Endocrine Pharm Flashcards
Cabergoline
Bromocriptine
Dopamine agonist
- DA from hypothalamus tonically inhibits Prolactin
- -prevent breast tenderness & engorgement
- -inhibit lactation
- -amenorrhea & galactorrhea
- –hyper-prolactinemia due to pituitary adenomas
- -paradoxically ↓ GH from GH-adenoma
- –DA usually ↑ GH release
- Cabergoline is more effective at ↓ prolactin
- -tolerated better
- -longer half life (2x week vs daily)
- may cause erythromelalgia*
- CI:
- -pregnancy unless they have prolactin-tumor
- -ergot related drugs
- -syncopal migranes
- inhibits excessive SNS tone (DIABETES)
- ↑ suppression of hepatic glucose production
- -↓ fasting & postmeal plasma FFA & TG levels
- ↓ cardiovascular end point problems in diabetics
Sermorelin
GHRH agonist
- GH deficiency treatment
- not as effective as GH
-determine origin of GH deficiency (hypo vs. pit)
Growth Hormone
- ↑ longitudinal bone growth
- ↑ mineral density after epiphyseal closure
- *↑ gluconeogenesis in hepatocytes
- *↓ glucose utilization in Muscle & Adipose (anti-insulin)
- *↑ lipolysis in adipocytes
- ↑ muscle mass → GH deficient individuals
- ↑ IGF-1 → most anabolic/growth effects
- -IGF receptor is RTK
- –binds insulin with 1/2 affinity
Somatropin
–Somatrem
GH agonist
- treat Growth Failure
- -GH deficiency (mainly children)
- -chronic renal disease
- -Turner’s syndrome
- cachexia im AIDS wasting
- ↑ GI function in short bowel syndrome
Adverse Effect:
- fluid retention, edema → ↓ w/ time
- musculoskeletal pain & stiffness
- Hyperglycemia → C.I. DM
- Hypothyroidism → C.I. hypothyroidism
- Somatrem is more immunogenic at **injection site
Mecasermin
IGF-1 agonist
- individuals who are not responsive to GH therapy (due to mutations of IGF or GH receptors, Ab to GH)
- -not as effective as GH therapy
- higher incidence of Hypoglycemia
- not FDA approved
Octreotide
–Lanreotide
Somatostatin analog
- ↓ secretion of pituitary & GI hormones
- -serotonin, gastrin, VIP, insulin, glucagon secretin
- -GH, thyrotropin
- ↑ intestinal absorptions of water & electrolytes
- ↓ pancreatic & gastric acid secretions
- ↑ intestinal transit time
USE:
- GH excess (acromegaly)
- other hormone secreting tumors
- excessive diarrhea
- ↓ tumor size/growth
ADVERESE:
- GI in 1/2 but subside
- gallstone & gallbladder sludge
- bradycardia, conduction disturbances
CONTRA:
- gall bladder disease
- DM
- thyroid problems (↓ TSH)
Pegvisomant
GH Antagonist
- return IGF-1 levels to NORMAL
- GH excess syndromes (acromegaly)
-may cause growth GH-secreting tumor (lack of neg feedback)
Gonadorelin
GnRH agonist–short acting
- pulsed IV administration → ↑ FSH & Prolactin release
- not available in US anymore
-treats infertility (ovulation & spermatogenesis)
-less likely to cause ovarian hyper stimulation & multi births
than direct LH or FSH
Leuprolide
- -Goserelin
- -Nafarelin
GnRH agonist–long acting (inhibits HPG activity)
- initially causes surge in of gonadotropin
- -tonic GnRH → ↓ receptors in pit & ↓ gonadotropin
- inhibits HPG axis activity
- -↓ testosterone & spermatogenesis
- *↓ androgen production in Prostate cancer
- *precocious puberty
- chemical castration
- treats endometriosis, PCOD, uterine leiomyomas
- Menopausal symptoms in women
- testicular atrophy in men
- -counter act testosterone sure w/ metastatic prostate tumors
-CI in pregnancy & breast feeding
Nafarelin is a nasal spray
Cetrorelix
–Ganirelix
competitive GnRH receptor antagonist
- suppresses LH → lower doses
- suppresses FSH → higher doses
- Suppression is used for Assisted Reproductive Technologies
- endometriosis & uterine fibroids
uFSH (Urofollitropin)
- -Follitropin alfa
- -Follitropin beta
FSH agonist
Follicular Phase
-FSH → development of ovarian follicles
→ estrogen synthesis (granulosa cells)
Men
-FSH → spermatogenesis & ABP in sertoli cells
Adverse Effect:
- ovarian enlargement
- Ovarian hyperstimulation syndrome (enlarge & fluid accum)
- Multiple births
- gynecomastia
- precocious puberty
uFSH → purified hMG; only FSH
- Follitropin is recombinant human FSH
- -more consistant
- -no urinary contaminants
hMG, Menotropins
gonadotropin mixture (used as FSH)
-isolated from urine of postmenopausal women
(no estrogen → no inhibition → ↑ FSH)
Human chorionic gonadotropin
- -Choriogonadotropin alfa (recombinant hCG)
- -Lutropin (recombinant LH)
LH agonist
-↑ w/ sustained high levels of estrogen
-LH → stimulates ovulation & luteinization of follicles
→ progesterone synthesis in luteal cells
→ testosterone synthesis in Leydig cells
- hCG first followed by hMG → male infertility
- hMG given first (9-12days) then hCG → ovulation
- hCG has longer half life than LH
- -differentiate b/w hypogonatotropic hypogonadism & constitutional delay of puberty (HH → no ↑)
-Lutropin only for use w. Follitropin alfa
Adverse Effect:
-ovarian enlargement
-Ovarian hyperstimulation syndrome (enlarge & fluid accum)
-Multiple births
-gynecomastia
-precocious puberty
Estrogen
- Ovary: prepare follicle cells for ovulation (w/ FSH)
- Uterus: endometrial cell division & growth (follicular phase)
- Vaginal epithelium proliferation
- Endocervical glands: regulates composition of mucus
- Breasts: ↑ ductal epithelial cells → pregnancy & puberty
- Puberty: 2º sex characteristics & closing of epiphysis
- -stromal & accessory sex organs in males
- Bone: maintain mass & prevent resorption
- Clotting: ↑ synthesis of cutting proteins & ↑ platelet adhesiveness
Metabolic: ↑ synthesis of liver proteins (binding globulins)
- ↑ HDL & ↓ LDL
- Na & H2O retention
Estradiol (endogenous)
Estrogen
- Primary hypogonadism–deficient pts age 11-13 → puberty
- postmenopausal HRT
- oral contraceptive
- suppress ovulation
- adrogen dependent cancers (prostate)
- -lowers serum testosterone → remission
Adverse: (dose dependent)
- migraines
- ↑ blood clotting and platelet aggregation (embolism
- HTN
- gallbladder disease
Contraindicated:
- estrogen dependent neoplasm (breast carcinoma
- thromboemoblic disorder
- pregnancy
- not orally active
- -creams or patches
Tamoxifen
–Toremifene ( ↑ HDL)
Anti-estrogen
-Selective estrogen receptor modulator (SERM)
- Antagonist → Breast
- –Agonist → Uterus & Bone
DOC: estrogen dependent breast cancer in premenopausal women
- in other tissues acts like AGONIST
- -prevents bone loss
- -may ↓ HDL
- -does not relieve hot flashes
-↑ risk of uterine cancer (agonist at uterus)
CI: Thromboembolic disease & Breast feeding
Raloxifene
Anti-estrogen SERM
- Antagonist → Breast and **Uterus (↓ uterine cancer)
- -Agonist → bone & liver
- **prevents post-menopausal osteoporosis
- ↓ RISK of invasive breast cancer
- -postmenopausal women w/ osteoporosis
- ↓ LDL in post-menopausal women
- may be used for HRT**
Adverse:
- hot flashes
- DVT, leg cramps
Clomiphene
Anti-estrogen SERM
- Antagonist → hypothalamus (inhibits neg. feedback)
- Agonist → everywhere else
- DOC: Infertility treatment in women w/ intact HPG axis
- -↑ LH and FSH secretion
- -reset ovarian responsiveness → ovulation
Adverse:
-multiple pregnancies
Fulvestrant
Anti-estrogen
- pure estrogen receptor antagonist
- treat Tamoxifen resistant tumors (breast cancer)
Anastrozole
–Letrozole
Aromatase inhibitor (aromatase only in granulosa cells)
- Non-steroidal competitive inhibitors of Aromatase
- breast cancer in post menopausal women?
*Exemestane
Aromatase inhibitor (aromatase only in granulosa cells)
-Steroid → irreversible inhibitor of aromatase
- DOC: breast cancer in postmenopausal women
- 2nd line for breast cancer in postmenopausal women whose cancer progressed during tamoxifen therapy
Adverse:
-Menopausal symptoms
Contra:
- Premenopausal women
- Pregnancy → category X
Progesterone
Progestin (Pregnane) (Tocolytic)
- Converts uterus to secretory state
- -needed to maintain pregnancy (↓ contractility)
- Endocervical glands → mucus composition
- Breast → lobuloalveolar development (preg. & puberty)
- ↑ body temp
-antagonize mineralcorticoid receptor
Use:
- *Oral contraceptive w/ or w/o Estrogen
- *prevent endometrial hyperplasia in HRT
- Treat: dysmenorrhea, endometriosis, hirsutism, uterine bleeding disorders
- -when Estrogen is CI
- ***-treat Endometrial cancer (mxn unknown)
Adverse:
- may ↓ HDL
- depression or drowsiness
TOCOLYTIC
- maintains length of pregnancy if given prophylactically from 16-37th week or delivery
- only use in women w/ history of birth <37 weeks
- not effective for acute preterm labor
–Desogestrel
Progestin (Gonane)
- selective progestin activity
- low to no androgenic properties
Mifepristone
Anti-progestin
- blocks binding of progesterone → progesterone receptor
- antagonizes glucocorticoid receptor → CUSHINGS
- terminates pregnancy
- -given w/ misoprostol
- prevent implantation if take w/in 72 hrs
CI:
- pregnancy or breastfeeding
- glucocorticoid therapy
Danazol
Anti-progestin
- Weak progestin, androgen and glucocorticoid →
- –suppresses ovarian function
-treat Endometriosis**
Adverse:
-hirsutism, deepening voice, acne, oily skin
Contra:
- liver dysfunction
- pregnancy or breastfeeding
–Drospirenone /ethinyl estradiol (Yaz)
Phenytoin, carbamazepine, StJW → ↓ effectiveness
OC ↓ effectivness of:
- anticoagulants
- anticonvulsants
- TCA
- guanethiden
- warfarin
- ORAL hypoglycemic agents
-combo of estrogen & spironolactone derivative
–mineralcorticoid antagonist
- ↓ water retention → reduces PMDD symptoms
- very low androgenic properties
- Inhibit ovulation → no LH surge
- ↓ implantation → change cervical mucosa & endometrium
- discontinuation → withdrawal bleeding at end of cycle
- ↓ endometrial & ovarian cancer
- ↓ acne
- ↓ PCOS
ADVERSE:
estrogen → weight gain, nausea, edema
Progestin → weight gain & depression
-thromboembolic & clotting disorders**
–↑ synthesis of coagulation factors & fibrinogen
–↑ risk of thromboembolic and clotting disorders
–↑ risk if >35 and smoke
-mild HTN
-Migraine (may be warning of stroke)
-Teratogenic - 1st trimester
-↓ Fertility → gonadotropin for 3 months after stopping
-Breast feeding
ABSOLUTE CI:
- *Thromboembolic phenomena
- *estrogen dependent neoplasms
- thrombophlebitis
- cerebrovascular disorders
- pregnancy
Testosterone
- -Methyltestosterone
- -Fluoxymesterone
- -Oxymethalone
- -Oxandrolone
Androgen
Virilizing (Androgenic) effects:
- spermatogenesis
- sexual development
Anabolic effects:
- ↑ bone density
- *↑ AA incorporation into muscle
- ↑ RBC mass
- antagonize catabolic effects of glucocorticoids
MEN → testicular deficiency
-avoid use for impotence in aging → ↑ risk prostate cancer
FEMALES → hypopituitarism (estrogen & androgens
-BOTH → protein loss
Adverse effects: MEN: -Inhibits release of LH and FSH --↓ testosterone production --↓ spermatogenesis WOMEN: -masculinization- deep voice, clitoral enlargement -loss of gonadotropins (atrophy of breast & uterus) -pregnant → pseudo-hermaphroditism BOTH -oily skin, acne -↓ HDL -psychological changes→ aggression, depression, psychosis
CI
-children → closes epiphyseal plate
Ketoconazole
Androgen synthesis inhibitor
-antifungal → need 4x anti fungal dose
- inhibits 17α hydroxylase → ↓ androgens then ↓ cortisol
- -higher dose inhibit cholesterol → pregnenolone (all steroids)
Women:
-hirsutism, premenstrual syndrome, cystic acne
Men
- prostate tumors
- SE of gynecomastia, ↓ libido, impotence
- HIGH DOSES in Cushing’s before surgery or radiation
- -**most effective inhibitor of steroid synthesis in pts w/ Cushings DISEASE (problem at pituitary; ↑ ACTH)
Spironolactone
Androgen synthesis inhibitor & Anti-androgen
- mineralcorticoid antagonist
- -competes w/ aldosterone for binding at low doses
- -competes for androgen & estrogen receptors at *↑ doses
- reduces 17α-OH activity→ ↓ glucocorticoids & androgens
Use:
- *hirsutism & PMS
- *precocious puberty (both sexes)
- HTN
- primary aldosteronism
- *ascites w/ cirrhosis
Adverse:
- hyperkalemia
- gynecomastia & impotence → men
- menstrual irregularites → women
Flutamide
- -Bicalutamide
- -Nilutamide
Anti-androgen
-↓ male accessory sex organ function
Use:
- prostate cancer w/ **Leuprolide (GnRH agonist)
- topically → male pattern baldness, hirsutism
Adverse:
- mild hepatotoxic
- Bicalutamide is less hepatotoxic
- -1x day dosing
- affects libido
Finasteride (Propecia)
–Dutasteride
5α-reductase inhibitors
- ↓ DHT
- ↑ testosterone
- ↑ TSH
- ↓ total serum PSA
- supress male sex accessory organ (prostate) w/o affecting libido
Use:
- BPH
- male pattern baldness
Adverse:
- impotence (ejaculation dysfunction too)
- ↓ libido
CI:
- pregnancy → teratogenic to male fetus
- may mask ↑ PSA due to prostate cancer
Corticotropin
-Cosyntropin
ACTH → ↑ glucocorticoids & androgens
- used diagnostically to distinguish b/w 1º (adrenal malfunction) and 2º (pituitary malfunction) adrenocortical insufficiency
- 1º = Addisons
- if ↑ in cortisol → pituitary problem
- no ↑ in cortisol → adrenal malfunction
Fludrocortisone
Mineralcorticoid–zona glomerulosa
(when and why)
- has both mineralcorticoid & glucocorticoid activity
- -high glucocorticoid
- -much more significant mineralcorticoid properties
- -(10 : 250)
- effects similar to aldosterone
- -↑ Na and H2O retention
- -↑ K and H loss
-use: salt-losing adrenogenital syndrome
–given w/ cortisone for replacement therapy in
–→ 1º adrenal insufficiency (problem w/ adrenal)
2º adrenal insufficiency → just cortisone
Aminoglutethimide
Mineralcorticoid synthesis inhibitor (tx cushing syndrome)
- inhibits cholesterol → pregnenolone (opposite of ACTH)
- -inhibits ALL steroid synthesis
- -inhibits aromatase enzyme– estrogen synthesis
-Tx in Cushing SYNDROME (not at pituitary)
–adrenal carcinoma or ectopic ACTH-tumor
-Tx Metastatic Breast and Prostate cancer that has not
responded to tamoxifen or anti-androgen
- can cause adrenal insufficiency → give w/ corticosteroids
- inhibits estrogen synthesis
- less effect on testosterone
Mitotane
Adrenocorticolytic (tx cushing’s DISEASE)
- selective atrophy of Zona Fasciculata & Reticularis
- -binds mitochondrial proteins → ↓ synthesis of corticosteroids
- 1º adrenal carcinoma when surgery or rad not possible
- can produce remission of Cushing’s DISEASE (at pituitary)
-severe GI distress
Metyrapone
Glucocorticoid synthesis inhibitor
- selective inhibitor of 11β-hydroxylase terminal enzyme in cortisol synthesis
- -↓ cortisol levels
- -↓ deoxycorticosterone → ↓ aldosterone
- -↑ 11-deoxycortisol → sustains aldosterone function w/o much glucocorticoid effect
- tests of adrenal function & short term management of Cushings
- only drug in this class → pregnant women
- hirsutism → androgen shunt
Glucocorticoid Effects
FAT, CHO, PROTEIN
- **↑ gluconeogenesis & glycogen storage → LIVER
- -catabolize protein → neg. nitrogen balance
- -↑ AA in blood
- -↑ activity & amount of enzymes
- **↑ Lipolysis
- -↑ plasma FFA
- **redistribution of body fat → moon face, buffalo hump
- **Antagonizes insulin → hyperglycemia & glycosuria
- -↓ glucose use in muscle and fat
CARDIOVASCULAR (can treat shock)
- ↑ vasc. responsiveness to SNS → hypertension
- ↑ cardiac output
- some Na and H2O retention → edema
- -↓ K+
ENDOCRINE
- immediate → ↓ release of CRH → ACTH
- Chronic → ↓ other endocrine systems
- -GH
- -LH → sex hormones → ↓ reproduction
- -TSH → Thyroid
- ↑ PTH → ↑ osteoclast → less Ca in bone
- Inhibits action of Vit D → ↓ Ca deposition into bones
- ↑ Epinephrine production in adrenal medulla
- ↓ catecholamine re-uptake
IMMUNE
- ↓ inflammatory & immunological responses (ulcers)
- -blocks all steps in inflammatory process
- -inhibits PLA2, COX2, Cytokines (TNFα), IgE (histamine)
- blocks early (edema, fibrin, PMN migration, phagocytosis)
- blocks late (collagen synthesis & deposition) wound heal
- Lympholytic effects (CLL & MM)
CNS
- mood elevation, insomnia, restlessness, anxiety
- depression or psychosis
GI
-peptic ulcers → ↓ immune response to H. pylori
Misc. side effects of long term use
- cataracts
- ↑ intraocular pressure
- glaucoma
- acne, skin atrophy/thinning, striae, bruising
CI → none for adrenocortical insufficiency -systemic bacterial infection -poorly controlled diabetes -osteoporosis peptic ulcer -heart disease or HTN w/ CHF
Hydrocortisone aka cortisol
-Cortisone (prodrug)
- EQUAL mineralcorticoid & glucocorticoid (1 : 1)
- replacement therapy → adrenal insufficiency
- -2º adrenal insufficiency (Addison’s)
- fludrocortisone → 1º insufficiency
- Cortisone is same except:
- -must be converted to hydrocortisone by liver
- -has 80% anti-inflammatory & sodium retaining potency
Prednisone (prodrug)
Prednisolone
Higher anti-inflammatory effects & minor salt-retaining
(4 : 0.3)
- Prednisone must be converted to prednisolone in liver to be active
- asthma treatment
Triamcinolone
Methylprednisolone
Highest anti-inflammatory effects & NO salt-retaining
(5 : 0)
-asthma treatment
Dexamethasone
–(Betamethasone?)
Highest anti-inflammatory effects & NO salt-retaining
(30 : 0)
- Cerebral edema
- -able to enter CNS
-used when endogenous cortisol levels have to be measured → doesn’t cross react
Fluticasone
Highest anti-inflammatory effects & NO salt-retaining
- most commonly prescribed glucocorticoid for:
- -INHALED and INTRANASAL use
Oxytocin
Uterine stimulant–DO
INDUCES LABOR at term → DOC --timed contractions-- on then off --augment labor --IV infusion PREVENTION of HEMORRHAGE --1st line is massage, then oxytocin? --IM route STIMULATION of MILK LET DOWN reflex --nasal application
ADVERSE
- water intoxication → ADH like effect
- uterine rupture (large dose)
- anaphylaxis
- sinus bradycardia of FETUS → extreme contractions
- -arrhythmias, fetal death
CI → any obstruction, scaring, or delivery complications
Ergonovine Maleate
–Methylergonovine Maleate
Uterine stimulant
- activation of 5HT & α-adrenergic receptors
- -→ contraction of uterine SM
- used AFTER labor and delivery of placenta
- -firm contractions → ↓ uterine bleeding
- -2º line after *uterine massage & *oxytocin → PPH
- NEVER use to induce labor → contractions too strong
- -→ fetal hypoxia
-Contra → Hepatic or Renal disease
Dinoprostone
Uterine stimulant
-synthetic prostaglandin E2
- expulsion of uterine contents: intrauterine fetal, **abortion
- -suppository
- CERVICAL RIPENING prior to delivery at term
- -gel to cervix
Adverse:
- ***-GI disturbances, vomiting diarrhea–can be very serious
- -only administer in presence of medical personnel
CI if mother or fetus have issues
- for abortions if pts has:
- -acute pelvic inflammation
- -acute cardiac, pulm, renal, hepatic disease
- -asthma, HTN, anemia, jaundice, or epilepsy
–Carboprost tromethamine
Uterine stimulant
-derivative of PGF2α
- abortion b/w 13-20th week (2nd trimester)
- treat PPH if 1) massage, 2) oxytocin, 3) ergots fail
Adverse:
-Vomiting and Diarrhea
CI for abortions if pts has:
- -acute pelvic inflammation
- -acute cardiac, pulm, renal, hepatic disease
- -asthma, HTN, anemia, jaundice, or epilepsy
Magnesium Sulfate
Tocolytic
- relaxes uterine muscle probably by direct effect–unkown
- used as **1st line drug depending on choice
- pre-eclamptic pts → prevent convulsions
- treat eclamptic pts (FDA approved)
-slowly given via IV → sig. hypoTN or systole if too fast
Nifedipine
Tocolytic (CCB)
- blocks L-type Ca channels → ↓ uterine contraction
- -starting to be 1st line tocolytic
-Do not combine w/ MgSO4 → CV collapse
Indomethacin
Tocolytic (NSAID)
- ↓ prostaglandin synthesis → PG lead to contractions
- -1st or 2nd line drug
ADVERSE
-partial closure of fetal ductus arteriosus
Nitroglycerin
Tocolytic
-Emergency use only → UTERINE RUPTURE only
Ethanol
Tocolytic
- Direct relaxant effect on myometrium
- inhibition of oxytocin release
-inhibits premature labor
*Thyroid hormones drug interactions
- Estrogen & tamoxifen ↑ TBG → ↓ effect
- Glucocorticoids & androgens ↓ TBG → ↑ effect
- Salicylates → displace thyroxine from TBG
- SNS stimulants → cardiotoxicity (weight loss)
- Iodides & Lithium → ↓ release or synthesis of T3/T4
- -Amiodarone contains iodide
- Antacids → ↓ absorption of thyroxine
- Phenytoin, carbemazepine, rifampin → ↑ metabolism
- Warfarin → hyperthyroidism ↑ degradation of vit K clotting factors → ↑ warfarin response (excess bleeding
Anti diabetic drugs → adjust dose for effects of T3
Corticosteroids → ↓ metabolism w/ hypo & ↑
Levothyroxine sodium
Sodium salt of T4
- DOC for treating hypothyroidism
- -may produce normal levels of T3 and T4
- -treat non endemic goiter, Hashimoto’s, thyroid carcinoma
- -Prevent goiter if taking drugs that interfere
- titrated to individual
- should keep TSH levels in normal range
- -TSH should be measured 4-6 weeks after adjusting T4
- ↑ gradually, esp w/ → myocardial dz or atherosclerosis
SE → symptoms of hyperthyroidism (looks like SNS stim)
DRUG INTERACTIONS
Liothyronine sodium
–Liotrix (4:1 → T4 to T3 → no advantage)
Sodium salt of T3
- Used for initial therapy of Myxedema (hypothyroidism) and myxedema coma
- -to achieve normal thyroid activity FASTER
- NOT for maintenance therapy
Propylthiouracil (PTU)
–Methimazole → DOC b/c no liver injury
Thioamide– hyperthyroidism treatment
- First line treatment for Graves disease
- ↓ synthesis of thyroid hormone in thyroid gland
- -↓ incorporation of Iodine, synthesis, prevent coupling
Methimazole → more potent & longer lasting
- -doesnt inhibit peripheral conversion (T4 → T3)
- -can cause birth defects
PTU → inhibits peripheral conversion → more rapid effect
- -LIVER INJURY OR FAILURE
- -should only be used if Methimazole can’t be
- -early pregnancy
- Granulocytopenia & agranulocytosis → most serious SE
- -first sign is SORE THROAT
- -reverses when drug is stopped
- Itching and skin rash
- Goiter due to ↑ TSH
Iodide
Hyperthyroidism treatment
- Excess Idodide → ↓ synthesis of T3 & T4
- -rapid ↓ in release of thyroid hormone
- ↓ vascularity & thyroid content → before thyroid surgery
- Prevents RADIOACTIVE iodine uptake
-not good solo treatment → wears of 2-8 weeks (thyrotoxicosis)
Radioactive Iodine
Hyperthyroidism treatment
-enters thyroid and gets trapped → β rays destroy tissue
- Hyperthyroidism in **elderly and **heart disease
- -low dose → diagnostic procedure
- -high dose → thyroid ablation
-causes hypothyroidism
Propanolol
β-blocker–Hyperthyroidism treatment
- ↓ S/S: tremor, tachycardia, anxiety, heat intolerance, sweat
- *-↓ peripheral conversion of T4 to T3 by liver
- -↓ potency of circulating thyroid hormone (specific to propranolol)
-used to prepare for surgery and waiting for other drugs to take effect
- CI in *asthma or *obstructive airway disease
- caution w/ diabetes
- VERAPAMIL if propranolol is CI
Vit. D
- -Cholecalciferol (D3)–skin
- -Ergocalcifero (D2)l–plants
- -Calcitriol–most active form
- binds to nuclear receptor → gene regulation
- stimulate osteoclast → RANKL
- ↑ intestinal Ca+ absorption (↑ phosphate too)
- ↓ renal Ca+ excretion (↓ excretion of phosphate too)
- ↑ bone resorption
- stimulate collagen synthesis in osteoblasts
- TX: osteomalacia, rickets, hypophosphatemia, hypoPTH
- ensure optimal Ca utilization
CAUTION w/ Sarcoidosis & Kidney stones
Calcium
- ↓ PTH secretion
- ALONE → can’t prevent or treat osteoporosis
- -needed for other treatment to work
- different rates of dissolution → varied absorption
- take throughout day (at least 2x)
- inhibits Iron absorption
- inhibits absorption of thyroid medication
CAUTION w/ Sarcoidosis & Kidney stones
Calcitonin (salmon calcitonin)
- ↓ bone resorption of Ca+ & phosphate
- -w/ time BOTH resorption & formation ↓
- antagonizes actions of PTH
- Prevent vertebral compression fractures (not other types)
- reduces back pain before change is seen
- INTRANASALLY or IV → destroyed in GI
- -allergic reactions
- -rhinitis & sinusitis
- -nausea & vomiting after INJECTION only
Teriparatide
Recombinant PTH
- MXN not fully understood–stimulates osteoblast & -clast
- -**intermittent spikes → ↑ formation > ↑ resorption
-Treat osteoporosis, ↓ fractures
- -**ONLY ANABOLIC osteoporosis therapy
- useful in pts w/ severely low bone mass
- -anabolic action ↓ w/ time
- treat hypoparathyroidism
-Hypercalcemia & Hypercalceiuria may occur
CI: OSTEOSARCOMA (caution if susceptible)
Denosumab
RANKL antibody
- inhibits RANKL → osteoclasts can’t mature
- -↓ bone resorption
- osteoporosis treatment in postmenopausal women w/ history of fractures
- ↑ bone mass and strength in cortical & trabecular bone
-1 injection/ 6 months
ADVERSE: hypocalcemia, cellulits, eczema
- suppresses bone FORMATION
- osteonecrosis of jaw w/ metastatic cancer
CI
ABSOLUTE: Hypocalcemia & pregnancy
Alendronate (oral) –100-1,000
- -Ibandronate (oral)– 1,000-10,000
- -Risedronate (oral)– 1,000-10,000
- -Etidronate (oral or IV)– 1
- -Zoledronic Acid (IV)– >10,000
- -Pamidronate (IV)– 100
Bisphosphonates
- Inhibit osteoclast activity and bone resorption
- replaces phosphate in Ca salt → blocks hydroxyapatite
- -strengthen bone, ↑ density
- -inhibit osteoclast resorption
-First line treatment for osteoporosis & paget’s disease
- oral absorption is very poor
- -take 2 hours before breakfast w/o Ca or Mg
- -4oz water to flush into stomach
- -remain upright 30-60 → ↓ GI irritation
IV- administer slowly → RENAL toxicity
ORAL adverse: abdominal pain, upper GI irritation, esophageal ulceration, constipation, diarrhea, flatulence
–not for pts w/ esophageal disease or can’t stand for 1 hr
ALL: nausea, vomiting,
–osteonecrosis of Jaw after major dental work
Cinacalcet
Calcium receptor agonist
- binds to calcium sensing receptor; esp. at parathyroid
- Blocks PTH release
- treat 2º hyperparathyroidism
- -chronic kidney disease & Parathyroid carcinoma
Albuterol
–Pirbuterol (better tolerated)
Short Acting β2 agonist (DoA 4-6 hours)
- fast acting → stop asthma attack in progress
- SM relaxation & stabilize mast cells
- DoA: 4-8 hours
SE: Tachycardia, nervousness & dizziness, tremor
- -short lived
- -tolerance develops
Levabuterol
Short Acting β2 agonist
- fast acting → stop asthma attack in progress
- SM relaxation & stabilize mast cells
-*more bronchodilation w/ fewer SE than albuterol
SE: Tachycardia, nervousness & dizziness, tremor
–short lived
Salmerterol
+ fluticasone (Advair)
Formoterol
+ mometasone
Long acting β2 agonist (DoA 12 hours)
- SM relaxation & stabilize mast cells
- used **prophylactically
- take 20 min to take affect
- -not for relief of Asthma attack in progress
-given w/ corticosteroid long term → ↑ sensitivity
SE: Tachycardia, nervousness & dizziness, tremor
- -short lived
- tolerance develops → down regulation of β2 receptors
*Ipratropim & Tiotropium
Muscarinic antagonist (why are SE minimal)
- not absorbed systemically → stay in lung (4ry ammonium)
- treat **COPD or Emphysema
- brochodilation develops more slowly than w/ β2 agonist
SE: cough, dry mouth, nausea
-potential ↑ in intraocular pressure
Tiotropium → longer DoA; 1x day use
*Theophylline
Brochodilator
- blocks adenosine receptors → ↓ bronchoconstriction & inflammatory mediators
- PDE inhibitor → ↑ cAMP → SM relax (Bronchodilation)
- -stimulated cardiac muscle
-low therapeutic index: OD → arrhythmia & seizures
- Phenytoin, rifampin, smoking, OC → ↑ clearance
- Cimetidine & erythromycin → ↓ clearance
SE:
CNS → nervousness & insomnia (like caffeine)
Cardiac → ionotropic & chronotropic→ tachycardia → arrythmias
Muscle → ↑ contractility of diaphragm ↓ fatigue
weak diuretic
Fluticasone
- -Budesonide
- -Flunisolide
- -Triamcinolone
- -Beclomethasone
Inhaled Corticosteroids
- ↓ inflammation and ↑ sensitivity to β agonist
- -effects begin w/in 1 week
- -very few side effects
–oral steroids for severe cases to bring symptoms under control
SE: oralpharyngeal candidiasis
- hoarsness
- small ↓ in bone density
Montelukast
- -Zafirlukast
- -Pranlukast
Zileuton
Leukotriene Inhibitor
- Block Leukotriene receptor
- -↓ asthmatic response to exercise & cold air
- -↓ need for steroids
Zileuton
- blocks 5-lipoxygenase → ↓ synthesis of LT
- -many ↓ asthma related to Aspirin or NSAIDS
- must be taken chronically
- will not stop an asthma attack in progress
SE: ↑ upper respiratory infections, sore throat, sleepiness
*Omalizumab
Asthma treatment
- IgE antibody → prevents binding to mast cells & basophils
- PREVENT allergic reactions
-SubQ injections → serious allergic & skin reactions
- Cromolyn sodium
- -Nedcromil
NOT a bronchodilator
- ↓ RELEASE of histamine from mast cells & prevent B-spasm
- treats asthma, esp. in CHILDREN
- used several times a day for prophylaxis
SE: BAD TASTE
Diphenhydramine (Bendryl)
Dimenhydrinate (Dramamine)
Promethazine
Sedating antihistamine (1st gen H1 antagonist)
- significant anti-ACh → motion sickness
- ↓ itch, Lewis triple response (flus, flare, wheal), edema
- ↓ salivary & lacrimal secretion
- small ↓ in bronchospasm
- small ↓ in vasodilation (H2 is still causing dilation)
**Promethazine → anti-emetic (DA, Musc, H1)
SE:
- sedation and ↓ motor skills
- CI in children
- dryness of mouth, urinary retention, constipation
- Teratogenic
- ↓ seizure threshold
- GI distress → ↓ if given w/ food
-AVOID Alcohol & CNS depressants
OD → atropine poisoning (excitement, convulsions, fixed dilated pupils)
Loratadine (Claritin)
–Deslortadine (active metabolite)
Non-sedating antihistamine (2nd gen H1 antagonist)
- do not enter brain → mainly peripheral receptors
- NOT anti-ACh
- -non-sedating & fewer side effects
- ↓ itch, Lewis triple response (flus, flare, wheal), edema
- small ↓ in bronchospasm
- small ↓ in vasodilation (H2 is still causing dilation)
-better at PREVENTING allergic rxn than treating them
- Teratogenic
- ↓ seizure threshold
- GI distress → ↓ if given w/ food
- AVOID Alcohol & CNS depressants
- Erythromycin & Ketoconazole may ↓ metabolism (3A4)
OVERDOSE → cardiac arrhythmias
Cetirizine (Zyrtec)
- -levocetirizine
- -acrivastine
Non-sedating antihistamine (2nd gen H1 antagonist)
- ONLY eliminated by the KIDNEY
- -avoid drug interactions or liver disease
- may inhibit release of histamine from mast cell
Azelastine
Nasal H1 antagonist
Non-competative H1 blocker
-↓ RELEASE of histamine from mast cells
-Allergic rhinitis
Magnesium Hydroxide
Aluminum Hydroxie
Acid-neutralizing agent / Osmotic laxative
- Magnesium→ ↑ gastric motility → diarrhea
- Aluminum → relax SM & ↓ gastric motility → constipation
- -combine to cancel out effects
- less absorption than bicarbonates
- form complexes and ↓ absorption of iron other drugs
- ↓ bioavailability of phenytoin, digitalis, propranolol
- alkalize urine → ↑ elimination of salicylate & phenobarbital
-toxicity may occur if renal function impaired
Cimetidine (Tagamet)
Ranitidine (Zantac)
–Famotidine
–Nizatidine
H2 antagonist
- Block H2 → ↓ H+,K+ ATPase pump → ↓ H+ ions
- -most effective ↓ NOCTURNAL acid formation
- treatment: duodenal & gastric ulcers, GERD, ZE syndrome
- pre-op → ↓ acidity incase of aspiration
- prevent development of stress ulcers
- *Severe allergic reactions → ↓ H2 mediated vasodilation along w/ H1 antagonist
SE: headache, dizziness, nausea
-↓ bioavailability of drugs absorbed at low pH
CIMETIDINE
- chronic high doses → anti-androgen effect
- -↓ libido, impotence, impotence
- treat masculinization (hirsutism)
- Inhibits CYP3A → ↓ metabolism of many drugs
- -warfarin, phenytoin, theophylline, phenobarbital, digoxin, quinidine, TCA, propanolol, nifedipine
Omeprazole (Prilosec)
- -Esomeprazole*
- -Lansoprazole*
- -Rabeprazole*
- -Pantoprazole*
PPI
- Irreversibly inhibit H+,K+ ATPase pump
- prodrugs → become active & trapped in Parietal cells only
- -highly lipophilic
- takes 2-5 days for full effect → lasts 1-2 days
- given for long periods – 1-2 months
- take on empty stomach ~30 min before meal
- best absorbed at alkaline pH
- DOC: GERD w/ esophagitis
- prevent GERD
- gastric & duodenal ulcers (prevent due to NSAIDS)
- high doses → Zollinger-Ellison syndrome
Adverse:
- GI effect: nausea, diarrhea, abdominal colic
- ↓ absorption of Calcium & Magnesium
- ↑ cough & URT infections (Pneumonia)
Omeprazole inhibits CYP2C19 → ↓ metabolism of
- -Phenytoinm diazepam, *warfarin,
- inhibits conversion of Clopidogrel
Misoprostol
Cytoprotective agent (PG analog)
- PG E1 analog → ↑ secretion of mucus & ↓ acid
- prevents ulceration due to NSAIDS
CONTRA → PREGNANCY → can induce contractions and cause abortion
Metoclopramide
- -Bethanechol → muscarinic agonist
- -Erythromycin → motilin
Prokinetic agent (D2 antagonist)
- blocks D2 → ↑ ACh release → ↑ motility & tone
- Antiemetic → acts on chemoreceptor trigger zone
- *Side effects:
- high doses → extrapyramidal symptoms, exacerbation of Parkinson’s
CI in pregnancy → methemeglobinemia in neonates
Dicyclomine
- -Glycopyrrolate
- -TCA
Antispasmodic (Antimuscarinic)
- Block M3 → ↓ intestinal overactivity, cramping, spasm
- -slightly ↓ acid secretion from ↓ Vagal activity
-SE: dry mouth, sedation, constipation
TCA → anti-muscarinic → treat IBS
Ondansetron
-setron
Anti-nausea / -emetic–Serotonin antagonist
- Selectively blocks 5HT3 receptors in CTZ & GI tract
- prevent vomiting due to
- -Chemotherapy & vagal stimulation
- -NOT effective → motion sickness
Receptors in the Chemreceptor trigger zone (CTZ)
- 5HT3
- D1
- Neurokinin 1
- Opioid receptors
Psyllium
Methylcellulose
Bulk-forming Laxative
SE: bloating and flatulence
Senna
Laxative
- stimulates peristalsis by action on mucosa of colon
- very mild
Lactulose
Osmotic Laxative
- disaccharide that can’t absorbed → ↑ osmotic pressure
- metabolized by colonic bacteria → lactic acid
- -gas, flatulence, abdominal dissension
- acidic environment → ionized ammonia to ammonium
- -traps it in colon → ↓ ammonia build-up w/ cirrhosis
Polyethylene glycol (Miralax)
Osmotic Laxative
-used in prep for colonoscopy or intestinal procedures
Lubiprostone
Anti-Constipation (PGE1 derivative)
- activates ClC-2 Cl- channels → ↑ intestinal fluid secretion
- -softens stool & ↑ intestinal motility
- reduces symptoms of chronic constipation
- -bloating, straining, hard stools
- doesnt alter electrolyte concentrations
Loperamide (Imodium)
–Diphenoxylate + atropine (CNS effects)
Antidiarrheal (opioid derivative)
- ↓ peristalsis by constrict circular m. & relax longitudinal m.
- -NO CNS effect → low abuse potential
CI:
- diarrhea due to organisms that penetrate intestinal mucosa
- -allows more time to invade
- Ulcerative colitis → toxic megacolon
Simethicone
Antiflatulent
-coats & dissipates gas
Octreotide
Somatostatin analogue
- ↓ release of gastrin, CCK, serotonin, histamine
- -↓ intestinal & pancreatic secretion
- -↓ GI motility & gallbladder contraction
- -↓ portal & splanchnic blood flow
Treats carcinoid & VIP tumors
Bismuth subsalicylate (Pepto Bismol)
- absorbs excess water
- -may absorb some microbial toxins
- -may destroy some pathogens
- Salicylate → ↓ PG synthesis → ↓ secretion & anti-inflamm
- Treats travelers diarrhea & other non-specific causes
CI: salicylate allergies & children → Reye syndrome
SucrALfate
Cytoprotective
- polymerizes in stomach acid → binds epithelium & exposed proteins from ulcer
- → forms a PROTECTIVE barrier
- may cause constipation → ALUMINUM
NAT2 (gain of function)
N-acetyltransferase 2 gene
-transfers acetyl to amine → amide on drug
Qualitative not quantitative difference
<>Slow acetylator alelle → recessive (r/r only)
- -Lupus → procainamide & hydralazine
- -Hepatoxoicity → isoniazid
<>Rapid acetylator allele → dominant (R/r or R/R)
–Isoniazid, hydralazine, procainamide, sulfonamide, dapsone
CYP2D6 (gene copy number)
second most important P450 enzyme
-SSRI, TCA, opioids
Metabolizers
-poor, intermediate, extensive (normal), ultra-rapid
H1
H2
H3
H4
- H1 → Gq → SM, endothelium, hypothalamus
- H2 → Gs → stomach, SM, heart, brain
- H3 → Gi → presynaptic in brain
- H4 → Gi → leukocytes in BM & blood
histamine actions
- vasodilation → hypoTN & shock (H1 & H2)
- tachycardia
- edema (H1)
- bronchospasm & ↑ secretions of lung (H1)
- ↑ gastric acid & pepsin
- ↑ catecholamine in high doese
- flush, flare, wheal
