Drugs Affecting Respiratory, Cardiovascular & Renal Systems PDF

Drugs affect on respiratory system 9/19/2024 1 Anatomies 9/19/2024 2 Definition The respiratory system provides a mechanism for the exchange of oxygen and carbon dioxide in the lungs. 9/19/2024 3 Cont… Most common con...

Drugs affect on respiratory system 9/19/2024 1 Anatomies 9/19/2024 2 Definition The respiratory system provides a mechanism for the exchange of oxygen and carbon dioxide in the lungs. 9/19/2024 3 Cont… Most common conditions of the upper respiratory system are:  Infections,  Allergic Rhinitis,  Coughs,  Common Cold, And  Congestion. 9/19/2024 4  Cont… Typically, upper respiratory infections are treated with: Antibiotic if bacteria and Comfort measures are used if viral:  Antihistamines to relieve allergy symptoms  Decongestants to reduce nasal edema,  Antitussives  Mucolytics, and  Expectorants to treat accompanying cough 9/19/2024 5 Disorders of the lower respiratory tract and drugs used: Disorders Drugs may used Asthma Bronchodilater Emphysema Xanthine derivatives. Chronic Bronchitis Corticosteroids, COPD Leukotriene modifiers, Mast cell stabilizers. 9/19/2024 6 Nasal decongestants Nasal congestion results from dilation and engorgement of blood vessels in the nasal mucosa. Drugs can relieve congestion by causing alpha mediated vasoconstriction 9/19/2024 7 Nasal Decongestants Drugs Topical (nasal spray, nasal drop)  Phenylephrine hydrochloride  Naphazoline hydrochloride  Tetrahydrozoline hydrochloride  Oxymetazoline hydrochloride  Xylometazoline hydrochloride Ephedrine (Oral) 9/19/2024 8  Drugs for allergic Rhinitis Allergic rhinitis is an inflammatory disorder that affects the upper airway, lower air way, and eyes. Major symptoms are:  Sneezing, Rhinorrhea  Pruritus (Itching)  Nasal Congestion  Conjunctivitis, 9/19/2024 9  List of drugs Antihistamines : Diphenhydramine(oral) Intranasal glucocorticoids: Dexamethasone) Intranasal: cromolyn sodium Sympathomimetics: Decongestants). Anti-cholinergic agents : Ipratropium 9/19/2024 10  Cough remedies: Drugs used to alleviates the cough. Non-Productiv Cough Productive Cough guaifenesin (xpectorants) Dextromethorphan. used to increasing the volume of secretions that facilitates removal by coughing 9/19/2024 11  Cough remedies Cough remedies in general can be categorized as: 1. Specific agents: To treat the cause of cough: e.g. anti-bacterials. 2. Non-specific agents: To relief symptoms:  Expectorants  Demulcents  Anti-tussives 9/19/2024 12  Expectorants Facilitate the removal of mucous by increasing its volume, and decreasing viscosity of bronchial secretion. They are of two types  Reflexing acting  Mucolytics i. Reflexing acting Examples: guanifenesin , ammonium chloride Uses :Relief of cough associated with respiratory tract infection (sinusitis, asthma, bronchitis, pharyngitis), especially when the cough is dry and nonproductive. 9/19/2024 13 Cont... ii. Mucolytics Examples: acetylcysteine Mucous is composed of water and glycoprotiens. Mucolytic agents break the disulfide bond and thereby decrease viscosity of mucous. 9/19/2024 14  Anti-tussives Antitussives are drugs that suppress cough, Examples:  Opioid alkaloids (codeine) and  Non opioid (dextromethorphan) MOA Binds to opiate receptors and blocks ascending pain pathways;  Anti-histamines. 9/19/2024 15  Dextromethorphan Dextromethorphan  The most effective non-opioid cough medicine acts in the CNS  It does not produce euphoria or physical dependence Indications:  Symptomatic relief of non-productive cough due to minor throat and bronchial irritation occurring with colds or inhales irritants. 9/19/2024 16  Anti-histamines Chlorpheniramine, dimenhydrate, Has sedative and anti-cholinergic effect Relief symptoms of cough. Pharyngeal demulcents Examples: eucalyptus, menthol They sooth the throat by forming a protective layer. 9/19/2024 17  Asthma 9/19/2024 18  Drugs used for the treatment of asthma Asthma is chronic reversible inflammatory disease due to tracheal and bronchial hyper responsiveness to various stimuli. Asthma = Airway Obstruction + Airway Inflammation 9/19/2024 19 9/19/2024 20  Antiasthmatics Antiasthmatic drugs fall in to two main pharmacologicalagents Anti-inflammatory classes: Bronchodilators Glococorticoids Beta2 agonists: Mast cell stabilizers I. Non selective -agonists e.g. adrenaline II. Selective -agonists e.g. salbutamol Methly xanthines Anti-cholinergics/parasymphatolytics 9/19/2024 21  Bronchodilators 1. Beta-2 agonists:  Short acting agents: salbutamol (albuterol), Terbutaline, Adrenaline, Ephedrine  Long acting agents: salmeterol, formeterol 9/19/2024 22  Salbutamol. Mechanism of action: Relaxes smooth muscles of the bronchioles by stimulating β2-adrenergic receptors. Indications/dosage/route: Route: Oral, inhalation Indications: -Bronchodilation -Prophylaxis of exercise-induced bronchospasm Dosage: Initial management 9/19/2024 Salbutamol, 200μg MDI 23 Advice to patient Avoid OTC products without consulting treating physician. Do not use solutions that contain a precipitate or are discolored. Contact treating physician if more than 3 inhalations are required within a 24-hour period to obtain relief. Wait at least 1 minute after 1 or 2 inhalations before taking a third dose. Keep spray away from eyes. Maintain adequate fluid intake (2000–3000 mL/d) to facilitate clearing of secretions. 9/19/2024 24  2. Anticholinergics Anticholinergics Include: Atropine Ipratropium bromide methyl nitrate, Have excellent bronchodilator effect and minimal side effects  Indications: Relief of bronhospasm in reversible air ways obstruction, especially COPD 9/19/2024 25  3. Methylxanthines: Methylxanthines: Theophylline, aminophylline Theophylline Indications:  Treatment of acute, severe and chronic persistant asthma and COPD.  It has also diuretic effect Aminophylline for acute severe asthma. 9/19/2024 26  Anti-inflammatory agents Corticosteroids Used both for Rx & prophylactic purposes Examples: Inhaled glucocorticoids:  dexamethasone  belcometasone  budesonide, Oral glucocorticoids: predinsolone Intravenous glucocorticoids:  hydrocortisone,  methyl predinsolone 9/19/2024 27 Clinical uses of Corticosteroids in bronchial asthma: Urgent Rx of severe asthma not improved with bronchodilator  IV, inhalation or oral. Nocturnal asthma prevention  Oral or inhalation Chronic asthma  Regular aerosol corticosteroids 9/19/2024 28 Mast cell stabilizers E.g. cromylon sodium MOA: Inhibit the release of histamine and other mediators It has no role once mediator is released &Used for casual prophylaxis. Clinical uses Exercise and antigen induced asthma Occupational asthma 9/19/2024 29  Drugs affecting on the Cardiovascular and Renal system [email protected] A/H/S/C 9/19/2024 30  Antihypertensive Drugs 9/19/2024 31 Introduction Antihypertensive drugs are used to treat hypertension, It is usually defined as a BP above 140 /90 mm Hg on multiple blood pressure measurements. 9/19/2024 32 Factors contribute for Hypertention Fluid accumulation Increase peripheral risestance (vasoconstriction) Increase Heart rate Increase force of contraction of heart muscle ( increase cardiac out put) Increase lipid degradation ( from adipose tissue) Uknown cause 9/19/2024 33  Hypertension Classification According to the level of diastolic blood pressure: 1. Mild hypertension with a diastolic BP between 95-105 mmHg 2. Moderate hypertension with a diastolic BP between 105 – 115mmHg 3. Severe hypertension with a diastolic BP above 115mmHg 9/19/2024 34 Antihypertensive therapies. Non pharmacological therapy Pharmacological therapy. 9/19/2024 35 1. Non-pharmacological Therapy Low NaCl diet Exercise Weight reduction Cessation of smoking Quit smoking 9/19/2024 36 Non-pharmacological Therapy Decrease in excessive consumption of alcohol Psychological methods (relaxation, méditation …etc) Dietary decrease in saturated fats. 9/19/2024 37 Pharmacological therapy Anti - hypertensive drugs are classified according to the principal regulatory site or mechanism on which they act. i. Diuretics ii. Sympathoplegic agents iii. Direct vasodilators iv. Angiotensin converting enzyme inhibitors v. Calcium channel blockers, 9/19/2024 38  Diuretics Diuretics 9/19/2024 39  i. Diuretics Lower BP by depleting the body sodium and reducing blood volume. Are effective in lowering blood pressure by 10 – 15 mmHg in most patients. Diuretics include: a) Thiazides and related drugs e.g. hydrochlorthiazide bendrofluazide, chlorthalidone, etc. b) Loop diuretics, e.g. furosemide (lasix), bumetanide (Bumex) ethacrynic acid, etc. c) Potassium sparing diuretics, e.g. spironolactone 9/19/2024 40 a. Thiazide Diuretics They increase urinary water and electrolyte particularly sodium excretion. Are appropriate for most patients with mild or moderate hypertension and normal renal and cardiac function. 9/19/2024 41  b. Loop diuretics Loop diuretics are more potent than thiazides. The antihypertensive effect is mainly due to reduction of blood volume. Loop diuretics are indicated in cases of severe HTN which is associated with:  Renal failure,  Heart failure or  Liver cirrhosis. 9/19/2024 42 c. Potassium sparing diuretics They are used as adjuncts with thiazides or loop diuretics to avoid excessive potassium depletion and to enhance the natriuretic effect of others. The diuretic action of these drugs is weak when administered alone. 9/19/2024 43  ii. Sympathoplegic agents Are depressants of sympathetic activity. Based on the site or mechanism of action sympathoplegic drugs are divided into: 1. Centrally acting antihypertensive agents 2. Adrenoceptor antagonists, 3. Adrenergic neuron – blocking agents 4. Drugs which deplete catecholamine stores 5. Drugs that interfere with norepinephrine synthesis 9/19/2024 44 1. Centrally acting antihypertensive agents E.g:- methyldopa, clonidine MOA Act by stimulating α2 – receptors. as a result, sympathetic out flow from the CNS is diminished and either total peripheral resistance or cardiac out put decreases. 9/19/2024 45 2. Adrenoceptor antagonists, E.g:-propranolol (beta blocker)  which decreasing cardiac out  prazosin (alpha blocker) which can produce peripheral vasodilation, decrease peripheral resistance and blood volume.  labetalol (alpha and beta blocker). 9/19/2024 46  iii. Direct vasodilators. These include:-  Arterial vasodilators, e.g. hydralazine It dilates arterioles but not veins. It is used particularly in severe hypertension.  Arteriovenous vasodilators, e.g. Na+ nitroprusside It is a powerful vasodilator that is used in treating hypertensive emergencies as well as severe cardiac failure. Adverse effects Metabolic acidosis, arrhythmias, excessive hypotension and death. 9/19/2024 47 iv. Angiotensin converting enzyme inhibitors. e.g. captopril, enalapril, etc. Are potent vasoconstrictor, which additionally stimulates the secretion of aldosterone. It lowers BP by decreasing peripheral vascular resistance. Adverse effects:  Maculopapular rash, angioedema, cough, granulocytopenia and diminished taste sensation. 9/19/2024 48  v. Calcium channel blockers e.g. nifedipine, verapamil, nicardipine, etc. MOA Inhibition of calcium influx in to arterial smooth muscle cells, resulting in a decrease in peripheral resistance. and may decrease heart rate and cardiac out put as well. Adverse effects:  Cardiac arrest, bradycardia, atrioventricular block and congestive heart failure. 9/19/2024 49 Summery For most patients with mild hypertension and some patients with moderate hypertension monotherapy with either of the following drugs can be sufficient.  Thiazide diuretics  Beta blockers  Calcium channel blockers  Angiotensin converting enzyme inhibitors  Central sympathoplegic agents 9/19/2024 50  Cont.. If mono-therapy is unsuccessful, combination of two drugs with different sites of action may be used.  Thiazide diuretics may be used in conjunction with a beta-blocker, calcium channel blocker or an angiotensin converting enzyme inhibitor. If hypertension is still not under control, a third drug e.g. vasodilator such as hydralazine may be combined. When three drugs are required, combining:  Diuretic,  Sympathoplegic agents or an ACE inhibitor, and 9/19/2024 51  Drugs for heart failure 9/19/2024 52  Drugs for heart failure Occurs when there is an inability of the heart to maintain sufficient cardiac out. Heart failure is usually caused by one of the following:  Ischaemic heart disease,  Hypertension,  Heart muscle disorders, and  Valvular heart disease. 9/19/2024 53  Cont… Drugs used to treat heart failure can be broadly divided into: 1. Drugs with positive inotropic effect. 2. Drugs without positive inotropic effect 9/19/2024 54 1. Drugs with positive inotropic effect They increase the force of contraction of the heart muscle. These include: a. Cardiac glycosides b. Sympathomimetics, and c. Methylxanthines 9/19/2024 55  a. Cardiac glycosides. E.g:- digoxin and digitoxin. They increase cardiac out put and alter the electrical functions. MOA Inhibition of the membrane-bound Na+ /K+ ATPase , results in an increased intracellular movement of sodium and accumulation of sodium in the cells. Leading to an increase in the intracellular calcium that acts on contractile proteins. 9/19/2024 56 c. Beta - adrenergic stimulants e.g. dobutamine, dopamine The increase in myocardial contractility by beta stimulants increase the cardiac out put. It is reserved for management of acute failure or failure refractory to other oral agents. 9/19/2024 57  e. Methylxanthines e.g. theophylline in the form of aminophylline Aminophylline has a positive inotropic effect, bronchodilating effect and a modest effect on renal blood flow. It is used for management of acute left ventricular failure or pulmonary edema. 9/19/2024 58 2. Drugs without positive inotropic effect. Diuretics, e.g. hydrochlorothiazide, furosemide  Are first – line drugs for treatment of patients with heart failure which reducing ventricular preload. Vasodilators, e.g. hydralazine, sodium nitroprusside  Reduction of both preload (through venous dilation) and after-load (through arteriolar dilation) ACEIs e.g. captopril, enalapril  Reduce both after load and preload. 9/19/2024 59  Drugs acting on the Blood Learning objectives  Antithrombotic  Drugs for anemia 9/19/2024 60  Antithrombotic 9/19/2024 61 Introduction Thrombosis involves the formation or presence of a blood clot in the vascular system. Anticoagulant, antiplatelet, and thrombolytic drugs are used in the prevention and management of thrombotic disorders. 9/19/2024 62  Anticoagulants Are drugs given to prevent formation of new clots. They do not dissolve formed clots.  E.g:-Heparin and warfarin  Warfarin are acts in the liver to prevent synthesis of vitamin K–dependent clotting factors Clinical indications include:  prevention or management of thrombophlebitis, DVT, and pulmonary embolism.  Heparin is also used in disseminated intravascular coagulation (DIC) The 9/19/2024 main adverse effect is bleeding. 63  Antiplatelet Drugs Mechanisms of antiplatelet drugs include:  Drugs that block platelet receptors: Thromboxane A2, = Aspirin Adenosine diphosphate (ADP)= clopidogrel  Are indicated for reduction of MI, stroke, and vascular death in patients with atherosclerosis. Glycoprotein = Abciximab Phosphodiesterase= Cilostazol 9/19/2024 64  Drugs for anemia 9/19/2024 65  INTRODUCTION Hematopoiesis the production of circulating erythrocytes, platelets and leukocytes from stem cells primarily in the bone marrow and requires constant supply of three essential nutrients: –  iron,  vitamin B12 and  folic acid Anemia – a deficiency in oxygen carrying erythrocytes 9/19/2024 66 Iron Iron forms the heme ring(hemoglobin), which binds oxygen and provides oxygen delivery to tissues. Causes of Iron Deficiency Anemia  Nutritional deficiency  Chronic blood loss 9/19/2024 67 Causes of iron deficiency anemia Nutritional deficiency Low intake of foods containing iron Reduced absorption as a result of mucosal damage Co - administration of drugs that chelate iron  Example: Antacids Post - Gastrectomy 9/19/2024 68 Causes of IDA Chronic blood loss Chronic nose bleeding Menorrhagia Occult GI bleeding Worm infestation & Ulcers: Example PUD. 9/19/2024 69  Rx of iron deficiency anemia Identify the cause and treat. Rx of IDA consists of admn of Oral or Parenteral iron preparation. 9/19/2024 70  VITAMIN B12 Acts as a coenzyme in the synthesis of DNA and is also essential for various metabolisms in the body. Deficiency of Vit B 12 results in: -  Megaloblastic anemia  Neurological syndrome involving spinal cord and peripheral nerves Causes: Malabsorption Treatment :Vit B12(cyanocoblamin) 9/19/2024 71 FOLIC ACID Required for essential biochemical rxns that provide precursors for the synthesis of:  Amino acids  Purines & DNA 9/19/2024 72 Cont Daily requirement is 50 -100g. Folic acid deficiency is not uncommon. Sources of folic acid include Yeast, Liver, kidney & Green vegetables 9/19/2024 73 Physiologic functions Plays a role in the biosynthesis of purines i.e., DNA. Aids in the production of RBCs works with vitamin-B12 & vit C to help the body digest and utilize proteins. 9/19/2024 74 Folic acid deficiency Common among elderly pts, poor pts & pregnant women. Results in Megaloblastic anemia 9/19/2024 75 Folate deficiency during pregnancy Congenital malformation in newborn children  Like spina bifida 9/19/2024 76 Causes Dietary deficiency Alcoholics with liver disease Hemolytic anemia Mal-absorption syndrome Pts with cancer Chronic skin diseases Pts on drugs that impair absorption or metabolism.  Phenytoin  Oral contraceptive  Isoniazid 9/19/2024 77  Cont.. N.B : Folic acid supplements to prevent folic acid deficiency should be considered in high-risk individuals including: Treatment  Pregnant women  Alcoholics &  patients with hemolytic anemia  Liver disease  Certain skin disease &  Patients on renal dialysis. 9/19/2024 78 Cont… Administration of folic acid in the setting of vitB12 deficiency will not prevent neurological manifestation. Even though it will largely correct the anemia caused by the Vit B12 deficiency. 9/19/2024 79  Drugs That Affect the Endocrine System 9/19/2024 80 DRUGS ACTING ON ENDOCRINE SYSTEM Introductions The endocrine system communicates with the nearly fifty million target cells in the body using a chemical “language” called Hormones. 9/19/2024 81  Cont… Pancreatic Hormone  A-cell (α):-produce glucagon  B-cell (β):- Insulin,  D-cell (γ):- Somatostatin Insulin- the storage and anabolic hormone of body. Glucagon- the hyperglycemic factor that mobilizes glycogen store 9/19/2024 82 The anterior and posterior pituitary hormones 9/19/2024 83  Functions of the Endocrine System  Water balance.  Uterine contractions and milk release.  Growth, metabolism, and tissue maturation.  Ion regulation.  Heart rate and blood pressure regulation.  Blood glucose control.  Immune system regulation  Reproductive functions control. 9/19/2024 84  Drugs That Affect Growth Hormone And Thyroid Hormones 9/19/2024 85  Growth Hormone (GH) –Somatotropin GH as Juvenile/Acromegaly GH = pituitary dwarfism Drugs For hypopitutary “Dwarfism” –Somatotropin For hyper pituitary ‘’Gigantism” – octreotide 9/19/2024 86 Thyroid hormones & drugs affecting thyroid functions Thyroid hormones Tri iodothyronine (T3) Tetraiodothyronine (T4) Calcitonin Actions of thyroid hormones  Increasing metabolic rate of tissues=increases HR, RR, temperature, oxygen consumption,  Increasing metabolism of fats, proteins, and CHO. 9/19/2024 87  Signs and Symptoms of Thyroid Dysfunction Bodily System or Hypothyroidism Hyperthyroidism Function Metabolism Decreased, Increased, anorexia, intolerance with increased appetite, to cold, weight gain intolerance to heat, weight loss CVS Bradycardia Tachycardia CNS Lethargy, sleepiness Nervousness, anxiety, insomnia, exophthalmos Skin Pale, cool, dry skin; warm, moist skin, Ovarian Heavy menses, loss of Irregular or scant menses function fetus possible 9/19/2024 88 Drugs for hypothyroidism (cretinism, myxeodema) Levothyroxine (T4) Liothyronine (T3) 9/19/2024 89  Clinical uses For hypothyroidism, Adverse effects Thyrotoxicosis Drug- drug interactions Drugs that reduce absorption:  Ca+2 supplements, sucralfate, iron supplements, aluminum antacids. Drugs that accelerate its metabolism  phenytoin, carbamazepine , refampine, Phenobarbital. 9/19/2024 90  Hyperthyroidism C/M Graves disease (diffuse toxic goiter) + exophthalmos High metabolic rate Nervousness, Tachycardia, 9/19/2024 91  Treatment strategies Surgical removal of thyroid tissues. Destruction of thyroid tissues with radioactive iodine. Suppression of thyroid hormone synthesis with antithyroid drugs. 9/19/2024 92  Drugs for hyperthyroidism 1. Thioureylenes Inhibits thyroid hormone synthesis Propylthiouracil MOA methimazole Inhibiting peroxidase Carbimazole Prevents the oxidation of iodide. Prevents iodinated thyrosines from coupling P/Ks Therapeutic uses Rapidly absorbed following For hyperthyroidism. Adverse effects oral administration. rash, headache, Plasma half – life is short. nausea, jaundice, Crosses placenta and breast pain in the joints. milk. 9/19/2024 93  What is diabetes mellitus? What is insulin? 9/19/2024 94  Function of Insulin Insulin=maintain blood glucose levels within normal limits (60 to 120 mg/dL). Forthe utilization of glucose in cellular metabolism and For the proper metabolism of protein and fat. 9/19/2024 95 Diabetes mellitus Insufficient insulin production Cellular resistance to insulin.  As a results in elevated blood glucose levels(hyperglycemia) 9/19/2024 96 Classification of DM Type I IDDM (or Juvenile type) Occurs predominantly in children & young adults who have no insulin secretion Type II NIDDM (or maturity onset type) usually occur after the age of 40years. 9/19/2024 97 Insulin Insulin lowers the blood glucose level by increasing utilization of glucose by peripheral tissue & Promoting synthesis & storage of glycogen 9/19/2024 98 Type of insulin preparation Short acting (Rapid onset)  E.g. Regular Insulin Intermediate acting  E.g. Lente insulin, NPH insulin Long acting  E.g. Protamine Zn insulin 9/19/2024 99 Therapeutic use IDDM NIDDM (Not controlled by diet & Oral hypoglycemic agents) For control of diabetes in  Pregnancy  Infections &  During surgery Also used in the Rx of hyperkalemia due to renal 9/19/2024 100 Adverse drug reaction Can be categorized as local or systemic Local Atrophy or Hypertrophy at site of injection Local hypersensitivity & Secondary infections Systemic Hypoglycemic coma & Immunologic rxn like hypersensitive & insulin resistance 9/19/2024 101  Oral hypoglycaemic agents Theseare only indicated for type -II DM and two major classes.  sulphonyl urea &  Biguanides. 9/19/2024 102 9/19/2024 103 1. Sulphonyl Ureas MOA: - stimulate pancreatic β-cell to produce insulin. Also inhibit gluconeogenesis and insulin degradation in the liver. First generation Second generation Tolbutamide Glimepiride Chlorpropamide Glibenclamide (Daonil) Acetohexamide Glipzide 9/19/2024 104 Glibenclamide (Daonil) Highly potent They have fewer side effects than first generation. S/E: Hypoglycemia DDI: with alcohol disulfram like reaction may occur C/I: hepatic impairment, renal insufficiency, pregnancy Dosage: 2.5-20mg Note:-In pregnancy the drug of choice is Insulin because it cannot cross placental barrier. 9/19/2024 105  2. Biguanide Metformin Action:  suppression of gluconeogenesis.  Enhances glucose uptake and utilization by muscles.  Reduce appetite consequently useful in the majority of type -II patients who are obese. Note:- Metformin do not cause hypoglycemia and called Euglycemic agent. Adverse effects  Anorexia, nausea, vomiting, abdominal discomfort and diarrhea.  Causes lactic acidosis. C/I: renal disease, hepatic disease, alcoholism Dosage: 500 - 2000mg p.o gd. 9/19/2024 106  Cornerstones of Diabetes Management Healthy eating(nutritional therapy) Exercise Monitoring Medication education 9/19/2024 107  STEROID HORMONES AND SEX HORMONES 9/19/2024 108 Learning objectives At the end of this section you will able to know:  Adreno-cortical hormones  Mel and Female sex hormons.  Drugs affecting reproductive system  Pharmacokinetics and pharmacodynamics of each drug with its clinical indication and side effects. 9/19/2024 109  Introduction  Adreno-cortical hormones control the metabolism of carbohydrate (CHO), Protein, Fat & water/ electrolytes 9/19/2024 110 Classification of adrenocorticosteroids Classified into √ Hydrocortisone (Cortisol) Glucocorticoids: √ Cortisone √ Aldosterone Mineralo-corticoids: √ Androgen Sex Hormones: √ Progesterone √ Estrogen 9/19/2024 111  Sex hormones (sex steroids) Androgens, Oestrogens and Progestogens. A. MALE SEX HORMONES I. Androgens (Testosterone) Testosterone is mainly produced in the testicles under stimulation of (LH). FSH in men, is responsible for spermatogenesis. Testosterone aids the libido. Methyltestosterone 30 mg PO daily; II. Anabolic steroids are synthetic drugs chemically related to the androgens. 9/19/2024 112  Cont.. Indications for Use To treat androgen deficiency states  (e.g., hypogonadism, delayed puberty, impotence, oligospermia) Increase in muscular work capacity. Adverse effects :  abuse  increased aggressiveness and violence.  Masculinizing effects on women. 9/19/2024 113  B. Female Sex Hormones 9/19/2024 114 Estrogens These drugs can be classified into three groups.  Natural: Estradiol, Esterone, Estriol  Semi-synthetic: Ethinylestradiol  Synthetic: Diethylstilbestrol 9/19/2024 115 pharmacokinatics It is absorbed from GI & skin & Rapidly metabolized in the liver 9/19/2024 116 Physiologic actions: Genital system Ovary √ Estrogen affects the ovary indirectly √ By influencing the secretion of gonado-trophin Uterus √ ↑ the growth & sensitivity of myometrium for oxytocin. Cervix: Makes cervical mucus thin & alkaline Anterior pituitary Inhibit release of gonadotrophins (FSH, LH) 9/19/2024 117  Metabolic action A. Retention of salt & water B. Plasma lipid level It increases the level of HDL & triglycerides While decreases the level of LDL & cholesterol C. Increases Ca++ bone deposition & D. It has a mild anabolic action Blood coagulation Enhance level of factor II, VII, IX, X 9/19/2024 118 Therapeutic use Contraceptive in combination with progestogens Functional uterine bleeding Dysmenorrhea Alleviation of menopausal disorder Osteoporosis 9/19/2024 119 Side Effects Thrombo-embolism Na+ & H2O retention Withdrawal bleeding Nausea 9/19/2024 120 Contraindication Hx of thromboembolism condition Undiagnosed uterine bleeding Endometrial carcinoma & Liver disease 9/19/2024 121  Progestogens A naturally occurring pro-gestational hormone It is synthesized by the  Corpus luteum  Placenta  Adrenal cortex & Testis 9/19/2024 122 Therapeutic use Hormonal contraception Functional uterine bleeding Dysmennorrhea, Ammenorrhea Endometrial Carcinoma Premenustral tension 9/19/2024 123  Hormonal Contraceptives UNPLANNED PREGNANCY 9/19/2024 124 Types of contraceptives 1. COCs (combined oral contraceptives) Consist of an estrogen plus a progestin  MOA of COCs  inhibit release of FSH and LH  thickens cervical mucus  modify the endometrium, 9/19/2024 125  Side effects of COC: Thromboembolic complication, (estrogen) Weight gain (progestin) & fluid retention (estrogen) Chloasma Nausea & vomiting, (estrogen) Hyperglycemia (progestin) Depressed mood, (progestin) 9/19/2024 Reduced lactation (estrogen component) 126  2. Progestin-only pills (POPs)  Also called minipills - Package contains 28 active tablets  Low dose of progestin and no estrogen  less effective than COCs, but safer  Advised for women contraindicate to estrogen (breastfeeding, high BP, thromboembolic disorder, smokers)  Used immediately postpartum with no effect on 9/19/2024 127  Cont… MOA  suppression of ovulation  Thicken cervical gland secretion  Modify endometrium (unfavourable for implantation) Side effects Safer than COCs Irregular bleeding  principal reason that women discontinue POPs. Hyperglycemia Wt. 9/19/2024 gain 128 Long-term method of birth control 1. Depot IM injection of long acting progestrogen e.g. Medroxyprogestrone acetate (Depoprovera®) Effective for up to 3 months MOA  Similar 9/19/2024 129 Cont.. 2. Subdermal Etonogestrel Implant (Implanon)  Etonogestrel containing rod is inserted under skin of upper arm, in the groove between the biceps and triceps  is among the most effective contraceptives available  Effective for up to 3 years MOA  Similar 9/19/2024 130 3. Intrauterine Devices (IUDs) Small plastic objects inserted into uterus progesterone 2 types  Hormone-releasing (progesterone)  Copper-releasing 9/19/2024 131  IUDs… a. the copper T 380A [ParaGard] - for 10 years b. the levonorgestrel releasing intrauterine system [Mirena]. - for 5 years  placed within 7 days of the onset of menses MOA  Spermicidal (both)  inhibit implantation (ParaGard)  thickening of the cervical mucus (Mirena) C/Is  women with a risk for STDs (risk for pelvic inflammatory disease (PID)) ADR  intense cramping upon IUD insertion minimized by applying a topical anesthetic (lignocaine) or by premedicating with ibuprofen 9/19/2024 132 B. Post coital /“morning after” pill/ emergency contraceptive pill
Used within 72 hrs Combined oral contraceptive pills can also be used Works mainly by preventing ovulation or fertilization MOA  delay or stop ovulation.  Inhibit fertilization  Inhibit implantation 95% effective within 24 hrs 9/19/2024 133 Side Effects of oral contraceptive Thromboembolic complication Weight gain & fluid retention Menstrual disorder Breast tenderness & fullness Skin changes Nausea & vomiting Depressed mood & Reduced lactation 9/19/2024 134 Contraindication In patients with CV diseases (HTN, CHD) Thromboembolic disease Breast Cancer DM Liver disease Women > 35 yrs (esp. smokers & hypertensive’s) 9/19/2024 135  Oxytocin to induce contraction during labor promotes breast milk ejection 9/19/2024 136  Oxytocin Actions:  Stimulates the uterus and produce physiologic type of contraction  Causes ejection of milk Use:  Induction of labor near term  Relief breast engorgement during lactation (cause milk ejection)  Reduce PPH. S/Es:  Risk of uterine rupture in woman with uterine scar  Water retention (act on ADH receptor) leading to water intoxication when given IV. 9/19/2024 137 Prostaglandins  Misoprostol (PGE1 analogue)  Carboprost (PGF2α analogue)  Dinoprostone (PGE2 analogue 9/19/2024 138 Clinical use of PGs Induce labor at anytime during pregnancy  Misoprostol To initiate cervical ripening prior to induction of labor  (Dinoprostone, Misoprostol) = intravaginally To induce abortion  (Mifepristone + Misoprostol) = early in pregnancy (within 7 weeks), also in the second trimester  (Carboprost or Dinoprostone) = 2 trimister only nd To protect against NSAIDs induced peptic ulcers (Misoprostol) 9/19/2024 139 Prostaglandins… A/Es:  Abdominal pain,  nausea, vomiting, diarrhea, fever, headache , Bronchospasm , vaginal bleeding etc.  Risk of uterine hyperstimulation C/Is:  Ectopic pregnancy,  hemorrhagic disorders,  use of anticoagulant drugs,  glucocorticoid therapy. 9/19/2024 140  Ergometrine (Ergonovine)  α-agonist  Causes sustained uterine contraction without relaxation in between It causes contractions of uterus as a whole i.e. fundus to cervix (tend to compress rather than to expel the fetus) Use:  To prevent PPH A/Es:  Nausea, vomiting,  Hypertension, Gangrene 9/19/2024 141  * Contraindications: a) presence of labor b) vascular disease c) impaired hepatic and renal functions * Precautions: a) Cardiac diseases b) Hypertension c) Multiple pregnancy 9/19/2024 142