SEXUAL PHARMACOLOGY Susan J Campling, RN, Psy.D Director of Special Projects Pine Grove Behavioral Health Hattiesburg MS 39402 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 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 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 Haroutunian Imperative “Every addiction presentation must have at least one brain slide.” 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 Brain Region of the Day The Insula!!! 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. • 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 Maternal love and romantic love are more alike than lust yet there is significant over- lap. 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 Direct Side Effects • Anorgasmia • Sex drive disorders • Dyspareunia • Anesthetic orgasm • Retrograde ejaculation • Priapism • Gynecomastia • Clitoral hypertrophy Direct Side Effects • Infertility/ sterility • Hormonal- gynecomastia, hypogonadism • Menstrual disorders What is priapism? Indirect Side Effects • Body image • Comfort • Odors/ taste alteration • Gastrointestinal side effects • Urinary tract • Neurological • Cardiovascular • Skin • Sensory impairment FYI • Agonist stimulate and facilitate a response in a pathway • Antagonist act against the pathway a Alpha 1 Adrenergic • Enhance desire and • Needed for starting the arousal • Promotes peripheral vasoconstriction (dose dependent) • Facilitate dopamine, testosterone, acetylcholine, vasopressin, prostaglandins • α receptors fight flight response • Norepinephrine engine but too much leads to premature ejaculation and impotence • Epinephrine/ norepi pass through • Doxazosin- Cardura- antagonist Alpha 2 Andrenergics • Decrease desire and • Clonidine- sexual arousal • Prompts vasoconstriction antagonizes alpha 1 activity • Can decrease anxiety related premature ejaculation • Can also cause impotence • agonist • Yohimbine• antagonist Bonus Question 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. 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 Excitatory • Testosterone • Zinc- needed for spermatogenesis: reduces GABA and endogenous opioids • Estrogens- essential to female desire, attraction, lubrication orgasm, satisfaction, • Histamine • Oxytocin/ vasopressin* 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 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 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 • Can cause psychotic states and sexual deviance • http://www.cdc.gov/hiv/resources/factshee ts/meth.htm (Everett H. Ellinwood, M.D., George King, Ph.D. and Tong H. Lee, M.D. Ph.D.) Dopamine Agonists Medications • Parlodel (bromocriptine) Conditions • Dopamine deficiency • Dostinex (cabergoline) • Permax (pergolide; no • • • • • longer used in US) Mirapex and Sifrol (pramipexole) Requip (ropinirole) Apokyn (apomorphine) Neupro (rotigotine) Norprolac (quinagolide) • • • • syndromes; Parkinson’s Disease Prolactinoma Restless leg syndrome Research on use in IVF 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) 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 Antidepressants SSRI • Increased cortisol • Clomipramine- • Increased opioids Anafranil • Fluoxetine- Prozac • Fluvoxamine- Luvox • Paroxetine- Paxil • Sertraline- Zoloft • Venlafaxine- Effexor • Trazadone-hybridsex drive; priapism • Increased prolactin • Increased 5-HT • Associated with hypo sexuality and hyper sexuality • Retarded ejaculation • Anorgasmia/ spontaneous orgasm Bupropion • Novel antidepressant • Does not generate • Side effects tend to be 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 activating • Preferred when depression is present but not anxiety • Actives limbic system • Influences areas where orgasm arises 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 DHEA/ DHEAS Adrenergic • DHEAS- precursor to • Promotes weight loss 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 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 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) Antipsychotic/Neuroleptics • • • • • Chlorpromazine-Thorazine Fluphenazine-Prolixin Mesoridazine-Serentil Haloperidol- Haldol Risperidone- Risperdal • • • • Valproic Acid (ac)- Depakote Carbamazepine- Tegretol Phenytoin- Dilantin Phenobarbital- What over the counter GERD medication may have androgen properties? • 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 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. Yohimbine • Inhibits platelet • Avoid with panic/ aggregation • Acts as a stimulant • Desire enhanced • Positive effects on erection and ejaculation • Synthetic and herbal forms anxiety • Sexual obsessions and compulsions • Sexual phobias • Combination formulations –Zumba 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 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 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