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302 Cards in this Set
- Front
- Back
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GnRH
AT LOW DOSES CAUSES THIS RESPONSE |
GnRH binds to LH & FSH receptors
→ Gs activation → ↑ cAMP. |
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GnRH
AT HIGH DOSES CAUSES THIS RESPONSE |
GnRH binds to LH/FSH receptors
→ Gq activation → phospholipase C activation → ↑ IP3 (↑ intracellular Ca++), DAG. |
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WHAT IS THE NET EFFECT OF GnRH
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RELEASE OF LH AND FSH
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***
GnRH IS RELEASED IN A PULSATILE MANNER, WHY THIS IS ESSENTIAL TO UNDERSTAND THERAPEUTICALLY |
CONTINUOUS ADMINISTRATION RESULTS IN RECEPTOR DOWN REGULATION (SENSITIZATION)
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this is a peptide hormone which is the major modulator of gonadotropin secretion
-produced by ovaries and testis in response to FSH |
INHIBIN
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in normally ovulating women, THIS exerts a positive feedback at the pituitary to GnRH
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estradiol
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Leuprolide & Gonadorelin
CLASS / MOA |
**FULL AGONISTS**
AT LOW DOSES INCREASE FSH/LH AT HIGH DOSES DECREASE FSH/LH |
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Leuprolide & Gonadorelin
THERAPEUTIC USE IS DIVIDED INTO THESE 2 BROAD CATEGORIES |
1- REPLACEMENT THERAPY
2- PITUITARY DESENSITIZATION |
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WHICH DOSE (therapy regimen) OF Leuprolide & Gonadorelin IS GIVEN FOR:
-idiopathic hypogonadotropic hypogonadism |
Low Dose (replacement therapy)
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WHICH DOSE OF Leuprolide & Gonadorelin IS GIVEN FOR:
induction of ovulation in women with hypothalamic amenorrhea |
replacement therapy
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WHICH DOSE OF Leuprolide & Gonadorelin IS GIVEN FOR:
-central precocious puberty AND -prostate cancer |
pituitary desensitization
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in males what is the role of LH?
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stimulates de novo synthesis of androgens (testosterone) by leydig cells
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in females, what is the role of FSH
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stimulate synthesis of estrogen,
promote growth of developing follicle |
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in females, what is the role of LH
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induce ovulation
stimulate progesterone synthesis |
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this hormone is
-secreted by trophoblastic cells -levels peak at 10 wks pregnancy -binds to LH receptors and has similar effect |
HCG
Chorionic gonadotropin |
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name 3 LH/FSH analogs
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Chorionic gonadotropin (CG)
Menotropins Urofollitropin |
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what is the main difference between
Menotropins & Urofollitropin |
Menotropins - equal mixture of FSH/LH
Urofollitropin - mostly FSH |
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What are the 3 uses of
Chorionic gonadotropin (CG) Menotropins Urofollitropin |
female infertility (induces ovulation)
Male infertility cryptorchidism |
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what are the + and - controls of GROWTH HORMONE
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+ = GHRH
- = SOMATOSTATIN |
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***
THE ACTION OF GROWTH HORMONE EXERTS ITS INTRACELLULAR EFFECTS VIA THIS PATHWAY |
ACTIVATION OF JAK-STAT PATHWAY
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WHAT TYPE OF PROTEINS ARE JAK'S
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TYROSINE KINASE
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THE INDIRECT EFFECTS OF GH ARE MEDIATED BY THIS PROTEIN
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IGF-1
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IGF-1 IS DIRECTLY RESPONSIBLE FOR THESE 3 PROCESSES
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CHONDROGENESIS
SKELETAL GROWTH GROWTH OF SOFT TISSUES |
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NAME 2 AGENTS USED TO TREAT LOW LEVELS OF GROWTH HORMONE
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SOMATROPIN RECOMBINANT
SOMATREM |
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SOMATROPIN RECOMBINANT & SOMATREM
KINETICS OF BOTH, DISADVANTAGE OF SOMATREM |
BOTH RECOMBINANT DNA TECHNOLOGY
BOTH EQUALLY EFFECTIVE SOMATREM IS MORE ANTIGENIC |
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SOMATROPIN RECOMBINANT & SOMATREM
USE |
TREAT CHILDREN WITH GH DEFICIENCY
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SOMATOSTATIN
inhibits ______ via this mechanism |
INHIBITS GH RELEASE VIA Gi PROTEIN (↓ cAMP)
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OCTREOTIDE
MOA |
somatostatin analog that ↓ GH release via Gi receptors (↓ cAMP).
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OCTREOTIDE
USE |
METASTATIC CARCINOID TUMORS THAT SECRETE VIP CAUSING DIARRHEA
INHIBITS DIARRHEA, AND FLUSHING |
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ACROMEGALY IS CHARACTERIZED BY EXCESSIVE SECRETION OF THESE 3 HORMONES
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GH, GHRH, IGF-1
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THIS IS THE DOC TO TREAT ACROMEGALY IN ADULTS
SURGERY/RADIATION IS A MORE PERMENANT SOLN |
bromocriptine
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bromocriptine
MOA |
stimulates GH secretion in a normally functioning pituitary
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BROMOCRIPTINE IS USED FOR TX OF ACROMEGALY AND THIS DISEASE, BECAUSE IT IS THIS TYPE OF DRUG
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PARKINSONS
D2 (ergot like) agonist |
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this is the major inhibitor of Prolactin synthesis and release.
what receptor does it bind to? type of receptor |
DOPAMINE
LACTOTROPE D2 RECEPTOR G protein |
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2 main causes of hyperprolactinemia
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prolactin secreting tumor
dopaminergic antagonist |
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main symptoms of hyperprolactinemia in
males vs females |
M- infertility, impotence, galactorrhea
F- galactorrhea, amenorrhea, infertility |
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name 2 drugs to treat hyperprolactinemia
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bromocriptine
cabergoline |
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how does bromocriptine help in hyperprolactinemia
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inhibits spontaneous TRH-induced release of prolactin
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Cabergoline
MOA |
D2 agonist with long T 1/2
more potent than bromocriptine |
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what are the main stimulatory signals causing release of ADH
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osmotic signals
pressure signals |
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in the kidney, ADH bind to this receptor and cause this action
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V2 receptor
increase H2O permeability and reabsorption in the collecting duct |
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Name 3 agents used to treat low ADH levels
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Vasopressin
Lypressin Desmopressin |
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Vasopressin & Lypressin & Desmopressin
USE WHICH IS PREFERRED AND WHY? |
CENTRAL DIABETES INSIPIDUS
DESMOPRESSIN; less pressor effect and longer acting |
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DESMOPRESSIN IS ALSO EFFECTIVE FOR THIS CONDITION
|
TYPE 1 VON WILLEBRAND DISEASE
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oxytocin
effects |
stimulates both the frequency and force of uterine contractions.
stimulates milk ejection |
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these are the only biologically active iodine containing compounds in our body
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thyroid hormones
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the oxidation of iodide to its active form is accomplished by THIS HEME CONTAINING ENZYME.
WHAT DOES IT USE AS ITS OXIDANT? |
THYROID PEROXIDASE
hydrogen peroxide |
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how is the potency of T3 different from T4?
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T3 is 5x's more potent
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this is the primary carrier of thyroid hormones
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Thyroxine-Binding "GOBLIN"
(TBG) |
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the primary effect of thyroid hormones is to
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promote normal growth/development especially in myelination of the CNS
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Hypothyroidism in children is called____ and is manifested by
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Cretinism;
severely impaired growth and mental retardation |
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in adults hypothyroidism is called _____
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Myxedema
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name 3 agents to treat Hypothyroidism
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Desiccated Thyroid
Levothyroxine Liothyronine |
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name 3 agents to treat Hyperthyroidism
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Propylthiouracil
Methimazole Radioactive Iodine (131 I) |
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what is the main contraindication for using all 3
Desiccated Thyroid Levothyroxine Liothyronine |
dont use in acute MI
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what are the main drug interactions of all 3
Desiccated Thyroid Levothyroxine Liothyronine |
May ↑ anticoagulant effects.
May ↓ digitalis effects. |
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what are the main drug characteristics of:
Dessicated thyroid |
get from pig thyroids (antigenic)
contains both T3 and T4 |
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what are the main drug characteristics of:
levothyroxine |
DOC TO TX HYPOTHYROID
CONTAINS ONLY T4 |
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what are the main drug characteristics of:
Liothyronine |
contains T3 only, quicker onset
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what are the 2 disease states of Hyperthyroidism
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Diffuse toxic goiter = Graves Disease
Toxic nodular goiter = Plummer disease |
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Propylthiouracil & Methimazole
MOA |
Interfere with iodination of tyrosyl residues in thyroglobulin,
inhibit coupling reaction by blocking thyroid peroxidase. |
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What is the unique action of Propylthiouracil, not demonstrated by Methimazole
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Propylthiouracil also blocks peripheral conversion of T4 to T3
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Propylthiouracil & Methimazole
SE |
generally minor however
Agranulocytosis may occur |
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Propylthiouracil & Methimazole
USE |
GRAVES DISEASE
PRIOR TO THYROIDECTOMY TO prevent thyroid storm |
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IODIDE CAN BE GIVEN IN THIS FORM WHICH IS ALSO KNOWN AS _____ SOLN
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saturated solution of Potassium Iodide (SSKI)
AKA Lugol's soln |
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SSKI
MOA |
high concentrations of Iodide prevent thyroid hormone synthesis by decreasing TSH and blocking action of TSH
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SSKI
USE |
-pre-op to reduce vascularity & increase firmness of Thyroid gland
-Thyroid storm |
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SSKI
SE |
chronic toxicity causes IODISM:
BURNING OF THE MOUTH, THROAT AND EYES WITH HEADACHE AND SKIN LESIONS |
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Radioactive Iodine (131 I)
MOA |
β-rays destroy parenchymal cells of thyroid with little or no damage to surrounding tissue
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Radioactive Iodine (131 I)
SE |
delayed hypothyroidism
Can cause chromosomal aberrations and should NOT be used in young patients or during pregnancy |
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Uncommon but life-threatening complication of hyperthyroidism
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THYROID STORM
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WHAT ARE THE Clinical Features OF THYROID STORM
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Extreme fever, tachycardia, nausea, vomiting, confusion, coma, death in 20% of patients.
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HOW DO YOU TREAT THYROID STORM?
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-Supportive measures (fluids, antipyretics, cooling blankets).
-Propylthiouracil given in large doses & iodates. -β-blockers, Ca2+ channel blockers to control tachyarrhythmias. -Dexamethasone for supportive therapy. |
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HOW IS THYROID HORMONE RELATED TO CHOLESTEROL?
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INVERSELY
hypercholesterolemia is a characteristic of hypothyroidism |
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corticosteroids bind receptors in target tissues --> gene expression --> protein synthesis
-When are their effects clinically noticed? |
after several hours
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HOW DO CORTICOSTEROIDS AFFECT THE INFLAMMATORY RESPONSE?
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INHIBIT GENES THAT CODE FOR CYTOKINE PRODUCTION
(decrease inflammation) |
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corticosteroids and aldosterone can bind to this receptor with EQUAL AFFINITY
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MINERALOCORTICOID RECEPTORS
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THIS ENZYME METABOLIZES CORTISOL-->CORTISONE (cortisone does not bind to mineralocorticoid receptors)
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11 B - hydroxysteroid dehydrogenase
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** THIS IS THE RATE LIMITING STEP IN STEROID HORMONE PRODUCTION
WHAT DOES IT DO? |
CHOLESTEROL-SIDE CHAIN CLEAVAGE ENZYME (P450 scc)
cholesterol --> pregnenolone |
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what are the 2 responses to ACTC seen in adrenal cortex, when does each occur, and what is the main effect?
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-Acute Phase: minutes, ↑ cholesterol substrate to steroidogenic enzymes
-Chronic Phase: hours, ↑ transcription of steroidogenic enzymes |
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this provides the main negative feedback to corticosteroid production.
--> this stimuli can however override this feedback and cause increased corticosteroids |
HPA axis
stress can override the HPA axis negative feedback mechanism |
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this is a synthetic peptide related to ACTH
**IS THE AGENT OF CHOICE TO TEST THE HPA AXIS!! |
COSYNTROPIN
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GLUCOCORTICOIDS INHBIT THIS ENZYME PREVENTING INFLAMMATORY RESPONSE
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PHOSPHOLIPASE A2
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how do corticosteroids effect:
Carbohydrate/protein metabolism |
Stimulates gluconeogenesis from amino acids
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how do corticosteroids effect:
Lipid Metabolism |
↑ lipolysis. Redistribution of fat: ↑ fat in neck “buffalo hump,” face “moon face,” loss of fat in extremities.
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how do corticosteroids effect:
CV System |
Like 1° aldosteronism: mineralocorticoid-induced ↑ in Na+ reabsorption
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how do corticosteroids effect:
Skeletal Muscle |
Adrenocortical insufficiency → ↓ work capacity (Addison’s disease).
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how do corticosteroids effect:
Blood |
↓ in circulating WBCs.
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how do corticosteroids effect:
CNS |
neuroses or psychoses in Addison’s & Cushing’s patients
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GLUCOCORTICOIDS IN MACROPHAGES AND MONOCYTES INHIBIT ________
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ARACHIDONIC ACID
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GLUCOCORTICOIDS IN BASOPHILLS INHIBIT ________
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LEUKOTRIENE FORMATION
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NAME 2
Short-Acting Glucocorticoids: (duration of action 8-12 hrs) |
Hydrocortisone
Cortisone |
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NAME 3
intermediate-Acting Glucocorticoids: (duration of action 18-36 hrs) |
Prednisone
Methylprednisolone Triamcinolone |
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NAME 2
long-Acting Glucocorticoids: (duration of action 1-3 days) |
Betamethasone
Dexamethasone |
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name 1:
Short acting and intermediate acting glucocorticoid which are PRODRUGS, REQUIRING LIVER TO ACTIVATE THEM |
CORTISONE (short)
PREDNISONE (intermediate) |
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NAME 2 GLUCOCORTICOIDS WHICH SHOULD NEVER BE USED IN LIVER FAILURE
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CORTISONE
PREDNISONE |
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which GLUCOCORTICOIDS have a salt retaining effect?
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short-acting > intermediate-acting
(long acting do not retain salt) |
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WHY DO YOU HAVE TO TAPER PTS OFF OF CORTICOSTEROIDS SLOWLY?
(name, describe) |
ACUTE ADRENAL INSUFFICIENCY
- life threatening severe complication of abrupt withdraw of steroids -SUPPRESSION OF HPA AXIS |
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NAME 3 ENDROCRINE CONDITIONS WHICH CORTICOSTEROID REPLACEMENT IS USED AS TX
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-Acute Adrenal Insufficiency
-Chronic Primary Adrenal Insufficiency -Congenital Adrenal Hyperplasia |
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NAME 3 CORTICOSTEROID INHIBITORS
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Aminoglutethimide
Ketoconazole Spironolactone |
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Aminoglutethimide
MOA / USE |
Inhibits P450 SCC enzyme (rate-limiting step).
Use: Cushing’s disease. |
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Ketoconazole
MOA / USE |
Inhibits C17-20 lyase.
Use: Cushing’s disease. |
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Spironolactone
MOA / USE |
Blocks mineralocorticoid receptor → ↓ Na+ reabsorption.
Use: hyperaldosteronism |
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Fludrocortisone
CLASS |
MINERALOCORTICOID
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Fludrocortisone
MOA |
Act on distal tubules of kidney to enhance reabsorption of Na+ from tubule into plasma.
↑ Urinary excretion of both K+ and H+. |
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Fludrocortisone
USE |
Addison’s disease
Severe salt-losing adrenogenital syndrome Orthostatic hypotension |
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Fludrocortisone
KINETICS |
EXTREMELY HIGH mineralocorticoid activity.
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what are the 3 naturally occurring estrogens
--> from most potent to least |
17 β-estradiol
Estrone Estriol |
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each of the estrogen molecules is an 18 C steroid which CONTAIN THIS STRUCTURE, WHY IS THIS IMPORTANT
|
PHENOLIC A RING
-->RESPONSIBLE FOR HIGH SELECTIVITY AND HIGH AFFINITY BINDING |
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steroidal estrogens are formed FROM THIS PRECURSOR
USES THIS CATALYST |
ANDROGENS --> ESTROGENS
USING AROMATASE |
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this is a monooxygenase enzyme complex in ER of ovaries/testicles, fat cells, placenta and various brain regions. uses NADPH and O2 as co-substrates to catalyze estrogen formation
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AROMATASE
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this is the major secretory product of the ovaries
|
estradiol
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IN MEN AND POSTMENOPAUSAL WOMEN THE PRINCIPAL SOURCE OF ESTROGEN IS ______, SYNTHESIZED BY THIS PRECURSOR
|
FAT CELLS
DHEA |
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What effect does estrogen have on:
*BONES* |
**
EFFECTIVE AT PREVENTING BONE LOSS (rather than restoring bone loss) |
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What effect does estrogen have on:
lipid metabolism |
increase TAG's and HDL
decrease total serum cholesterol and LDL |
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What effect does estrogen have on:
Proteins |
increase binding "Goblins"
CBG, TBG SSBG, etc |
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Estrogens
MOA |
binds receptors in nucleus → interacts with estrogen response elements → ↑ or ↓ transcription of hormone-regulated genes
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name 4 Synthetic Steroidal Estrogen Agonists
|
-Conjugated Estrogens
-Ethinyl Estradiol -Mestranol -Estradiol Cypionate |
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Name 1 Nonsteroidal Estrogen Agonist
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Diethylstilbestrol (DES)
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Diethylstilbestrol (DES)
SE |
congenital & developmental anomalies in offspring of DES-treated women
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Name 2 Antiestrogens
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Clomiphene
Tamoxifen |
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Clomiphene
MOA |
Estrogen receptor blocker (competitive antagonist)
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Clomiphene
KINETICS |
Racemic mixture of cis and trans isomers
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what activity does each the estrogen Cis Vs Trans- isomers have
|
cis isomer has estrogenic activity;
trans isomer has antiestrogenic activity |
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Clomiphene
USE |
Infertility = Stimulates ovulation
↑ Amplitude of LH and FSH pulses |
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how does Clomiphene affect estrogen feedback?
--> effect |
Opposes (-) feedback of endogenous estrogens
→ ↑ gonadotropin secretion & ovulation |
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Clomiphene
SE |
Adverse Effects:
Ovarian hyperstimulation (multiple births) ovarian cysts |
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Tamoxifen
MOA |
Estrogen receptor blocker (competitive antagonist)
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Tamoxifen
KINETICS / EFFECT |
Pure trans isomer (antiestrogenic activity).
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Tamoxifen
USE |
BREAST CANCER (if estrogen dependent tumor)
|
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Tamoxifen
elimination |
bi-phasic
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Raloxifene
MOA |
Selective estrogen receptor modulator
|
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HOW DOES Raloxifene DIFFER FROM clomiphene and tamoxifen
|
NO effect on reproductive tissues.
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Raloxifene
USE / WHY |
osteoporosis
-partial agonist effects on bone resorption |
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NAME 2 AROMATASE MODULATORS
|
Amastrazole
Exemestane |
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Amastrazole & Exemestane
ARE BOTH USED FOR ____ GIVE MECHANISM BEHIND ITS EFFECTS |
hormone-dependent breast CA
Estrogen deprivation by aromatase inhibition |
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Amastrazole
MOA |
Reversible, selective aromatase inhibitor
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Exemestane
MOA |
Irreversible, steroidal, aromatase inactivator
(“suicide inhibition”) |
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Synthetic progestin classes:
this is a 21C skeleton which is highly selective for and has similar activity to progesterone |
Medroxyprogesterone
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Progesterone effect on:
Neuroendocrine Actions |
↓ frequency of hypothalamic pulse generator,
↑ amplitude of LH pulses from pituitary |
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Progesterone effect on:
reproductive tract |
↓ estrogen-driven endometrial proliferation
→ development of secretory endometrium. -maintains pregnancy (suppresses menstruation, uterine contractility) |
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Progesterone effect on:
CNS |
1° ↑ in body temperature at midcycle
|
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name 3 uses of progesterone
|
Oral contraception
Hormone replacement therapy Ovarian suppression |
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Mifepristone
Class |
Antiprogestin
Progesterone & glucocorticoid blocker (competitive inhibitor). |
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Mifepristone
MOA |
Abortion pill
Progesterone blockage → ↑ PG → ↑ myometrium contractions → blastocyst detachment → also softens cervix → facilitates expulsion of detached blastocyst. |
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WHEN DO YOU USE
Mifepristone |
TO ABORT A PREGNANCY
Can be administered through day 49 of pregnancy. |
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what are the effects of ESTROGENS FOUND IN COMBINATION ORAL CONTRACEPTIVES
|
Estrogens
-↓ FSH → prevent development of dominant follicle. -↑ progestin actions (↓ LH surge). -stabilize endometrial lining (bleeding cycle control). |
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WHAT ARE THE EFFECTS OF PROGESTINS IN COMBINATION ORAL CONTRACEPTIVES
|
Progestin
-makes cervical mucus viscous -causes endometrial involution/atrophy BLOCKS ovulation |
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COMBO ORAL CONTRACEPTIVES:
ESTROGEN COMPONENT SE |
Nausea, vomiting
Cramping Fluid retention Dizziness, headache Breast discomfort |
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COMBO ORAL CONTRACEPTIVES:
PROGESTERONE COMPONENT SE |
Spotting, breakthrough bleeding
Weight gain Acne Hirsutism |
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combo oral contraceptives
CARDIOVASCULAR EFFECTS |
women > 35 years who smoke, ↑ risk of MI (no risk in non-smokers)
Venous thromboembolism Hypertension |
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combo oral contraceptives
what is risk for breast CA |
NOT associated with ↑ risk of breast cancer
|
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name 7 benefits for using combination oral contraceptives
|
↓ Risk of ovarian CA.
↓ Risk of endometrial CA. ↓ Fibroadenomas. ↓ Fibrocystic breast Dz. ↓ Acute PID. ↓ Blood loss during menses. Greater cycle regularity. |
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Name 5 Contraindications for using Combination oral contraceptives
|
-Presence or Hx of thrombotic Dz
- >35 years who smoke heavily -estrogen-dependent breast CA -Hx of stroke. -Pregnancy |
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Name 6 drugs which ↓ effectiveness of combination oral contraceptives. THEREFORE ADVISE PTS TO USE A BACKUP METHOD OF CONTRACEPTIVES
|
phenobarbital
phenytoin penicillins sulfonamides tetracyclines theophylline |
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name 2
Progestin-Only Contraceptives |
Norethindrone
Norgestrel |
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Norethindrone & Norgestrel
MOA |
Progestin
-↓ LH surge. -makes cervical mucus viscous -causes endometrium involution/atrophy. |
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Norethindrone & Norgestrel
how are they taken? effectiveness |
taken daily without interruption
slightly less effective |
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NAME 3
Long-acting progestin preparations |
Norgestrel
Medroxyprogesterone Intrauterine device |
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Norgestrel
KINETICS |
Subdermal implants work up to 5 years
|
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Medroxyprogesterone
KINETICS |
IM injections given every 3 months
|
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IUD
KINETICS |
Release low amounts of progesterone locally that is inserted on a yearly basis
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WHAT ARE THE MAIN SIDE EFFECTS OF
Long-acting progestin preparations |
Spotting, breakthrough bleeding
↓ HDL and ↑ LDL. Edema Weight gain Abdominal bloating Acne Hirsutism Impaired glucose tolerance |
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WHAT IS THE RISK OF CV Dz of
Long-acting progestin preparations |
NO evidence for ↑ risk of CV disease.
|
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|
Preven (Plan B)
USE |
emergency contraceptive
MUST BE TAKEN WITHIN 72 HOURS OF INTERCOURSE OR EFFECTIVENESS DECREASES |
|
|
Preven (Plan B)
WHAT IS IT COMPOSED OF? |
HIGH DOSES of combination oral contraceptives
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*THE FORMATION OF TESTOSTERONE IS ACCOMPLISHED BY THIS PRECURSOR, USING THIS ENZYME
|
ANDROSTENEDIONE
17B-HYDROSTEROID DEHYDROGENASE |
|
|
circulating testosterone is bound tightly to this glycoprotein
|
SHBG
(sex hormone binding globulin) |
|
|
TESTOSTERONE AT ITS ACTIVE SITE IS CONVERTED TO THIS HORMONE, BY THIS ENZYME
|
DHT
5-alpha-REDUCTASE |
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STEROID 5-alpha-REDUCTASE COMES IN THESE 2 FORMS, WHERE IS EACH LOCATED
|
5-alpha-REDUCTASE-1; non-genital skin and liver
5-alpha-REDUCTASE - 2; urogenital tract of men and women |
|
|
testosterone is not given orally because
|
extensive 1st pass metabolism
|
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NAME 3 THERAPEUTIC TESTOSTERONE ANDROGENS
|
Testosterone aqueous
Testosterone cypionate Fluoxymestrone |
|
|
what effects does
Testosterone cypionate have? |
Androgenic & anabolic effects.
|
|
|
what effects does
Fluoxymestrone have? |
MOSTLY ANABOLIC effects (HIGHLY ABUSED)
minor androgenic activity |
|
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Danazol
class |
Androgen
(testosterone) |
|
|
Danazol
MOA |
interacts with progesterone, androgen receptors.
Suppresses pituitary-ovarian axis, ↓ output of FSH, LH |
|
|
Danazol
EFFECTS / USE |
Weakly androgenic
USE: endometriosis, fibrocystic breast disease, hereditary angioedema |
|
|
Danazol
**** SE |
*****
PANCREATITIS |
|
|
Androgen (testosterone)
androgen effects are used to treat ______ due to _____ |
use in hypogonadism
-due to inadequate androgen secretion |
|
|
Androgen (testosterone)
anabolic effects are used to treat ___(2)___ |
osteoporosis
severe burns |
|
|
Androgen (testosterone)
Use: growth |
used in conjunction to promote skeletal growth in prepubertal boys with pituitary dwarfism
|
|
|
Androgen (testosterone)
SE in females |
masculinization, facial hair, deep voice, male pattern baldness
|
|
|
Androgen (testosterone)
SE in young |
premature closure of epiphysis of long bones,
increased aggression, premature CAD |
|
|
name 4 ANTIANDROGENS
|
Spironolactone
Flutamide Ketoconazole Cimetidine |
|
|
Spironolactone
MOA |
INHIBITS 17a-HYDROXYLASE C17-20 LYASE COMPLEX
|
|
|
Spironolactone
USE (2) |
-FEMALE HIRSUTISM
(decreases testosterone) -HYPERALDOSTERONISM |
|
|
Spironolactone
SE in males |
impotence
|
|
|
Flutamide
MOA |
DHT receptor blocker
(COMPETITIVE INHIBITOR) |
|
|
Flutamide
USE |
prostatic cancer
|
|
|
Flutamide
SE |
hepatitis
|
|
|
Ketoconazole
MOA |
Interferes with C17-20 lyase → ↓ testosterone
|
|
|
Ketoconazole
USE |
prostatic cancer (↑↑↑ doses)
|
|
|
Ketoconazole
SE |
hepatotoxic
|
|
|
Cimetidine
MOA |
H2 receptor blocker
(also androgen receptor blocker at ↑↑↑ doses) |
|
|
Cimetidine
USE / SE |
Zollinger-Ellison syndrome
males may develop gynecomastia hirsutism in women |
|
|
Finasteride
MOA |
Blocks 5α-Reductase 1 & 2
|
|
|
Finasteride
USE |
prostatic hyperplasia (BPH), male-pattern baldness
|
|
|
Finasteride
SE |
IMPOTENCE
|
|
|
Sildenafil & Vardenafil & Tadalafil
MOA / EFFECT |
PDE-5 inhibitor → ↑ cGMP → vasodilation of corpus cavernosum
|
|
|
Sildenafil & Vardenafil & Tadalafil
SE |
headache, dyspepsia, color vision disturbance
|
|
|
DO NOT USE _________ WITH Sildenafil & Vardenafil OR Tadalafil
--> WHY? |
** DO NOT USE WITH ORGANIC NITRATES (↓↓↓ BP → DEATH) **
|
|
|
this condition is characterized by; infant with malabsorption of Ca and low phosphate levels
|
rickets
|
|
|
which 2 types of diuretics affect Ca levels in the blood
-- how for each of them |
Loop diuretic = loose Ca (increase Ca excretion hypercalciuria)
Thiazide Diuretics: Save Ca (decrease Ca in urine - hypocalciuria) |
|
|
name 3 drugs to treat
Hypocalcemia |
Calcium chloride
Calcium gluconate Calcium gluceptate |
|
|
what are the 4 modaliltes used in the treatment of
Hypercalcemia |
-fluid replacement
-corticosteroids -Calcitonin -IV Bisphosphates |
|
|
Name 2 IV Bisphosphates
|
-Pamidronate
-Alendronate |
|
|
Pamidronate & Alendronate
MOA |
potent inhibitor of osteoclastic bone resorption
|
|
|
this is a unique characteristic of phosphate in children
-likely accounts for this phenomenon |
+ phosphate balance, higher PO4 in kids then in adults.
could explain physiologic anemia of childhood |
|
|
how is excess phosphate handled in the body
|
decreases Ca levels in blood by precipitating out in soft tissue (CaPO4)
|
|
|
x linked trait due to defective intestinal or renal handling of phosphate. Results in Rickets and dwarfism
|
familial hypophosphatemia
|
|
|
extreme hypophosphatemia can cause this RBC condition
|
acute hemolytic anemia with impaired tissue oxygenation
|
|
|
**HOW DOES CHRONIC RENAL FAILURE AFFECT CALCIUM & PHOSPHATE LEVELS
-WHY*** |
INCREASED PO4, DECREASED Ca
the decreased Ca causes increased PTH, but since kidneys bad, still have HYPERPO4 |
|
|
** HOW DO YOU TREAT HYPERPHOSPHATEMIA IN CHRONIC RENAL FAILURE??
--MECHANISM |
ALUMINUM HYDROXIDE, or CALCIUM CARBONATE
-bind to the PO4 and enhances its secretion |
|
|
low Ca levels stimulate the release of this hormone
|
PTH
|
|
|
** WHAT IS THE ACTION OF PTH ON BONE
|
** INCREASES BONE RESORPTION TO INCREASE CIRCULATING Ca LEVELS
|
|
|
PTH
3 - Effects on Kidney |
1) ↑ Ca reabsorption.
2) ↓ PO4 renal tubular resorption 3) Stimulates 25-OHD → 1,25-dihydroxyvitamin D (calcitriol) conversion |
|
|
how is hypoparathyroid treated
|
vitamin D
|
|
|
Calcitonin
MOA |
Direct inhibition of osteoclast bone resorption.
↑ Urinary excretion of Ca & PO4 |
|
|
name 1 Calcitonin analog
|
Salmon Calcitonin
|
|
|
Salmon Calcitonin
USE (3) |
Hypercalcemia
Paget’s disease Postmenopausal osteoporosis |
|
|
Vitamin D is a hormone& a major regulator of Ca
-where is it synthesized, and what is its precursor |
in the skin
cholesterol |
|
|
Vitamin D
MOA |
positive regulator of Ca
Calcitriol interacts with DNA causing gene transcription |
|
|
Vitamin D deficiency results in inadequate absorption of ___
|
Ca and PO4
|
|
|
Vitamin D deficiency results in
this condition in 1- kids 2- Adults |
kids = rickets
adults = osteomalacia |
|
|
name 3 agents used to treat Vitamin D deficiency
|
Ergocalciferol
Dihydrotachysterol Calcitriol |
|
|
Ergocalciferol
Dihydrotachysterol Calcitriol *** WHAT IS THE DIFFERENCE BETWEEN THEM AND WHEN DO YOU USE EACH*** |
*** Ergocalciferol & Dihydrotachysterol ARE PRODRUGS, CONVERTED TO ACTIVE FORM BY KIDNEY. DO NOT USE IN RENAL FAILURE!!!!!
Calcitriol - ACTIVE AS GIVEN CAN BE USED IN RENAL FAILURE!!! |
|
|
if pt is on dialysis and has Vit D deficiency, what drug do you give?
|
Calcitriol
|
|
|
this is a condition of low bone mass, results in fractures with minimal trauma
|
osteoporosis
|
|
|
differentiate between the 2 types of PRIMARY OSTEOPOROSIS
|
TYPE 1- loss of trabecular bone, cuz of ↓ estrogen
TYPE 2 = loss of cortical and trabecular bone, men and women,long-term modeling inefficiency, dietary inadequacy, ↑ PTH with ↑ age |
|
|
what is the cause of SECONDARY OSTEOPOROSIS
|
Systemic illness or medication (long-term glucocorticoids, phenytoin
|
|
|
what are the 3 primary regulators of adult bone mass
|
physical activity,
reproductive endocrine status, Ca++ intake |
|
|
name 7 Drugs used in the prevention and treatment of OSTEOPOROSIS
|
Calcium Carbonate
Vitamin D & analogs Estrogen Raloxifene Calcitonin Bisphosphonates Thiazide Diuretics Testosterone |
|
|
Calcium Carbonate
advantage |
inexpensive
|
|
|
Raloxifene
CLASS / MOA |
Selective estradiol receptor modulator:
Estrogen agonist in liver, bone; antiestrogen in breast |
|
|
Calcitonin
MOA |
Inhibits osteoclastic bone resorption.
|
|
|
Bisphosphonates
NAME 3 |
Alendronate
Pamidronate Ibandronate |
|
|
WHAT IS THE EFFECT OF Bisphosphonates
|
Suppress bone resorption
|
|
|
Bisphosphonates
ALL CAN CAUSE THIS SE -SO WHAT DO YOU ADVISE YOUR PATIENTS |
ESOPHAGEAL IRRITATION.
MUST TAKE PILL WHILE SITTING UP (& 30 min after) TO DECREASE THIS SE |
|
|
THIS IS A SKELETAL CONDITION OF DISORDERED BONE REMODELING
|
PAGETS DISEASE
|
|
|
the alterations in bone remodeling seen in Pagets disease can cause these 4 complications
|
deafness
spinal cord compression cardiac failure pain |
|
|
Diabetes
what is the cause of POLYURIA in each mellitus vs insipidus |
DM = glucosuria osmotic diuresis
DI decreased amount of or response to ADH |
|
|
how can you differentiate between the 2 types of Diabetes insipidus
|
Give desmopressin
central DI (improves) nephrogenic DI (unresponsive) |
|
|
CENTRAL DIABETES INSIPIDUS
-PROBLEM -MAIN CAUSE -DOC TO Tx |
-defect in ADH release
-head injury -DOC: Desmopressin |
|
|
NEPHROGENIC DIABETES INSIPIDUS
-PROBLEM -2 MAIN CAUSES |
-inability to respond to ADH
-LITHIUM (SE) & DEMECLOCYCLINE (used to Tx SIADH) |
|
|
NEPHROGENIC DIABETES INSIPIDUS
-DOC TO TREAT ALL CAUSES EXCEPT FOR LITHIUM INDUCED WHICH IS TREATED WITH _____ |
DOC = THIAZIDE DIURETIC (HCTZ)
-IF LITHIUM INDUCED Tx WITH AMILORIDE |
|
|
AMILORIDE
MOA IN LITHIUM INDUCED NEPHROGENIC DI |
blocks Na channels, Li closely resembles Na and uses its channels to escape, so amiloride essentially blocks both Na and Li "channels"
|
|
|
what is the target receptor of both
LITHIUM & DEMECLOCYCLINE |
V2 receptor
|
|
|
primary nocturnal enuresis can be treated with these 2 drugs
|
Desmopressin and TCA (like imipramin)
|
|
|
insulin actions in
FAT |
promote TAG storage
↑ LPL decrease lipolysis |
|
|
insulin actions in
MUSCLE |
↑ protein and glycogen synthesis
|
|
|
insulin action in
LIVER |
store GLU as glycogen
↑ TAG synthesis |
|
|
name 3 therapeutic uses for V2 Agonists
|
Central DI (desmopressin: DOC)
type I von Willebrand’s disease 1° nocturnal enuresis |
|
|
insulin release from B cells of pancreas is stimulated by these 2 factors
|
↑ blood glucose
vagal nerve stimulation |
|
|
Insulin signaling is via this activity of insulin receptor β subunit
-what is the response? |
tyrosine kinase
migration of GLUT vesicles to membrane surface |
|
|
**
WHAT ARE THE 6 STEPS TO RELEASE INSULIN FROM PANCREATIC B CELLS |
1) Glucose enters cells by facilitated diffusion through GLUT2 (glucose transporter)
2) → inside cells glucose is phosphorylated by hexokinase 3) ↑ ATP/ADP → 4) closes K+ channel → 5) cell depolarization → Ca++ influx → 6) → insulin release. |
|
|
what is the defective inzyme in MODY?
|
glucokinase
|
|
|
*THESE DRUGS EFFECTIVELY BLOCK THE K CHANNELS IN B-CELLS AND INCREASE INSULIN SECRETION
-WHICH PTS SHOULD BE ON THESE DRUGS? |
SULFONYLUREA DRUGS
ALL TYPE 2 DM PTS |
|
|
this drug keeps the B-cell K channels open --> hyperpolarizing cell ==> no insulin is released
-what condition is it used to treat? |
Diazoxide
insulinoma |
|
|
WHAT IS THE PROBLEM WITH TYPE 1 DM
|
NO B-CELLS
NO INSULIN |
|
|
TYPE 1 DM
-TX -HOW TO MONITOR |
administer exogenous insulin
monitor via HbA1C |
|
|
this is the best advise to give TYPE 2 DM pts.
--> explain |
EXERCISE
cuz it will decrease insulin resistance |
|
|
these drugs reduce the progression of diabetic nephropathy and proteinuria. ALL DIABETICS SHOULD BE ON ONE
|
ACE INHIBITOR / ARB
|
|
|
WHAT ARE THE 3 MAIN ADVERSE REACTIONS TO INSULIN
|
Hypoglycemia (predictable)
lipodystrophy allergic rxn (now is rare) |
|
|
the insulin molecule has these 3 components
|
A chain - C-peptide - B chain
|
|
|
if pt is suspected of insulin overdose how can you be sure?
|
check C-peptide levels,
Endogenous C-peptide is at a 1:1 ratio with insulin exogenous insulin does NOT HAVE C-peptide |
|
|
name 2 ultra short acting insulin preparations
onset duration |
Lispro & Aspart
<15 min 3-6 hrs |
|
|
what are the 2 main advantages of ultra-short acting insulin preps
|
-↓ risk of hypoglycemia
-HbA1C improved |
|
|
name 1 Short Acting insulin prep
onset duration |
Regular (R) insulin
30 min 6-8 hrs |
|
|
Regular (R) insulin
SE |
RISK OF HYPOGLYCEMIA
|
|
|
regular insulin is most useful in this emergent situation
|
Diabetic ketoacidosis emergencies
|
|
|
** THE ADDITION OF ______ TO ANY SHORT/ULTRA SHORT ACTING INSULIN INCREASES ITS DURATION OF ACTION TO 24 HRS
|
PROTAMINE
|
|
|
name 3 intermediate acting insulin preps
|
-NPH
-lispro + protamine -aspart + protamine |
|
|
name 2 Prolonged action insulin preps
|
glargine
detemir |
|
|
glargine & detemir
what the 2 main advantages of theses |
no peak plasma levels keep a rather steady basal level
- less risk of hypoglycemia |
|
|
NAME 4 SULFONYUREA'S AND HOW THEY ARE GROUPED TOGETHER
|
1st Generation:
Chlorpropamide 2nd Generation: Glipizide Glyburide Glimepiride |
|
|
Sulfonylureas
MOA |
**Block K+ channel on β cells of pancreas→ cell depolarization
→ Ca++ influx → insulin release ALSO: ↓ glucagon & ↑ insulin binding |
|
|
Chlorpropamide (1st Generation SULFONYLUREA)
-SE -(not used much anymore) |
disulfiram reaction
hypoglycemia |
|
|
Metformin
MOA |
*↓ Gluconeogenesis
Also stimulates glycolysis, ↑ tissue glucose uptake |
|
|
ADVANTAGE TO METFORMIN
|
DOES NOT CAUES HYPOGLYCEMIA
|
|
|
Pioglitazone & Rosiglitazone
MOA / ACT VIA ____ |
Insulin sensitizers: ↑ tissue sensitivity to insulin
Act via PPARs to ↑ transcription (probably ↑ insulin receptors) |
|
|
Pioglitazone & Rosiglitazone
SE |
possibly MI or other CV events DO NOT USE IN CHF
also GI and hypoglycemia |
|
|
Acarbose
CLASS/MOA |
glucosidase inhibitor:
Inhibit α-glucosidase in intestinal brush border → ↓ absorption of starch, disaccharides→ prevents post-prandial rise in blood glucose. |
|
|
Acarbose
MAIN SE -ADVANTAGE |
Flatulence
** NO HYPOGLYCEMIA ** |
|
|
*** NAME 2 ORAL HYPOGLYCEMIC DRUGS THAT DO NOT CAUSE HYPOGLYCEMIA AS A SIDE EFFECT
|
******
METFORMIN & ACARBOSE ****** |
|
|
Nateglinide & Repaglinide
MOA |
Same as sulfonylureas
Block K+ channel on β cells of pancreas → cell depolarization → Ca++ influx → insulin release |
|
|
Nateglinide & Repaglinide
SE |
HYPOGLYCEMIA
|
|
|
Exenatide
MOA |
Incretin mimetic: ↑ insulin release
|
|
|
Exenatide
USE |
TYPE 2 DM ONLY
|
|
|
Exenatide
SE |
Hypoglycemia
|
|
|
Sitagliptin
MOA |
Inhibits dipeptidyl peptidase (DDP-4) → ↑ incretin t½
RESULTS IN ↑ GLUCOSE DEPENDENT INSULIN SECRETION |
|
|
Sitagliptin
USE |
TYPE 2 DM ONLY
|
|
|
Pramlintide
MOA |
Synthetic amylin analogue
1) ↓ intestinal food absorption (including glucose) 2. Inhibits glucagon 3. ↓ appetite |
|
|
Pramlintide
SE |
Hypoglycemia
|
|
|
Pramlintide
USE |
TYPE 1 OR 2 DM
(NOT DEPENDENT ON B CELL FUNCTION) |
|
|
** WHAT IS THE ONLY Miscellaneous Metabolic Agents for Diabetes WHICH CAN BE USED IN A TYPE 1 DIABETIC?
|
Pramlintide
|
|
|
WHAT ARE INCRETINS,
WHAT ARE THEIR EFFECTS WHAT BREAKS THEM DOWN? |
Incretins are intestinal hormones secreted in response to food intake
→ ↑ insulin secretion dipeptidyl peptidase BREAKS THEM DOWN |
|
|
YOU Dx PT WITH DM WHAT IS 1ST TREATMENT?
|
2 WEEK TRIAL OF DIET AND EXERCISE
|
|
|
IF DIET AND EXERCISE DOES NOT CORRECT DM WHAT IS NEXT STEP?
IF NORMAL DO THIS IF ABNORMAL DO THIS |
CHECK LFT
NORMAL --> CHECK KIDNEYS ABNORMAL--> START ON REGULAR INSULIN |
|
|
AFTER NORMAL LFT, YOU CHECK KIDNEYS, IF NORMAL _____
IF ABNORMAL ____ |
KIDNEYS:
NORMAL --> Rx METFORMIN ABNORMAL--> Rx ANY ORAL HYPOGLYCEMIC AGENT EXCEPT METFORMIN!!! |
|
|
DOC FOR TYPE 2 DM WHO IS OBESE, WITH NORMAL KIDNEY FUNCTION
|
METFORMIN
|
|
|
WHAT IS THE BIGGEST RISK OF A DIABETIC ON:
B- BLOCKERS |
HYPOGLYCEMIA
|
|
|
WHAT IS THE BIGGEST RISK OF A DIABETIC ON:
THIAZIDE DIURETICS |
HYPERGLYCEMIA
|
