Transcript Document 7377814

GLUCOCORTICOIDS AND
MINERALOCORTICOIDS
Corticosteroids

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Adrenal glands produce glucocorticoids
and mineralocorticoids
Glucocorticoids:
– Involved in cholesterol, fat, and protein
metabolism
Corticosteroids


Adrenal glands produce glucocorticoids
and mineralocorticoids
Glucocorticoids:
– Involved in cholesterol, fat, and protein
metabolism

Mineralocorticoids:
– Involved in regulating electrolyte and
water balance
Cortisol
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
Principal adrenal steroid hormone
Responsible for:
– Gluconeogenesis
– Protein catabolism
– Anti-inflammatory reactions
– Stimulation of fat deposition
– Sodium and water retention
Corticosteroids


Adrenal hormones excluding sex
hormones
Steroid production follows a circadian
rhythm
Properties of
glucocorticosteroides used in
clinics
 Anti-inflammatory
 Immune-depressive
 Anti-allergic
 Anti-shock
 Anti-toxic
Anti-inflammatory action of
GCS
 Nonspecific
inflammation
 Auto-immune component
 Hyperergic character
 Therapy of despair
Mechanism of anti-inflammatory action of GCS
GCS
activation of lipomoduline
decreasing of activity of phospholipase А2
slowing down of arachidonic acid
metabolites production
(prostaglandins, leucotriens,
thromboxan А2)
stabilization
of cellular and
lyzosomal
membranes
depression of
histamine, serotonin,
bradykinine releasing
decreasing of
leucocytes’
migration processes,
depression of
phagocytes activity
decreasing of capillaries’
wall permeability
Indications for administration of
GCS
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Insufficiency of adrenal cortex
Rheumatoid illnesses (rheumatoid arthritis, rheumatism,
system red lupus etc.)
Chronic active hepatitis
Bronchial asthma
Ulcerative colitis
Nephritic syndrome
Auto-immune hemolytic anemia
Shock and collapse of any etiology
Brain, lungs, larynx edema
Acute allergic reactions
Transfusion reactions
Heavy infections (hiding behind the etiotropic drugs!)
Liver disesaes
Doses and terms of GCS therapy
Situation
Acute cases (shock,
collapse, brain, lungs
edema, septic shock,
asthmatic condition etc.)
Subacute and acute
attacks of chronic
processes (rheumatoid
diseases, ulcerative colitis,
bronchial asthma etc.)
Primary and secondary
insufficiency of adrenal
Daily dose
Terms of
treatment
200-5001-3 days
800-1000 mg
i.v.
20-50 mg
(rarely till
200 mg)
4-6
weeksseveral
months
2,5-10 mg
life-long
Corticosteroids

Act as anti-inflammatory and
immunosuppressive agents in treating
diseases of different origins:
– Hematologic
– Allergic
– Inflammatory
– Neoplastic
– Autoimmune
Administration of GCS
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Insufficiency of adrenal cortex
Rheumatoid illnesses (rheumatoid arthritis,
rheumatism, system red lupus etc.)
Chronic active hepatitis
Bronchial asthma
Ulcerative colitis
Nephritic syndrome
Auto-immune hemolytic anemia
Shock and collapse of any etiology
Brain, lungs, larynx edema
Acute allergic reactions
Transfusion reactions
Heavy infections (hiding behind the etiotropic
drugs!)
Liver diseases
Doses and terms of GCS therapy
Situation
Daily dose
Terms of
treatment
Acute cases (shock,
collapse, brain, lungs
edema, septic shock,
asthmatic condition etc.)
200-500800-1000
mg i.v.
1-3 days
Subacute and acute
attacks of chronic
processes (rheumatoid
diseases, ulcerative
colitis, bronchial asthma
etc.)
Primary and secondary
insufficiency of adrenal
cortex
20-50 mg
(rarely till
200 mg)
4-6
weeksseveral
months
2,5-10 mg
life-long
Hydrocortisone acetate
Prednisolone
Prednisolone
Prednisolone
Becotide = Beclometh
(beclomethasone dipropionate)
Kenalog
(triamcinolone acetonide)
Kenalog
(triamcinolone acetonide)
Fluocinar – Sinaflan – Sinalar
(Fluocinole acetonide)
Dexamethasone
Dexamethasone
Addison’s Disease
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Life-threatening deficiency of
glucocorticoids and mineralocorticoids
Treated with daily corticosteroids
Symptoms of Addison’s
Disease
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Debilitating weakness
Hyperkalemia
Hyperpigmentation of skin
Low levels of serum sodium and
glucose
Reduced blood pressure
Weight loss
Cushing’s Disease
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Caused by an overproduction of
steroids or excessive administration of
corticosteroids
Symptoms:
– Protruding abdomen; round, puffy face;
fat over the shoulder blades
Reasons for Using
Corticosteroids
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Inhibit inflammation
Useful in treating asthma, rashes, and
skin disorders
Available in many different dosage
forms
Problems with
Corticosteroids
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Lessen the ability of leukocytes to
destroy infection which decreases
fever, redness, and swelling
Also may cause infection to spread
Corticosteroid Dispensing
Issues
Warning!

Take caution in patients with
diabetes, uncontrolled hypertension,
CHF, severe infection or altered
immunity, or peptic ulcer disease
with active GI bleeding
Corticosteroids
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Usage must be tapered off, not
abruptly stopped
May cause withdrawal symptoms
– Anorexia, nausea, vomiting, myalgia,
arthralgia, lethargy, headache,
sluggishness, weight loss, postural
hypotension, fever and depression
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Doses should be given in the morning
Adverse Effects of
Glucocorticoids
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Cardiovascular effects
Dermatologic effects
Gastrointestinal effects
Immune system effects
Metabolic effects
Musculoskeletal effects
Neuropsychiatric effects
Ophthalmic effects
Adrenal Sex Hormones
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Androgens are produced by:
– The testes
– The ovaries
– Adrenals
– Peripheral fat tissue
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Most important male hormone is
testosterone which is produced by the
testes
Responsibilities of
Testosterone
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Initiating sperm production
Behavioral characteristics
Libido
Sexual potency
Muscle mass and strength
Fat distribution
Bone mass
Erythropoiesis
Prevention of baldness
Hypogonadism
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Deficient hormone production and
secretion
Androgens must be replaced by
medications
– May cause virilization, muscle building,
and hematologic stimulation of
erythropoiesis
– Can be used to treat anemia, breast
cancer, or endometriosis
Androgen’s Side Effects
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Virilization
Hirsutism
Acne
Hepatoxicity
High levels of erythrocytes
Oily skin
Gynecomastia
Priapism
Male Impotence
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Failure to initiate or maintain an
erection until ejaculation
Causes:
– Testosterone deficiency
– Alcoholism
– Cigarette smoking
– Psychological factors
– Medications
Drugs That May Cause
Impotence
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Alcohol (most
significant)
Amphetamines
Antihypertensives
Corticosteroids
Estrogens
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H2 blockers
haloperidol
lithium
Opiates
Some
antidepressants
Drug List
Agents for Male
Impotence
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alprostadil (Caverject, Edex, Muse)
danazol (Danocrine)
methyltestosterone (Android, Testred)
oxymetholone (Anadrol)
papaverine
testosterone (Androderm, AndroGel, Striant,
Testoderm)
Drug
List for Male
Agents
Impotence –
Phosphodiesterase
Inhibitors
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sildenafil (Viagra)
tadalafil (Cialis)
vardenafil (Levitra)
sildenafil (Viagra)
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1st oral therapy for impotence
Allows an erection to occur naturally
Take at least 1 hour before activity
sildenafil Dispensing
Issues
Warning!
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Potentially lethal interaction with
nitrates
tadalafil (Cialis)
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Duration of action is 36 hours
Faster onset and longer duration than
others in this class
tadalafil Dispensing
Issues
Warning!
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Potentially lethal interaction with
nitrates
Drugs of female sex
hormones
Estrogens
estron
(oil solution
of folliculin)
estradiol
ethynilestradiol
(microfollin)
synestrol
Gestagens
progesterone
oxyprogesterone caproate
alilestrenol (turinal)
Estrogens
 Uses
– Hormone replacement therapy (HRT)
– Palliative and preventive therapy
during menopause
 Actions
– Protecting the heart from
atherosclerosis
– Retaining calcium in the bones
– Maintaining the secondary female
sex characteristics
Sites of Action of the
Estrogens
Administration of drugs
of female sex hormones
estrogens
1) Genital hypoplasia, primary and secondary amenorrhea
2) Sexual underdevelopment of women
3) After ovary-ectomia
4) Climacteric disorders
5) Lactation depression
6) Weak labor activity
(estrogen background)
7) Prostate cancer of men, breast cancer of women after
the age of 60
8) A part of contraceptive agents
Effects of Progesterone on the Body
 Decreased
uterine motility
 Development of secretory
endometrium
 Thickened cervical mucus
 Breast growth
 Increased body temperature
 Increased appetite
 Depressed T-cell function
 Anti-insulin effect
Administration of
gestagens
1) miscarriage, habitual abortion
2) dysfunctional uterus bleedings, algomenorrhea
3) as component of contraceptives
4) Climacteric disorders
5) As part of fertility programs
6) Treat specific cancers with specific receptor site
sensitivity
Hormonal contraceptives
1) combined estrogen-gestagen
a) monophased (bisecurin, non-ovlon,
rigevidon, marvelon, demulen)
b) double-phased (anteovin, neo-eunomin)
c) triple-phased (tri-regol, trisiston)
2) monohormonal gestagen (mini-pilli)
exluton, ovret, continuin
3) postcoital hestagen (postinor)
4) depot-contraceptives - of prolonged action
norplant (levonorgestrel)
depot-provera (medroxyprogesterone acetate)
Complications in case of administration of
hormonal contraceptives
hypertension
thrombo-embolia
hypercoagulation
dyspeptic disorders (nausea, vomiting)
migraine
depression
obesity
cholestatic jaundice
breast cancer, cancer of uterus cervix
ischemic heart disease
myocardium infarction
stroke
embryotoxic and teratogenic action
Focus on the Fertility Drug
Prototype: Clomiphene
Indications: Treat ovarian failure in patients with
normal liver function and normal endogenous
estrogens; unlabeled use: treat male sterility
 Actions: Binds to estrogen receptors, decreasing
the number of available estrogen receptors, which
gives the hypothalamus the false signal to increase
FSH and LH secretion, leading to ovarian
stimulation
 PO route: Onset 5–8 days; duration 6 weeks
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T½: 5 days, with hepatic metabolism and
excretion in the feces
Abortifacients
 Use
– Evacuate the uterus by stimulating
intense uterine contractions
 Types
– Carboprost (Hemabate)
– Dinoprostone (Cervidil, Prepidil Gel,
Prostin E2)
– Mifepristone (RU-486, Mifeprex)
Androgens and Their
Indications
 Testosterone
others)
(Duratest, Testoderm,
– Hypogonadism; breast cancer
 Danazol
(Danocrine)
– Block the release of FSH and LH in women
 Fluoxymesterone
(Halotestin)
– Hypogonadism; breast cancer
 Testolactone
(Teslac)
– Breast cancers
ANABOLIC STEROIDS
Phenobolinum, Retabolil, Methandrostenolonum
-
PHARMACOLOGICAL EFFECTS
Stimulation of protein synthesis
Depression of phosphor and Ca++ excretion
Increase of bones, muscles and parenchymatous
organs mass
Stimulation of regeneration
ADMINISTRATION
Aplastic anemia (bone marrow suppression)
Osteoporosis, bone fractures
Exhausted diseases
Prolonged treatment with GCS
COMPLICATIONS
Hepatitis, sexual disorders (impotence), edemas,
masculinization, nausea, vomiting
Female Hormones
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Can prevent conception, ease
symptoms of menopause, and help
prevent osteoporosis
2 main female hormones:
– Estrogen
– Progesterone
Estrogen
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Formed in the ovaries when FSH is released
Responsible for:
–
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–
–
–
–
–
–
Endometrial growth
Increased cervical mucus
Cornification of vaginal mucosa
Growth of breast tissue
Increased epiphyseal closure
Sodium retention
Carbohydrate metabolism
Calcium utilization
Estrogen Deficiency
Symptoms
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Irregular bleeding and cycles
“hot flashes” that start in the face and
move down through the body
Atrophic vulvovaginitis, excessive
dryness
Dyspareunia
Frequent infections
Menopause
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As women reach menopause estrogen
production decreases
HRT can be used to supplement
estrogen levels
estrogens Dispensing
Issues
Warning!
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Patients should not smoke during
therapy, whether birth control or
HRT
Estrogen’s Side Effects
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Nausea
Vomiting
Bloating
Weight gain
Breast tenderness
Breakthrough bleeding
Glucose intolerance
HRT
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Reduces symptoms of menopause
Decreases bone loss
Lowers risk of cardiovascular disease
Small risk of breast cancer
Drug List
Estrogens
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conjugated estrogen (Enjuvia,Premarin)
conjugated estrogenmedroxyprogesterone (Premphase,
Prempro)
estradiol (Alora, Climara, Esclim,
Estrace, Estraderm, Estrasorb, Estring,
Femring, Menostar, Vivelle, Vivelle Dot)
Drug List
Estrogens
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estradiol-levonorgestrel (Climara Pro)
estradiol-norethindrone (Activella,
CombiPatch)
estradiol-norgestimate (Ortho-Prefest)
Drug List
Estrogens
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estropipate (Ogen)
ethinyl estradiol (Estinyl)
ethinyl estradiol-norethindrone (Femhrt)
estrogenmedroxyprogesterone
(Premphase, Prempro)
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Provides estrogen and progesterone
replacement
Prevents uterine cancer
Progestins
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Used primarily in birth control and to
prevent uterine cancer
Also used for menstrual dysfunction
Progestin’s Side Effects
Similar to pregnancy:
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Weight gain
Depression
Fatigue
Acne
Hirsutism
Drug List
Progestins
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levonorgestrel (Norplant II)
medroxyprogesterone (Depo-Provera,
Provera)
norethindrone (Micronor)
Contraceptives
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Most OCs are combinations of
estrogen and progestin
Interfere with hormones responsible
for regulation of the menstrual cycle
Change the consistency of cervical
mucus
Alter the endometrial lining
Benefits of OCs
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Prevention of pregnancy
Regulates menstrual cycle
Reduces menstrual flow
Lessens severe menstrual cramps and
pain
Protects against ovarian and
endometrial cancer, benign breast
disease, ectopic pregnancy,
fibroadenomas, and ovarian cysts
Oral Contraceptives
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There are different combinations of
estrogen and progestin as well as
differing strengths
Tricycling – taking meds for 3 - 21 day
cycles without a pill-free interval
Drug List
Contraceptive
Agents
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estradiol cypionatemedroxyprogesterone (Lunelle)
ethinyl estradiol-desogestrel (Cyclessa,
Desogen, Kariva, Mircette, Ortho-Cept)
ethinyl estradiol-drospirenone (Yasmin)
Drug List
Contraceptive
Agents
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estradiol cypionatemedroxyprogesterone (Lunelle)
ethinyl estradiol-desogestrel (Cyclessa,
Desogen, Kariva, Mircette, Ortho-Cept)
ethinyl estradiol-drospirenone (Yasmin)
Drug List
Contraceptive
Agents
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ethinyl estradiol-ethynodiol diacetate
(Demulen)
ethinyl estradiol-etonogestrel
(NuvaRing)
ethinyl estradiol-levonorgestrel (Levlen,
Nordette, Seasonale, Tri-Levlen,
Triphasil, Trivora-28)
Drug List
Contraceptive
Agents
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ethinyl estradiol-norelgestromin (Ortho
Evra)
ethinyl estradiol-norethindrone
(Estrostep Fe, Femhrt, Loestrin Fe,
Ovcon)
ethinyl estradiol-norgestimate (Ortho
Tri-Cyclen, Ortho Tri-Cylcen Lo)
Drug List
Contraceptive
Agents

ethinyl estradiol-norgestrel (Lo/Ovral,
Low-Ogestrel, Ovral)
ethinyl estradiol-desogestrel
(Cyclessa, Desogen, Kariva,
Mircette, Ortho-Cept)
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Inhibits ovulation
Includes 2 days of placebo followed by
5 days of low-dose estrogen
May be safer for smokers
ethinyl estradiollevonorgestrel (Seasonale)
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Taken for 3 months at a time
Patient only has 4 menses per year
Prevents egg release from the ovaries,
increases mucus thickness, and
thickness of the endometrial lining
ethinyl estradioldropirenone (Yasmin)
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Drospirenone is related to
spironolactone (a diuretic)
Causes less bloating and less weight
gain
May cause weight loss due to excess
water loss
ethinyl estradiolnorelgestromin (Ortho-Evra)
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Transdermal contraceptive
Suppresses gonadotropins
A new patch is applied every 7 days
for
3 weeks then the 4th week is
patch free
Some Oral Contraceptive
Interactions
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Antibiotics
Anticonvulsants
Antifungals
Benzodiazepines
Bronchodilators
Corticosteroids
Lipid-lowering agents
TCAs
Emergency Contraception
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In great demand
Patients want them to be available
OTC
Discussion
What is one of the arguments for
emergency contraceptives being
OTC?
Discussion
What is one of the arguments for
emergency contraceptives being
OTC?
Answer: After making a doctor’s
appointment and then going to
the get the prescription,
sometimes it is too late to take
the medication
Drug List
Contraceptive Agents
Emergency
Contraceptives
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levonorgestrel (Plan B)
norgestrel (Ovrette)
Home Pregnancy Tests

Critical organ systems develop in the
first month which is affected by
– Mother’s diet
– Environment (smoking)
– Medications
– Consumption of alcoholic beverages
Home Pregnancy Tests
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Based on detecting human chorionic
gonadotropin (HCG)
Levels can be measured as early as 68 days after conception
Results are given within 1-5 minutes
Tests are better than 95% accurate
Drugs Used at Birth
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Often no drugs are necessary for
delivery, but in some cases they are
To restart labor
To decrease uncontrolled bleeding
Drug List
Drugs Used at Birth
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methylergonovine (Methergine)
oxytocin (Pitocin)
oxytocin (Pitocin)
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Natural hormone that stimulates
uterine contractions
Drug should be used as a last resort
oxytocin’s Side Effects
For the woman:
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Vomiting
Irregular heart rate
Tachycardia
Postpartum
bleeding
For the child:
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Bradycardia
Arrhythmias
Jaundice
Sexually Transmitted
Disease

Refer to Figure 14.7 for the structural
anatomy of the male and female
genital systems
Gonorrhea
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
Most commonly reported STD
Caused by Neisseria gonorrhoeae that
attaches to mucosal cells in:
– Oropharyngeal area
– Eye
– Joints
– Rectum
– Male and female genitalia
Gonorrhea

If untreated, it can cause systemic
infection including
– The heart, meninges, eyes, pharynx, and
joints

Eye infections occur most often in
newborns and can cause blindness
Syphilis
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Caused by Treponema pallidum
Incubation averages three weeks
Infection develops in 3 stages:
– Primary stage
– Secondary stage
– Tertiary stage
Primary-Stage Infection
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Small, hard-based sore develops at
site of infection
May be painless and patient may be
unaware
Fluid in the sores is highly infectious
Bacteria enters the bloodstream and
lymphatic system
Secondary-Stage
Infection
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Produces skin rashes, patchy hair loss,
malaise, and mild fever
Symptoms subside after a few weeks
and disease becomes latent
After 2-4 years of latency, the disease
is usually no longer infectious
Tertiary-Stage Infection
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

Occurs after an interval of at least 10
years
Lesions appear as a rubbery mass in
many organs and sometimes the skin
May cause extensive damage
Congenital Syphilis
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Crosses the placenta into the fetus
Results in neurologic damage if
pregnancy occurs during the tertiary
stage
Pregnancy during primary or
secondary stage is likely to produce a
stillborn child
Genital Herpes

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Caused by herpes simplex virus
Lesions appear after 1 week of
incubation
Infectious vesicles appear and heal
within 2 weeks
Virus becomes latent until reactivated
Candidiasis

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
Caused by Candida albicans
Yeast-like fungal infection that can
cause infection in genital area of men
and women and the mouth (thrush)
Can cause itching and a thick, yellow,
cheesy discharge
Vaginitis
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
Caused by Gardnerella vaginitis
Results from interaction between this
organism and anaerobic bacterium in
the vagina
Symptoms: frothy discharge with fishy
odor and vaginal pH of 5 to 6
Vaginitis

May also be caused by Trichomonas
vaginalis


Normally found in both sexes, but
causes infection if vaginal pH changes
Causes profuse yellowish or creamcolored discharge with a disagreeable
odor, irritation, and itching
Drug List
Agents for STDs
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acyclovir (Zovirax)
azithromycin (Zithromax)
ceftriaxone (Rocephin)
clotrimazole (GyneLotrimin, Mycelex)
doxycycline (Doryx, Vibramycin)
Drug List
Agents for STDs
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erythromycin
fluconazole (Diflucan)
ketoconazole (Nizoral)
metronidazole (Flagyl)
miconazole (Monistat)
Drug List
Agents for STDs
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penicillin G benzathine (Bicillin L-A)
spectinomycin (Trobicin)
tetracycline (Sumycin)
tioconazole (Vagistat-1)
valacyclovir (Valtrex)