Pharmacology Introduction (PDF)

Pharmacology introduction:................................................ 1 Indirect Sympathomimetics:................................................9 Parasympathomimetics are classified into:..................... 4 Cholinergic Antagonists: Parasympatholytics.....

Pharmacology introduction:................................................ 1 Indirect Sympathomimetics:................................................9 Parasympathomimetics are classified into:..................... 4 Cholinergic Antagonists: Parasympatholytics............... 10 Sympathomimetic drugs agonist........................................ 6 Sympatholytic (Adrenergic antagonist)......................... 12 Selective D1 agonist:................................................................7 Adrenergic Antagonists....................................................... 12 Alpha & Beta agonist:............................................................7 Alpha Blockers....................................................................... 13 Selective α1 Agonists.............................................................. 8 Beta-Blockers......................................................................... 13 Selective β1 Agonists.............................................................. 8 Alpha & Beta Blockers......................................................... 14 Selective β2 Agonists.............................................................. 8 Selective α1 & Nonselective β Blockers............................. 14 Pharmacology: is the science that deals with the study of drugs, which includes the following branches: Pharmacodynamics Pharmacokinetics Pharmacotherapeutics Toxicology Pharmacodynamics: The effects of drugs on the body, which includes: 1. Mechanism of action (MOA): active part of the cell which forms chemical bonds with drugs. These active parts are: Enzymes Ion channels Cell membrane Receptors DNA synthesis Chemical reaction (neutralization reaction), e.g., Antacid Physical reaction (Adsorption); e.g., charcoal, which is used in toxicity 2. Clinical use (desired effects of drugs) 3. Side effects (undesired effects of drugs) Pharmacokinetics: - is the effect of the body on drugs which includes: Absorption: Transfer of drugs from the site of administration to blood circulation which occurs in the small intestine Factors affecting absorption: A- factors related to the patient: 1. Food: The presence of food ↓ absorption with some exceptions such as antifungal drugs. 2. Health state: either constipation (↑ absorption) or diarrhoea (↓ absorption). B- factors related to drugs: 1. Liquid is more absorbed than solid. 2. Parenteral (injection) is more absorbed than oral 3. Particle size: small size is highly absorbed than large. 1  MED39 1 Pharmacology team 4. Lipid-soluble is more absorbed than water-soluble. Bioavailability: The amount of drug that reaches systemic (blood) circulation. ↑ Bioavailability means ↑ absorption (orally) ↓ Bioavailability means ↓ absorption in such case, we administer the drug other Chapter 1 Distribution: Spread of drugs all over the body to reach different body organs. Factors affecting distribution: ▪ Binding to plasma protein ▪ ↑ Binding to plasma proteins → inactive drugs have a long duration of action (t½). ▪ ↓ Binding to plasma proteins → active drugs Metabolism: The first step of drug elimination in which modification in the chemical structure of drugs. takes place, mainly occurs by liver enzymes. Other sites: GIT, plasma (contains esterase enzyme), kidney, and brain (10%) Aim: a. Conversion of drugs from active (lipid-soluble) to inactive (water-soluble) so it can be excreted. b. Conversion of prodrugs (inactive drugs) to active, e.g., captopril. c. Conversion of drugs from active to active (prolongation of action). d. Conversion of active drugs to toxic metabolites (rare cases). Factors affecting metabolism: 1. Healthy state of the liver (most important). 2. Age. 3. Sex: Drug metabolism occurs in males more than females because androgens [help more synthesis of enzymes]. 4. Drug-drug interaction: 1. Metabolic inducer: Drugs stimulate metabolism which may inactivate other drugs. 2. Metabolic inhibitor: Drugs inhibit metabolism which may cause toxicity of other drugs. Excretion: Removal of drugs outside the body. Site: Kidney (mainly) Other sites: GIT, sweating, lacrimation, salivation, and exhalation Water-soluble drugs (polar) → excretion is more than non-polar drugs. Healthy state of kidney is an important factor in excretion. Pharmacotherapeutics: The art of treatment of disease (Proper choice of drugs with proper dose for each health problem). Toxicology: The science that deals with the study of drug toxicity, which includes: 1. Toxic dose 2. Toxic symptoms 3. Treatment of toxicity 2 Page  MED39 MED39 1 ‫ أمساء علوان‬:‫الدكتورة‬ Pharmacology team Drugs: Any substance of any source which can be used for treatment, diagnosis, and prevention of diseases. Sources of drugs: 1. Synthetic drugs 2. Natural drugs that include: Plant (most important source) as digoxin and atropine Animal as insulin (from horse) Microorganism like fungus (penicillin) Marine (cod liver oil) omega 3 Soil as Zn+2, Mg+2, Ca+2 Route of administration: 1. External: -not reach to blood o produce local effects 2. Internal: -reach blood o orally, parenteral, inhalation, or rectal. Terminology Chapter 1 Agonist: Drug which binds to sympathetic receptor to produce similar effects to the normal neurotransmitter. Antagonist: Drugs bind to sympathetic receptor to block or inhibit the effects of normal neurotransmitter. Tolerance: Loss of drug’s response in which there is a need to increase drug dose to get the same effect (e.g., paracetamol). Tachyphylaxis: Rapid occurrence of tolerance. Dependence: Severe craving to drug in which sudden stop may cause central withdrawal effects which occur as (insomnia, anxiety, and nervousness) e.g., Diazepam. Addiction: Severe craving to drug in which sudden stop may cause peripheral and central withdrawal effect (death may occur) e.g., Morphine, Heroin. Potency: Strength of drugs (concentration of active constituents). Efficacy: Maximum response produced by drug. Onset of action: Time between drug administration and occurrence of effects. Duration of action: Time between occurrence of effects and reoccurrence of the symptoms of disease (effect of drug disappears). Therapeutic index (TI): The degree of drug safety. So, an increase in TI means a safe drug, while a decreased TI means a toxic drug. e.g., In paracetamol, the ED50 = 500mg and TD50=20g, so: TI= (20×1000)÷500=40 In paracetamol, TI= 40 means it’s a safe drug. Drug monitoring: 1. Parameters such as blood glucose, BP. 2. Free of symptoms such as fever, headache. Page 3  MED39 1 Pharmacology team 3. Concentration of drugs in blood. Terminology: 1. Parasympathetic stimulators (Parasympathomimetics). 2. Parasympathetic inhibitors (parasympatholytics). 3. Sympathetic stimulator (sympathomimetic). 4. Sympathetic inhibitor (sympatholytic). Chapter 1 Parasympathomimetics are classified into: Parasympathomimetics (cholinergic agonist): Drugs bind to parasympathetic receptors (N, M) to produce a similar effect to the natural neurotransmitter (ACh). Effects: 1. ↑ Memory and learning. 2. Eye: Miosis ↓ intraocular pressure (IOP) → ↑ drainage of aqueous humour. 3. Cardiac work: ↓ Contraction, ↓ COP, ↓ HR. 4. B.C which will lead to asthma. 5. GIT: ↑ HCl secretion (hyperacidity), ↑ motility (diarrhoea). 6. Nausea and vomiting. 7. Urinary Bladder: Contraction of the wall and relaxation of sphincter → Frequency of urination. 8. Blood vessels: V.D via ↑ NO (indirect effect) which will lead to: A) Hypotension B) Congestion (nasal congestion, redness of eyes). 9. Uterus: ↑ Contraction of wall (abortion). 10. Saliva: ↑ Watery secretion (parasympathetic increases watery secretion and sympathetic decreases it). 11. ↑ Sweating and lacrimation. 12. Contraction of skeletal muscle → by stimulating the nicotinic receptor. Note: All peripheral effects are results from stimulating the muscarinic receptor (M) except in the skeletal muscle which is by stimulating of nicotinic receptors (N). Muscarinic receptors: M1: Parietal cells of the stomach → ↑ HCl secretion. M2: Heart → ↓ HR. M3: All over the body. M4 & M5: In the CNS. Parasympathomimetics are classified into: 1. Direct agonist: The drug binds to the receptor to produce effects directly. It works on the M receptors only. 2. Indirect agonist: The drug increases acetylcholine, then acetylcholine will bind to the receptor and give the effect. It works on both M and N receptors. 4 Page  MED39 MED39 1 ‫ أمساء علوان‬:‫الدكتورة‬ Pharmacology team Direct agonist drugs: Sjogren’s disease Pilocarpine (eye drops): MOA: Stimulates all the M agonists (non-selective). is an autoimmune disease which comes out as dry eye & dry CU: Glaucoma, Sjogren’s disease. mouth the drug is helpful. Bethanechol (oral and parenteral): MOA: M agonist. CU: Glaucoma, postoperative urine retention & paralytic ileus. (Where this drug make contraction of UB which prevents the urine retention and increases the motility of the GIT especially the small intestine) Cevimeline (oral): MOA: Selective M3 agonist. CU: Sjogren’s disease. Indirect agonist drugs: MOA: Ach esterase inhibitors → so it increases the duration of Ach in the body. Chapter 1 Types: Reversible Ach esterase inhibitors: o Block the enzyme for a short duration. Irreversible Ach esterase inhibitors: o Toxic compounds. o The body is under control of the parasympathetic (it takes the upper-hand). Reversible drugs: 1. Physostigmine: o CU: a) Eye drop in glaucoma, b) I.V in acute state such as poisoning. which means that we can use it as antidote for cholinergic antagonist. 2. Neostigmine & Pyridostigmine: CU: Postoperative urine retention and paralytic ileus, Myasthenia gravis. o 3. Donepezil & Rivastigmine: o More selective on central esterase. Notes: They differ in the type of esterase o Used either orally or transdermal patches which they act on: o CU: Dementia, which may be caused by o Donepezil: More selective on Ach degenerative diseases such as esterase in CNS. Alzheimer’s, Parkinson’s disease, or o Rivastigmine: Inhibits both ACh drug-induced as anticholinergic drugs. esterase and butyryl choline esterase. Irreversible compounds: Organophosphate Compounds (Cpd) These are toxic compounds such as: Insecticides: Parathion, Malathion 🐛 War Gases: Sarin, Soman 💣 They lead to: Severe miosis 👁️ Severe sweating with salivation 💦 Bradycardia Convulsion 🤯 Bronchoconstriction 🫁 Decreased B.P (Blood Pressure) Fever 🤒 Diarrhoea and increased urination 🚽 Page 5  MED39 1 Pharmacology team Treatment of toxicity by organophosphate compounds: Non-Pharmacological Treatment: 🚑  First Aid: o Airways 🌬️ o Breathing 🫁 o Circulation 💓  Washing body and changing clothes 👕🚿 Chapter 1  Artificial oxygen 🧬  Ice bag “❄️ ” Pharmacological Treatment: 💊 That is done by Atropine I.V → M- Diazepam: Skeletal Pralidoxime (PAM): I.V antagonist used to block M muscle relaxant (for (Ach esterase reactivator) receptors (Reverse the effect) convulsion) Acetylcholine-like Side Effects for Direct & Indirect Drugs: Miosis 👁️ Congestion Bradycardia Abortion Bronchoconstriction 🫁 Nausea and vomiting 🤢 Hyperacidity Increased salivation and sweating 💦 Diarrhoea Frequency of urination 🚽 Hypotension Contraction of skeletal muscles 💪 Sympathomimetic drugs agonist Sympathomimetic (Adrenergic agonists): drugs bind to sympathetic receptor to produce similar effects to natural neurotransmitters (adrenaline, noradrenaline and dopamine) Catecholamines synthesis. tyrosine → dopa (dihydroxyphenylalanine) → dopamine → norepinephrine (noradrenaline) → epinephrine (adrenaline) Receptors of sympathetic system Receptor Location Action α1 Eye Mydriasis BV Vasoconstriction (VC) → Increase BP, decongestion Sphincter of Constriction U Bladder α2 Nerve Autoregulation of Sympathetic → Stimulate α2 receptors → Terminals Decrease release of neurotransmitter β1 Eye Production of aqueous humor → IOP Heart Increase cardiac work (↑ Contraction, ↑ Cardiac Output, ↑ HR) 6 Page  MED39 MED39 1 ‫ أمساء علوان‬:‫الدكتورة‬ Pharmacology team Kidney Renin release → Conversion of angiotensinogen (released from liver) to angiotensin I which is converted to angiotensin II by angiotensin-converting enzyme → Increase blood pressure β2 Bronchi Bronchodilation (mainly) Uterus Wall Relaxation used to prevent premature labor Urinary Relaxation Bladder Wall Blood Vessels Vasodilation of BV of skeletal muscles → Increase O2 supply and warmth sensation → Improve their work. Coronary artery → Vasodilation to increase O2 supply to the heart Liver Glycogenolysis → Increase blood glucose β3 Adipose Lipolysis (no clinical use till now) tissue Wall of U Relaxation of detrusor muscle → Urine retention Bladder D1 Renal Blood Vasodilation → ↑ Renal Perfusion → ↑ Glomerular Filtration Rate Chapter 1 Vessels (GFR) (agonist drugs clinically used in renal failure) Alpha1 & Beta receptors agonist CNS → anxiety and decrease in memory and learning GIT → ↓ HCL secretion and ↓ motility → constipation , ↓ watery secretion of saliva Adrenergic agonists drugs: divided into: Direct &indirect Direct adrenergic agonists Selective D1 agonist: 1) Dopamine (polar drug) CU: acute renal failure ROA: parenteral SE: high dose may cause tachycardia (β1), hypertension (α1) 2) Fenoldopam (parenteral) → peripheral V.D CU: acute hypertension SE: hypotension Alpha & Beta agonist: e.g: (Adrenaline=polar drug) ROA: P (IM, IV) MOA: Stimulates the following receptors: o Alpha1: Acute hypotension, vasoconstriction (VC) ▪ To prevent bleeding ▪ Used in combination with local anesthesia for prolongation of the action of the drug, prevents bleeding and hypotension o Beta1: Cardiac arrest (IV) o Beta2: Acute bronchial asthma at resistant Adrenaline is the drug of choice in case of anaphylactic shock as it stimulates α1 and β1,2 receptors. In this case, we administer it (IM) not (IV). Anaphylactic shock: hypotension, bronchoconstriction, ↓ HR Side Effects: Increase BP & HR. Page 7  MED39 1 Pharmacology team Selective α1 Agonists ① Phenylephrine: Clinical use: Direct nasal decongestant orally in combination with an analgesic or flu drug (because it will increase BP). (IV): In case of acute hypotension. It has a short duration of action (3 times a day). ② Midodrine: Orally for chronic hypotension. Chapter 1 It has a long duration of action. ③ Oxymetazoline (nasal drops): For nasal congestion (when the cause is not flu). SE: Reflex bradycardia, hypertension, weak mydriasis, and urine retention. Selective β1 Agonists Dobutamine: CU: For acute heart failure (IV). Note: Dopamine is used in heart failure if the patient is suffering from renal failure. SE: Tachycardia or arrhythmia. Selective β2 Agonists ① Salbutamol (inhalation or oral): CU: For acute bronchial asthma and to prevent premature labor. Note: Salbutamol is used to prevent premature labor only if it is taken from the beginning of the pregnancy; if used late, it will delay labor for only 72 hours. Characteristics: a. Rapid onset (about 30 minutes). b. Short duration (4-6 hours). ② Salmeterol (by inhalation only): For chronic bronchial asthma. Characteristics: a. Slow onset (1 hour). b. Long duration (12 hours). ③ Clenbuterol: Has an anabolic effect. CU.: Is illegal for athletes. Chronic bronchial asthma (now, it is not used because of its illegal effect). ④ Ritodrine (orally): CU.: To prevent premature labor. SE.: Hyperglycemia → glycogenolysis in the liver Tachycardia: β2 → vasodilation in the coronary artery increases oxygen supply leading to tachycardia, and also by a lesser action on β1, leads to tachycardia & tremors. Note: Tremors happen when picking up an object. Contraindications: Diabetes mellitus. 8 Page  MED39 MED39 1 ‫ أمساء علوان‬:‫الدكتورة‬ Pharmacology team Selective β3 Agonists ① Mirabegron: CU: Orally in case of urinary bladder over-activity in adults, not children, because in children it is due to psychological causes. SE: Tachycardia (β1) & Tremor (β2). Indirect Sympathomimetics: Effects: There are two types of effects: Peripheral effect: (the same effects as direct sympathomimetics) Central effects: Alertness, euphoria, insomnia, anxiety, dysphoria, agitation, loss of appetite, dependence. Increases the release of catecholamines. MOA: Decreases the re-uptake of catecholamines. Chapter 1 Amphetamine (Oral): EX: a. High central and peripheral effects. b. High dependence potential. c. Known as a drug of abuse. d. Previously used in attention deficit syndrome (hyperkinetic children) to decrease movement, increase obedience, and enhance attention. Also used for the treatment of narcolepsy and obesity. Hypertension SE: Tachycardia Psychosis, hallucinations, and drug dependence. Cathinone and Cathine: Active constituents of Qat with amphetamine-like effects. Qat decreases blood glucose levels in the first two hours of chewing, then increases it, making it not helpful for diabetic patients. EX: Ephedrine (Plant Extract, Used Orally): Lower central effect than amphetamine, but higher peripheral effect. Clinical use: In combination with cough or flu preparations. 1. With cough preparations → BID (twice daily, most common) 2. With flu preparations → acts as a decongestant due to vasoconstriction Pseudoephedrine (plant extract and used orally): Very low central effects and peripheral effects less than Ephedrine. Clinical use: Indirect nasal decongestant used in combination with flu preparation. SE: Side Effects of Ephedrine and Pseudoephedrine: 1. Urine retention, constipation, increased heart rate (HR) and blood pressure (BP). 2. Loss of appetite. 3. Insomnia (if taken at night). Note: No dependence on Ephedrine and Pseudoephedrine. They’re classified as OTC (Over The Counter) drugs, meaning they can be taken without a prescription and do not produce toxic effects. Page 9  MED39 1 Pharmacology team Cholinergic Antagonists: Parasympatholytics Cholinergic antagonists are drugs that bind to parasympathetic receptors to block or inhibit the effects of the neurotransmitter acetylcholine. 1. Decreasing memory and learning 🧠 2. Causing sedation 😴 3. Inducing mydriasis, ↑ IOP by decreasing the drainage of aqueous humor 👁️ 4. Bronchodilation (BD) 🫁 Chapter 1 5. Increasing cardiac work, leading to tachycardia 💓 6. Reducing watery secretion, resulting in dry mouth and dry skin 7. Causing urine retention through contraction of sphincters and relaxation of the bladder wall 8. Decreasing HCL secretion and motility, leading to constipation 9. Relaxing the wall of the uterus 🤰 10. Relaxing skeletal muscle 💪 There is no parasympathetic innervation to the liver and blood vessels. Note: BV by an “indirect effect” where decreased nitric oxide (NO) prevents its vasodilation effect. Mechanism of Action: M-receptor antagonist (non-selective) Examples: ① Atropine (plant extract) Duration of action: 3-4 hours CU: IV injection  Antidote for cholinergic agonist  Preanesthetic medication to decrease salivation and watery secretions from respiratory system.  Bradycardia (Essential) ② Hyoscine (plant extract) orally & parenterally Clinical uses:  Drug of choice for nausea and vomiting induced by motion sickness  Antispasmodic in gastrointestinal and urinary system spasms 🌀 ③ Tropicamide (eye drop) Clinical use as a mydriatic for retina examination and iritis 👁️ Duration of action: 4-6 hours ④ Ipratropium Bromide (inhalation) Clinical use as a bronchodilator in acute bronchial asthma 🫁 Duration: 4-6 hours, hence called Short Acting M-Antagonist (SAMA) ⑤ Tiotropium (inhalation) Clinical use as a bronchodilator in acute asthma 🫁 Duration: 24 hours, hence called Long Acting M-Antagonist (LAMA) ⑥ Clidinium (oral) MOA: Selective M3 antagonist Clinical use: GIT spasm, can be used in combination with anti-anxiety medication for irritable bowel disease (Librax). ⑦ Tolterodine (oral) MOA: Selective M3 antagonist Clinical use: More selective on the urinary system for spasms and incontinence in the elderly in case of non-infectious urgency ⑧ Glycopyrrolate (oral/parenteral) MOA: Selective M3 antagonist 10 Page  MED39 MED39 1 ‫ أمساء علوان‬:‫الدكتورة‬ Pharmacology team CU: More selective on the salivary gland, used as preanesthetic medication and for drooling of saliva in conditions like Parkinson’s disease ⑨ Oxybutynin (oral) MOA: Non-selective M-antagonist Clinical use: Urine incontinence in children with autonomic nervous system defects ⑩ Orphenadrine (oral/parenteral) MOA: Blocks M-receptors and Nm receptors on skeletal muscles CU: Skeletal muscle relaxant for muscle spasms due to local trauma, sometimes used in combination with analgesics like paracetamol 💪 ⑪ Procyclidine MOA: Blocks M receptors and Nm receptors in skeletal muscles Clinical use: For drug-induced parkinsonism ⑫ Benzatropine MOA: Blocks M receptors and Nm receptors in skeletal muscles Clinical use: Adjuvant therapy in Parkinson’s disease Side Effects of Cholinergic Antagonists (Atropine-like SE): Chapter 1 1. Mydriasis 👁️ 5. Constipation 2. Increased IOP 6. Urine retention 🚽 3. Dry skin and dry mouth 7. Dementia 🧠 4. Tachycardia 💓 8. Sedation 😴 Contraindications of Cholinergic Antagonists: 1. Glaucoma 👁️ 5. Prostatic enlargement 2. Sjogren’s disease 6. Myasthenia gravis 3. Tachyarrhythmia 💓 7. Elderly 👵👴 4. Intestinal obstruction Note: Prostatic enlargement and glaucoma are age-related diseases. Page 11  MED39 1 Pharmacology team Sympatholytic (Adrenergic antagonist) These drugs cause: 1. Relief of anxiety 2. Decrease in aqueous humor production ➟ decrease in IOP 3. Miosis 4. Decreased myocardial contraction ➟ lower cardiac output, HR, and BP. 5. Bronchoconstriction 6. Decreased renin release Chapter 1 7. Increased urination frequency 8. Increased GIT motility ➟ diarrhoea 9. Hypoglycemia due to decreased glycogenolysis 10. Hyperlipidemia with inhibited lipolysis 11. Vasodilation ➟ congestion and hypotension (α1) 12. Inhibition of β2 receptors ➟ vasoconstriction in blood vessels of skeletal muscles and coronary arteries, causing fatigue and cold extremities Note: An imbalance between blood supply and required oxygen is termed angina pectoris. Adrenergic Antagonists The classification of adrenergic antagonists depends on their mechanism of action, which is determined by the type of receptor they target. Selective α2 Agonist MOA: Inhibits the release of catecholamines, preventing sympathetic receptor binding and subsequent effects. Note: Stimulation of α2 receptors blocks sympathetic actions and vice versa. Clonidine (Oral Use) CU: Treats chronic hypertension, especially in patients with psychological issues or addiction. Characteristics: Stimulates α2 receptors. Activates the imidazoline ring in the CNS, leading to sedation. Side Effects: Bradycardia Hypotension Peripheral effects Diarrhea Sedation Central effects Alpha-Methyldopa (Oral Use) Mechanisms of Action: 1. Stimulation of α2 agonists. 2. Formation of a false neurotransmitter “L-Dopa,” reducing the levels of true dopamine. Clinical use: Exclusive to chronic hypertension treatment in pregnant women. Side Effects: 1. From α2 stimulation: ▪ Decreased heart rate and blood pressure (bradycardia). ▪ Diarrhoea 2. From decreased dopamine: ▪ Central effects: depression, extrapyramidal-like side effects. 12 Page  MED39 MED39 1 ‫ أمساء علوان‬:‫الدكتورة‬ Pharmacology team ▪Peripheral effects (hormonal): hyperprolactinemia, leading to galactorrhea, gynecomastia, and infertility. 3. Hemolytic anemia (rare). Contraindications: Not to be used in patients with G6P dehydrogenase deficiency due to the risk of hemolytic anemia. Alpha Blockers Nonselective Alpha Blockers MOA: Inhibit α1 → Vasodilation (VD) Inhibit α2 → Increase in catecholamine levels; however, adrenaline will only work with β receptors, resulting in an increased heart rate and bronchodilation (since α receptors are blocked). Example: Phenoxybenzamine Use: Orally, in combination with propranolol to also block β receptors. Chapter 1 CU: Pheochromocytoma SE: ▪ Hypotension ▪ Tachycardia (direct effect, not reflex) Selective Alpha 1 Blockers Effects of Drugs: a. Decrease in blood pressure. b. Increase in heart rate by reflex mechanism c. Congestion d. Relaxation of the urinary bladder sphincter Examples: Prazosin, Doxazosin, Terazosin, etc., used orally. Clinical Use: Chronic hypertension in patients suffering from benign prostatic hyperplasia (BPH) Note: If the patients have only hypertension without BPH, this type of drug is not given, and vice versa. Tamsulosin Use: Orally MOA: Selective α1a blocker in the sphincter of the urinary bladder. Clinical Use: Urine retention in prostatic enlargement (BPH) without hypertension Side Effects of Alpha 1 Blockers Postural hypotension (can be treated by Midodrine) Reflex tachycardia Congestion Beta-Blockers Nonselective β Blockers: These are very common. ① Timolol: Eye drops used for glaucoma. ② Propranolol: Oral medication that undergoes first-pass metabolism and has a short duration, requiring dosing three times daily. Page 13  MED39 1 Pharmacology team  Clinical Uses: 1. Cardiac diseases such as hypertension, arrhythmia, all types of anginas (except vasospastic angina), and heart failure. Administered in small or intermittent doses to decrease mortality rates. 2. Performance anxiety as symptomatic treatment. 3. Thyrotoxicosis, as thyroxine stimulates sympathetic β receptors. 4. Migraine headaches, the only drug used prophylactically for migraines. 5. In combination with nonselective α blockers for Pheochromocytoma. Chapter 1 6. To prevent oesophageal bleeding caused by hepatic cirrhosis or esophageal varices. ③ Nadolol: Similar to propranolol but with a longer duration of action. Preferred in hepatic patients and as a prophylactic for esophageal bleeding. Doesn’t bypass first-pass metabolism. β-Blockers Side Effects 1. β1: Decrease in heart rate ➟ hypotension. 2. β2: May cause bronchial asthma, hypoglycemia, fatigue, and cold extremities. 3. β3: Hyperlipidemia. 4. Vivid dreams ➟ dreams like reality. Contraindications 1. Bronchial asthma. 2. Diabetes mellitus. 3. Raynaud’s disease patients. 4. Patients with hyperlipidemia. Selective β1 Blockers Betaxolol: Eye drops → decrease intraocular pressure, used for glaucoma. Esmolol: (IV) administration with a short duration of action (10-20 minutes), Clinical Use: Emergency hypertension Arrhythmia during surgery. Bisoprolol & Atenolol: Oral use Clinical Use: 1. hypertension with cardiac disease. 2. Atenolol is preferred in hypertension with angina. Nebivolol: Used in hypertension due to its vasodilation effects, which occur by increasing nitric oxide (NO) release. Side Effects 1. Bradycardia. 2. Hypotension. Alpha & Beta Blockers Selective α1 & Nonselective β Blockers Labetalol: Oral or parenteral. Clinical Use: 1. Antagonizes adrenaline in cases of overdose or Pheochromocytoma. 2. Acute and chronic hypertension in pregnant women. 14 Page  MED39 MED39 1 ‫ أمساء علوان‬:‫الدكتورة‬ Pharmacology team Carvedilol: Oral Clinical Use: heart failure to decrease mortality rate. Side Effects of α1 & β Blockers 1. Bradycardia. 2. Hypotension. 3. Hypoglycemia. 4. Bronchoconstriction. 5. Cold extremities (at large doses). Chapter 1 Page 15