهم بعدين‬  > - Sj2) S respiratory system → in the sympathetic stimulation (fight or flight ‫ → بنكون عم نتنفس بسرعة→ ) الكر و الفر‬so bronchodilation happen to help increase air flow to the lungs The activation of the following receptors The eyes causes: α1 > contraction of pupillary dilator muscle T of the iris causing > - mydriasis α1 agonists are used for the examination of the retina , because it causes mydriasis ( dilation of the pupil) which allows the doctor to examine clearly β2 > - increase the secretion of humor aqueous j Q: If a patient had glaucoma, what could be used for him (in the case of beta receptors)? We use beta2 blockers , to prevent the production of the aqueous humor  - or B3 L the ability to urinate decreases due to the muscles' reactions. relaxes [ when Be receptors activately are - contracts upon Stimulation of 21 receptor. So if someone was suffering from urinary frequency (abnormal frequent urination)، ‫سؤولة عن التحكم في‬4‫عصاب ا‬D‫ثانة بسبب ضرر في ا‬4‫ثانة العصبية )وهي مشكلة في ا‬4‫أو ا‬ ( ‫التبول‬ W e treat them with beta 2 or 3 agonists or alpha 1 agonists to relax the detrusor muscle and contract the trigone muscle and sphincter helps keep the bladder closed off, which prevents leakage or involuntary urination. We might also use cholinergic blockers (‫)حكينا عنهم قبل‬, e.g. darifenacin, solifenacin , tolterodine, Sotostop Adrenergic agonists beta 3 ‫كمان عنا‬ urine out ‫ ممكن نستخدمه‬agonist flow we ‫ت زي الدوارالي‬T‫لهاي الحا‬ can use cholinergic antagonists ‫حكينا عنه قبل‬ e.g.Mirabegron  > - inhibitor for both advenergic and cholinergic. J B1 is more dominant (in Sympathetic reaction) ‫ ممكن يكون عنده مستقبل[ يشتغلو عكس بعض‬organ‫ في نفس ال‬: ‫نقطة مهمة‬ Like beta 1 and alpha 2 receptors with renin secretion But! One is dominant more than the other So in juxtaglomerular beta 1 is more dominant  ‫ عالجسم‬neurotransmitters ‫ه^ بدنا نشوف تأثير ال‬ [‫درينال‬D‫ هو ا‬adrenergic agonist ‫ا نيجي ل^دوية اهم‬4 (adrenaline = epinephrine). isoprotenol ‫ و‬norepinephrine ‫كمان عنا‬ ‫طيب ه^ هدول كأدوية‬ They aren’t found in pharmacies, they are used in emergency rooms and ambulances (paramedics) ‫وتركيزها بكون‬ ‫عالقلب‬ ‫كيف بدي اعرف أي واحد استخدم منهم؟‬ Depending on their affinity to the receptors  receptors affinities ‫ خلينا نراجع ال‬، ‫قبل ما نشوف كل واحد فيهم‬ ↓ receptors B receptors Adrenaline > - highest affinity Isoprotend > - highest to affinity to B N (B , B2 , Ps) binds to X1 = 2 adrenaline > - p, = &2 and B , noradrenaline noradrenaline - > B, andBy Isoprotend- doesn't bind to x1 ( lowest affinity ( ‫ستخدام‬T‫ لكل دوا بيجي فرق ا‬affinity ‫رتباط و ال‬T‫وبناًء على ا‬ Adrenaline → originally is a stress hormone produced at the adrenal gland - mainly - and also could be synthesized at the nerve endings. Epinephrine (adrenaline) is given to asthmatic patients to cause bronchodilation and inhibit the release of allergy mediators (e.g. Histamine) decreases mucous and WBCs ……  Jayl0y9 ,& - 46s note : (12) · Ss Neurotransmitter , & 19 Jds J5 HR Systole and diastole L ② epinephrine has a relatively high affinity to B1 ↓ So it increases heart rate I - increases Systolic and diastolic ③ B2- causes pressure. & relaxation ↓ So diastolic pressure activation of X - decreases ①high affinity to x > - and vaso constriction HR b decreases b high peripheral /2 5.. resistance B1j  ② Be activated > - increasing heart rate and Systolic and diastolic pressure. !S , HR-51j 7 because the peripheral ① x1 activated > - increasing resistance is too peripheral resistance. high b So the heart slows down to protect itself this drops the heart rated [bradycardia reflex] and this happens to prevent the I heart from hard working too against high pressure.  B1 increases heart ? rate. increase in & systolic diastolic I blood pressure E lowers HR -B2 and diastolic pressure. Iso doesn't & proterend activate X1 b So low peripheral resistance. Good luck