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by: Merritt Windler

PharmacologyII HSCI302

Merritt Windler
GPA 3.52


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This 22 page Class Notes was uploaded by Merritt Windler on Wednesday September 23, 2015. The Class Notes belongs to HSCI302 at Drexel University taught by VincentZarro in Fall. Since its upload, it has received 19 views. For similar materials see /class/212573/hsci302-drexel-university in Health Sciences at Drexel University.


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Date Created: 09/23/15
PAR ALtELLi 7 LUMEN OF STOMACH K H Gastric acid Match drugs with receptors in above slide Ranitidine o HZReceptor antagonist 0 Blocks action of histamine on parietal cells in stomach9 decreasing acid production by these cells 0 Used in treatment of dyspepsia peptic ulcer disease GI re ux disease 0 MOA competitive inhibitors of histamine at the parietal cell H2 receptor suppressing normal secretion of acid by parietal cells and the mealstimulated secretion of acid 0 Histamine released by ECL cells in stomach is blocked from binding on parietal cell H2 receptors which stimulate acid secretion 0 Other substances that promote acid secretion like gastrin and ACH have a reduced effect on parietal cells when H2 receptors are blocked Omeprazole o MOA it is a proton pump inhibitor that suppresses gastric acid secretion by specific inhibition of the HKATPase in the gastric parietal cell 0 Acts specifically by binding on the proton pump and blocking acid production9therefore reducing gastric acidity o Indicated for the treatment of duodenal ulcers benign gastric ulcers gastroesophageal re ux disease heartburn and other symptoms associated with ERD erosive espohigitis and long term treatment of pathological hypersecretory conditions Misoprostol o Is a prostaglandin E1 PGEl analogue used for the treatment and prevention of stomach ulcers stimulates increased secretion of the protective mucus that lines the GI tract and increases mucosal blood ow thereby increasing mucosal integrity 0 MOA inhibits gastric acid secretion by a direct effect on parietal cells through binding to the prostglandin receptor which is a receptor that is mediated by G proteins that normally activate adenylate cyclase 0 Indirect inhibition of adenylate cyclase may be dependant on guanosine5 triphosphate GTP 0 Increased secretion of bicarbonate o Decreased volume and pepsin content in gastric secretion 0 Prevents harmful agents from disrupting the tight junctions between the epithelial cells which stops back diffusion of H ions into gastric mucosa o Increases thickness of mucus layer 0 Enhanced mucosal blood ow as result of direct vasodilation o Stabilizes tissue39s lysozymesvascular endothelium o Improves mucosal regeneration capacity Dicyclomine 0 Used in treatment of functional bowelIBS used to treat or prevent spasm in the muscles of the GI tract also inhibits GI propulsive motility and decreases acid secretion and controls excessive pharyngeal tracheal and bronchial secretions o MOA achieved via dual mechanism 0 Speci c anticholinergic effect antimuscurainic at the acetylocholine receptor sites 0 A direct effect upon smooth musclemusculotropic 0ndans etron o MOA a selective serotonin 5HT receptor antagonist the receptors are both in the central medullary chemoreceptor zone and peripherally in the GI tract 0 The inhibition of the 5HT receptors inhibits visceral afferent stimulation of the vomiting center 0 Used for prevention of nausea and vomiting associeated with the emetogenic cancer chemotherapy postoperation and radiation also for treatment of postoperative nausea and vomiting 0 Is a highly speci c seritoning 5HT receptor antagonist having no other effect on other seritonin receptors and low af nity for dopamine receptors 0 Serontonin 5HT receptors are located on nerve terminals in vagus in the peripherery and centrally in the chemoreceptor trigger zone of the area postrema 0 Normally with N0 DRUGS chemotherapeutic agents release serotonin from enterochromaffin cells of small intestine by causing degenerative changes in GI tract the serotonin then stimulates the vagal and splachnic nerve receptors that project to medullary vomiting center as well as the 5 HT receptors in the area postrema thus initiating the vomiting re ex Aluminum Hydroxide o Treats heartburn or indigestion ANTACID o MOA restores acidbase balance attenuating the pepsin activity and increasing bicarbonate and prostaglandin secretion Is a basic inorganic salt that acts by neutralizing hydrochloric acid in gastric secretions it is slowly solubilized in stomach and reacts with HCL to form aluminum chloride and water 0 Also inhibits action of pepsin by increasing pH and Via adsorption o Cytoprotective effects may occur through increases in bicarbonate ionHC03 and prostglandins Works chemically not on a receptor Lomotil o MOA htt c0urseswashin t0nedu con39 bess emesis emesishtml Cimetidine Ranitidine Famotidine Nizatidine H2 blockers block histamine receptorsgt dec H secretion by parietal cells use peptic ulcers gastritis mild esophageal reflux tox cimetidine potent P450 inhibitor and antiandrogenic effects gynecomastia etc can cross BBB and placenta cimetidine and ranitidine dec renal excretion of creatinine omeprazole Iansoprazole irreversible inhibit HK ATPase in stomach parietal cells use peptic ulcers gastritis esophageal reflux Zollinger Ellison Bismuth Sucralfate bind ulcer base provide physical protection and allows H003 secretion to reestablish pH gradient in mucous layer use incr ulcer healing traveler39s diarrhea Misoprostol moa PGE l analog incr production and secretion of gastric mucous barrier dec acid production use prevent NSAID ulcers maintain PDA induce labor tox diarrhea dont use in women who could be prego abortifactant Pirenzapine Propantheline muscarinic antagonists block M1 R on ECL cells gt dec histamine secretion block M3 R on parietal cells gt dec H secretion use peptic ulcers tox tachycardia dry mouth difficulty focusing eyes Dry as a bone Blind as a bat etc Octreotide somatostatin analogue use acute variceal bleeds acromegaly VlPoma carcinoid tumors tox nausea cramps steatorrhea Aluminum OH anatacid overuse constipation and hypophosphatemia proximal muscle weakness osteodystroiphy seizures hypo K Magnesium OH antacid overuse diarrhea hyporeflexia hypotension cardiac arrest hypo K 9 Calcium carbonate antacid overuse hyperCa rebound acid increase hypoK 1O InfliXimab monoclonal antibody to TNF proinflammatory use Crohns RA tox respiratory infection fever hypotension Sulfasalazine sulfapyridine 5aminosalicylic acid activated by colonic bacteria antibiotic antiinflammatory use UC Crohn39s tox malaise nausea sulfonamide toxicity reversible oligospermia 12 Ondansetron 5HT3 anatagonist use control vomiting post op and in patients on chemo tox headache constipation Metoclopromide D2 R antagonst and 5HT agonist incr resting tone contractility LES tone motility use diabetic and postop gastroparesis tox Parkinsonian restlessness drowsiness fatigue depression nausesa diarrhea interacts with digoxin and diabetic agents DEC SEIZURE THRESHOLD DONT use in SMALL BOWEL OBSTRUCTION Drugs that decrease seizure threshold Metoclopromide Buproprion Tramadol Enflurane Chapter 25 Estrogens and Androgens o Steroid Hormones o NON POLAR Do not travel well need carrier protein Lipid cholesterol based so cross cell membrane easily Act on intracellular receptors Includes 5 Major classes of steroid hormones I Estrogens I Androgens I Mineralcorticoids I Glucocorticoids I Progestragens o 5 Major classes 0 Peptide Hormones o POLAR 0 Protein based travel through blood easily 0 Protein based cannot pass freely though cell membrane I Need to interact with a gate or receptor to get in 0 Act on Gprotein coupled receptor 0 O O O 0 Includes I ACTH I FSH I TSH I LH I GH I OXY I Vasopressin o Peptide hormones originate from released by pituitary gland in brain produced by many different organs and tissues I Heart pancreas GI tract adipose ESTROGENS Estrogens o Estradiol is the most potent estrogen produced and secreted by the ovary o It is the principal estrogen in premenopausal women 0 Estrone is a metabolite of estradiol 13 as potent as estradiol I Is the primary circulating estrogen after menopause o Estriol is another metabolite of estradiol I Present in significant amounts during pregnancy because it the primary estrogen produced by the placenta 0 Synthetic Estrogens are used in hormone replacement therapy 0 Example Drug Ethinyl Estradiol I Undergoes less ofa first pass metabolism than naturally occurring steroids and are thus more effective when administered orally at lower doses MOA for Estrogens After dissociation from their binding sites on sex hormone binding globulin or albumin in the plasma the steroid hormones diffuse across the cell membrane and bind with high affinity to specific nuclear receptor proteins 9 then the activated steroid receptor complex interacts with nuclear chromatin to initiate hormone specific RNA synthesis Resulting in the synthesis of specific proteins that mediate a number ofphysiologic functions 0 Note there are other pathways involving these hormones that lead to more rapid reactions I Example activation of an estrogen receptor in the membranes of hypothalamic cells has been shown to couple to G protein thereby initiating a second messenger cascade Example estrogen mediated dilation of coronary arteries occurs by the increased formation and release of nitric oxide in prostacyclin in endothelial cells Therapeutic Uses of Estrogen 0 Most frequently used for contraception and postmenopausal hormone therapy I Concerns over risks of hormone therapy lead to patients being given the lowest possible effective dose for the shortest possible time to relieve menopausal symptoms 0 Used to be used to prevent osteoporosis because it reduces bone reorption therefore decreasing the loss of bone density but due to side effects is no longer prescribed for this purpose because of risks including endometrial and breast cancer as well as cardiovascular 1ssues Natural Occuring Estradiol 0 An estrogen when taken orally is rapidly metabolized by the liver Synthetic ethinyl Estradiol 0 An estrogen that is well absorbed after oral administration I Metabolized more slowly by liver 0 Undergoes less first pass effect allowing for decrease of dose 0 MOA negative feedback of its estrogen component I Provides negative feedback of the release of LH and FSH preventing estradiol synthesis and ovulation 0 NOTE most adverse effects of combo oral contraceptives are due to estrogen component of the drug EstrogenNo longer recommended as therapy for osteoporosis 0 Risk of CV problems and breast and endometrial cancer o Estrogen Effects on the body 0 Good reduces bone resorption decreases loss ofbone density and the increase ofHDL and decrease of LDL I Benefits ofpostmenopausal estrogen therapy decrease risk of hip fractures decrease hot ashes reverses vaginal atrophy 0 Bad Increases clotting factors platelet adhesiveness decreases AT3 Increases chance of cardiovascular issues supports horone sensitive breast cancers 0 Theraputic Uses of Gonadal Hormones 0 Replacement therapy contraception management of menopausal symptoms 0 What is the significance of aromatase in the synthesis of estradiol 0 It is the enzyme responsible for a key step in biosynthesis of estrogen responsible for aromatization of androgens and estrogens SERM s o SERMs a class of estrogenrelated compounds that interact at estrogen receptors intracellular but have different effects on tissues depending on the tissues 0 SERMs Effects on estrogen receptors 0 Good ProEstrogen agonist on bone increasing bone density AntE antagonist on breast tissue cancer cells competes with cancer cells 0 Bad ProE agonistin endometrium can cause endometrial cancer 0 Includes Drugs 0 Tamoxifen NolvadeX I Used as palliative treatment for breast cancer patients used psotmastectomy I Good effect on breast cancer and bone density I Bad effect on endometrial cells uterine cancer 0 RalXifen Evistra I Good effect on breast cancer cells and bone density I Has little or no effect on uterine cells 0 Much lower risk of causing uterine cancer Aromatase Inhibitors o MOA permanently binds to the enzymes preventing them from converting testosterone to estrogen 0 Used in treatment of 0 Advanced breast cancer in post menopausal women 0 Women whos cancer is progressed with tamoxifen and evista SERMs 0 Includes the Drugs 0 Exemestane Armostin o Anastrozole ArmideX Progestogen 0 Includes the DrugsHoromones o Progesterone I Naturally secreted from 0 Corpus luteum during the second half ofmenstrural cycle and placenta I Theraputic uses of progesterone 0 Hormonal deficiency contraception 0 Control of uterine bleeding dysmenorrhea endometriosis o Infertility prevention of endometrial hyperplasia I Negative feedback of progesterone 0 High levels ofit inhibit production of gonadotropins preventing ovulation thickens cervical mucus I Effect on endometrium o Promotes development ofa secretory endometrium that can accomidate implantation of embryo 0 Synthetic Progesteogens Proestins I A progesterone utilized because they are more stable to first pass effect and allow for much smaller dose I MOA ofprogesterone ONLY contraception on ovulation 0 Increase levels ofprogesterone causing decrease in FSH and LH preventing ovulation I Most commonly used synthetic hormones used 0 Ethinyl Estradiol and Norethidrone I Progestin ONLY drugs utilized in contraception o NORETHIDRONE OrthoMicronor o a Form oflow dose progestin only contraception o Inconsistently inhibits ovulation in 50 of cycles and rely mostly on progestogenic effect of thickening of cervical mucus o MOA inhibits release of LH and thickens cervical mucus o CERAZETTE 0 An intermediate dose ofprogestin only contraceptive o Inhibits follicular development to greater degree and more consistently inhibits ovulation in 97 99 of cycles same cervical mucus thickening o MEDROXYPROGESTERONE DepoProvera o A high dose progestin only contraceptive 0 Completely inhibits follicular development and prevents ovulation same cervical mucus changes Combination Contraception Estrogen and Progestins o Necon o TriNorinyl o LoEstrin Androgens o The most important androgen in the body TESTOSTERONE o Adverse effects of androgen therapy 0 Females masculinization acne growth of facial hair deepening of voice male pattern baldness excessive muscle development 0 Males Priapism impotence decreased in sperm gynecomatia acne increase in growth of facial hair I Stimulate growth ofprostate increase risk ofprostate cancer 0 Drugs include o ANDROGEL o ANDRODERM o DEPOTESTOSTERONE 0 Therapeutic uses of antiandrogens o Prostate cancer benign prostatic hyperplasia BPH male patterned baldness o 5 AlphaReductatse Inhibitors treates BPH and male pattern baldness o FINASTERIDE Proscar o DUTASTERIDE Avodart 0 Pure androgen receptor antagonists o BICALUTAMIDE Casodex 0 Used in treatment of prostate cancer Chapter 27 Respiratory Drugs Drugs Used to Treat Asthma o Beta2 Adrenergic Agonists o Corticosteroids o Cromolyn o Ipratropium o LeukotrineAntagonists o Montelukast o Zileuton o Omalizumab o Theophyline Drugs Used to Treat COPD 0 Beta Adrenergic Agonists o Corticosteroids o Ipratropium 0 Asthma is a condition ofbronchoconstriction and in ammation 0 Treatment includes I ALBUTEROL an adrenergic agonist that stimulates sympathetics o It is a selective beta agonist I IPRATROPIUM a muscarinic antagonist Inhibitor I Corticosteroids treat in ammatory effect I MONTELUCAST Singulair a leukotriene receptor antagonist I ZILEUTON ZY o CR a lypoxygenase inhibitor I OMALIZUMAB an anti IgEmonocolonal antibody used via injection I THEOPHYLINE very old drug used to treat asthma not used very often anymore 0 Pros and Cons ofInhaled steroids I Pros high first pass effect I Con hard to separate alpha and beta adrenergic receptors can also affect the heart 0 Treatment for different frequencies of Asthma I Intermittent less than 2 days of treatment required a week 0 No daily meds Mild persistent asthma attack more than two days per week but not daily 0 Low dose inhaled corticosteroids Moderate persistent asthma attack daily 0 Low to medium dose ofinhaled corticosteroids and long acting beta two agonist Severe Persistent continual asthma attacks 0 High dose inhaled corticosteroids and long acting beta two agonist Chapter 26 Drugs Affecting the Endocrine System Corticosteroids o Hydrocortisone o Prednisone o Methylprednisolone o Dexamethazone Inhibitors ofAdrenocorticoid Biosynthesis or Function 0 Spronolactone Mineralocorticoid o Aldosterone o Glucocorticoids and mineralocorticoids are 0 Administered topically inhalation parenteral orally 0 Both or their receptors are intracellular 0 Clinical uses include I Cushings syndrome I Organ transplant I Malignancies I Chronic in ammation 0 Glucocorticoids keep cells alive and functioning wants to keep glucose level up to supply glucose to the brain need it for energy 0 Cortisol is the principal naturally occurring human glucocorticoid I Its production is dinural it peaks in the morning and then decreases then peaks once in the afternoon before decreasing o Hydrocortisone is a glucocorticoid o Mineralcorticoid makes kidney retain sodium 0 Aldosterone is a mineralocorticoid I Acts on kidney tubutles and collecting ducts causing reabsorption of Na and bicarbonate and water while decreasing reabsorption of K which with H is then excreted in the urine 0 Helps to control the body s water volume and concentration of electrolytes Hydrocortisone 0 Used in relief ofin ammatory and pruritic manifestations of corticosteroid responsive dermatosis also used to treat endocrine disorders like Addison s disease as well as immune and allergic disorders like arthritis 0 MOA binds to cytosolic glucocorticoid receptor after binding the newly formed receptor ligand compleX translocate into cell nucleus where it binds to many glucocorticoid response elements AKA GRE in the promoter region of the target genes Prednisone o Aglucocorticoid receptor agonist o MOA in its active form it crosses cell membrane and binds with high affinity to specific cytoplasmic receptors inducing inhibition ofleukocyte infiltration at the site of in ammation 0 Interference in function ofmediators of in ammatory response suppression of humoral immune responses and reduction in edema scar tissue Involve phospoholipase A2 inhibitory protienslipocrtins which control the biosynthesis of potent mediators ofin ammation such as prostaglandins and leukotrienes Methylprednisolone MOA unbound glucocorticoids cross cell membranes and bind with high affinity to cytoplasmic receptors modifying transcription and protein synthesis inhibit leukocyte infiltration at the site ofin ammation and interfere with the mediators of the in ammatory response 0 ChaDter 28 Gastrointestinal and quot ir Drugs Antimicrobial Agents 0 Antibiotics to treat H Pylori Infection H2 Histamine Receptor Blockers o Ranitidine Cimetidine H2 receptor antagonist blocks action of histamine on parietal cells in shtomach therefore decreasing acid production by these cells Proton Pump Inhibitors o Omeprazole binds to proton pump that control exchange of H and K between the parietal cells and the lumen of the stomach inhibiting its function Prostaglandins o Misoprstol binds to protglandin receptor inhibiting acid secretion by binding to protglandin receptors which normally would activateadenylatecyclase 0 Increase secretion of bicarbonate Antimuscarinic Agents 0 Dicyclomine has direct effect on smooth muscle musculotropic as well as having an anti muscarinic effect at the ACH receptor sites Antacids 0 Calcium or Aluminum Hydroxide works chemically not on a specific receptor TUMS o Restores acidbase balance by attenuating the pepsin activity and increasing bicarbonate and prostaglandin secretion 0 Is a basic inorganic salt that neutralizes HCL in acid secretions Emesis o Irritation or toxins cause release of serotonin by specialized cells in the epitherlium which sensitizes or stimulates afferent neurons that project to the emesis center of the brainstem o This is why chemotherapy causes vomiting they cause the free radical release which stimulates the serotonin o Triggers in the blood stream may also stimulate emesis thru their action on the area postrema where there is an incomplete blood brain barrier which allows it to be sensitive to chemicals in the blood 0 What is the most important neurotransmitter in the vomiting center 0 Serotonin o ONDANSETRON Zofran decreases nausea and vomiting by blocking the serotonin o Lomotil Decreases diarrhea by stimulating the opioid receptor in the GI tract Chapter 30 Introduction to Antibiotics Selective Toxicity the ability to injure or kill an invading microorganism without harming the cells of the host Factors in the appropriate selection of an antibiotic Ways ofidentifying the appropriate antibiotic for a particular patient Meaning of quotbroad spectrum What is the blood brain barrier o How may it be affected by an infection meningitis How do we use quotcategoriesquot of antibiotic use in pregnancy 0 CATEGORY A No human fetal risk or remote possibility of fetal harm 0 CATEGORY B no controlled studies show human risk animal studies suggest potential toxicity 0 CATEGORY C animal fetal toxicity demonstrated human risk unde ned 0 CATEGORY D human fetal risk present but benefits may outweigh risks 0 CATEGORY X human fetal risk present but does NOT outweigh benefits contraindicted in pregnancy Narrow Antibiotic Spectrum act only on a single or limited group of microorganisms 0 Ex penicillin Extended Antibiotic Spectrum 0 Ex ampicillin Broad Antibiotic Spectrum are affective against gram positive organisms and also against a significant number of gram negative bacteria Chapter 3 1 Principles of Antimicrobial Therapy and Cell Wall Inhibitors Empiric Antimicrobial Therapy treatment by experience on a ritically ill patient take best guess on what to perscribe Differences between Prokaryotic cell and Eukaryotic cell 0 Prokaryotic lacks nucleus has peptidoglycan cell wall I Peptidoglycan responsible for maintaining cell wall rigidity and integrity and determines cell shape 0 Eukaryotic has cell nucleus some have walls but not mad of peptidoglycan Apply therapeutic index to Antibiotic therapy 0 Large TI very safe Characteristics of BetaLactam antibiotics o Betalactum ring and side R group I Side R group is responsible for the spectrum ofactivity the actions of the drug 0 Interfere with the last stage of peptidoglycan sythnesis 0 Most effective against gram positive bacteria Bacteriocidal Kill or lyse bacteria cell Bacteriostatic inhibit further growth of a bacteria Staining Bacteria Gram Positive or Negative 0 Gram Positive I Cell wall is very thick peptidoglycan layer I The very thick peptidoglycan layer of gram positive cell wall retains dye during gram staining I Cell wall more easily crossed by antibiotics o Gram Negative I Has thin peptidoglycan layer but has additional outter membrane layer made ofpolysaccharides I Cell wall is much more difficult for antibiotics to cross Betalactamase an enzyme produced by the BACTERIA that break open the betalactamase ring deactivating the antibiotic 0 Specific type ofbetalactamase produced specifically for penicillins I Penicillinase Natural Penicillins o G and V Penicillinase resistant betalactam Antibiotic o METHICILLIN o NAFCILIN o DICLOXACILLIN EXtended Broad Spectrum beta lactam antibiotics o AMPICILLIN o AMOXICILLIN o Adverse side effects I Hypersensitivity and diarrhea Resistance the ability ofa prokaryotic bacteria microorganism to withstand the effects of antibiotics o Caused by over use incorrect diagnostics noncompliance growth in animals I Bacteria mutates to resist antibiotics acquiring betalactamase activity decreasing the permeability of the drug 0 Resistance evoleves naturally via natural selection thru genetic mutations and transfer of genetic material via conjucation Cephalosporins o What happens with increased generations of cephalosporins I Gram negative activity increases and gram positive activity decreases o CEPHALEXIN Ke eX first generation 0 CEFACLOR Ceclor second generation 0 CEFRTRIAXONE Rocephin third generation 0 CEFEPRIME MaXipime fourth generation BetaLactamase Inhibitors o MOA binds to betalactamase enzyme and prevents it from hydrolyzing the betalactum ring I Blocking the effect ofbeta lactamases I EX CLAVULONIC ACID 0 Combo of antibiotic of amoxicillin and cavulonic acid 0 AUGMENTIN o Vancomycin structure 0 NO beta lactam ring 0 Instead a glycopeptide antibiotic I Inhibits proper cell wall synthesis in gram positive bacteria I Used to treat 0 Life threatening infections by gram positive bacteria that are unresponsive to other antibiotics Chapter 23 Pituitary and Thyroid I Overview 0 Hypothalamus Signaling Hormone Release I Starting in Hypothalamus Releasing Factorgt Anterior Pituitary gt Trophic Stimulating Factor Target Organgt Release of Hormonegt Negative Feedback eventually shuts off Ant Pituitary Gland o Hormones ofthe Posterior Pituitary I OXYTOCIN Contracts uterus helps with milk ejection I AND VASOPRESSIN ADH acts on collecting duct to reabsorb water only 0 Hypothalmic and Anterior Pituitary Hormones I Corticotropin ACTH and I Leuprolide Leupron does the same thing as releasing factor of gonadotrph 0 Drugs Affecting the Thyroid I Thyroid Hormone T4 Levothyroxine Synthroid I Propylthiouracilblocks production ofthe thyroid hormone hormone I Hyperthyroidism High T3 T4 low TSH 0 Treat with Propylthiouracil Can have surgery I131 thyroid ablation o AKA Graves Disease I Hypothyroidism Low T3 T4 High TSH 0 Treat by prescribing Throid hormone T3 or T4 I Better to treat with T4 bc I The hormone is Triiodothyronine T3 BUT T4 is longer acting so better therapy so go with Sythroid LEVOTHYROXINE T4 0 And body converts it to T3 which is the actual hormone anyway 00 o AKA MYXEDEMA I Thyroid o Stimulates metabolism 0 Intracellular receptorfor almost all hormones I Drug 1 Propylthiouracil o MOA blocks enzyme that works with iodine and thyroid hormone Chapter 25 Estrogens and Androgens Estrogens E5tradi01 E5tr0ne Eth139nyl estradl39ol Me5tran01 Selective EstrogenReceptor Modulators SERMs C10m139phene RaloX139fene Tam 0X139fen Frog estogens De50g estrel Dr0p139re0ne Lev0n agestrel Medoxypr0g esterone N0relgestr0m in M0rethin drone N0rgestimate Pr0gester0ne AntiProgestin M139fepr139st0ne Andro gens Danzol FIuoxym esterone 0xandr010ne Testosterone Estrogens o MOA after dissociation from their binding sites on seX hormonebinding globulin or albumin in the plasma steroid hormones diffuse across cell membrane and bind with high affinity to specific nuclear receptor proteins 0 2 estrogen receptor subtypes alpha and beta mediate the effects of the hormone o the activated steroid receptor complex interacts with nuclear chromatin to initiate hormone specific RNA synthesis of specific proteins that mediate a number of functions 0 An example activation of an estrogen receptor in the membranes fhythamic cells has been shown to couple to a G protein initiating second messenger cascade o USES contraception and postmenopausal hormone therapy 0 Previously before they were used for osteoporosis decrease reorption ofbone but has no effect on bone formation decreases frequency of hip fracture o ADVERSE SIDE AFFECTS hypertension thromboembolism myocardial infarction nausea peripheral edema headache Selective Estrogen Receptor Modulators o MOA drugs compete with estrogen for binding to the estrogen receptor in breast tissue 0 Tamoxifen only competed with estrogen for binding to estrogen receptor in breast tissue first developed I Metabolized by cytochrome P450 CYP450 enzymes 0 Raloxifene does what tamoxifen does but also decreases bone resorption and overall bone turnover leading to bone density increasing and fractures decreasing second generation I Lowers total cholesterol and LDL in the serum has no effect on HDL or TG Less uterine cancer causing because doesn t effect endometrium Used in treatment of prophylaxis ofbreast cancer in high risk women and also prevention ofosteoporosis in postmenopausal women Clomiphene acts as partion estrogen agonist and interferes with negative feedback of estrogens on the hypothalamus increases secretion of gonatotropinreleasing hormone and gonadotropins leading to stimulating ovulation I Treats infertility associated with anovulatory cycles I Not effective in treating infertility with women with ovulatory dysfunction due to pituitary or ovarian failure 0 SERMs are readily absorbed after administration Progestogens o Progesterone the natural progestogen is produced in response to LH by both females in corpus luteum and by males in testes and also synthesized in adrenal cortex in both sexes O o MOA 0 Cause increase in hepatic glycogen probably through an insulin mediated mechanism 0 Cause decrease in Na reabsorption in the kidney due to competition with aldosterone at the mineralocorticoid receptor 0 Cause an increase in body temperature 0 Cause decrease in plasma amino acids 0 Cause increase in excretion of urinary nitrogen o USES treatment ofhormonal deficiency and for contraceptorn For contraceptorions they are used with estrogens 0 Control of dysfunctional uterine bleeding reatment of dysmenorrhea and management of endometriosis Contraceptives 0 Major classes of contraceptives O 0 Combination oral contraceptives comvine estrogen and progestin are most common type of oral contraceptives o Transdermal Patch 0 Vaginal ring 0 Progestin only pills o Injectable projestin Androgens o Are a group of steroids that have anabolic and or masculinizing effects in both males and females 0 Testosterone is the most important androgen in humans is synthesized by leydig cells controlled by hypothalamus through FSH and LH steroidogenesis in the testes and in smaller abounts by the thecal cells in the ovary of the female and by the adrenal gland in both sexes 5alphadihydrotestosterone DHT is also secreted by testes dehydoepiandroesterone DHEA in small amounts also sereted by tested 0 MOA bind to specific nuclear receptor in target cell 0 Testosterone is an active ligand in muscle and liver tissues I But in other tissues it must be metabolized to derivatives such as DllT OO 0 USES O Adronergic Effects adrogenic steroids used for males with inadequate androgen secretion Anabolic Effects anabolic steroids treat senile osteoporosis and chronic wasting associated with human immunodeficiency virus or cancer Endometriosis I Danazol a mild androgen used to treat endometriosis the ectopic growth of endometrium and fibrocystic breast disease 0 Inhibits release of FSH and LH but has no effect on aromatase o Benign increase in the size of the prostate called benign prostatic hyperplasia is treated in 3 ways 0 5alpha Reductase Inhibitors I Finasteride and dutrasteride I MOA reduce size ofprostate gland I Side effects decreased libido and ED 0 Alpha1 Adrenergic Antagonists I Terazosin doxazosin tamsulosin alfuzosin I MOA releave outlet obstruction of the bladder by reducing tension of prostatic smooth muscle in the prostate prostate capsule and bladder neck I Side Effects orthostatic hypotension and dizziness 0 Combination therapy 0 O I With both create greatest symptom reduction Regulation for Secretion ofTestosterone HYPOTHALAMUS Gonadotrophin releasing hormone9Anterior Pituitary Gland Leutinizing Hormone9Testes9 Testosterone or DHT negative feedback to Anterior pituitary to stop LH or to hypothalamus to stop GRH


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