The main endocrine glands are as follows:
The functions of the endocrine system are:
producing and secreting hormones
🞑 whichregulate body activities suchasgrowth,
development and metabolism.
maintaining the body during times of stress
contributing to the reproductive process.
1. Drugs Used in Diabetes
Lossof pancreaticBcells→ absolute dependence on
insulin(diet + insulin ± oral agents)
Usually adult onset
↓ response to insulin → (diet → oral hypoglycemics ±
🞑 Normally, K+ efflux inpancreatic β cellsmaintains
hyperpolarization of membranes, and insulin is released
only whendepolarization occurs.
🞑 Glucose acts as an insulinogen by increasing intracellular
ATP→ closure of K+ channels→ membrane
depolarization →↑ Ca2+ influx → insulin release.
🞑 Theacute action of sulfonylureas is to block K+ channels
→ depolarization → insulinrelease.
Drugs: Second generation:
🞑 Glyburide alsocalled Glibenclamide (5– 10 mg/ d)
🞑 Glipizide: has the shortest half-life (2–4 hours)
🞑 Glimepiride – long acting & potent
🞑 Gliclazide: has a half-life of 10 hours
Symptoms: lip/tongue tingling, lethargy, confusion,
sweats, tremors, tachycardia, coma, seizures
Treatment: oral glucose, IV dextrose if unconscious, or
glucagon (IM or inhalation)
Drug interactions mainly with1st generation drugs →↑
hypoglycemia with cimetidine, insulin, salicylates,
“Euglycemic,” ↓ postprandial glucose levels, but does not
cause hypoglycemia or weight gain
🞑 Metformin ↑ tissue sensitivity to insulin and/or ↓
🞑monotherapy or combinations (synergistic with
🞑possible lactic acidosis; GI distressis common
Pioglitazone And Rosiglitazone
🞑 bind to nuclear peroxisomeproliferator-activating
receptors (PPAR)involved in transcription of insulin-
responsive genes → sensitization of tissuesto insulin, plus ↓
hepaticgluconeogenesisand triglycerides and ↑ insulin
🞑 lesshypoglycemia thansulfonylureas,but still induceweight
gain and edema and have potential liver toxicity.
glucosidase inhibitors primarily act to decrease
🞑 by slowing the rate at which carbohydrates are
absorbed from the gastrointestinal tract.
They act by competitively inhibiting glucosidases
🞑 a group of enzymesintheintestinalbrushborder
epithelial cells (glycoamylase, sucrase, maltase, and
Agents Affecting Glucagon-like Peptide-1 (GLP-1)
GLP-1 is an incretin released from the small intestine.
It augments glucose-dependent insulin secretion.
🞑is a long-acting GLP-1 receptor full agonist
🞑used in combination with other agents in type 2
🞑S/Es: nausea, hypoglycemia when used with oral
Sitagliptin and Other Gliptins
🞑inhibits dipeptidyl peptidase (DPP-4) thereby
inhibiting the inactivation of GLP-1.
🞑 isSodium-glucoseCotransporter-2 (SGLT-2)Inhibitor in
the proximal tubule, increasing glucose excretion.
🞑 isa syntheticversionof amylin that ↓
the rate at which food is absorbed from the intestine,
glucose production, and
🞑 It isused in type 1 and type 2 diabetes.
Estradiol is the major natural estrogen.
ationale for syntheticsisto
↑ oral bioavailability,
↑ half-life, and
↑ feedback inhibition of FSHand LH.
🞑 Ethinyl estradiol and mestranol—steroidal
🞑 General: Nausea, Breast tenderness, Endometrial
hyperplasia, ↑ gallbladder disease, cholestasis, Migraine,
🞑 ↑ blood coagulation-via ↓ antithrombin III and ↑ factors II,
VII, IX, and X (only at high dose)
🞑 Cancer risk
↑ endometrial cancer (unless progestins are added)
↑ breast cancer—questionable, but caution if other
risk factors are present
Clomiphene (fertility pill)
🞑 Mode of action:
estrogen antagonist; ↓ feedback inhibition →↑ FSHand LH
→↑ ovulation→ pregnancy
🞑 Use: fertility drug
🞑 Dose:50 mgPO× 5 d; if noovulation ↑ to 100 mg × 5 d
@ 30 d later;
ovulation usually 5–10 d postcourse, time coitus with
expected ovulation time
🞑 Adverse effect:
↑ multiple births
Selective estrogen-receptor modulators (SERMs):
🞑Variable actions depending on “target” tissue
E-receptor agonist (bone), antagonist (breast), and
partial agonist (endometrium)
ossible ↑ risk of endometrial cancer
🞑 Usedinestrogen-dependent breast cancerand for
prophylaxis in high risk patients.
🞑 E-receptor agonist (bone), antagonist breast & uterus
🞑 When used in menopause, there is no ↑ cancer risk
🞑 Use:prophylaxis of postmenopausalosteoporosis,breast
Comparison of Tamoxifen & Raloxifene in Various Tissues
Drug Bone Breast Endometrium
Tamoxifen Agonist Antagonist Agonist
Raloxifene Agonist Antagonist Antagonist
🞑 Progesterone isthe major natural progestin.
🞑 Rationale for synthetics is ↑ oral bioavailability & half-
life relative to progesterone and ↑ feedback inhibition of
gonadotropins, especially LH.
🞑 Medroxyprogesterone (Depo-Provera)
🞑 Desogestrel isa syntheticprogestindevoid of
androgenic & antiestrogenic activities, commonto other
Norethindrone (0.35mg), Norgestrel (0.75mg)
⯈ Thesecontain low dose of progestin without any estrogen.
⯈ Theseare lesseffective than combined OCPs.
⯈ Breakthrough bleeding is as high as 25%.
⯈ Thickening of cervical mucusis major mechanismof minipills.
⯈ Minipills are preferred in women where estrogen is contra-
🗸Smokers, >35 years of age
isk factors of thromboembolism
⯈ Subdermal placement in the upper arm (contraception for
⯈ Contain etonogestrel (metabolite of desogestrel)
⯈ The implant is asreliable assterilization, and the
contraceptive effect is reversible when removed.
⯈ Progestin implants and intrauterine devices are known as
long-acting reversible contraceptives (LARC).
⯈ Adverse effects: irregular menstrual bleeding and
Progestin intrauterine device
⯈ Various levonorgestrel-releasing intrauterine devices offer a
highly effective method of contraception for 3 to 5 years.
⯈ It should be avoided in patients with pelvic inflammatory disease
or a history of ectopic pregnancy.
⯈ The levonorgestrel intrauterine device is a highly effective
treatment for heavy menstrual bleeding.
⯈ The non-hormonal copper intrauterine device provides
contraception for up to 10 years.
⯈ Thecontraceptive vaginal ring contains ethinyl estradiol and
⯈ Thering is inserted into the vagina and left in place for 3
⯈ After 3 weeks, the ring is removed, and withdrawal bleeding
occursduring the 4th week.
isa syntheticpreparation of thyroxine
identical structure to that of the natural hormone.
is the drug of choice for most patients who require thyroid
Absorption of oral levothyroxine is reduced by food.
should be taken on an empty stomachin the morning, at
least 30 to 60 minutesbefore breakfast.
can produce nearly normal levels of both T3and T4.
Thyroid peroxidase enzyme catalyzes three reactions
(oxidation, organification and coupling).
Carbimazole, methimazole and propylthiouracil act by
inhibiting this enzyme.
Carbimazole is a prodrug and acts after conversion to
is a first-line drug for hyperthyroidism.
safer and moreconvenientthanPTU,and henceis
preferred for most patients— except women who
are pregnant or breast-feeding.
ADRs: Agranulocytosis, hypothyroidism, avoid during
the first trimester.
🗸 PTUismuchlike methimazole, but withfour significant
PTUcan cause severe liver injury, but methimazole doesn’t.
PTUhas a shorter half-life than methimazole
PTUcrossesthe placenta less readily than does methimazole.
PTUblocks conversion of T4to T3in the periphery, whereas
🗸 There are three groups for whom PTUispreferred:
Pregnant women, but only during the first trimester.
(Methimazole is preferred during the second and third
Patients experiencing thyroid storm (Because PTUcan block
conversionof T4 to T3, it may be more effective than
Patients who are intolerant of methimazole.
🗸 Adverse Effectsof PTU
Themost commonundesired effect isrash.
Liver Injury (Liver toxicity is unrelated to dosage or
duration of treatment)
PTUmay alsocause nausea, arthralgia, headache,
dizziness, and paresthesias.
🞑Potassiumiodide plusiodine (Lugol’ssolution)
preoperatively →↓ gland size,fragility, and
🞑No long-term use because thyroid gland
“escapes” from effects after 10 to 14 days
I131: most commonly used drug for hyperthyroidism