1. SEXUAL PHARMACOLOGY Susan J Campling, RN, Psy.D Director of Special Projects Pine Grove Behavioral Health Hattiesburg MS 39402

2. In the very act of giving, I experience my strength, my wealth, my power. This experience of heightened vitality and potency fills me with joy. Erich Fromm, The Art of Loving

3. Objectives Understand the relationship between common medications and sexuality including hyper-sexuality Identify relevant brain structures, chemistry, and processes inherent to sexuality Discuss ethical considerations related to this discussion

4. Ethical Considerations Potential for abuse/ addiction Forced sterilization/ impotence Lack of informed consent for patients Potential for social abuse Who gets these medications? ED medications, birth control, anti androgens Potential for clinician prejudices Lack of research with women Information overload

5. Haroutunian Imperative “Every addiction presentation must have at least one brain slide.”

7. Localized Sex Brain Activity Cerebral cortex- all cortical regions Temporal parietal regions- important for integrating information and abstract concepts Anterior insula (c) - reflect on the state of our bodies, memory Hippocampus-manages our memories Septum-located near amygdala; smell activation; pleasure Amygdala- (sc)orchestrates powerful emotions Nucleus acumens (sc)- pleasure, cognition and motor functions Striatum (sc)- reward but also averse, novel intense stimuli

8. Brain Region of the Day The Insula!!!

9. Insular Cortex Sensation of pain is judged for intensity and quality Area where pain is judged through imagination IBS – abnormal processing of visceral pain Empathy and compassion Perception of a full bladder and abdominal distention Sensation of non-painful warmth and coldness Homeostasis is controlled via autonomic functions through the regulation of the sympathetic and parasympathetic systems.

10. Bodily self-awareness Sense of agency and body ownership Processes a person's sense of disgust both to smells and to the sight of contamination and mutilation— even when just imagining the experience Orgasm Integration of information relating to bodily states into higher-order cognitive and emotional processes Larger in people who meditate Activated when drug abusers are exposed to environmental cues that trigger cravings; people, places and things Body memories? Anticipation butterflies in stomach

11. Maternal love and romantic love are more alike than lust yet there is significant over- lap.

12. Ivanka Savic and Per Linstrom, Stockholm Brain Institute, April 2008, Pet and MRI Differences in cerebral asymmetry and functional conductivity between homo and heterosexual subjects

13. Direct Side Effects Anorgasmia Sex drive disorders Dyspareunia Anesthetic orgasm Retrograde ejaculation Priapism Gynecomastia Clitoral hypertrophy Back to medications

14. Direct Side Effects Infertility/ sterility Hormonal- gynecomastia, hypogonadism Menstrual disorders What is priapism?

15. Indirect Side Effects Body image Comfort Odors/ taste alteration Gastrointestinal side effects Urinary tract Neurological Cardiovascular Skin Sensory impairment

17. FYI Agonist stimulate and facilitate a response in a pathway Antagonist act against the pathway a

18. Alpha 1 Adrenergic Enhance desire and arousal Promotes peripheral vasoconstriction (dose dependent) Facilitate dopamine, testosterone, acetylcholine, vasopressin, prostaglandins α receptors fight flight response Norepinephrine Needed for starting the engine but too much leads to premature ejaculation and impotence Epinephrine/ norepi pass through Doxazosin- Cardura- antagonist

19. Alpha 2 Andrenergics Decrease desire and sexual arousal Prompts vasoconstriction antagonizes alpha 1 activity Can decrease anxiety related premature ejaculation Can also cause impotence Clonidine- agonist  Yohimbine- antagonist 

20. What is lordosis? Beta 2 Andrenergic Activity Smooth muscle dilation Pulmonary Vasodilator Promotes performance anxiety Part of fight flight response Albuterol- agonist Labetalol (Trandate)- antagonist Atenolol- β 1 antagonist GABA Sedating Reducing anxiety and panic Diminishes active sexual response Promotes lordosis Valium and Xanax stimulate GABA receptors Alcoholism, the GABA system is down-regulated and the neuron may eventually become dependent on alcohol to enable GABA to function. Bonus Question

22. Excitatory Biochemistry Cholinergic (acetocholine)- stimulate theta waves; mediates all types of sexual thoughts, attitudes and memories; limbic; hippocampus Cortisol (acute)- high levels associated with psychoses, derangement, aggression Cortisol (chronic)- decreased sex drive to bizarre psychotic behavior DHEA/ DHEAS- most abundant androgen Dopamine- pleasure, increase sex drive, promotes orgasm

23. Excitatory Testosterone Zinc- needed for spermatogenesis: reduces GABA and endogenous opioids Estrogens- essential to female desire, attraction, lubrication orgasm, satisfaction, Histamine Oxytocin/ vasopressin*

24. Inhibitory Estrogen- men baldness and Gynecomastia Melatonin- causes gonadal recession in animals MAO- breaks down monoamines (NE, E, 5-HT, DA) MAO B enzymes break down DA and phenyl ethylamine (PEA) Opioids-most powerful sexual inhibitory neurotransmitter; testosterone decreased in male opiate addicts

25. Progesterone- “anti-aphrodisiac” Prolactin- elevated levels in nursing mothers; reduces sex drive in both men and women Serotonin-restrains excessive excitement Thyroid- sub therapeutic deceases sex drive and is associated with depression; elevated is toxic to tissue metabolism

26. Drugs and Medical Conditions that are Associated with Hypersexuality Stimulants Cocaine, Adderall, Ritalin,… Generally thought to enhance libido through increased sexual pleasure and endurance Increased autoerotic behaviors (Everett H. Ellinwood, M.D., George King, Ph.D. and Tong H. Lee, M.D. Ph.D.) Can cause psychotic states and sexual deviance http://www.cdc.gov/hiv/resources/factshee ts/meth.htm Why would stimulants possibly lead to impotence?

27. Dopamine Agonists Medications Parlodel (bromocriptine) Dostinex (cabergoline) Permax (pergolide; no longer used in US) Mirapex and Sifrol (pramipexole) Requip (ropinirole) Apokyn (apomorphine) Neupro (rotigotine) Norprolac (quinagolide) Conditions Dopamine deficiency syndromes; Parkinson’s Disease Prolactinoma Restless leg syndrome Research on use in IVF Anything that floods D into what brain structure can become addictive?

28. Anxiolytics Benzodiazepines Increases GABA, progesterone, cholinergic activity Decreases testosterone, cortisol, serotonin Is associated with hyper-sexuality Xanax, Librium, Klonopin, Ativan Bus Par*- 5HT agonist- does not impact GABA; some research suggests decreased paraphilia fantasy and transvestic fetishism (Federoff, 1992)

29. Antidepressants MAO MAOIs Marplan Nardil Parnate Side effects include erectile dysfunction, orgasms diminished, ejaculation retarded Can treat hyper sexuality Have a lot of dietary restrictions A lot of medication restrictions

30. Antidepressants SSRI Increased cortisol Increased opioids Increased prolactin Increased 5-HT Associated with hypo sexuality and hyper sexuality Retarded ejaculation Anorgasmia/ spontaneous orgasm Clomipramine- Anafranil Fluoxetine- Prozac Fluvoxamine- Luvox Paroxetine- Paxil Sertraline- Zoloft Venlafaxine- Effexor Trazadone-hybrid-  sex drive; priapism

31. Bupropion Novel antidepressant Side effects tend to be activating Preferred when depression is present but not anxiety Actives limbic system Influences areas where orgasm arises Does not generate sexual stimuli but reinforces stimuli that is already occurring Increases DHEAS in women which may have an anti-aging effect Psychosis risk Hyper-sexuality rare

32. Oxytocin and Vasopressin Oxytocin-coitus, birth, breastfeeding; increases male fantasies; makes skin a sexual organ (female), dissociative Vasopressin-antidiuretic hormone; increases cognition and memory LHRH-high dose lowers testosterone (SO) Pulsating dose-  testes size; nocturnal emissions; spontaneous erections

33. DHEA/ DHEAS Adrenergic DHEAS- precursor to estrogic and androgenic steroids May be metabolized into sexual pheromone substances in the skin and involved in sexual attraction through touch and smell DHEA rhythmic DHEAS constant diurnal levels Promotes weight loss Promotes bone growth No consistent research to indicate increased sexual response except in females with adrenal insufficiency Study 2010 demonstrated increased DHEA-S levels in women when viewing sexual and humorous films but not anxiety invoking movies Available OTC

34. Hormones- Male Inhibitory Cyproterone-(Androcur)-? decreased sexual fantasies, behavior, masturbation, intercourse and erection Medroxyprogesterone (Provera)- decreased libido, sexual arousal, fantasies, urges and behaviors Leuprolide (Lupron) LH- decreases testosterone and estrogen Goserolin (Zoladex) LH- decreased testosterone and estrogen Cimetidine- Tagamet (has slight anti-androgen effects)

35. Antipsychotic/Neuroleptics Chlorpromazine-Thorazine Fluphenazine-Prolixin Mesoridazine-Serentil Haloperidol- Haldol Risperidone- Risperdal Valproic Acid (ac)- Depakote Carbamazepine- Tegretol Phenytoin- Dilantin Phenobarbital- Hypo sexuality/ hyper sexuality (rare) Priapism Anorgasmia Orgasm without ejaculation Anesthetic orgasm May be useful for hyper sexuality Anticonvulsant medications impact hormonal regulation and generally decrease sexual desire What over the counter GERD medication may have androgen properties?

36. Miscellaneous Opioid Antagonists-Naltrexone- some early + studies, kleptomania, trichotillomania,internet porn or pathological gambling. Vivitrol marketed for alcohol. Cold medication- Mucenex DM- MD synthetic morphine Asthma- Beta 2 agonists (albuterol, epinephrine Primatene), xanthines (theophylline, caffeine over reactivity), corticosteroids (HPA; paranoia, depression, aggression), anticholinergic (atrovent) dry mouth and vagina.

37. Yohimbine Inhibits platelet aggregation Acts as a stimulant Desire enhanced Positive effects on erection and ejaculation Synthetic and herbal forms Avoid with panic/ anxiety Sexual obsessions and compulsions Sexual phobias Combination formulations –Zumba

38. ED Medications Do not enhance desire directly, utilizes nitric oxide, a penile vasodilator substance, enhances responsiveness to stimuli, can cause deafness, not to be used with nitrates Cialis, Viagra, Levitra

39. Medical Conditions MS Tumors-hypothalamic, frontal cortex, temporal lobes, septal nuclei, etc. TBI Nero syphilis Mania Kleine Levine-Sleeping Beauty Syndrome Fetal alcohol and PDD Epilepsy

40. Summary Human sexuality is a complex process that can be impacted by multiple direct and indirect medication effects Our understanding of the structures associated with sexual responses is an evolving process Research is needed with women and GLBT around the physiology of sexuality