Endo Pharm (1) Flashcards
Another name for anterior pituitary
Adenohypophysis
ACTH
adrenocorticotropic hormone
What inhibits the process of Prolactin
Dopamine
Endocrine-secreting pituitary tumors
Growth Hormone (Giantism, acromegally)
ACTH (Cushing’s Disease)
Prolactin (prolactinoma) (MOST COMMON)
Pituitary tumors do not secrete these hormones
TSH, FSH, LH
Pituitary extracts (GH availability)
No longer used
Due to risk of Prion Disease: Creutzfeldt-Jakob Disease (CJD)
Recombinant GH
licensed for short stature associated with growth hormone deficiency (GHD)
Genotropin, Humatrop, Hutropin, et al
Injections (SQ or IM)
Treatment with GH
GH deficient states Some short stature children: Normal GH but delayed growth Turner syndrome (45,X)
Experimental:
Muscle augmentation in elderly
Intrauterine growth retardation
Adverse Effects with GH
Usually well tolerated, esp children Hypothyroidism possible MYALGIA, ARTHRALGIA GLUCOSE INTOLERANCE Possible stimulation of tumor growth
Symptoms of acromegaly
Diabetes
Soft tissue swelling
Teeth gaping
Macroglosia (large tongue)
GH excess: Pituitary Adenoma before epiphyseal plate closure
Giantism
GH excess: Pituitary Ademona after epiphyseal Plate closure
Acromegaly
Most common cause of acromegaly
pituitary tumor
Excess GH in adults leads to:
Glucose intolerance leading to DM Cardiact enlargement leading to CHF HTN Renal failure Soft tissue swelling including: head, shoe, nose, lips, ears, fingers.
Options for treating GH excess disorders
GH inhibity hormone (Somatostatin) (secretion)
GH receptor antagonist (receptors)
Somatostatin
Somatostatin from the hypothalamus inhibits the pituitary gland’s secretion of growth hormone and thyroid stimulating hormone. In addition, somatostatin is produced in the pancreas and inhibits the secretion of other pancreatic hormones such as insulin and glucagon.
Indications for Somatostatin (receptor) Agonists
Utility in acromegaly & carcinoid syndrome
for growth limitation: controversial
Somatostatin (receptor) Agonists choices
Octreotide (Sandostatin, Sandostating LAR)
Lanreotide (Somatuline LA, Autogel)
GH receptor Blockade indication
Acromegaly not responsive to surgery or somatostatin analogs
GH receptor blockade med?
Pegvisomant (Somavert)
also administered via SQ injections
Main function of prolactin
Other functions of prolactin:
Lactation (main)
Stress response sexual response fluid balance Immunologic (?) Other
Prolactin deficient symptoms
Probably none other than lactation failure
Pathophysiology of Prolactin excess states
Loss of prolactin inhibiting factor (dopamine)
excess of thyrotopin-releasing factor (TRF)
Results in galactorrhea & Hypogonadism (Low FSH & LH)
Causes of Prolactin Excess States
Pituitary adenoma
Primary hypothyroidism
Drug induces
Drugs that induce prolactin excess states
Phenothiazines & other dopamine blockers
In female: typical hyperprolactinemia cases
amenorrhea
galactorrhea
in adult male: typical hyperprolactinemia cases
reduced libido muscle mass decrease reduced facial hair growth erectile dysfunction gynecomastia is possible
Treating Hyperprolactinemia
dopamine agonists
Ergot type:
Bromocriptine (parlodel)
Cabergoline (Dostinex)
Non-Ergot type:
Parkinson’s treatment agents
Most common ause of druge induced hyperprolactinemia
antiphychotic agents
what is contraindicated in psychotic patients?
Dopamine agonists
Dopamine agonists in contraindicated in what?
Psychotic patients
Lowest effective dose (meds) for prescribing dopamine agonists
Cabergoline (Dostinex) (o.5 mg tabs (1/2 tab PER WEEK))
Bromocriptine (Parlodel) 2.5 mg tablets (1/2 tab at bedtime (qhs)
Common side effects of prescribing dopamine agonists
nausea & orthostatic hypotension
SLIGHT risk of hypertension/CVA
TRF
thyrotropin releasing hormone
TRF regulates what?
In hypothalamus
TSH and prolactin
T3
Triiodotyronine (T3)
T4
Tetraiodothyronine (T4, thyroxine, levothyroxine)
Special T3/T4 function
Increase sensitivity to catecholamines
THEREFORE EXCELL T3/T4 PRODUCES SYMPTOMS 7 SIGNS OF SYMPATHETIC AGONIST EXCESS
Thyroid hormone products
Preferred:
Levothyroxine (T4, syntroid, levoxyl, levo-t, unithyroid)
Use “never required”:
Liothyronine (T3, Cytomel, Triostat)
Liotrix (Thyrolar)-4:1 ratio of T4:T3
Desiccated Thyroid (Bovine Thyroid) Armour thyroid, thyroid strong, thyrar)
Levothyroxine doses
from .025 to .3 mg (tablets)
Full replacement dose usually .1-.2 mg
Toxicity dose related to dose and T4 effects
Levothyroxine caution?
ADVANCE DOSE CAUTIOUSLY IN PATIENT >65
increases metabolism and cardiac oxygen requirements
Plummer’s disease
Toxic Nodular Goiter
causes Hyperthyroidism
two diseases of hyperthroidism
Grave’s disease
Toxic Nodular Goiter (Plummer’s disease)
Causes pf hypothyroidism (Primary (gland failure))
Hashimoto’s thyroiditis
Absence/Destruction
Low Iodine Intake
Hypothyroid symptoms
Poor memory Inability to concentrate Hair loss Weight gain Cold intolerance Weakness Fatigue Dry skin Menstrual irregularities Cognitive decline
Hypothyroidism treatment
First choice: Thyroxine (T4) daily
Lag time for Thyroid-Pituitary Axis
Long lag time 6-8 weeks
where is T4 metabolized
liver (CYP450)
Age factor in Hypothyroidism treatment
Low & slow for > 65 y/o
dose typically 75% of young adults
Adverse effects of thyroxine
similar symptoms of hyperthyroidism
Symptoms of hyperthyroidism
Restlessness Insomnia Tremor Weight loss Heat intolerance Weakness Fatigue Muscle cramps Menstrual irregularities anxious HTN
Increase in sympathetic receptor sensitivity
Hyperthyroidism treatment
Quickly control symptoms
Beta adrenergic blokade (control sypathetic agonist type symptoms)
Utilize anti-thyroid agents
Prevent thyroid storm
Definitive treatment
Thyroid excision or destruction
BetaBlockers in hyperthyroidism
Control cardiovascular syptoms: Tachycardia Anginga Tremors Agitation
Non-selective agent best:
Propranolo (Inderal)
CAUTIONS in asthmatics, acute CHF
Anti-thyroid agents
Thioamides Anion Inhibitors Iodides Iodinated contrast media Radioactive iodine
Thioamides
Blocks SYNTHESIS of T3/T4
anti-thyroid drugs are also a class of drugs that are used to control thyrotoxicosis.
act principally by blocking the synthesis of T4 by preventing iodination of tyrosine residues.
How long does it take for thioamides to deplete T3/T4 stores?
3-4 weeks
does not block iodide uptake
Two examples of thioamides
Propylthiouracil (PTU)
Q6-8 hrs
BEST CHOICE FOR PREG PATIENTS
Methimazole (Tapazole)
single daily dose
Thioamine Adverse effects
Rash
Edema
Agranulocytosis
anion inhibitors
Prevent REUPTAKE OF IODINE
limited usefulness (drug induced hyperthyroidism
Main choice: POTASSIUM PERCHLORATE
Can cause aplastic anemia
Iodides
Suppress T3/T4 RELEASE
Quick onset of action
Escape from suppression occurs in 2-8 weeks
Interferes with thioamide action and radioactive iodine
start thioamides first
AVOID IF RADIOACTIVE IODINE USE IS LIKELY
Iodinated contrast media
bock T4 to T3 CONVERSION
Onset of action within a few days
Choices: Iopanpoic acid (Telepaque) Diatrizoate sodium (Hypaque) Ipodate sodium (oragrafin)
Radioactive Iodine (I131)
Oral prep, rapidly absorbed
destroys thyroid gland within a few weeks
> 30 years of safe use
CONTRAINDICATED IN PREGNANCY!!!
Thyroid storm
uncommon form of hyperthyroidism
AKA thyrotoxic crisis
Cause: Stress, coexisting illness, idiopathic
Symptoms: High fever Tachycardia/arrhythmia Diarrhea/vomiting/dehydration Coma
Thyroid storm treatment
Hospitlization and:
Beta Blocker (propranolol) Calcium channel blocker (diltiazem) Potassium iodide: block T3/T4 release Propylthiouracil (PTU) Hydrocortison: CV stability, reduce T4 to T3 conversion
Androgen
Male sex hormone:
For use in hypogonadal men and women
Enhance libido
Enhance general quality of life (?)
Maintain/enhance muscle mass & strength
reduce risk of falling in elderly
increase RBC production
Available Androgens
Orally active:
ethyltestosterone
Fluoxymeterone (Halotestin)
Oxandrolone (Oxandrin, Anavar)
Testosterone:
Gel formation (Androgel)
Patch (testoderm, Androderm)
Pellets for IM injection (Testopel)
Other IM injection options: Testosterone cypionate, enanthate, proprionate
Androgen Adversities
Liver damage/hepatoma risk (mainly oral preparations)
INCREASED HEMATOCRIT: = VASCULAR THROMBOSIS
INCREASED LIBIDO: = INCREASED AGGRESSIVENESS
Oily skin/acne
Best approach to decreased levels of adrogens
use symptoms and lab values (total T <200 ng/dl)
aromatase
Aromatase: An enzyme involved in the production of estrogen that acts by catalyzing the conversion of testosterone (an androgen) to estradiol (an estrogen). Aromatase is located in estrogen-producing cells in the adrenal glands, ovaries, placenta, testicles, adipose (fat) tissue, and brain.
aromatase inhibitors
reduce production of estrogens
choices:
Anastozole (Arimidex)
Letrozole (Femara)
Exemestane (Aromasin)
Side effects (hypoestrogenism)
Indications for aromatase inhibitors
Breast Ca treatment
reduces risk of recurrence
gradually replacing tamoxifen (Nolvadex)
Breast CA prevention
Ovulation induction
Anti-Androgen strategies
Block steridogenesis
Ketoconazole (Nizoral)
Drug interaction issues (CYP450 inhibitor)
Block T to DHT conversion
Finasteride (Propecia)
Inhibit androgen receptors
Androgen Receptor Blockers
Cyrpoterone acetate
Also blocks progesterone receptors
Flutamide (Eulexin)
Bicalutamide (Casodex)
Nilutamide (Nilandron)
Antiandrogen Ultilization
Women:
Hirsutism, masculinization
PCO most common indication
Men
Male pattern baldness
Prostatic hypertrophy
Prostate Ca treatment
Androgenic alopecia
Male Pattern Baldness
Important Endocrine Event (testosterone conversion)
Testosteron (T) is converted to >
Dihydrotestosterone (DHT) by the action of …
5-Alpha reductase
BPH Medical treatment
Alpha sympathetic receptor blocking drugs
5-Alpha reductase inhibitors
Male pattern baldness medical treatment
5-alpha reuctase inhibitors
Minoxidil (Rogaine)
5-Alpha reductase inhibitor (drugs)
Finasteride (Propecia)
Dutasteride (Avodart)
Anti-Androgen Side effects
Women:
diminished libido
Men: Diminishe libido Erectile dysfunction Decline in muscle mass/strength diminished sense of well-being gynecomastia
Androgen Cause with Pregnancy
MASCULIZATION OF THE FEMALE FETUS
Anti-androgen caution with pregnancy
INCOMPLETE MASCULINIZATION OF A MALE FETUS
Ambiguous genitalia
intersex
Ambiguous genitalia is a rare condition in which an infant’s external genitals don’t appear to be clearly either male or female. In a baby with ambiguous genitalia, the genitals may be incompletely developed or the baby may have characteristics of both sexes.
