rxp international presents gender and psychiatric drugs
TRANSCRIPT
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OverviewOverviewIntroductionPharmacologyGender-Specific DisordersHormonal ContraceptivesPregnancy and LactationMenopauseWrap Up
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IntroductionIntroductionGender Differences in Life SpanGender Differences in Life Span
Life Expectancy at Birth, by Race and Sex, 1970 - 2008
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IntroductionIntroductionGender Differences in Life SpanGender Differences in Life Span◦ “Men die from disease, Women live with
disease”
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IntroductionIntroductionGender Differences in Life SpanGender Differences in Life Span
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IntroductionIntroductionGender Differences in Gender Differences in PrescribingPrescribing
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IntroductionIntroductionGender Differences in Prescribing
◦Why are women more likely to be diagnosed and given prescriptions for psychotropics?
◦Popular Hypotheses: Morbidity Reporting Stereotyping
Prescribing bias
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IntroductionIntroductionGender Differences in Prescribing
◦ Morbidity Hypothesis “Epidemiology studies in the U.S and world-wide
consistently show higher incidence of mood and anxiety disorders in women compared to men”
Estradiol and progesterone influence synthesis, metabolism and turnover of CNS NTs (5HT, NE, DA) associated with changes in mood
Estrogen influences NT, neuroendocrine, neuromodulatory systems, circadian rhythms, density of receptors in CNS
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IntroductionIntroductionGender Differences in Prescribing
◦Reporting Hypothesis Women report their symptoms more
frequently Morbidity studies often rely on self-report
measures and women are more likely to share both physical and emotional symptoms than men
Men more likely to suffer from Alexithymia experience depression as irritability Treat with alcohol
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IntroductionIntroductionGender Differences in Prescribing
◦Stereotyping Hypothesis Professional journal advertisements Disease Model: Physicians work on model
of pathology with expression of “negative” emotions (nervousness, worry, sadness/tearfulness) as signs of disease Masculine- “stiff upper lip” and stoicism as normal Female- crying as pathological/intolerable
Classic depression
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PharmacologyPharmacology
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PharmacologyPharmacologyPharmacokinetics
◦What the body does to the drug: “ADME”
◦In order for a drug to work Reach the right target (receptor) in the
right concentration Too much—Adverse Effects Too little—No or minimal effect Right amount is still no guarantee—Why?
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PharmacologyPharmacologyPharmacokinetics
◦Women develop more adverse effects and fatal reactions to medicines than men 8/10 drugs withdrawn from market Jan
1997-Jan 2001 due to greater risks in women
◦The FDA evaluated sex differences in bioequivalence from 1977-1995 Cmax greater in women 87% of the time AUC greater in women 71% of the time
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PharmacologyPharmacology
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PharmacologyPharmacology
Changes ChildhoodPediatrics
ChangesMenstrual Cycle
Changes Pregnancy
Changes Elder Years
Changes based on Sex
Absorption ⇓Gastric pH ⇑ Skin absorption
(infants)⇑Rectal pH
⇓Gastric emptying time (premenstrually)
⇓Gastric emptying time
Gastric pH⇑⇓Motility and intestinal blood flow
⇑Gastric pH⇓Gastric emptying time
⇓ GI blood flow
⇓ Gastric emptying time⇓Alchohol dehydrogenase
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Adapted from: Women's Health Across the Lifespan: A Pharmacotherapeutic Approach, Laura Marie Borgelt, Mary Beth O'Connell, Judith Ann Smith, Karim Anton Calis, 2010.
Pharmacokinetics Female Lifespan Factors -Absorption
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PharmacologyPharmacology
Changes ChildhoodPediatrics
ChangesMenstrual Cycle
Changes Pregnancy
Changes Elder Years
Changes based on Sex
Distribution ⇑Vd for hydrophilic drugs⇓Protein binding
⇑Vd for hydrophilic drugs due to increase in TBW
⇑ Blood volume⇓Serum Albumen⇑Crossover between fetal maternal barrier
⇓Vd for hydrophilic drugs⇑Vd for lipophilic drugs⇓Protein binding
⇑Vd for lipohilic drugs⇓Vd for hydrophilic drugs
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Adapted from: Women's Health Across the Lifespan: A Pharmacotherapeutic Approach, Laura Marie Borgelt, Mary Beth O'Connell, Judith Ann Smith, Karim Anton Calis
Pharmacokinetics: Female Lifespan Factors - Distribution
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PharmacologyPharmacologyPharmacokinetics: Female Lifespan Factors -
Metabolism
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Changes ChildhoodPediatrics
ChangesMenstrual Cycle
Changes Pregnancy
Changes Elder Years
Changes based on Sex
Metabolism Phase I and II below 100% until age 2
Variable effects
Phase I⇑Hydrolysis⇓Oxidation⇓CYP1A2⇓CYP2C19⇑CYP2A6⇑CYP2D6 (3rd trimester)⇑CYP3A4Phase II: no change
Phase I variable changes on CYP activityPhase II: No change
Phase I⇑Oxidation⇑CYP1A2⇑CYP2D6⇑CYP3A4 induction(e.g., ⇑ 90% vs 50% men for St John’s Wort)Phase II: ⇓Conjugation
Adapted from: Women's Health Across the Lifespan: A Pharmacotherapeutic Approach, Laura Marie Borgelt, Mary Beth O'Connell, Judith Ann Smith, Karim Anton Calis
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PharmacologyPharmacologyPharmacokinetics: Female Lifespan Factors -
Elimination
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Changes ChildhoodPediatrics
ChangesMenstrual Cycle
Changes Pregnancy
Changes Elder Years
Changes based on Sex
Elimination GFR reaches adult level by age 2
⇑GFR in luteal phase⇓GFR in early follicular phase
⇑Renal blood flow⇑GFR
⇓Creatinine clearance
⇓Creatinine clearance
Adapted from: Women's Health Across the Lifespan: A Pharmacotherapeutic Approach, Laura Marie Borgelt, Mary Beth O'Connell, Judith Ann Smith, Karim Anton Calis
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Adapted from: Psychiatric disorders in women: psychopharmacologic treatments. Fanhauser, M.P. J American Pharm Assoc. 1997 22
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Adapted from: Psychiatric disorders in women: psychopharmacologic treatments. Fanhauser, M.P. J American Pharm Assoc. 1997
PharmacologyPharmacologyAntipsychotics
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PharmacologyPharmacology
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PharmacologyPharmacology
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1. Kornstein, et al., 2000 and Hildebrandt et.al., 2003)
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PharmacologyPharmacologyClinical Psycopharmacology
Differences in Bone Cortical Densities
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PharmacologyPharmacologyClinical Psycopharmacology
◦Gender and Mood Stabilizers Men
More likely to experience tremor with lithium treatment
Women More likely to develop hypothyroidism with lithium
Factor most predictive of hypothyroidism was weight gain during the first year
Carbamazepine, Oxcarbazepine, Topiramate may lower the efficacy of oral contraceptives
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PharmacologyPharmacologyClinical Psycopharmacology
◦Gender and Neuroleptics Women
Estrogen may have antidopaminergic properties by binding to DA receptor
Significantly higher plasma concentrations of APs (CPZ, Fluphenazine, Olanzapine, Clozapine)
Require lower doses and show more dyskinesias Greater risk for TD with long term neuroleptic use
Men Require up to 2x dose as women for maintenance
with APs (Milkerson, Hulting, & Rane, 2001)
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PharmacologyPharmacologyClinical Psycopharmacology
◦Gender and Benzodiazepines Panic disorder occurs disproportionately in
women
29•Adapted from: Psychiatric disorders in women: psychopharmacologic treatments. Fanhauser, M.P. J American Pharm Assoc. 1997
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