Introduction to Pharmacology PDF

so as III 15 65 at it IN 2 III 3 I I It 211 5 www.md Is g I...

so as III 15 65 at it IN 2 III 3 I I It 211 5 www.md Is g I Jim 188117 Dr. Abdulrahman A. Almehizia 1/21/2024 1 is Introduction to Pharmacology Pharmacology can be defined as the study of substances that interact with living systems through chemical processes These interactions usually occur by binding of the substance to regulatory molecules and activating or inhibiting normal body processes  Medical pharmacology: the science of substances used to prevent, diagnose, and treat disease  Toxicology: is the branch of pharmacology that deals with the undesirable effects of chemicals on Coco living systems, from individual cells to humans to complex ecosystems.‫ يمكن تعريف علم األدوية بأنه دراسة املواد التي تتفاعل مع األنظمة الحية من خالل العمليات الكيميائية‬.‫ تحدث هذه التفاعالت عادةً عن طريق ارتباط املادة بالجزيئات التنظيمية وتنشيط أو تثبيط العمليات الطبيعية في الجسم‬ 2 ‫ علم املواد املستخدمة للوقاية من األمراض وتشخيصها وعالجها‬:‫علم األدوية الطبية‬. ‫ من الخاليا الفردية إلى البشر إلى النظم البيئية‬،‫ هو فرع من فروع علم األدوية يتعامل مع التأثيرات غير املرغوب فيها للمواد الكيميائية على األنظمة الحية‬:‫علم السموم‬ PHRM 201 ‐ Pharmacology ‐ Lecture 1 3 Dr. Abdulrahman A. Almehizia 1/21/2024 Drugs am to a f Drug defined as a chemical substance (typically of known structure), when administered living organism, produces a biological effect It is used to treat, cure, prevent, or4diagnose a disease or to promote well‐being This target molecule is called a receptor. ‫تأثيرا‬ ‫ تنتج‬،‫ وعند إعطائها لكائن حي‬،(‫ الدواء هو مادة كيميائية )عادةً ما تكون ذات بنية معروفة‬ ً.‫بيولوجيًا‬ Examples:.‫ يستخدم لعالج أو شفاء أو منع أو تشخيص مرض أو لتعزيز الرفاهية‬.‫ يسمى هذا الجزيء املستهدف باملستقبل‬ o Aspirin :‫ األمثلة‬ o Antibiotics Drug Drug + Response/Effect Receptor Receptor Drug‐Receptor Complex PHRM 201 ‐ Pharmacology ‐ Lecture 1 4 Dr. Abdulrahman A. Almehizia 1/21/2024 Drugs Cosmetics on the other hand, are defined as articles applied to the human body for If cleansing, beautifying,3promoting attractiveness, or4altering the appearance Example: perfumes, lipsticks, hair dyes, and deodorants Drugs may be synthesized within the body (e.g., hormones) or may be chemicals not synthesized in the body (i.e., xenobiotics) 4 Poisons are drugs that have almost exclusively harmful effects. However, Paracelsus (1493–1541) famously stated that “the dose makes the poison,” meaning that any substance can be harmful if taken in the wrong dosage mi Toxins are usually defined as poisons of biologic origin, i.e., synthesized by plants or 2 animals, in contrast to inorganic poisons such as lead and arsenic 00 ‫عرف مستحضرات التجميل بأنها مواد توضع على جسم اإلنسان للتطهير أو التجميل أو تعزيز الجاذبية أو تغيير املظهر‬ َّ ُ‫ ت‬،‫ من ناحية أخرى‬ ‫ ومزيالت العرق‬،‫ وصبغات الشعر‬،‫ وأحمر الشفاه‬،‫ العطور‬:‫ مثال‬ (‫ قد يتم تصنيع األدوية داخل الجسم )مثل الهرمونات( أو قد تكون مواد كيميائية غير مصنعة في الجسم )مثل املواد الغريبة‬ ‫ مما يعني أن أي مادة يمكن أن تكون ضارة إذا تم تناولها‬،"‫( بشكل مشهور أن "الجرعة تصنع السم‬1541-1493) ‫ صرح باراسيلسوس‬،‫ ومع ذلك‬.‫ السموم هي أدوية لها تأثيرات ضارة بشكل شبه حصري‬.‫بجرعة خاطئة‬ PHRM 201 ‐ Pharmacology ‐ Lecture 1 5 Dr. Abdulrahman A. Almehizia 1/21/2024 Ideal Drug ‫ما هي خصائص الدواء املثالي؟‬  What are the properties of an ideal drug? The Big Three: 1. Effectiveness:  An effective drug is the one that gives the responses for which it is Ek 1. Effectiveness given 2. Safety, and 3. Selectivity to  Effectiveness is the most important property a drug can have E effect for irity :‫الفعالية‬ ‫ الدواء الفعال هو الذي يعطي االستجابات التي من أجلها يتم إعطاؤه‬ ‫< الفعالية هي الخاصية األكثر أهمية التي يمكن أن يتمتع بها الدواء‬ PHRM 201 ‐ Pharmacology ‐ Lecture 1 6 Dr. Abdulrahman A. Almehizia 1/21/2024 Ideal Drug  What are the properties of an ideal drug? The Big Three: 2. Safety: 1. Effectiveness  A safe drug is defined as the one that cannot produce harmful 2. Safety, and effects. 3. Selectivity  There is no such thing as an absolute safe drug 100  All drugs have the ability to cause injury, especially with high 0 doses and prolonged use g  Examples: Aspirin when taken chronically in high therapeutic e doses, can cause life threatening gastric ulceration.  The chances of producing adverse effects can be reduced by I proper drug selection and2 proper dosing :‫السالمة‬.‫عرف الدواء اآلمن بأنه الدواء الذي ال يمكن أن يُحدث تأثيرات ضارة‬ َّ ُ‫ ي‬ ‫ ال يوجد ما يسمى بالدواء اآلمن املطلق‬ 8 ‫ وخاص ًة مع الجرعات العالية واالستخدام لفترات‬،‫ جميع األدوية لديها القدرة على التسبب في اإلصابة‬ ‫طويلة‬ PHRM 201 ‐ Pharmacology ‐ Lecture 1 ‫ يمكن أن يسبب األسبرين عند تناوله بشكل مزمن بجرعات عالجية عالية تقرحات معدية تهدد‬:‫ أمثلة‬ 7 Dr. Abdulrahman A. Almehizia 1/21/2024 Ideal Drug  What are the properties of an ideal drug? The Big Three: 3. Selectivity: 1. Effectiveness  A selective drug is defined as the one that elicits only the response for which it is given. 2. Safety, and  A selective drug would not produce side effects. 3. Selectivity  Almost, there is no such thing as a selective drug.  Most medications cause side effects. Common examples include the drowsiness that can be caused by many antihistamines :‫االنتقائية‬.‫ يتم تعريف الدواء االنتقائي بأنه الدواء الذي يثير فقط االستجابة التي يتم إعطاؤه من أجلها‬ 8.‫ ال ينتج الدواء االنتقائي أي آثار جانبية‬.‫ ال يوجد شيء اسمه دواء انتقائي تقريبًا‬ ‫ ومن األمثلة الشائعة النعاس الذي يمكن أن تسببه العديد من مضادات‬.‫آثارا جانبية‬ ً ‫ تسبب معظم األدوية‬ PHRM 201 ‐ Pharmacology ‐ Lecture 1 8 Dr. Abdulrahman A. Almehizia 1/21/2024 Drug‐Body Interactions The interactions between a drug and the body are divided into two classes: A. Pharmacodynamic processes: the actions of the drug dynamic on the body  These properties determine the group in which the drug is classified, and they play the major role in deciding whether that group is appropriate therapy for a particular symptom or disease B. Pharmacokinetic processes: the actions of the body on inetic the drug Emma c 855 metabolism and excretion wow distribution,  Absorption, 2581 of drugs (ADME) stolid idea 2 1 4546 3 is 2 f 81,6 ‫تفاعالت الدواء مع الجسم‬ :‫ تنقسم التفاعالت بني الدواء والجسم إلى فئتني‬ ‫ أفعال الدواء على الجسم‬:‫ العمليات الديناميكية الدوائية‬.‫أ‬ dyaenmic onBody 6441155 ‫عالجا مناسبًا ألعراض أو‬ ً ‫ وتلعب الدور الرئيسي في تحديد ما إذا كانت هذه املجموعة‬،‫تحدد هذه الخصائص املجموعة التي يصنف فيها الدواء‬ sina.h.gr ‫مرض معني‬ Linetic ondrug ‫ أفعال الجسم على الدواء‬:‫ العمليات الحركية الدوائية‬.‫ب‬ PHRM 201 ‐ Pharmacology ‐ Lecture 1 10 Dr. Abdulrahman A. Almehizia 1/21/2024 Drug‐Body Interactions Iii  Types of Drug‐Receptor Interactions: Agonist D Agonist drugs bind to and activate the receptor, which directly or indirectly brings the effect/response iii said o Receptor activation involves a change in conformation, some receptors incorporate effector machinery in the same molecule, other receptors are linked through one or more intervening coupling molecules to a separate effector molecule E Pharmacologic antagonist drugs, by binding to a receptor, compete with and prevent binding by other molecules Antagonist o For example, acetylcholine receptor blockers such as atropine are antagonists because they prevent access of acetylcholine and similar agonist drugs to the acetylcholine receptor site, and they stabilize the receptor in its inactive state ‫أنواع تفاعالت الدواء مع املستقبل‬: Oo ‫االستجابة‬/‫ مما يؤدي بشكل مباشر أو غير مباشر إلى التأثير‬،‫ ترتبط األدوية املحفزة باملستقبل وتنشطه‬ o o ‫ وترتبط مستقبالت أخرى من خالل جزيء اقتران متدخل واحد أو أكثر بجزيء مؤثر منفصل‬،‫ حيث تتضمن بعض املستقبالت آلية املؤثر في نفس الجزيء‬،‫تغييرا في التكوين‬ ً ‫ يتضمن تنشيط املستقبل‬ ‫ مع الجزيئات األخرى وتمنع ارتباطها بها‬،‫ عن طريق االرتباط بمستقبل‬،‫ تتنافس األدوية املضادة الدوائية‬ PHRM 201 ‐ Pharmacology ‐ Lecture 1 11 ‫ كما تعمل على تثبيت املستقبل في حالته غير النشطة‬،‫ تعتبر حاصرات مستقبالت األستيل كولني مثل األتروبني مضادات ألنها تمنع وصول األستيل كولني واألدوية املحفزة املماثلة إلى موقع مستقبل األستيل كولني‬،‫ على سبيل املثال‬  ‫ أن تنشط أنظمة املستقبالت املؤثرة الخاصة بها إلى أقصى مدى يمكن للنظام أن يصل إليه‬،‫ عند إعطائها بتركيزات كافية إلشباع مجموعة املستقبالت‬،‫ يمكن لألدوية املحفزة‬:‫ املحفزات الكاملة‬1/21/2024 Dr. Abdulrahman A. Almehizia o ‫ بغض النظر عن مدى ارتفاع التركيز‬،‫ ترتبط بنفس املستقبالت وتنشطها بنفس الطريقة ولكنها ال تثير استجابة كبيرة‬:‫ املحفزات الجزئية‬ ‫ ليس لها نشاط في غياب محفز أو محفز عكسي ولكن يمكنها منع نشاط أي منهما‬:‫ التضاد املحايد‬ Drug‐Body Interactions a Full agonists: o Agonist drugs, when administered at concentrations sufficient to saturate the receptor pool, can activate their the system is capable a receptor‐effector systems to the maximum extent of which 0 100 of Partial agonists: swi o Bind to the same receptors and activate them in the same way but do not evoke as great a response, no matter how high the concentration o.sn o Is Neutral antagonism: o Has no activity in the absence of an agonist or inverse Of agonist but can block the activity of either Inverse agonist: am I o A substance that binds to the same receptor binding‐site as an agonist for that receptor, but which exerts the opposite pharmacological effect. SI wEI PHRM 201 ‐ Pharmacology ‐ Lecture 1 13 Dr. Abdulrahman A. Almehizia 1/21/2024 Pharmacokinetic Principles a Absorption:  A drug is administered into one body compartment, e.g., the gut, and must move to its site of action in another compartment, e.g., the brain in the case of an antiseizure medication  This requires that the drug be absorbed into the blood from its site of administration t Distribution:  The drug must be distributed to its site of action, permeating through the various barriers that separate these compartments. Permeation:  For a drug given orally to produce an effect in the central nervous system, these barriers include the tissues that make up the wall of the intestine, and the blood‐brain barrier Elimination:  After bringing about its effect, a drug should be eliminated by metabolic inactivation, by excretion from the body, or by a combination of these processe :‫االمتصاص‬ ‫ مثل الدماغ في حالة األدوية املضادة للصرع‬،‫ ويجب أن ينتقل إلى موقع عمله في حجرة أخرى‬،‫ مثل األمعاء‬،‫يتم إعطاء الدواء في حجرة واحدة من الجسم‬ ‫يتطلب هذا أن يتم امتصاص الدواء في الدم من موقع إعطائه‬ :‫ التوزيع‬ ‫ ويخترق من خالل الحواجز املختلفة التي تفصل بني هذه الحجرات‬،‫يجب توزيع الدواء إلى موقع عمله‬. :‫ النفاذية‬ ‫ وحاجز الدم‬،‫ فإن هذه الحواجز تشمل األنسجة التي تشكل جدار األمعاء‬،‫تأثيرا في الجهاز العصبي املركزي‬ ً ‫لكي يحدث الدواء الذي يتم إعطاؤه عن طريق الفم‬ ‫في الدماغ‬ PHRM 201 ‐ Pharmacology ‐ Lecture 1 16 :‫ اإلخراج‬ ‫ أو عن طريق مزيج من هذه العمليات‬،‫ أو عن طريق اإلخراج من الجسم‬،‫ يجب إخراج الدواء عن طريق التعطيل األيضي‬،‫بعد إحداث تأثيره‬ Dr. Abdulrahman A. Almehizia 1/21/2024 Pharmacokinetic Principles Mechanisms of absorption of drugs from the GI tract: :‫ آليات امتصاص األدوية من الجهاز الهضمي‬ ‫ االنتشار السلبي‬.1 ‫ االنتشار امليسر‬.2 1. Passive diffusion ‫ النقل النشط‬.3 2. Facilitated diffusion ‫ البلعمة الخلوية‬.4 3. Active transport 4. Endocytosis PHRM 201 ‐ Pharmacology ‐ Lecture 1 19 Dr. Abdulrahman A. Almehizia 1/21/2024 Pharmacokinetic Principles Mechanisms of absorption of drugs from the GI tract: a The driving force is the concentration gradient across a membrane separating two body compartments The drug moves from an area of high conc. to lower conc. Does not involve a carrier, is not saturable, and low structural yo Agents enter the cell through specialized specificity transmembrane carrier proteins that Most drugs are absorbed by this facilitate the passage of large molecules mechanism These carrier proteins undergo conformational changes, allowing the passage of drugs or endogenous molecules into the interior of cells. ‫ القوة الدافعة هي تدرج التركيز عبر الغشاء الذي يفصل بني حجرتني من‬ Does not require energy, can be ‫الجسم‬ saturated, and may be inhibited by ٍ ‫ يتحرك الدواء من منطقة ذات تركيز‬.‫عال إلى منطقة ذات تركيز أقل‬ compounds that compete for the carrier ً ‫ وخصوصيته البنيوية منخفضة‬،‫ وال يمكن تشبعه‬،‫حامال‬ ‫ ال يتضمن‬.‫ تدخل العوامل إلى الخلية من خالل بروتينات ناقلة متخصصة عبر الغشاء تسهل مرور الجزيئات الكبيرة‬ ‫ مما يسمح بمرور األدوية أو الجزيئات الذاتية إلى داخل‬،‫ تخضع هذه البروتينات الناقلة لتغييرات تكوينية‬.‫الخاليا‬ PHRM 201 ‐ Pharmacology ‐ Lecture 1 20 Dr. Abdulrahman A. Almehizia 1/21/2024 Pharmacokinetic Principles S Involves specific carrier proteins Used to transport drugs of Energy dependent; adenosine exceptionally large size across the cell triphosphate (ATP) membrane Capable of moving drugs against a Involves engulfment of a drug by the concentration gradient cell membrane and transport into the Saturable process cell by pinching off the drug‐filled Selective and may be competitively vesicle inhibited Vitamin B12 is transported across the gut wall by endocytosis PHRM 201 ‐ Pharmacology ‐ Lecture 1 21 Dr. Abdulrahman A. Almehizia 1/21/2024 Pharmacodynamic Principles Pharmacodynamics describes the actions of a drug on the body Most drugs exert effects, both beneficial and harmful, by interacting with specialized target macromolecules called receptors, which are present on or in the cell The drug–receptor complex initiates alterations in biochemical and/or molecular activity of a cell by a process called signal transduction PHRM 201 ‐ Pharmacology ‐ Lecture 1 32 Dr. Abdulrahman A. Almehizia 1/21/2024 Pharmacodynamic Principles  Major receptor families: A receptor is defined as any biologic molecule to which a drug binds and produces a measurable response Enzymes, nucleic acids, and structural proteins can act as receptors for drugs or endogenous agonists Receptors are divided into four families: 1. Ligand‐gated ion channels, 2. G protein–coupled receptors, 3. Enzyme‐linked receptors, and 4. Intracellular receptors PHRM 201 ‐ Pharmacology ‐ Lecture 1 33 Dr. Abdulrahman A. Almehizia 1/21/2024 Pharmacodynamic Principles  Dose‐Response Relationships: Agonist drugs mimic the action of the endogenous ligand for the receptor (for example, isoproterenol mimics norepinephrine on β1 receptors of the heart) The magnitude of the drug effect depends on: 1. Receptor sensitivity to the drug and 2. The drug concentration at the receptor site, which, in turn, is determined by both the dose of drug administered and by the drug’s pharmacokinetic profile, such as rate of absorption, distribution, metabolism, and elimination PHRM 201 ‐ Pharmacology ‐ Lecture 1 34 Dr. Abdulrahman A. Almehizia 1/21/2024 Pharmacodynamic Principles  Dose‐Response Relationships: As the concentration of a drug increases, its pharmacologic effect also gradually increases until all the receptors are occupied (the maximum effect) Plotting the magnitude of response against increasing doses of a drug produces a graded dose– response curve Two important drug characteristics: potency and efficacy, can be determined by graded dose– response curves g Taoist the EC50 for Drugs A and B indicate that Drug A is more potent than Drug B, because a lesser amount of Drug A is needed to obtain 50% effect shift 8,95 so PHRM 201 ‐ Pharmacology ‐ Lecture 1 35 Dr. Abdulrahman A. Almehizia 1/21/2024 At Pharmacodynamic Principles  Dose‐Response Relationships: 1. Potency: A measure of the amount A B of drug necessary to produce an effect The concentration of drug  Therapeutic preparations of drugs reflect their producing 50% of the potency. For example, candesartan and irbesartan are maximum effect (EC50) is angiotensin receptor blockers used to treat often used to determine hypertension potency 46 S A  The therapeutic dose range for candesartan is 4 to 32 B mg, as compared to 75 to 300 mg for irbesartan  Therefore, candesartan is more potent than irbesartan (it has a lower EC50 value). PHRM 201 ‐ Pharmacology ‐ Lecture 1 36 Dr. Abdulrahman A. Almehizia 1/21/2024 Pharmacodynamic Principles  Dose‐Response Relationships: 2. Efficacy: am Is the magnitude of response a drug causes when it interacts with a receptor Efficacy is dependent on the number of drug–receptor complexes formed and the intrinsic activity of the drug (its ability to activate the receptor and cause a cellular response) Maximal efficacy of a drug (Emax) assumes that the drug occupies all receptors, and no increase in response is observed in response to higher concentrations of drug. Efficacy is a more clinically useful characteristic than potency, since a drug with greater efficacy is more therapeutically beneficial than one that is more potent. PHRM 201 ‐ Pharmacology ‐ Lecture 1 37 Dr. Abdulrahman A. Almehizia 1/21/2024 Pharmacodynamic Principles  Dose‐Response Relationships: PHRM 201 ‐ Pharmacology ‐ Lecture 1 38 Dr. Abdulrahman A. Almehizia 1/21/2024 Pharmacodynamic Principles  Therapeutic index: The therapeutic index (TI) of a drug is the ratio of the dose that produces toxicity in half the population (TD50) to the dose that produces a clinically desired or effective response (ED50) in half the population: Therapeutic Index = TD50/ED50 The TI is a measure of a drug’s safety, because a larger value indicates a wide margin between doses that are effective and doses that are toxic The TI of a drug is determined using drug trials and accumulated clinical experience These usually reveal a range of effective doses and a different (sometimes overlapping) range of toxic doses Although high TI values are required for most drugs, some drugs with low therapeutic indices are routinely used to treat serious diseases. In these cases, the risk of experiencing adverse effects is not as great as the risk of leaving the disease untreated PHRM 201 ‐ Pharmacology ‐ Lecture 1 39 Dr. Abdulrahman A. Almehizia 1/21/2024 Pharmacodynamic Principles  Therapeutic index: we 0 PHRM 201 ‐ Pharmacology ‐ Lecture 1 40 PHRM 201 - Pharmacology - Lecture 2 1/28/2024 3 Drug Nomenclature  Chemical name: When a drug is first discovered, it is given chemical name Chemical name is usually too complex and not suitable for general prescribing When a drug is approved by FDA, it is given generic name and brand name → It describes the substance chemically :‫االسم الكيميائي‬ ‫اسما كيميائيًا‬ ً ‫ يتم إعطاؤه‬،‫ عندما يتم اكتشاف دواء ألول مرة‬ ‫ االسم الكيميائي عادة ما يكون معق ًدا للغاية وغير مناسب للوصف العام‬ 5 Dr. Abdulrahman A. Almehizia 5 PHRM 201 - Pharmacology - Lecture 2 1/28/2024 Drug Nomenclature  Chemical name: When a drug is first discovered, it is given chemical name Chemical name is usually too complex and not suitable for general prescribing When a drug is approved by FDA, it is given generic name and brand name → It describes the substance chemically :‫االسم الكيميائي‬ ‫اسما كيميائيًا‬ ً ‫ يتم إعطاؤه‬،‫ عندما يتم اكتشاف دواء ألول مرة‬ ‫ االسم الكيميائي عادة ما يكون معق ًدا للغاية وغير مناسب للوصف العام‬ 5 Dr. Abdulrahman A. Almehizia 5 PHRM 201 - Pharmacology - Lecture 2 1/28/2024 Drug Nomenclature  Generic name (Official, Approved): This name is used and chosen by official bodies Internationally there is one common generic name for a drug However, many older drugs still have more than one non-proprietary names, e. g.:  “meperidine” and “pethidine”  “lidocaine” and “lignocaine” for the same drugs :(‫ معتمد‬،‫االسم العام )رسمي‬ ‫ يستخدم هذا االسم ويختاره الهيئات الرسمية‬ ‫ يوجد دوليًا اسم عام واحد شائع للدواء‬ ‫ على سبيل‬،‫ ال يزال العديد من األدوية القديمة تحمل أكثر من اسم غير خاص‬،‫ ومع ذلك‬ :‫املثال‬ 7 Dr. Abdulrahman A. Almehizia 7 PHRM 201 - Pharmacology - Lecture 2 1/28/2024 Drug Nomenclature to  Proprietary name (Trade name, Company name): The name is given by the company which markets the drug It is the commercial property of a pharmaceutical company It indicates a particular formulation of a particular substance by a particular manufacturer Brand names are designed to be catchy, short, easy to remember and often suggestive, e. g. LOPRESOR (Metoprolol:β1- blocker) suggesting drug for lowering blood pressure Different brand names in different countries 8 :(‫ اسم الشركة‬،‫االسم التجاري )االسم التجاري‬ ‫ االسم الذي تعطيه الشركة التي تسوق الدواء‬ ‫ هو امللكية التجارية لشركة أدوية‬ ‫ يشير إلى تركيبة معينة ملادة معينة بواسطة شركة مصنعة معينة‬ ‫إلى دواء‬A.‫يشير‬ Dr. Abdulrahman ‫ مما‬LOPRESOR (Metoprolol:β1- blocker) ‫ على سبيل املثال‬،‫ األسماء التجارية مصممة لتكون جذابة وقصيرة وسهلة التذكر و غالبًا ما تكون موحية‬ Almehizia 8 PHRM 201 - Pharmacology - Lecture 2 1/28/2024 Drug Nomenclature to  Proprietary name (Trade name, Company name): The name is given by the company which markets the drug It is the commercial property of a pharmaceutical company It indicates a particular formulation of a particular substance by a particular manufacturer Brand names are designed to be catchy, short, easy to remember and often suggestive, e. g. LOPRESOR (Metoprolol:β1- blocker) suggesting drug for lowering blood pressure Different brand names in different countries 8 :(‫ اسم الشركة‬،‫االسم التجاري )االسم التجاري‬ ‫ االسم الذي تعطيه الشركة التي تسوق الدواء‬ ‫ هو امللكية التجارية لشركة أدوية‬ ‫ يشير إلى تركيبة معينة ملادة معينة بواسطة شركة مصنعة معينة‬ ‫إلى دواء‬A.‫يشير‬ Dr. Abdulrahman ‫ مما‬LOPRESOR (Metoprolol:β1- blocker) ‫ على سبيل املثال‬،‫ األسماء التجارية مصممة لتكون جذابة وقصيرة وسهلة التذكر و غالبًا ما تكون موحية‬ Almehizia 8 PHRM 201 - Pharmacology - Lecture 2 1/28/2024 Development Durg A. Sources of Drugs a Natural Is.tk few Biosynthetic Sources of IS Synthetic Drugs 16 Dr. Abdulrahman A. Almehizia 16 PHRM 201 - Pharmacology - Lecture 2 1/28/2024 Clinical Testing ‫االختبارات السريرية‬ Clinical trials occur in four phases: :‫ تتم التجارب السريرية في أربع مراحل‬  The first three phases are done before a new drug is marketed. ‫تتم املراحل الثالث األولى قبل تسويق الدواء الجديد‬.  The fourth is done after marketing has begun called post marketing surveillance. Preclinical Phase I Phase II Phase III Phase IV testing Subjects: Subjects: This is done after Testing Subjects: healthy volunteer patients marketing has and patients Test: Tests: begun. experime Tests: biological effect therapeutic Known post- ntation safety and on humans utility and marketing effectiveness pharmacokinetics dosage range surveillance (ADME) 25 Dr. Abdulrahman A. Almehizia 25 PHRM 201 - Pharmacology - Lecture 3 2/2/2024 3 II Routes of Drug Administration 1. Enteral Route: a. Oral:  Most common route idio s  Advantages: convenience /patient compliance  Disadvantages: i. The pathways involved in oral drug absorption are the most complicated ii. Low gastric pH inactivates some drugs  Different preparations: i. Solutions/suspensions 55 98in Enteric-coated preparations ii. Tablets S iii. Capsules Extended-release preparations www.isi aS www.a.si am 6 Dr. Abdulrahman A. Almehizia 6 PHRM 201 - Pharmacology - Lecture 3 2/2/2024 Routes of Drug Administration mix IT 1. Enteral Route…cont’d: b. Buccal (between gum and cheeks) and sublingual (under the tongue):  Advantages: 1. Allow direct absorption and rapid onset of action 2. Ease of administration 3. Rapid absorption 4. Bypass of the harsh gastrointestinal (GI) environment 5. Avoidance of first-pass metabolism  Examples: Buccal: Nicotine for smoking cessation, midazolam for seizure control Sublingual: Nitroglycerine is often given by this route iww 7 Dr. Abdulrahman A. Almehizia 7 PHRM 201 - Pharmacology - Lecture 3 2/2/2024 imtyasw.sGH a.mg 501 Iii Wi Wi 81 Jw Routes of Drug Administration It 1 2. Parenteral: The parenteral route introduces drugs directly into the systemic circulation Used for drugs that are poorly absorbed from the GI tract (heparin) or unstable in the GI tract (insulin) Used for patients unable to take oral medications (unconscious patients) Used in circumstances that require a rapid onset of action Parenteral administration provides the most control over the dose of drug delivered to the body This route of administration is irreversible and may cause pain, fear, local tissue damage, and infections 8 Dr. Abdulrahman A. Almehizia 8 PHRM 201 - Pharmacology - Lecture 3 2/2/2024 Routes of Drug Administration 2. Parenteral: w̅ Four major parenteral routes: intravascular (intravenous or intraarterial), intramuscular, 10 subcutaneous, and intradermal 9 Dr. Abdulrahman A. Almehizia 9 PHRM 201 - Pharmacology - Lecture 3 2/2/2024 Routes of Drug Administration 2. Parenteral: a. Intravenous (IV): The most common parenteral route Useful for drugs that are not absorbed orally (bioavailability F=1.0) IV delivery permits a rapid effect and a maximum degree of control over the amount of drug delivered Disadvantages: i. Unfavorable reactions can occur ii. Careful determination of dose and close monitoring of the patient’s response is required iii. Drugs in an oily vehicle, precipitate blood constituents or drug combinations that cause precipitates to form can NOT be given by IV 10 Dr. Abdulrahman A. Almehizia 10 PHRM 201 - Pharmacology - Lecture 3 2/2/2024 Routes of Drug Administration 2. Parenteral…cont’d: b. intramuscular (IM): Appropriate for self-administration Drugs administered IM can be in aqueous solutions (absorbed rapidly), or in specialized i a preparations (absorbed slowly) depot so wise I o Depot preparations often consist of a suspension of drug in a non-aqueous vehicle (such as polyethylene glycol) o As the vehicle diffuses out of the muscle, drug precipitates at the site of injection o The drug then dissolves slowly, providing a sustained dose over an extended interval Disadvantages: i. Can be painful 11 Dr. Abdulrahman A. Almehizia 11 PHRM 201 - Pharmacology - Lecture 3 2/2/2024 Routes of Drug Administration 2. Parenteral…cont’d: is swims c. Intra-arterial: waddiswani A drug is injected directly into an artery to localize its effect in a particular tissue or organ, such as in the treatment of liver tumors and head and neck cancers Diagnostic agents sometimes are administered by this route Disadvantages: i. Wrong intra-arterial administration can cause serious complications and requires careful management 12 Dr. Abdulrahman A. Almehizia 12 PHRM 201 - Pharmacology - Lecture 3 2/2/2024 Routes of Drug Administration 2. Parenteral…cont’d: c. Intrathecal: The BBB and the blood-CSF barrier often prevent or slow the entrance of drugs into the CNS Drugs are injected directly into the spinal space Brain tumors or serious CNS infections may be treated by this method 13 Dr. Abdulrahman A. Almehizia 13 PHRM 201 - Pharmacology - Lecture 3 2/2/2024 Routes of Drug Administration 2. Parenteral…cont’d: d. Subcutaneous: 0 Injection into a subcutaneous site can be done only with drugs that are not irritating to tissue; otherwise, severe pain, necrosis, and tissue sloughing may occur The rate of absorption following subcutaneous injection of a drug often is constant and slow to provide a sustained effect injection minimizes the risks of hemolysis or thrombosis associated with IV injection and may provide constant, slow, and sustained effects 14 Dr. Abdulrahman A. Almehizia 14 PHRM 201 - Pharmacology - Lecture 3 2/2/2024 Routes of Drug Administration 2. Parenteral…cont’d: e. G Intradermal: Intradermal (ID) injections have the longest absorption time of all parenteral routes because there are fewer blood vessels and no muscle tissue These types of injections are used for sensitivity testing because the patient's reaction is easy to visualize, and the degree of reaction can be assessed. 15 Dr. Abdulrahman A. Almehizia 15 PHRM 201 - Pharmacology - Lecture 3 2/2/2024 Routes of Drug Administration 3. Pulmonary Absorption: www.T Gaseous and volatile drugs may be inhaled and absorbed through the pulmonary epithelium and mucous membranes of the respiratory tract Access to the circulation is rapid by this route because the lung’s surface area is large. Advantages: i. Instantaneous absorption of a drug into the blood ii. Avoidance of hepatic first-pass loss 1 a iii. In the case of pulmonary disease, local application of the drug at the desired site of action Examples: o Anesthetics o Ventolin 16 Dr. Abdulrahman A. Almehizia 16 PHRM 201 - Pharmacology - Lecture 3 2/2/2024 Routes of Drug Administration win I 4. Topical Application: a) Mucous Membrane: Drugs are applied to the mucous membranes of the conjunctiva, nasopharynx, oropharynx, vagina, colon, urethra, and urinary bladder primarily for their local effects Absorption from these sites is generally excellent b) Eye: Topically applied ophthalmic drugs are used primarily for their local effects The use of drug-loaded contact lenses and ocular inserts allows drugs to be better placed where they are needed for direct delivery 17 Dr. Abdulrahman A. Almehizia 17 PHRM 201 - Pharmacology - Lecture 3 2/2/2024 AtRoutes of Drug Administration 4. Topical Application: c) Skin: Transdermal Absorption: my This route of administration achieves systemic effects by application of drugs to the skin, usually via a transdermal patch The rate of absorption can vary markedly, depending on the physical characteristics of the skin at the site of application, as well as the lipid solubility of the drug 18 Dr. Abdulrahman A. Almehizia 18 PHRM 201 - Pharmacology - Lecture 3 2/2/2024 Routes of Drug Administration o 5. Rectal (suppository):  Advantages: i. Partially by-pass first pass metabolism ii. Prevent destruction of the drug in the GI environment iii. Useful if the drug induces vomiting when given orally, or if the patient is unconscious  Disadvantages: i. Drugs may irritate the rectal mucosa ii. o Not a well-accepted route by patients  Examples: Paracetamol (analgesic/antipyretic) 19 Dr. Abdulrahman A. Almehizia 19 PHAR 201 ‐ Pharmacology ‐ Lecture 4 I Genetic Factors This has lead to the introduction of a new field of study called pharmacogenetics o The dose of a drug to produce same effects may vary 4–6 folds among different individuals. This is mainly due to the differing rates of drug metabolism as the amount of microsomal enzymes is genetically controlled o Example:  Hemolysis (the destruction of red blood cells) by primaquine (anti malarial) and sulfonamides in persons with G6PD deficiency  G6PD deficiency is a genetic disorder often affects males. It happens when the body doesn't have enough of enzyme called glucose‐6‐phosphate dehydrogenase (G6PD). G6PD helps red blood cells work. It also protects them from substances in the blood that could harm them 14 Dr. Abdulrahman A. Almehizia 14 PHAR 201 ‐ Pharmacology ‐ Lecture 4 FDA Pregnancy Categories FDA Category Risk in Fetus Example Animals Humans A ‐ Definitely No Levothyroxin B No No studies available Paracetamol C Yes No studies available Ciprofloxacin Evidence of risk D ‐ Potential benefits may Phenytoin warrant use Definite fetal Thalidomide X Definitely Yes abnormalities Isotretinoin Dr. Abdulrahman A. Almehizia 28 PHAR 201 ‐ Pharmacology ‐ Lecture 4 FDA Pregnancy Categories  Isotretinoin (Roaccutane®):  Isotretinoin causes birth defects in up to 35% or more of infants whose are exposed during pregnancy  The chance of having a baby with a birth defect applies even if the medication has been taken for a short time  Birth defects: Dr. Abdulrahman A. Almehizia 29 PHAR 201 ‐ Pharmacology ‐ Lecture 4 FDA Pregnancy Categories  Thalidomide:  Thalidomide is a compound that was developed in the 1950s by the West German pharmaceutical company Chemie Grünenthal GmbH  It was originally intended as a sedative or tranquilizer but was soon used for treating a wide range of other conditions, including colds, flu, nausea and morning sickness in pregnant women  Birth defects: Dr. Abdulrahman A. Almehizia 30 PHRM 201 - Pharmacology - Lecture 5 2/17/2024 115.6419 f I Introduction The autonomic nervous system (ANS) + the endocrine system → coordinates the regulation and integration of body functions The endocrine system sends signals to target tissues by varying the levels of blood-borne hormones The nervous system exerts effects by the rapid transmission of electrical impulses over nerve fibers that terminate at effector cells, which specifically respond to the release of neuromediator substances Drugs that produce their primary therapeutic effect by mimicking or altering the functions of the ANS are called autonomic drugs The autonomic agents act either by stimulating portions of the ANS or by blocking the action of the autonomic nerves 4 Dr. Abdulrahman A. Almehizia 4 PHRM 201 - Pharmacology - Lecture 5 2/17/2024 He Introduction The nervous system is divided into two anatomical divisions: 1. The central nervous system (CNS): composed of the brain and spinal cord 2. The peripheral nervous system (PNS): neurons located outside the brain and spinal cord (any nerves that enter or leave the CNS) The peripheral nervous system is subdivided into: a. The efferent neurons: carry signals away from the brain and spinal cord to the peripheral tissues b. The afferent neurons: bring information from the periphery to the CNS 5 Dr. Abdulrahman A. Almehizia 5 PHRM 201 - Pharmacology - Lecture 5 2/17/2024 Introduction Organization of The Nervous System Central Nervous System Peripheral Nervous System CNS PNS Efferent Afferent Autonomic Nervous System Somatic Nervous System ANS SNS Sympathetic Parasympathetic Enteric 6 Dr. Abdulrahman A. Almehizia 6 PHRM 201 - Pharmacology - Lecture 5 2/17/2024 Introduction 8 8 Dr. Abdulrahman A. Almehizia 8 PHRM 201 - Pharmacology - Lecture 5 2/17/2024 Introduction The efferent portion of the PNS is divided into two major functional subdivisions: Is 1. The somatic nervous system: involved in the voluntary control of functions, such as contraction of the skeletal muscles essential for locomotion 94182. The ANS: regulates the everyday requirements of vital bodily functions without the conscious participation of the mind  Because of the involuntary nature of the ANS as well as its functions, it is also known as the visceral, vegetative, or involuntary nervous system  It is composed of efferent neurons that innervate visceral smooth muscle, cardiac muscle, vasculature, and the exocrine glands, thereby controlling digestion, cardiac output, blood flow, and glandular secretions 9 9 Dr. Abdulrahman A. Almehizia 9 PHRM 201 - Pharmacology - Lecture 5 2/17/2024 Anatomy of the ANS 1. Efferent neurons: The ANS carries nerve impulses from the CNS to the effector organs through two types of efferent neurons: Pre i. The preganglionic neurons:  The cell body is located within the CNS  The preganglionic neurons emerge from the brainstem or spinal cord a and make a synaptic connection in ganglia  The ganglia function as relay stations between the preganglionic neuron and the second nerve cell, the postganglionic neuron ii. The postganglionic neurons: Post  The cell body originates in the ganglion  It is generally nonmyelinated and terminates on effector organs, such as visceral smooth muscle, cardiac muscle, and the exocrine glands a 10 10 Dr. Abdulrahman A. Almehizia 10 PHRM 201 - Pharmacology - Lecture 5 2/17/2024 Anatomy of the ANS 3. Sympathetic neurons: The sympathetic and the parasympathetic neurons originate in the CNS and emerge from two different spinal cord regions The preganglionic neurons of the sympathetic system come from the thoracic and Be lumbar regions (T1 to L2) of the spinal cord The preganglionic neurons are short in comparison to the postganglionic ones Axons of the postganglionic neuron extend from the ganglia to tissues they innervate and regulate In most cases, the preganglionic nerve endings of the sympathetic nervous system are highly branched, enabling one preganglionic neuron to interact with many postganglionic neurons 12 12 Dr. Abdulrahman A. Almehizia 12 PHRM 201 - Pharmacology - Lecture 5 2/17/2024 Anatomy of the ANS 4. Parasympathetic neurons: The parasympathetic preganglionic fibers arise from cranial nerves III (oculomotor), VII Be (facial), IX (glossopharyngeal), and X (vagus), as well as from the sacral region (S2 to S4) of the spinal cord and synapse in ganglia near or on the effector organs The preganglionic fibers are long, and the postganglionic ones are short, with the ganglia close to or within the organ innervated In most instances, there is a one-to-one connection between the preganglionic and postganglionic neurons, enabling discrete response of this system 5. Enteric neurons: It is a collection of nerve fibers that innervate the gastrointestinal (GI) tract, pancreas, and gallbladder, and it constitutes the “brain of the gut” 13 13 Dr. Abdulrahman A. Almehizia 13 PHRM 201 - Pharmacology - Lecture 5 2/17/2024 Anatomy of the ANS 14 14 Dr. Abdulrahman A. Almehizia 14 PHRM 201 - Pharmacology - Lecture 5 2/17/2024 Functions of the Sympathetic Nervous System The sympathetic nervous system is involved in preparing the body for stress- related activities The parasympathetic nervous system is associated with returning the body to routine day-to-day operations The two systems have complementary functions, operating in tandem to maintain the body's homeostasis 15 15 Dr. Abdulrahman A. Almehizia 15 PHRM 201 - Pharmacology - Lecture 5 2/17/2024 Functions of the Sympathetic Nervous System 1. Effects of stimulation of the sympathetic division: The effect of sympathetic stimulation is an increase in heart rate and blood pressure, mobilization of energy stores, and increase in blood flow to skeletal muscles and the heart while diverting flow from the skin and internal organs Sympathetic stimulation results in dilation of the pupils and bronchioles Reduces GI motility and affects function of the bladder and sexual organs 16 16 Dr. Abdulrahman A. Almehizia 16 PHRM 201 - Pharmacology - Lecture 5 2/17/2024 Functions of the Sympathetic Nervous System 2. Fight or flight response: The changes experienced by the body during emergencies are referred to as the “fight or flight” response These reactions are triggered both by direct sympathetic activation of effector organs and by stimulation of the adrenal medulla to release epinephrine (E) and lesser amounts of norepinephrine (NE) 17 17 Dr. Abdulrahman A. Almehizia 17 PHRM 201 - Pharmacology - Lecture 5 2/17/2024 Functions of the Parasympathetic Nervous System The parasympathetic division is involved with maintaining homeostasis within the body It is required for life, since it maintains essential bodily functions, such as digestion and elimination The parasympathetic division usually acts to oppose or balance the actions of the sympathetic division and generally predominates the sympathetic system in “rest-and-digest” situations 18 18 Dr. Abdulrahman A. Almehizia 18 PHRM 201 - Pharmacology - Lecture 5 2/17/2024 Anatomy of the ANS In 19 19 Dr. Abdulrahman A. Almehizia 19 PHRM 201 - Pharmacology - Lecture 5 2/17/2024 Anatomy of the ANS A ganglion is a group of neuron cell bodies in the periphery.... These ganglia are the cell bodies of neurons with axons that are associated with sensory endings in the periphery, such as in the skin, and that extend into the CNS through the dorsal nerve root. The ganglion is an enlargement of the nerve root 20 20 Dr. Abdulrahman A. Almehizia 20 PHRM 201 - Pharmacology - Lecture 5 2/17/2024 jon Neurotransmitters Communication between nerve cells and between nerve cells and effector organs occurs through the release of specific chemical signals (neurotransmitters) from the in nerve terminals The release is triggered by arrival of the action potential at the nerve ending leading to depolarization An increase in intracellular Ca2+ initiates fusion of synaptic vesicles with the presynaptic membrane and release of their contents The neurotransmitters rapidly diffuse across the synaptic cleft, or space (synapse), between neurons and combine with specific receptors on the postsynaptic (target) cell 22 22 Dr. Abdulrahman A. Almehizia 22 PHRM 201 - Pharmacology - Lecture 5 2/17/2024 A Neurotransmitters  Types of neurotransmitters: Although over 50 signal molecules in the nervous system have been identified, norepinephrine (NE), epinephrine (E), acetylcholine (Ach), dopamine (D), serotonin (SR), histamine, glutamate, and γ-aminobutyric acid (GABA) are most commonly involved in the actions of therapeutically useful drugs Each of these chemical signals binds to a specific family of receptors Acetylcholine and norepinephrine are the primary chemical signals in the ANS, whereas a wide variety of neurotransmitters function in the CNS 24 24 Dr. Abdulrahman A. Almehizia 24 PHRM 201 - Pharmacology - Lecture 5 2/17/2024 Neurotransmitters The autonomic nerve fibers can be divided into two groups based on the type of neurotransmitter released: 1. Cholinergic nerves 2. Adrenergic nerves 25 25 Dr. Abdulrahman A. Almehizia 25 PHRM 201 - Pharmacology - Lecture 5 2/17/2024 w̅ Neurotransmitters 1. Cholinergic nerves: Transmission is mediated by acetylcholine (ACh.) ACh mediates the transmission of nerve impulses across autonomic ganglia in both the sympathetic and parasympathetic nervous systems Acts on Nicotinic & Muscarinic (GPCR) receptors It is the neurotransmitter at the adrenal medulla Transmission from the autonomic postganglionic nerves to the effector organs in the parasympathetic system, and a few sympathetic system organs, also involves the release of acetylcholine In the somatic nervous system, transmission at the neuromuscular junction (the junction of nerve fibers and voluntary muscles) is also cholinergic Action terminated by acetylcholinesterase (AChE) 26 26 Dr. Abdulrahman A. Almehizia 26 PHRM 201 - Pharmacology - Lecture 5 2/17/2024 Neurotransmitters 1. Cholinergic nerves…cont’d: Drugs that mimic:  Cholinergic drugs, parasympathomimetic on  Cholinergic agonists: initiates a response Drugs that block:  Anticholinergic, parasympatholytic  Cholinergic antagonists - prevents a response 27 27 Dr. Abdulrahman A. Almehizia 27 PHRM 201 - Pharmacology - Lecture 5 2/17/2024 Neurotransmitters 2. Adrenergic nerves: son Norepinephrine (NE) is the neurotransmitter In the sympathetic system, NE mediates the transmission of nerve impulses from autonomic postganglionic nerves to effector organs Epinephrine (E) is secreted by the adrenal medulla (not sympathetic neurons) also acts as a chemical messenger in the effector organs Acts on adrenergic receptors Drugs that mimic:  Adrenergic drugs, sympathomimetics, or adrenomimetics  Adrenergic agonists - Drugs initiate a response Drugs that block:  Adrenergic blockers, sympatholytic or adrenolytic  Adrenergic antagonists - prevent a response 28 28 Dr. Abdulrahman A. Almehizia 28 PHRM 201 - Pharmacology - Lecture 5 2/17/2024 Neurotransmitters 2. Adrenergic nerves…cont’d: 4 types of adrenergic receptor organ cells (all GPCRs): I blood return to heart → 1. α-1: vasoconstriction of blood vessels → increase f BP increase circulation → increase 2. α-2: in the brain stem and in the periphery inhibit sympathetic activity → lower blood pressure → inhibits release of NE → decrease in vasoconstriction → decrease BP 3. β-1: increase heart rate & force of contraction 4. β-2: relaxation of smooth muscle in bronchi, uterus, peripheral blood vessels 29 29 Dr. Abdulrahman A. Almehizia 29 PHRM 201 - Pharmacology - Lecture 5 2/17/2024 y Neurotransmitters 30 30 Dr. Abdulrahman A. Almehizia 30 PHRM 201 - Pharmacology - Lecture 5 2/17/2024 Neurotransmitters Acetylcholine Norepinephrine Epinephrine All preganglionic neurons of ANS; all postganglionic Most sympathetic neurons of postganglionic neurons; Adrenal medulla Site of release parasympathetic system; adrenal medulla (20% of (80 % of secretion) Some sympathetic secretion) postganglionic neurons to sweat glands Nicotinic (Nn or Nm), α1, α2, β1, β2 Receptor Muscarinic (M1, M2, M3, α1, α2, β1 (adrenergic) (adrenergic) M4, M5) - cholinergic Reuptake into nerve terminals; diffusion of Metabolic synaptic cleft, metabolic transformation by Termination of Enzymatic degradation by transformation by catechol-O-methyl- activity cholinesterase monoamine oxidase transferase within (within nerve terminal) or liver cahtechol-O-methyl- transferase within liver) 31 31 Dr. Abdulrahman A. Almehizia 31 PHRM 201 - Pharmacology - Lecture 5 2/17/2024 Cholinergic Agonists 1. Direct-Acting Cholinergic Agonists 2. Indirect-Acting Cholinergic Agonists: Anticholinesterase Agents (Reversible) 3. Indirect-Acting Cholinergic Agonists: Anticholinesterase Agents (Irreversible) 32 32 Dr. Abdulrahman A. Almehizia 32 PHRM 201 - Pharmacology - Lecture 5 2/17/2024 Introduction The cholinergic drugs act on a receptors activated by acetylcholine (ACh) Act by either stimulating (agonists) or blocking (antagonists) receptors of the ANS Neurotr