RxP International presents Gender and Psychiatric Drugs

1

OverviewOverviewIntroductionPharmacologyGender-Specific DisordersHormonal ContraceptivesPregnancy and LactationMenopauseWrap Up

2

IntroductionIntroductionGender Differences in Life SpanGender Differences in Life Span

Life Expectancy at Birth, by Race and Sex, 1970 - 2008

3

IntroductionIntroductionGender Differences in Life SpanGender Differences in Life Span◦ “Men die from disease, Women live with

disease”

4

IntroductionIntroductionGender Differences in Life SpanGender Differences in Life Span

IntroductionIntroductionGender Differences in Gender Differences in PrescribingPrescribing

6

IntroductionIntroductionGender Differences in Prescribing

◦Why are women more likely to be diagnosed and given prescriptions for psychotropics?

◦Popular Hypotheses: Morbidity Reporting Stereotyping

Prescribing bias

7


◦ 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

8


◦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

9


◦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

10

11

12

13

PharmacologyPharmacology

14

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?

15

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◦Women develop more adverse effects and fatal reactions to medicines than men 8/10 drugs withdrawn from market Jan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

16


17


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

18

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




Changes Pregnancy

Changes Elder Years


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

19

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

PharmacologyPharmacologyPharmacokinetics: Female Lifespan Factors -

Metabolism

20



Changes Pregnancy

Changes Elder Years


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


PharmacologyPharmacologyPharmacokinetics: Female Lifespan Factors -

Elimination

21



Changes Pregnancy

Changes Elder Years


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: Psychiatric disorders in women: psychopharmacologic treatments. Fanhauser, M.P. J American Pharm Assoc. 1997 22

Adapted from: Psychiatric disorders in women: psychopharmacologic treatments. Fanhauser, M.P. J American Pharm Assoc. 1997

PharmacologyPharmacologyAntipsychotics

23


24


25

1. Kornstein, et al., 2000 and Hildebrandt et.al., 2003)

PharmacologyPharmacologyClinical Psycopharmacology

Differences in Bone Cortical Densities

26


◦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

27


◦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)

28


◦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

30

Health & Medicine

RxP International presents Gender and Psychiatric Drugs