2. December 1, 2009 Priya Vasudevan MD 22 January 2010

3. Articles Aesthetic Procedures Sex difference in drug activity Von willibrands disease Drug eluting stents

5. Botulinum toxin Dermal fillers Laser hair reduction Laser photo rejuvenation Microdermabrasion and chemical peels

7. Facial Aging Changes

8. Botulinum toxin Neurotoxin from C. botulinum Inhibits Ac choline @ NM junction Chemical denervation

9. Key points Dynamic facial lines and wrinkles in the upper 1/3 of face. One treatment every 3-4 months. Short procedure time and dramatic results Small margin of error with injection placement ; High patient expectations

11. Dermal fillers Temporarily restore soft tissue volume Vary by composition, duration of action, ease of administration. Desirable outcomes depends on physician’s knowledge and injection skills Requires practice to consistently achieve desirable results

12. Key points Facial wrinkles and folds in the lower two thirds of the face ; lip enhancement Every 3 to 24 months; varies widely with product composition and treatment area Immediate results Post procedure swelling and bruising. Requires practice.

14. Laser Hair Reduction Unwanted hair growth is a common aesthetic complaint of men and women. Density of body hair is predetermined at birth Non visible pigmented hairs become pigmented terminal hairs due to hormonal changes with aging.

15. Mechanism of Action Selective photo thermolysis. Energy is absorbed and concenterated in the target by a light absorbing pigment called chromophore. Target is heated and damaged whereas the surrounding skin absorbs minimal energy and remains unaffected.

16. Key points Indication Duration Advantages Disadvantages Unwanted hair removal Series of six treatments with at least 1 month interval. Faster and less painful Risks of burns, hyper/ hypo pigmentation, reduced effectiveness with fine hair.

18. Laser Photorejuvenation Skin changes occur with aging are due to cumulative sun exposure. Photo aging changes are mottled hyperpigmentation, solar lentigines, telengiectasias, erythema, textural changes with fine lines and laxity.

19. Key Points Benign epidermal pigmented and vascular lesions. Series of six treatments q 2-4 weeks based on the severity of lesions and device used. Results last upto several years. Highly selective for lesions without damaging surrounding skin. Risks of burns, hyper and hypopigmentation.

21. Microdermabrasion Are exfoliation procedures used to superficially resurface the skin. Skin rejuvenation with exfoliation are based on principles of wound healing. By wounding and removing the superficial layers in a controlled manner, cell renewal is stimulated with regeneration of healthier epidermis and dermis.

22. Key points Benign epidermal pigmentation, rough skin texture, acne, fine lines, superficial acne scars. Series of six treatments q 2-4 weeks with monthly or quarterly maintenance; short term results Safe for all skin types and few absolute contraindications Worsening telengiectasias and erythema possible; minimal change with single treatment.

23. Chemical peels Benign epidermal pigmentation, acne superficial acne scars, rough skin texture. Series of six treatments per month with monthly to quarterly maintanence treatments. Short term results. Inexpensive Less control over the depth of exfoliation; post procedure skin peeling. Risk of scarring. Hyper / Hypo pigmentation with deeper peeling.

24. Quiz Which one of the following procedures is most effective for reducing dynamic wrinkles in the upper one third of the face? (check one) A. OnabotulinumtoxinA (Botox, formerly known as botulinum toxin type A) injection. B. Dermal filler injection. C. Microdermabrasion. D. Chemical peel.

25. Which of the following statements about microdermabrasion is/are correct? (check all that apply) A. It is used to treat benign epidermal pigmentation. B. It has few absolute contraindications. C. It offers immediate, dramatic results. D. It is unsafe for pigmented skin.

28. Balloon angioplasty and stenting Many advances has been made since the advent of percutaneous coronary intervention. Three types of intervention, Balloon angioplasty, Bare metal stent and drug eluting stent. A major limitation of Balloon angioplasty is lesion restenosis. Coronary stents have been developed to combat the stenosis that occur with just the balloon angioplasty

29. Cont Bare metal stents effectively addresses two of the mechanism leading to restenosis – elastic recoil and vessel constriction during healing. Drug-eluting stents are coated with a drug delivery system that allows the controlled release of drug over time, for first 30-45 days and inhibits tissue proliferation

31. Choosing a Stent Balloon angioplasty is seldom used alone. Two factors are taken into consideration, one is the presence of clinical and technical factors associated with restenosis, they benefit from drug eluting stent. Multiple randomized controlled studies show that drug eluting stents have a better outcome than bare metal stents in patients with DM, long and complex stenosis, total coronary artery occlusion, restenosis of bare metal stents, acute MI. Second, patients ability to comply with dual anti platelet therapy is carefully considered.

32. Postprocedural Medical Therapy Following stent placement, strict adherence to dual antiplatelet therapywith aspirin 162-325 mg daily, and clopidogrel,75 mg daily With bare metal stents, minimum recommendation is one month of dual antiplatelet therapy. With drug-eluting stents atleast one year of therapy is recommended.

34. Drug-Eluting Stents

36. Which one of the following have drug-eluting stents been shown to do? (check one) A. Reduce short-term restenosis and long-term stent thrombosis. B. Reduce short-term restenosis and increase long- term stent thrombosis. C. Increase short-term restenosis and reduce long- term stent thrombosis. D. Increase short-term restenosis and long-term stent thrombosis.

37. Which one of the following medications or combinations of medications should patients take after stent placement? (check one) A. Aspirin alone in a dosage of 162 mg once daily. B. Clopidogrel (Plavix) alone in a dosage of 75 mg once daily. C. Aspirin (162 to 325 mg) plus clopidogrel (75 mg) once daily. D. Warfarin (Coumadin) with a target International Normalized Ratio of 2.0 to 3.0.

38. For which of the following groups of patients have drug-eluting stents been shown to improve outcomes compared with bare-metal stents? (check all that apply) A. Patients without diabetes. B. Patients with long and/or complex stenoses. C. Patients with acute myocardial infarction. D. Patients with total coronary artery occlusions.

39. Von Willebrand disease Is an inherited condition characterized by deficiency of vwFactor, which is essential in hemostasis. The disease leads to bleeding from an impaired platelet adhesion and aggregation. Prevalence of VWD has been reported to be as high as 1.3 %,however only about 0.01 % of the population had clinically recognized symptoms with abnormal test results.

40. Classification

42. Diagnosis

44. Management Three main approaches to the treatment of VWD Increasing the plasma concentration of VWF by releasing endogenous VWF stores with desmopressin Replacing VWF by using human plasma derived, viral inactivated concentrates Promoting hemostasis using hemostatic agents like antifibrinolytic agents and topical agents OR REFER TO HEMATOLOGIST

45. Women with VWD Menorrhagia may be the first sign of VWD in women although other causes must be ruled out first Oral contraceptives are the first line of choice, Mirena is an alternative in select patients Demopressin, antifibrinolytics or VWF concentrates have been used in women desiring pregnancy Some women require procedures like endometrial ablation or hysterectomy.

46. Pregnancy and Childbirth Refer to genetic counselor before or during pregnancy. To pediatric hematologist for evaluation of infant after delivery. Before any invasive procedures or during labor and delivery, patients should receive factor viii and VWF:R co assays Should receive VWF replacement with VWF concentrates opposed to desmopressin

47. Which one of the following statements about laboratory testing for von Willebrand disease (VWD) is correct? (check one) A. The best single laboratory test to screen for VWD is measurement of fibrinogen levels. B. Laboratory testing to screen for bleeding disorders should be performed in all patients undergoing a surgical procedure. C. Initial tests help exclude other bleeding disorders. D. Isolated low platelet count, prolongation of partial thromboplastin time, or low fibrinogen levels are most likely caused by VWD. E. Bleeding time testing is recommended to screen for VWD and other bleeding disorders.

48. Which of the following statements about the treatment of patients with VWD and clinically significant menorrhagia is/are correct? (check all that apply) A. Dilation and curettage is recommended. B. If pregnancy is desired, desmopressin (DDAVP), antifibrinolytics, or von Willebrand factor concentrates may be considered. C. The levonorgestrel-releasing intrauterine device (Mirena) is an option. D. Combined oral contraceptives are the treatment of choice.

49. Sex Based Differences in Drug Activity Pharmacokinetics Involves the rate and extent of the drug movement through the body including absorption, distribution, metabolism and excretion.

50. ABSORPTION Variations in GI motility, gastric pH and enzymatic activity affect the absorption of oral medications. Women tend to have less gastric acid and tend to have slower GI transit times than men Medications that require an acidic environment for absorption may have lower bioavailability in women Prolonged GI transit time can diminish the absorption of medications like metoprolol, verapamil.

51. Women should wait longer after eating before taking medications that must be administered on an empty stomach. Examples include ampicillin, captopril, levothyroxine, loratidine and tetracycline. Absorption of alcohol also differs in men and women. Women will have higher blood alcohol level than men.

52. DISTRIBUTION Influenced by several factors, including BMI, body composition, plasma volume, and plasma protein – binding capacity. These differences should be considered when calculating loading or bolus dosages. Women should receive smaller doses to mitigate unnecessary adverse reactions. Medications that require loading dosages calculations include anti arrhythmics, aminoglycosides, heparin…

53. Women have larger fat stores than men which may account for greater volumes of drug distribution. Lipophilic medications, such as BZD and NM blockers, have longer duration of action in women. BZD should be initiated at a lower dosages in women Hydrophilic substances like alcohol and FLQ antibiotics distribute into smaller volumes in women, producing higher initial plasma concentration and greater effects.

54. METABOLISM The initial phase of metabolism oxidizes, reduces, or hydroxylates compounds through the CYP450 system. Warfarin demonstrate a difference in dosage requirement based on sex. Studies indicate that women need b/w 2.5 and 4.5 mg less warfarin per week than men. Metabolic processes like glucorinadation, acetylation, are accelerated in men causing some medications to clear faster including acetaminophen, digoxin, caffeine, propranalol.

55. EXCRETION Three aspects of excretion affect renal clearance: GFR, tubular secretion and tubular reabsorption. GFR remains consistently higher in men. After adjusting for body size, GFRs are 10-25 % slower in women Medications that are excreted unchanged in the urine are cleared slower in women To account for variations in clearance, women should receive lower dosages based on GFR

56. Pharmacodynamics Is the study of drug mechanism of action, including the physiologic and biochemical effects on the body, and the relationship between drug concentration and the rate and extent of pharmacologic response.

59. Which one of the following statements about sex-based drug effects is correct? (check one) A. Women require higher loading dosages of aminoglycosides and heparin. B. Women should receive lower dosages of warfarin (Coumadin). C. Women require higher dosages of morphine to achieve analgesia. D. Women should avoid acidic beverages when taking medication requiring an acidic gastric environment. E. Lipophilic medications, such as benzodiazepines, have a shorter duration of action in women.

60. Which one of the following medications has been shown to require a higher dosage in women than men? (check one) A. Digoxin for heart failure. B. Opioids for analgesia. C. Haloperidol (formerly Haldol) for psychosis. D. Aspirin for secondary prevention after a cardiovascular event.

61. Which of the following medications has/have demonstrated enhanced effectiveness in women compared with men? (check all that apply) A. Ketoconazole antibiotics. B. Selective serotonin reuptake inhibitors. C. Typical antipsychotics. D. Tricyclic antidepressants.

62. Thank You!