NCM106-Pharmacology-REVIEWER-final.pdf

NCM106 PHARMACOLOGY LECTURE / GARCIA MODULE 1: FUNDAMENTAL CONCEPTS OF PHARMACOLOGY  Metabolism O...

NCM106 PHARMACOLOGY LECTURE / GARCIA MODULE 1: FUNDAMENTAL CONCEPTS OF PHARMACOLOGY  Metabolism OUTLINE  Exercise I Topic 1  Elimination A Subtopic A o pharmacoKineTics (Katawan Tableta) B Subtopic B  Pharmacodynamic i SubSub o Action of the DRUG on the body II Topic 2 o Example: receptor interaction, dose-response A Subtopic A phenomena, mechanism of action and toxic action o pharmacoDynaMics (Drugs Man) PHARMACOKINETIC PHASE DRUG DEFINITION  Process of drug movement to achieve drug action  Pharmacology  This phase describes the time course and disposition of a o Branch of biomedical science, encompassing clinical drug in the body, based on its absorption, distribution, pharmacology, that is concerned with the effects of metabolism and elimination drugs/ pharmaceuticals and other xenobiotics on  4 Processes: living systems, as well as their development and o Absorption chemical properties o Distribution  Medical Pharmacology/Therapeutics o Metabolism/Biotransformation o Area of pharmacology concerned with the use of o Elimination chemicals in the prevention, diagnosis and treatment of disease, especially in humans WATER AND LIPID SOLUBILITY OF DRUGS  Drugs o A chemical substance of known structure, other than  Ionized and Polar drugs a nutrient of an essential dietary ingredient, which o More water-soluble, hence increased clearance (less when administered to a living organism produces a absorption) biological effect  Non-ionized and non-polar drugs o A pharmaceutical drug, also called medicine, is a o More lipid-soluble, hence increased absorption (less chemical substance used to treat, cure, prevent or clearance diagnose a disease or to promote well-being  Drugs that are LIPID soluble and NONIONIZED are  Toxicology absorbed faster than water soluble and ionized drugs o Area of pharmacology concerned with the undesirable  Remember the mnemonic: LUNA effects of chemicals on biologic systems o Lipid soluble o Unionized PHASES OF DRUG ACTION o Neutral molecules  Pharmaceutic Phase o Are Absorbed o Dissolution of drugs  “like dissolves like” – therefore, drugs that are lipid soluble,  Pharmacokinetics Phase unionized and neutrally charged will pass through the lipid o Describes what the body does to a drug membrane  Pharmacodynamic Phase o Describes what the drug does to a body WEAK ACIDS AND BASES PHARMACEUTIC PHASE  pH determines the fraction of drug molecules charged (ionized) versus uncharged (non-ionized)  A process where drugs in solid form (tablet capsule) must disintegrate into small particles to dissolve into liquid  weak acid is better absorbed in acidic environment o Phenobarbital is better absorbed in the acidic  Disintegration environment of the stomach o Breakdown of a tablet into smaller particles  Weak acid is better excreted in basic environment  Dissolution o Aspirin is better excreted in a basic urine o Dissolving of the smaller particles in the GI fluid before absorption  Weak base is better excreted in acidic environment o Amphetamine is better excreted in acidic urine PHARMACOKINETIC VS. PHARMACODYNAMIC  Weak base is better absorbed in basic environment  Pharmacokinetic o Allopurinol is better absorbed in the basic o Action of the BODY in the drug environment of the small intestines o Concerned with: (LADMEE)  Liberation ABSORPTION  Absorption Liberation  Transfer of a drug from its site of administration to the  Distribution again'tion bloodstream metabolism patataslamang Iiiination  NCM106 PHARMACOLOGY LECTURE / GARCIA  Affected by 3 major factors o Route of administration o Blood flow RBC o Concentration  Defined as the process by which the drug reaches the systemic circulation  For example, an oral dosed drug must first reach the epithelial lining of the stomach or intestines, transverse the lipid membrane barrier of the cells – only then can it be absorbed into the blood for distribution o Look first at the graph on the left, and focus on the solid-colored graph for IV. You’ll notice na mataas na siya agad, kasi direcho siya sa dugo. And in time the dose decreases because the drug gets eliminated. Next look at the curve with grids for Oral AUC. As you can see, pataas muna siya, kasi shempre wala pa siya agad sa dugo. But as more and more drug gets absorbed the concentration in the blood increases. Now the greater the area under the curve is, the higher the bioavailability. o But notice that this is only for single dose. And as you can see, in time, bumababa concentration Paano mo ma-maintain that drug has high concentration or high bioavailability or high AUC? Give multiple doses. Look at the next graph. Try to apply this by studying the  Passive H i concentration computation below o Occurs mostly by diffusion (higher to lower  Oral Route concentration) o Most common route of drug administration o No energy to cross the membrane o Absorption is slower  Active o Subject to first-pass effect o Requires a carrier, such as enzyme/protein  Buccal and Sublingual o Energy is required o Direct absorption into the systemic venous circulation  Pinocytosis  bypasses the first pass effect o Cells carry drug across their membrane by engulfing o Buccal facial vein internal jugular vein the drug particles o Sublingual lingual vein internal jugular vein o Cell drinking brachiocephalic (innominate) vein superior vena  Endocytosis cava right atrium o Large drugs bind to receptors, are internalized and  Intravenous released after vesicle breakdown o Instantaneous and complete absorption that bypasses o Reverse: exocytosis first-pass effect o Cell eating  100% bioavailability  Other factors that affect absorption o Potentially more dangerous; inadvertent systemic o Lipid/water solubility introduction of bacteria through the IV line o Ionization o Difficult to reverse effects o Acidity of the stomach  Intramuscular o Blood flow o Absorption is faster and more complete than oral o pH  bypasses first-pass effect, higher bioavailability o Presence/absence of food o Large volumes may be delivered if drug is not too o Pain/stress irritating  First- Pass Effect/ Hepatic First Pass  5g of MgSO4 o The process in which the drug passes to the liver first o Anticoagulants cannot be given by this route because o Warfarin undergoes first-pass metabolism they may cause bleeding (hematomas)  Bioavailability o IM Injections to Buttocks o Percentage of the administered drug dose that  Superolateral = safe reaches the systemic circulation  Superomedial = gluteus medius gait o Factor that affect include the drug form, GI mucosa,  Inferomedial = sciatica food and other drugs and changes in liver metabolism  Subcutaneous o Oral route – less than 100% bioavailabity o Bypasses the first pass effect o Slower absorption than intramuscular route patataslamang  NCM106 PHARMACOLOGY LECTURE / GARCIA  No blood vessels in the subcutaneous space  Only free drugs (drugs that are not bound to protein) are o Large volume doses are less feasible active and can cause a pharmacologic response o Anticoagulants do not cause hematomas when  When two highly-protein drugs are given concurrently, administered via this route they compete for protein-binding sites, thus causing more  Rectal Suppository free drug to be released in the circulation o Partial avoidance of the first-pass effect o Free protein binding sites: liver/kidney disease, o Useful for large amounts of drugs with unpleasant malnourishment, elderly tastes and for patients who are vomiting o Abscess, tumors, exudates, body glands hinder drug  Inhalational distribution o Offers delivery closest to the respiratory tissues o Very rapid absorption with minimal systemic effects METABOLISM o Convenient for drugs that are gases at room temperature (nitrous oxide, nitric oxide) or easily  Liver volatilized (anesthetics) o Primary site of metabolism o Metabolizes lipid-soluble drugs to water-soluble drugs  Topical Creams for excretion. However, some drugs are transformed o Application to skin, mucous membranes of the eye, into active metabolites ear, nose, throat, airway, or vagina for local effect o Slowest route of drug administration  Half-life o Absorption varies with the area of application and o Time it takes for one half of the drug concentration to drug formulation be eliminated o Ordered by increasing ability to retard evaporation  Short half life – 4-8 hrs  (more evaporation) tinctures > wet dressings >  Long half life – 24 hrs or longer lotions > gels > aerosols > powders > pastes >  By knowing the half life, the time it takes for a creams > foams > ointments (less evaporation) drug to reach a steady state of serum o Using dermatologic drug preparations for skin concentration can be computed inflammation  Acute inflammation = dying agents (tinctures, wet ELIMINATION dressings, lotion)  Termination of drug action (may involve metabolism into  Chronic inflammation = lubricating agents inactive state and/ excretion out the body) (creams, ointments)  Metabolism + Excretion  Transdermal o Acid urine promotes elimination of weak base drugs o Application to the skin for systemic effect o Alkaline promotes excretion of weak acid (aspirin) o Absorption occurs very slowly but bypasses the first- o Creatinine clearance – most accurate test to pass effect determine renal function  Oral – route of administration that undergoes significant  First- Order Elimination first-pass effect o Rate of elimination is proportionate to the  Rectal – partially bypass concentration  IV, IM, SC, SL, Inhalational, Topical, Transdermal –  Concentration decreases exponentially over time completely bypass o Characteristic half-life of elimination: concentration decreases by 50% for every half-life DISTRIBUTION o Most common type of elimination  The process by which the drug becomes available to body o Firs order kinetics is easier to understand because the fluids and body tissues rate of elimination is just halved every half-life  If the rate of elimination of a drug starts at 10 units/hour, after 1 half-life it would be 5 units B /hour (10 divided by 2). After 2 half-lives it would be 2.5 units/hour (5 divided by 2) and so on I t  Zero- Order Elimination/ Michaelis – Menten Kinetics concentration  o o Rate of elimination is constant regardless of Concentration decreases linearly over time  Constant amount of drug being excreted over o Drugs are distributed in the plasma, so many drugs time are bound to protein o Occurs when drugs have saturated their elimination  >89% - high protein-bound drugs mechanism  61-89% - moderately high  If for example its elimination rate is 5 units/hour,  30-60% - moderate after 1 half-life it’s 5 units/hour; after 2 half-lives  140 gestation) should receive antenatal corticosteroid therapy mm Hg or diastolic blood pressure >90 mm Hg) and with betamethasone (Celestone) or dexamethasone. An proteinuria (≥300 mg in 24-hour urine collection) in a off-label use, administration of antenatal corticosteroids normotensive pregnant patient after 20 weeks’ gestation. accelerates lung maturation and lung surfactant  The condition is most often observed after 20 weeks development in the fetus in utero, decreasing the gestation, intrapartum, and during the first 72 hours incidence and severity of respiratory distress syndrome postpartum, though late postpartum preeclampsia- (RDS) and increasing survival of preterm infants. eclampsia may present more than 48 hours but less than 4 Antenatal therapy decreases infant mortality, RDS, and weeks postpartum. intraventricular bleeds in neonates born between 24 and 34 gestational weeks. ECLAMPSIA o Goal of Therapy:  To delay delivery by 48 hours to maximize the  A new-onset grand mal seizures in a patient with effect of the glucocorticoids preeclampsia.  Believed to be related to decreased levels of vasodilating prostaglandins with resulting vasospasm. salt waterretentionancrea mp cnea.rs sexnormonementeronean menwitnnoon tamanwitnmustain manninizingeratineman teminizingenenonman increanamouasuga sugar iniaseariacotinteution ÉI DRUGS FOR GESTATIONAL HYPERTENSION GESTATIONAL HYPERTENSION motherwith high blood patienwimmaintenanamedia  Elevated blood pressure without proteinuria after 20 gestational weeks in patient normotensive before pregnancy.  Most common serious complication of pregnancy.  Can have devastating maternal and fetal effects. PREECLAMPSIA  A Gestational hypertension with proteinuria. patataslamang  NCM106 PHARMACOLOGY LECTURE / GARCIA  Potentiate the analgesic action of the opioids and minimize emesis. o NARCOTIC AGONISTS  Given for active labor  Administered parenterally or via regional blocks.  When administered with neuraxial anesthesia, a lower dose of anesthetic is required for effective pain relief, thereby LABOR AND DELIVERY AND NEONATAL DRUGS minimizing side effects.  These drugs interfere with pain impulses at the DRUGS FOR PAIN CONTROL DURING LABOR subcortical level of the brain.  During the first stage of labor, uterine contractions produce  To effect pain relief, opioids interact with mu and progressive cervical effacement and dilation. As the first kappa receptors. stage of labor progresses, uterine contractions become  For example, morphine sulfate activates both mu stronger, longer, and more frequent, and discomfort and kappa receptors. increases.’ o OPIOIDS WITH MIXED NARCOTIC  Pain and discomfort in labor are caused by uterine AGONISTANTAGONIST EFFECTS contraction, cervical dilation and effacement, hypoxia of  Exert their effects at more than one site—often the contracting myometrium, and perineal pressure from an agonist at one site and an antagonist at the presenting part. Pain perception is influenced by another. physiologic, psychological, social, and cultural factors, in  Two most commonly used narcotic- particular, the woman’s past experience with pain, agonistantagonist drugs are butorphanol tartrate anticipation of pain, fear and anxiety, knowledge deficit of and nalbuphine. the labor and delivery process, and involvement of support  With dose-ceiling effect persons.  Nonpharmacologic Measures  Ambulation  Supportive positioning of the gravid uterus and promotion of uterine perfusion  Touch and massage  Hygiene and comfort measures  Support persons  Breathing and relaxation techniques  Transcutaneous electrical nerve stimulation  Hypnosis  Acupuncture  Hydrotherapy (warm-water baths or showers) ANALGESIA/SEDATION  Systemic medications used during labor include sedative tranquilizers, narcotics agonists, and mixed narcotic agonist-antagonists; these may be administered orally (sedative-hypnotic drugs), intravenously (IV), or intramuscularly (IM). o SEDATIVE-TRANQUILIZERS  Most commonly given for false labor, latent labor, or with ruptured membranes without true labor  Minimize maternal anxiety and fear  Promote rest and relaxation and decrease fear and anxiety, but they do not provide pain relief.  The sedative drugs most commonly used are barbiturates or hypnotics— generally secobarbital sodium (Seconal) and pentobarbital sodium (Nembutal)  Other drugs, such as phenothiazine derivatives and hydroxyzine, can be given alone during early labor or in combination with narcotic agonists when the patient is in active labor. patataslamang  NCM106 PHARMACOLOGY LECTURE / GARCIA ANESTHESIA  It represents the loss of painful sensations with or without loss of consciousness during labor and delivery  Two types of pain are experienced in childbirth 1. Visceral pain from the cervix and uterus is carried by sympathetic fibers and enters the neuraxis at the thoracic 10, 11, 12, and lumbar 1 spinal levels. Early labor pain is transmitted to T11 and T12 with later progression to T10 and L1. 2. Somatic pain is caused by pressure of the presenting part and stretching of the perineum and vagina. This pain is the pain of the transition phase and the second stage of labor and is transmitted to the sacral 2, 3, and 4 areas by the pudendal nerve. REGIONAL ANESTHESIA  Achieves pain relief during labor and delivery without loss of consciousness. Injected local anesthetic agents temporarily block conduction of painful impulses along sensory nerve pathways to the brain.  Allows the patient to experience labor and childbirth with relief from discomfort in the blocked area.  Two types of Regional Anesthesia 1. Local anesthetic agents for local infiltration (e.g., episiotomy) Local anesthetic agents may be administered alone, and the anesthetic agent primarily administered is lidocaine (Xylocaine). Burning at the site of injection is the most common side effect. 2. Regional blocks Also known as a saddle block, is injected in the subarachnoid space at the T10 to S5 dermatome. This anesthesia may be a single dose or administered as a combined spinal-epidural. Spinal anesthesia is administered immediately before patataslamang  NCM106 PHARMACOLOGY LECTURE / GARCIA delivery or late in the second stage when the fetal head is on the perineal floor.  Postdural puncture headache is a primary concern, occurring 6 to 48 hours after dural puncture; it may also occur after accidental dural puncture with epidural anesthesia.  Treatment for Postdural Headache o Analgesics o Increased fluids o Bed rest o Epidural blood patch (10 to 20 mL) is the most effective means to treat postdural headache  Lumbar Epidurals o May be administered as a single injection, intermittent injections, continuous patientcontrolled epidural anesthesia (PCEA), and as a combined spinalepidural. o Epidurals may be administered as a single anesthetic agent or with opioids or epinephrine. o Single-dose epidural anesthesia is infrequently used as analgesia and is limited to the single dosing action. o Intermittent epidural bolus dosing was once commonly used for pain relief. Doses of the local anesthetic were injected intermittently via an epidural catheter. o Limitations of this method included the need for frequent injections and decreased pain control because of the dosing schedule.  Caudal (Type of Epidural Anesthesia) o Indication  Pain in first and second stages of labor. Infrequently used o Where given  Active labor o Area blocked  Perineum; masks uterine contractions o Injection site  Epidural space through sacral hiatus o Considerations patataslamang  NCM106 PHARMACOLOGY LECTURE / GARCIA  Increased need to use forceps or vacuum extraction because there is a loss of urge to push. Risk of systemic toxic reactions.  Level of anesthesia is more difficult to obtain.  Paracervical Block o Indication  Pain during first stage of labor. Due to high incidence of fetal bradycardia, paracervical block is infrequently administered. o Where given  Active phase of first stage; may be repeated periodically until 8cm dilated  Approaches of Labor Induction o Area blocked 1. Mechanical Methods  Uterus, cervix, and vagina; masks uterine 2. Prostaglandins contractions. o Injection site METHANICAL METHODS  Submucosa of the fornix of the vagina lateral to  One mechanical method involves insertion of a 36F the cervix. indwelling catheter through an undilated cervix and o Considerations internal os with subsequent inflation of the 30-mL balloon.  Rapid absorption (because injected into a very The indwelling catheter bulb provides a mechanical vascular area). stimulation similar to “stripping of the membranes.” When  Does not provide anesthesia for delivery or the catheter “falls out,” the patient is started on IV episiotomy repair. oxytocin.  Has variable effects on labor progress.  A second mechanical method is insertion of an  Pudendal Block extraamniotic saline infusion with a balloon catheter into o Indication the space between the internal cervical os and the  For low forceps deliveries, episiotomy, and placental membrane to induce labor. laceration repair. Infrequently used.  A third mechanical method is membrane “stripping.” With o When given membrane stripping, there is release of prostaglandin F2  Immediately before birth. from the decidua or prostaglandin E2 from the cervix o Area blocked  Perineum; pudendal nerves. PROSTAGLANDINS o Injection site  Transvaginally, behind each sacrospinous  Labor induction uses administration of dinoprostone, the ligament to block pudendal nerves. naturally occurring form of prostaglandin E2 (PGE2). It is o Considerations thought that intracervically or intravaginally administered  Not useful for pain management in first stage of PGE2 acts to create cervical effacement and softening labor through a combination of contraction-inducing and  RELATIVE CONTRAINDICATIONS TO REGIONAL cervicalripening properties, possibly secondary to an ANESTHESIA increased submucosal water content and collagen o Severe gestational hypertension (increased risk of degradation resulting from collagenase secretion in profound hypotension associated with underlying response to PGE2. disease state).  One approach uses prefilled syringes of commercially o Coagulation disorders and risk of bleeding secondary prepared dinoprostone cervical gel 0.5 mg (Prepidil gel), to decreased platelets (patient should have a normal which is introduced just inside the cervical os. partial thromboplastin time and platelet count).  A second approach is the placement in the posterior o Generalized sepsis or local infection at needle vaginal fornix of a vaginal insert dinoprostone (Cervidil) insertion site. containing 10 mg of controlled-release dinoprostone at 0.3 mg/h. DRUGS THAT ENHANCE UTERINE MUSCLE CONTRACTILITY  Uterotropic drugs enhance uterine contractility by stimulating the smooth muscle of the uterus. Oxytocin, the ergot alkaloids, and some prostaglandins constitute the uterotropics patataslamang  NCM106 PHARMACOLOGY LECTURE / GARCIA ornerier m canoruterinecontractionity www.ncontraueaute ao release oxytocin aosecsonia nipplestimulation minding gorimpertonic contraction uterine ampetonic Dicationanaeteacement contraction mum suninvolution return previous.ie ingmar Iginaniantneutemia involution returnoitneutemitoprenean Betongivingmetneraineane Be OXYTOCIN  In addition to labor induction, IV oxytocin can also be used for labor augmentation. It facilitates smooth-muscle contraction in the uterus of a patient already in labor but experiencing inadequate uterine contractility (tightening and shortening of uterine muscles). The patient with patataslamang  NCM106 PHARMACOLOGY LECTURE / GARCIA uterine inertia (uterine inactivity or hypotonic contractions) may be more responsive to oxytocin than the patient who has not begun labor; therefore a lower starting dose will be needed. ERGOT ALKALOIDS  The ergot alkaloids (one of a large group of alkaloids derived from a fungus) act by direct smooth-muscle-cell receptor stimulation. These drugs are not used during labor, because they can cause sustained uterine contractions (tetanic contractions), which would result in fetal hypoxia and possibly rupture of the uterus. The uterus becomes more sensitive to these drugs too. After delivery, however, sustained contractions are effective in the prevention or control of postpartum hemorrhage and the promotion of uterine involution.  The most commonly used ergot derivative is methylergonovine maleate (Methergine). Methylergonovine maleate can be given by mouth but is most frequently administered by the IM route.IV administration is not recommended and is given only in emergency situations SURFACTANT THERAPY IN PRETERM BIRTH SYNTHETIC SURFACTANT  One approach to respiratory difficulties in the preterm infant is surfactant replacement therapy. This is used to prevent the development of respiratory distress syndrome POSTPARTUM AND NEWBORN DRUGS (RDS) (respiratory disease of the newborn with absence,  During the puerperium (the period from delivery until 6 deficiency, or alteration in surfactant production). weeks postpartum), the maternal body physically recovers Surfactant (a lipoprotein in the alveoli that reduces surface from antepartal and intrapartal stressors and returns to its tension of pulmonary fluids and keeps alveoli open during prepregnant state. expiration) replacement therapy is also used to decrease  Purposes of Pharmacologic and Nonpharmacologic the severity of RDS after diagnosis. Supplementing the Measures amount of endogenous surfactant available to maintain 1. Prevent uterine atony and postpartum hemorrhage distention of the alveolar sacs is the focus of this therapy. 2. Relieve pain from uterine contractions, perineal wounds, and hemorrhoids 3. Enhance or suppress lactation (production and release of milk by mammary glands) ‘ 4. Promote bowel function 5. Enhance immunity patataslamang  NCM106 PHARMACOLOGY LECTURE / GARCIA PAIN RELIEF FOR PERINEAL WOUNDS AND HEMORRHOIDS  Pregnancy and the delivery process increase the pressure on perineal soft tissue. The tissue may become ecchymotic or edematous. Increased edema, ecchymosis, and pain may occur if an episiotomy (incision made to enlarge the vaginal opening to facilitate newborn delivery) or perineal laceration is present. The perineum is assessed for Redness, Ecchymosis, Edema, Discharge, and Approximation (REEDA).  Hemorrhoids that developed during pregnancy may be exacerbated by the pushing during labor. Comfort measures (ice packs immediately after birth, tightening of the buttocks before sitting, use of peribottles and cool or warm sitz baths) and selected topical agents (witch hazel and dibucaine ointment) may relieve pain and minimize discomfort.  Rectal suppositories should not be used by women with fourth-degree perineal lacerations. PAIN RELIEF FOR UTERINE CONTRACTIONS  “Afterbirth pains” may occur during the first few days postpartum when uterine tissue experiences ischemia during contractions, particularly in multiparous patients and when breastfeeding. Nonsteroidal agents may be used to control postpartal discomfort and pain, with narcotic agents reserved for more severe pain such as that experienced by the patient after cesarean delivery, tubal ligation, or extensive perineal laceration. LACTATION SUPRESSION patataslamang  NCM106 PHARMACOLOGY LECTURE / GARCIA  In the past, lactation was commonly controlled through drug therapy with one of three agents: chlorotrianisene (Tace), Deladumone OB (combination of estrogen plus androgen in the form of estradiol valerate and testosterone enanthate), or bromocriptine mesylate (Parlodel). Estrogenic substances are much less popular than in the past because of the increased incidence of thrombophlebitis associated with the high dosage needed to suppress lactation and concerns about potential carcinogenic effects.  Presently nonpharmacologic measures are recommended for lactation suppression, such as wearing a supportive bra 24 hours a day for 10 to 14 days or using axillary ice packs PROMOTION OF BOWEL FUNCTION  Constipation is common during the postpartum period. The residual effects of progesterone on smooth muscle decrease peristalsis. This decreased paristalsis, added to decreased liquid intake during labor, decreased activity, and relaxation of the abdominal muscles, amplifies the problem. Patients who deliver by cesarean section are even more likely to experience constipation and flatus (intestinal gas). patataslamang  NCM106 PHARMACOLOGY LECTURE / GARCIA RUBELLA VACCINE  Maternal rubella, also called German measles, is a potentially devastating infection for the fetus, depending on gestational age. If an unimmunized woman (rubella titer contracts the virus during the first trimester, a high rate of abortion and neurologic and developmental sequela associated with congenital rubella syndrome (transmission of the rubella virus to the fetus via the placenta) may result. Cataracts, glaucoma, deafness, heart defects, and mental retardation are seen with this syndrome.  When infection occurs after the first trimester, there is less risk of fetal damage because of the developmental stage of the fetus. There is no treatment for maternal or congenital rubella infection. The goals are immunization and prevention of rubella in patients of childbearing age IMMUNIZATIONS RHO(D) IMMUNE GLOBULIN  An Rh-negative patient who lacks the Rh factor in her own blood may carry a fetus who is either Rh-negative or Rh- positive. During pregnancy, minimal amounts of fetal blood may cross the placenta. Also, an abortion (spontaneous, therapeutic, or induced), amniocentesis, ectopic pregnancy, previa, and abruption result in some mixing of maternal and fetal blood. Subsequently, anti-D antibodies develop in an Rh-negative mother with an Rh-positive fetus; with the development of these antibodies, the mother becomes sensitized patataslamang  NCM106 PHARMACOLOGY LECTURE / GARCIA ftp.tnk paytomemon cantiintmintain.nu anormatiora aamaminatnemeaing cutting iterminimoom IMMUNIZATION DURING THE NEWBORN PERIOD BEFOE DISCHARGE HEPATITIS B VACCINE firetrauineaivenatnian  The American Academy of Pediatrics and the Centers for Disease Control and Prevention (CDC) have recommended that immunization against hepatitis B virus (HBV) begin in the newborn period. HBV infection may result in serious long-term liver disease, cancer, and death in adulthood DRUGS ADMINISTERED TO THE NEWBORN IMMEDIATELY AFTER DELIVERY aldrin a management a mania Yhintation anomunctiviti aromtneinnertotneouturtmanner ypassetannan inomanottmentneen nerscenix reaposibility therionave erythromycin micointment patataslamang  NCM106 PHARMACOLOGY LECTURE / GARCIA  the amount of estrogen is fixed throughout the cycle, but the amount of progestin varies; reduced in the first half to provide for some proliferation of the endometrium and increased in the second half to promote secretory development of the endometrium. This simulates the normal physiologic process of menstruation while still inhibiting ovulation. o Triphasics  are the newest form of phasic COC products delivering low doses of both hormones with minimal side effects, including breakthrough bleeding. With triphasics, the amount of either WOMEN’S REPRODUCTIVE HEALTH AND estrogen or progesterone varies throughout the MENOPAUSE cycle in different ratios during three phases.  Women have specific health care needs throughout their reproductive and postreproductive life cycle. Women’s EXTENDED-CYCLE COC PRODUCTS reproductive life cycle begins with menarche, the start of  Loestrin 24 Fe is a 24-day monophasic hormonal regimen spontaneous menstruation, and continues through of 20 mcg of ethinyl estradiol tablets and 1 mg of menopause, the permanent cessation of menstruation. norethindrone acetate, plus 4 ferrous fumarate tablets. It Successful contraception is essential to the health and provides 24 days of active hormonal therapy and 4 days of well-being of sexually active women of reproductive age. hormone-free pills containing an iron supplement. Successful adaptation to menopause, control of menopausal symptoms, and continued sexual wellness is CONTINUOUS DOSING COC PRODUCTS essential to the health and well-being of older women.  Seasonale (Jolessa) is a continuous dosing combined hormone contraception pill. The 91-day regimen includes ESTROGEN-PROGESTIN COMBINATION PRODUCTS 84 days of active pills and 7 days of inert pills.  All estrogen-progestin combination products (also known as combined hormone contraception [CHC] products) ORTHO-EVRA TRANSDERMAL PATCH contain a synthetic version of estrogen and a compound known as progestin.  The Ortho-Evra patch is aweekly form of combined hormone contraception, consisting of 750 mcg of ethinyl estradiol and 6 mg of the progestin norelgestromin ETHINYL ESTRADIOL (EE) (NGMN) delivered through a transdermal system. It is a  Most commonly used synthetic estrogen found in CHC thin plastic patch placed on the skin of the buttocks, products. An older form of estrogen, mestranol, is found in stomach, upper outer arm, or upper torso. The patch is higher-dose (≥50 mcg) oral combination products. placed once a week for 3 weeks in a row. The fourth week Mestranol is converted into ethinyl estradiol in the body. is patch-free to allow for withdrawal bleeding.  The patch works in a similar manner to COC pills by PROGESTINS inhibiting ovulation, thickening cervical mucus to prevent sperm penetration, and preventing a fertilized egg from  natural or synthetic hormones that have progesterone-like implanting in the uterus. effects. Progesterone is the naturally occurring sex hormone produced in the ovaries of women. Progestogen  Advantages: refers to any synthetically produced progesterone o Not having to remember to take a pill daily. compound. The term progestin will be used to describe the o Less menstrual flow and cramping, acne, iron- compound used in CHC products. Not only do progestins deficiency anemia, excess body hair, premenstrual have contraceptive properties, they serve to balance out symptoms, and vaginal dryness with the patch. the effects of estrogen. o Reduces the risk for ovarian and endometrial cancers, PID, breast cysts, ovarian cysts, and osteoporosis COMBINED ORAL CONTRACEPTION PRODUCTS (loss of bone mass predisposing the patient to fractures).  Most commonly used methods of reversible contraception o Fewer occurrences of ectopic pregnancy in the world.  Disadvantages  Ease of use, high degree of effectiveness, and relative o Skin reaction at the site of application, menstrual safety. cramps, and a change in vision or the inability to wear  92% to 99.3% effective for contraception. contact lenses.  Types of combined oral contraception products o Not as effective for women who weigh more than 198 o Monophasics, or nonphasic pills lb.  provide a fixed ratio of estrogen to progestin o Exposes patients to higher levels of estrogen. - throughout the menstrual cycle. Increased risk for venous thromboembolism (VTE). o Biphasics or phasic pills patataslamang  NCM106 PHARMACOLOGY LECTURE / GARCIA o Other side effects include temporary irregular SPERMICIDES bleeding, weight gain or loss, breast tenderness, and nausea.  Spermicides are chemical agents that inactivate sperm before they can travel through the cervix and into the upper genital tract. The most common form of spermicide NUVARING TRANSVAGINAL CONTRACEPTION is nonoxynol-9  NuvaRing is a 2-inch–diameter flexible indwelling ring inserted into the vagina. It is nonbiodegradable, BARRIER METHODS transparent, and colorless to almost colorless. NuvaRing releases 15 mcg of EE and 120 mcg of the progestin  Both male and female condoms are available over- etonogestrel per day, similar to the quantities of estrogen thecounter without a prescription. The female condom is a and progestin found in lower-dose COC products. polyurethane (plastic) pouch with flexible rings at each end. It is inserted deep into the vagina like a diaphragm. PROGESTIN-ONLY CONTRACEPTION PRODUCTS The ring at the closed end holds the pouch in the vagina. The ring at the open end stays outside the vulva. Male  Do not contain estrogen. The estrogen component of condoms are available in latex, lambskin, and contraceptives increases the risk of circulatory disorders. polyurethane. Latex condoms offer very good protection Allow contraception to be available for women who cannot against STIs and HIV take estrogenprogestin combination products. PROGESTIN-ONLY ORAL CONTRACEPTION PILL INTRAUTERINE CONTRACEPTION  Intrauterine devices (IUDs) and intrauterine systems  Alteration in cervical mucus, making it thick and viscous, (IUSs) are safe methods of contraception with high patient which blocks sperm penetration. satisfaction rates  Interference with the endometrial lining, which makes o ParaGard T 380A implantation difficult.  It releases copper, which primarily interferes with  Decreased peristalsis in the fallopian tubes, slowing the the contractions within the uterus impeding sperm transport of ovum. migration.  In approximately 50% of cycles, interference with the LH  A secondary effect is an inflammation of the surge inhibiting ovulation. endometrium, which also obstructs sperm motility and prevents implantation in the rare case that DEPO-PROVERA conception should occur  Highly effective, long-acting injectable progestin in the  It should be inserted up to day 7 of the menstrual form of depotmedroxyprogesterone acetate cycle, and can remain in place for up to 10 years.  With a theoretical and typical use efficacy rate of 99% and o Mirena levonorgestrel-releasing intrauterine system 97%, respectively. (LNG-IUS)  One of the most effective hormonal methods of  It causes cervical mucus to become thicker so contraception at 97% to 99%. sperm cannot enter the upper reproductive tract  Convenient dosing schedule. or reach the ovum.  It impairs sperm migration by changing the  Responsible for thickening of the cervical mucus, thinning uterotubal fluid. of the uterine endometrium, and decrease in fallopian tube  Alterations in the endometrium prevent motility. implantation in the rare case that conception  Inhibits both FSH and LH secretion from the anterior occurs with the device in place. The LNG-IUS pituitary gland. may also suppress ovulation.  No protection against STIs.  Both the ParaGard and the LNG-IUS can be inserted as  May cause a loss of bone mineral density. early as 6 weeks postpartum. There are no contraindications with breastfeeding women and IMPLANTABLE PROGESTINS intrauterine contraception.  Nexplanon is a single-rod device containing 68 mg of the  Contraindications to the LNG-IUS are known or suspected progestin etonogestrel; it is placed in the same location as pregnancy, uterine anomalies, and risk for acquiring an Implanon. STI. The LNG-IUS may be effective at preventing  Contains barium, a radio-opaque substance that can help endometrial cancer and invasive cervical cancer. locate the device on twodimensional x-ray, ultrasound, magnetic resonance imaging (MRI) and computed MEDICAL ABORTION tomography (CT) scanning if necessary.  Refers to the termination of pregnancy that is less than 63  Nexplanon may not be as effective in women who have a days from the first day of the LMP, or less than 9 weeks’ BMI greater than 30 (obese) or are on medications that gestation. induce liver enzymes. o Methotrexate  medication that stops the pregnancy in the OTHER METHODS OF CONTRACEPTION uterus. It may also be used to treat an early patataslamang  NCM106 PHARMACOLOGY LECTURE / GARCIA ectopic pregnancy that is encapsulated and less  Actaea racemosa, or black cohosh, is used in the over- than 3 cm in size. thecounter preparations of Remifemin and Estroven. o Mifepristone Limited studies show that black cohosh may decrease hot  first marketed as RU486, is an anti-progestin that flashes. blocks the hormone progesterone. Without  St. John’s wort may be helpful for menopausal women progesterone, the lining of the uterus breaks experiencing mild depression or mood alterations down, ending support for the embryo.  Ginseng may improve sleep, mood changes, and sense of o Misoprostol well-being, while valerian is thought to help with insomnia  given to cause the uterus to contract and expel the products of conception. BIOIDENTICAL HORMONE THERAPY MENOPAUSE  It includes estrogen-like compounds that have been  It refers to the transitional process experienced by women derived from plants. These compounds are biochemically as they move from the reproductive years into the similar or identical to those produced by the ovaries. nonreproductive stage of life  The most common commercially available compounds are  Stages estrone, estradiol, estriol, testosterone, and micronized 1. Perimenopause or Premenopause progesterone. The route of administration can be  Includes the years before the natural cessation of oral,sublingual, implantable, injectable, or in vaginal spontaneous menstruation. suppository form.  Women may experience short cycles (less than  Pellet therapy is a form of bioidentical hormones, usually every 25 days), long cycles (more than every 35 estradiol and estriol, aswell as progesterone and days), heavy bleeding, light bleeding, or periods testosterone, implanted subcutaneously, in unnoticeable of longer or shorter duration. areas. Usually one pellet is placed and has a duration of 4  Women may start to skip periods or abruptly stop to 6 months. A new pellet is then inserted menstruating altogether.  Oligomenorrhea (very scant periods) or HORMONE THERAPY menorrhagia is common.  Hormone therapy (HT) is used only for the relief of  Most common symptoms are hot flashes (caused symptoms related to menopause, most commonly hot by a surge in LH levels) and vaginal dryness flashes, vaginal dryness, and associated sleep disorders. (caused by estrogen withdrawal). Other HT includes estrogen-progestin therapy (EPT) for use with symptoms include insomnia, headaches, women who have an intact uterus, and estrogen therapy irritability, anxiety or other variations in mood, (ET) for use with women who have had a hysterectomy. cognitive difficulties, memory lapses, joint aches,  HT is available in oral preparations, transdermal and decreased libido applications, and vaginal preparations. Vaginal 2. Menopause preparations are creams, suppositories, or rings. All  Refers to the permanent end of spontaneous vaginal preparations contain estrogen only and are very menstruation caused by cessation of ovarian effective in treating vaginal dryness function.  Three types of estrogens are used in HT products  It is documented as having occurred once a o Natural or biological estrogens (including bioidentical woman has stopped menstruating for 1 year estrogens) 3. Postmenopause  derived from plants, minerals, or animals and are  It is the stage when the body adapts to a new composed of estrones and estradiols. hormonal environment. o CEE  The production of estrogen and progesterone  are mixtures of natural estrogens isolated from from the ovaries decreases during the late the urine of pregnant mares. Although CEEs are premenopausal and early postmenopausal derived from nonhuman sources, they are periods naturally occurring estrogens. o Synthetic estrogens PHARMACOLOGIC AND COMPLEMENTARY AND  include ethinyl estradiol and mestranol, which are ALTERNATIVE THERAPY FOR PERIMENOPAUSAL AND both the same estrogens found in CHC products. MENOPAUSAL SYMPTOMS OTHER DRUGS FOR MENOPAUSAL SYMPTOMS COMPLIMENTARY ALTERNATIVE MEDICINE  Selective serotonin reuptake inhibitors (SSRIs)  Soy has been made available in many over-the-counter o reduce the number and severity of vasomotor nutritional supplements; however, natural soy products are symptoms in women. SSRIs also have the added considered more effective at treating hot flashes benefit of reducing depression, which may relieve  Red clover extract is also used to treat hot flashes, irritability and mood changes associated with although research studies using red clover extract are menopause. inconclusive.  Clonidine (Catapres, Kapvay) patataslamang  NCM106 PHARMACOLOGY LECTURE / GARCIA o a medication used for hypertension, also reduces the or have not had improvement in T-score after using number and severity of vasomotor symptoms in the bisphosphonates for osteoporosis. A 60-mg dose women. is given subcutaneously every 6 months.  Gabapentin (Neurontin) o is an antiseizure medication that reduces the number MEN’S REPRODUCTIVE HEALTH AND and severity of vasomotor symptoms in menopausal REPRODUCTIVE DISORDERS women.  Reproductive health implies that men and women at developmentally appropriate life stages are fertile (i.e., OSTEOPOROSIS able to produce gametes [sperm or eggs]). It entails the  It is a progressive, debilitating skeletal disease that affects ability to engage in sexual intercourse with ejaculation by older men and women. Women older than 50 years are at the male. greatest risk since the loss of estrogen during menopause is directly related to loss in bone mineral density. SUBSTANCES RELATED TO MALE REPRODUCTIVE  Hormone Therapy is no longer recommended for the DISORDERS treatment of osteoporosis but should be considered as a preventive measure in postmenopausal women who are at ANDROGENS risk.  Bisphosphonates, which can reduce the breakdown of  Androgens, or male sex hormones, control the bone microstructure, and selective estrogen receptor development and maintenance of sexual processes, modulators (SERMs). SERMs are a new class of synthetic accessory sexual organs, cellular metabolism, and bone estrogens. and muscle growth. Testosterone is the principal male sex hormone and is an anabolic steroid. It is the prototype of the androgen hormones, synthesized primarily in the MEDICATIONS testes and, to a lesser extent, in the adrenal cortex  Menostar (estradiol transdermal system) o is 14 mcg of 17-β estradiol in a transdermal, once- aweek patch used for prevention of postmenopausal osteoporosis.  Alendronate (Fosamax) man main mm o is a bisphosphonate used to treat osteopenia and osteoporosis.  Ibandronate sodium (Boniva) o is a once-a-month bisphosphonate indicated for the treatment and prevention of osteoporosis in postmenopausal women.  Risedronate (Actonel) o is also available in a daily or weekly dose. It has similar directions for use and side effects as the bisphosphonates.  Reclast o is a bisphosphonate that is administered IV in a 5-mg dose yearly. The IV dose should be administered over 15 minutes.  Raloxifene (Evista) aeration among o is a SERM that increases bone mineral density, decreases bone turnover, and reduces vertebral fractures. Evista is taken orally once a day in 60-mg tablet.  Teriparatide (Fortéo) o is a parathyroid hormone used for treatment of postmenopausal osteoporosis. It is administered 20 mcg subQ on a daily basis.  Salmon calcitonin (e.g., Fortical, Miacalcin) o is composed of calcitonin, a naturally occurring hormone that regulates calcium in the body and promotes bone metabolism. It is delivered via intranasal spray in a 200-IU dose administered daily.  Denosumab (Prolia) o is an osteoclast inhibitor used in women who are at a high risk for osteoporotic fracture, have had a fracture, patataslamang  NCM106 PHARMACOLOGY LECTURE / GARCIA  is an oral nonsteroidal antiandrogen drug used as an antihormonal agent in the treatment of metastatic prostate cancer. o Bicalutamide ( Casodex)  is more selective for the peripheral androgen receptor and has less activity at the central androgen receptor on the hypothalamicpituitary axis. o Spironolactone (Aldactone)  is a weak potassium-sparing diuretic used primarily to treat high blood pressure, heart failure, and ascites in patients with liver disease. It has been used to treat acne vulgaris, polycystic ovary syndrome, and female hirsutism. o Finasteride (Propecia/Proscar)  a synthetic compound, inhibits conversion of testosterone to 5-alpha-dihydrotestosterone (DHT). This orally active agent decreases the concentration of dihydrotestosterone in plasma and in the prostate without elevated plasma concentrations of LH or testosterone. Finasteride is used to treat benign prostatic hypertrophy (BPH) and male pattern baldness (MPB). DRUGS USED IN OTHER MALE REPRODUCTIVE DISORDERS ANABOLIC STEROIDS  Anabolic steroids, or anabolic-androgenic steroids (AAS), DELAYED PUBERTY are a class of steroid hormones related to the hormone  Treatment is not initiated before 14 years of age and after testosterone. a full evaluation. Therapy for 3 to 6 months or less before  Increase protein synthesis within cells, which results in the epiphyseal closure may result in linear growth without buildup of cellular tissue (anabolism), especially in adverse permanent effects on hypothalamic, pituitary, or muscles. gonadal maturation  Have androgenic and virilizing properties, including the development and maintenance of masculine PITUITARY, THYROID, AND ADRENAL DISORDERS characteristics such as the growth of the vocal cords and body hair.  Inadequate pituitary function can be another cause of hypogonadism wine innaew aim man see ovary mentoraonaatestacinan ANTIANDROGENS tryin Meno  Also known as androgen antagonists  Block the synthesis or action of androgens  Used in the treatment of benign prostatic hypertrophy, advanced prostatic cancer, and as hormonal therapy in the anana pituitary ora matterlanai treatment of endometriosis.  For treatment of male-pattern baldness, acne, hirsutism, virilization syndrome in women, and precocious puberty in boys, although their effectiveness is not well established. o Gonadotropin-releasing hormone (Gn-RH),  or a synthetic analogue such as leuprolide, is the venominteron most effective inhibitor of testosterone synthesis. When such agents are given over time, LH and testosterone levels fall. o Ketoconazole  an antifungal drug, has testosterone suppressing effects similar to those of GnRH analogues when given at doses higher than those required for antifungal activity. SEXUAL DYSFUNCTION o Flutamide patataslamang  NCM106 PHARMACOLOGY LECTURE / GARCIA  lackofsexualarousal Refers to the inability to experience sexual desire, BENIGN PROSTATE HYPERPLASIA erection, ejaculation, and/or detumescence—the phases  As a man ages, the glandular units in the prostate gland of the sexual response cycle. Inhibited sexual desire can begin to undergo tissue hyperplasia (abnormal increase in result from androgen deficiency, an affective disorder, or the number of cells), resulting in prostatic hypertrophy discord in the sexual relationship. (enlargement of the gland). The enlarged prostate gland o Ejaculatory dysfunction contributes to overall lower urinary tract symptoms either  (impaired ejection of seminal fluid from the male through direct bladder outlet obstruction or from resistance urethra) can be psychogenic or a result of drug within the enlarged gland itself. therapy, androgen deficiency, or sympathetic menianprostateitaperiansia degeneration. o Erectile dysfunction (ED)  is the inability to achieve or maintain an erection satisfactory for sexual performance. ED happens when not enough blood flows to the penis during sexual stimulation. Phosphodiesterase (PDE) inhibitors facilitates erections by enhancing blood flow to the penis I pig atmanntiitarina INFERTILITY AND SEXUALLY TRANSMITTED  Natural products INFECTIONS o To self-treat sexual problems or to enhance their sexual performance, consumers use a wide variety of MEDICATIONS USED TO TREAT DISORDERS IN WOMEN’S herbs and plant-derived compounds HEALTH (phytochemicals).  Yohimbine IRREGULAR OR ABNORMAL UTERINE BLEEDING  which is obtained from the bark of the African  Describes many different medical conditions or yohimbe tree, is an alpha-adrenergic pathologies related to the menstrual cycle. Irregular antagonist that affects both the central and uterine bleeding. peripheral nervous system. Studies have  Also known as abnormal uterine bleeding (AUB). shown that men experience a positive effect or improvement in erection.  It encompasses a wide range of variable bleeding patterns  Saw palmetto in women, such as amenorrhea, menorrhagia,  is a popular herbal remedy used to treat metrorrhagia, menometrorrhagia, intramenstrual bleeding, symptoms related to BPH and can help and dysfunctional uterine bleeding (DUB). shrink enlarged prostate glands.  Ginkgo biloba leaves AMENORRHEA  have been shown to treat peripheral vascular  Refers to the absence of menses. disease and enhance cerebral blood flow.  Primary amenorrhea patataslamang  NCM106 PHARMACOLOGY LECTURE / GARCIA o is defined as no menses by age 14 years of age insulin results in altered glucose metabolism and without secondary sex characteristics, or no menses hyperinsulinemia. by age 16 years with secondary sex characteristics. It o Pharmacologic treatment may be caused by abnormalities in the structures of  If the woman wants to prevent preganancy, the female reproductive tract, chromosomal Estrogen-progestin combination contraception alterations, or endocrine disorders. products are prescribed if the patient is a  Secondary amenorrhea candidate. CHC products suppress LH and o is the absence of a spontaneous menstrual period for follicle-stimulating hormone (FSH) secretion, limit 6 consecutive months in women who have androgen symptoms, and regulate menstruation experienced menstrual cycles in the past. by providing a withdrawal bleeding period.  Progestational Challenge Test  If the woman attempts to conceive, two drugs, o Administered to determine the underlying cause of metformin and clomiphene citrate, are used. amenorrhea after pregnancy has been ruled out. o Metformin (Glucophage) o It uses an oral progestin administered for a limited  inhibits the production of glucose in the liver and time to confirm that the hypothalamus-pituitary- increases peripheral cell sensitivity to insulin, ovarian (HPO) responses (the hormonal system effectively treating insulin resistance and mediating the menstrual cycle) are intact. decreasing androgen levels. o Patient is given either micronized progesterone o Clomiphene citrate (Clomid or Serophene) (Prometrium) 400 mg by mouth (PO) at bedtime for 10  is used in conjunction with metformin, or alone to days or medroxyprogesterone acetate (Provera) 5 to promote a dominant follicle and induce ovulation; 10 mg PO for 5 to 10 days. The progestational activity it is described in “Medications Used to Promote thickens the endometrial lining and increases Fertility.” secretory activity. When the medication is discontinued, progesterone levels decrease, resulting ABNORMAL UTERINE BLEEDING PATTERNS in a breakdown of the endometrial lining and  The normal menstrual cycle occurs every 25 to 35 days withdrawal bleeding. and lasts 2 to 7 days with an estimated blood loss of no more than 80 mL. METABOLIC SYNDROME  Menorrhagia  Polycystic Ovarian Syndrome (PCOS) o is regular uterine bleeding greater than 80 mL or o A form of metabolic syndrome caused by the lasting more than 7 days.Women with menorrhagia oversecretion of luteinizing hormone (LH). LH is the may describe their periods as very heavy or state the hormone responsible for stimulating ovulation, or mid- need to change a tampon or sanitary pad frequently. cycle release of an ovum from the dominant follicle in  Metrorrhagia the ovary. o is irregular uterine bleeding greater than 80 mL or o Oversecretion of LH causes the formation of several lasting more than 7 days. Women with menorrhagia follicular cysts in the ovaries instead of one dominant describe their periods as irregular and heavy. They follicle. The presence of several follicles increases may state that they have no idea when bleeding will estrogen levels; however, ovulation does not occur. occur, and that when it does happen it will soak o The cycle then becomes anovulatory (the absence of through sanitary products or clothing. ovulation), and the luteal phase, or the second half of  Menometrorrhagia the menstrual cycle in which progesterone is o is a combination of these two. Intramenstrual bleeding dominant, is inhibited. The endometrium of the uterus is an episode of bleeding, usually light, that occurs is exposed to “unopposed” estrogen from the between menstrual periods. anovulatory cycles. o Unopposed estrogen DYSFUNCTIONAL UTERINE BLEEDING  refers to levels of estrogen that are not balanced by a progestational (progesterone) effect.  Most common classification of irregular bleeding. Unopposed estrogen can cause abnormal  Diagnosis is made when no organic pathology can be thickening of the endometrial lining, increasing determined to cause the irregular bleeding. the patient’s risk for endometrial hyperplasia and  Pharmacologic treatment of DUB primarily involves uterine cancer. normalizing the bleeding pattern and correcting anemia o These patients will complain of skipped menstrual that may have resulted from chronic or acute blood loss. cycles, long menstrual cycles (35 days or greater) or  Increasing levels of estrogen by administration of an no menstruation for several months. extraneous estrogen drug product is usually effective in o Insulin resistance is a hallmark of PCOS. Insulin stopping prolonged DUB in conjunction with estrogen- resistance is the body’s inability to respond to progestin combination products. elevated glucose levels. Although insulin is secreted  Depot-medroxyprogesterone acetate (Depo-Provera) when glucose levels are high,“resistance” to the intramuscular (IM) injection or IUS/LNG (Mirena) inserted patataslamang  NCM106 PHARMACOLOGY LECTURE / GARCIA into the uterus are the products used for extended the inhibition of cyclooxygenase (COX). The COX progestin therapy enzyme converts arachidonic acid into  Pharmacologic Management of Irregular Bleeding prostaglandins, which cause constriction of the o Nonsteroidal antiinflammatory drugs (NSAIDs) can be uterine arterioles, necrosis of the endometrial used for the treatment of menorrhagia. NSAIDs block lining, uterine contractions, and menstrual pain. the production of prostaglandin, which decreases both Usually nonselective and COX-2 inhibitors are excessive bleeding and uterine cramps. used.  mefanamic acid (Ponstel) 500 mg PO once,  naproxen sodium (Anaprox) followed by 250 mg PO every 6 hours for 2 to 3  diclofenac potassium (Cataflam) days. Mefanamic acid should be taken with food  ibuprofen (Motrin) o CHC products can be used to decrease and regulate  naproxen (Naprosyn) DUB. Monophasic products and products that have a  celecoxib (Celebrex) dosage schedule of 21/7, 24/4, or 84/7 are first-line  mefenamic acid (Ponstel) drug therapy if the patient is a candidate for CHC o