Endocrine Pharmac😍

Prolactin Inhibiting Hormone (PIH) = Dopamine (DA)

• DA acts through D2 Receptors.

• Dopamine D2 Agonists decrease prolactin.
• Examples:
• Bromocriptine
• ↓↓ Insulin resistance → used in DM
• But cause Valvular fibrosis in heart
• Bromance ↓↓ pancharayadi () → but causes Heartbreak (Valvular fibrosis)
• Can be used in Pregnancy
• Cabergoline (Long acting)
• DOC: Pituitary adenoma/ Prolactinoma
• DOC: Supress Lactation
• Recent update → Can be used in Pregnancy 🗸
• Mnemonic: BCD (Bromocriptine, cabergoline, dopamine)

• Uses of Dopamine Agonists
• Dopamin: Diabetes mellitus type 2 (Bromocriptine)
• Agonists: Acromegaly (by decreasing GH)
• Suppress: Suppression of lactation
• Plasma: Parkinsonism (Bromocriptine can be used)
• Prolactin: Hyperprolactinemia in Pituitary Adenoma (Cabergoline)
• Bromance (Bromocriptine) → in Parkil (Parkinsonism) → Panchara (DM)

Treatment for Acromegaly

• Trans-sphenoidal surgery

• Relapse Management:
• Patients unfit for a second surgery: 
• Radiotherapy → Gamma knife stereotactic radiotherapy

• Decreased GH release:
• Somatostatin analogues
• Octreotide
• Lanreotide (Long acting octreotide derivative)
• Cabergoline
• Bromocriptine

• GH receptor antagonist:
• Pegvisomant
• S/E: Visual field defects
• Mnemonic: Peg () adichal kazhcha povum (Visual field defect) → Grow cheyyicha antiye (GH receptor antagonists) keripidikkum
• Mnemonic: Soman (somatotrophs) Peg (Pegvismoant) adichapo Kayyi veerthu vannu (spade like hand)

GHRH Analogue

• Tesamorelin
• HIV related atrophy

Insulin

• Indications:
• All patients with type 1 DM.
• Uncontrolled patients with type 2 DM.
• Diabetes in pregnancy.
• Diabetic Ketoacidosis.
• Hyperkalemia

• Routes of Administration:
• Subcutaneous (MC route):
• Self-administration possible.
• All insulin preparations can be given.
• Site of administration:
• Entire abdomen (except around umbilicus).
• Anterior thigh.
• Lateral thigh.
• Arm.
• Intravenous:
• Only regular insulin can be given.
• Insulin of choice in diabetic Ketoacidosis → Regular insulin.
• Inhalational:
• Afreeza → Short acting insulin → Given before every meal.

Methods of Insulin Delivery

• CSII (Continuous subcutaneous insulin infusion) / Insulin Pump
• most preferred

• Insulin pen (dose adjustable)

• Multi-dose vial

• Pre-filled syringes

Sites of Injection

• Upper outer arms

• Abdomen

• Buttock

• Upper outer thighs

Insulin pump (Best)

• Mimics artificial pancreas
1. Basal insulin → continuous secretion
2. Bolus insulin → mealtime, proportionate to carbohydrate intake

Insulin injection at same site

• lipoatrophy

Insulin Analogues:

• Rapid/Ultra short acting:
• LISPRO
• ASPART
• GLULISINE

• Ultra-Long/Long Acting:
• GLARGINE
• DETEMIR
• DEGLUDEC (Longest Acting)
• These are peakless insulins.
• Have low risk of hypoglycemia.

• Side Effects:
• Hypoglycemia
• Hypokalemia

Important

• Most preferred site:
• Anterior abdominal wall (2cm from umbilicus)

• Most preferred route:
• CSII

• MC side effect:
• Hypoglycemia

• β-blockers contraindicated
• they mask hypoglycemia

Types of Insulin

• Composed of two polypeptide chains:
• A-chain: 21 amino acids
• B-chain: 30 amino acids
• First protein:
• Completely sequenced (By Sanger).
• Produced by recombinant DNA technology.
• Zinc stabilizes insulin structure.
• Prolong insulin action

 

Somogyi Effect

• So much insulin at Night

• 4 AM: Sugar falls
• Early morning hypoglycemia
• d/t excess insulin at bedtime/less food

• Release of counter-regulatory hormone (Glucagon)

• Pre-breakfast hyperglycemia

• Red: Insulin levels in Somogyi effect

• Green: Insulin in Dawn phenomenon

Dawn Phenomenon

• Insulin sensitivity down in middle of night

• Decreased insulin receptor sensitivity (4–7 AM)

• 4 AM: Blood sugar rises (↓ GLUT-4 in T2DM)

• 7 AM: Pre-breakfast hyperglycemia

NOTE

• Pioglitazone → PPAR γ

• Saroglitazor → PPAR α + γ

• Lanifibranor → Pan PPAR (α + β + γ)

• Telmisartan, Losartan → PPAR-γ

• PPAR-γ (Proliferator-activated receptor γ)
• Nuclear receptor
• Helps differentiation of mesenchymal preadipocytes to adipose cells in peroxisome
• Also binds thiazolidinedione
• Class of insulin-sensitizing drugs
• Used in treatment of T2DM

• Mnemonic: PPAR γ
• ARBS
• Zones
• Fibrates → PPAR α
• Pappa Pappa movie → Animal (ARBS) → in Zoo (Zones)

Classification of Drugs

Special Points

• G means glucocorticoid (anti-inflammatory).

• M means mineralocorticoid (Na+ and H2O retaining)

Benefits

• decrease the risk of:
• RDS
• IVH, NEC
• Neonatal mortality

• Note: Does not decrease the risk of neonatal jaundice

• Administered to all pregnant women between 24 to 34 weeks of gestation

Contraindication

• Clinical chorioamnionitis

Replacement:

Other Uses:

• Inflammation

• Autoimmune diseases

• Transplantation

• Anticancer therapy except in Kaposi sarcoma

• Asthma

Drugs in Osteoporosis

• PTH stimulate Osteoclast → Cause osteoporosis

• Calcitonin inhibit Osteoclast → Prevent osteoporosis

• Drugs ending with “tide” → always IV

• Mnemonic:
• den OS mab , Rem OS mab
• → Antibody against osteoporosis

• Drugs used in osteoporosis
1. Nutritional factors:
• Calcium (1200 mg/day, includes dietary).
• Vitamin D (800 IU per day).
2. Drugs inhibiting osteoclast:
• Calcitonin
• Estrogens
• SERMs
• Denosumab
• Cinacalcet
• CasR agonist
• Used in HyperPTH
3. Drugs stimulating osteoblast:
• PTH1-34 → Teriparatide, Abaloparatide → Max: 2yrs (↑↑ R/o Osteosarcoma)
4. Drugs with Dual action:
• Strontium
• Romosozumab → Sclerostin ⛔ → Made in India
• Also Sodium fluoride

Drugs Inhibiting Osteoclast

1. Calcitonin: 
• Given Intranasally.
• S/E: Liver toxicity, Ca Breast

2. Bisphosphonates:
• Alendronate (oral)
• Risedronate (oral)
• Alan () rise () and eat
• Pamidronate (IV)
• Zoledronate (once yearly IV → Longest acting → S/E: Renal failure)
• Inhibit osteoclasts.
• DOC for
• Osteoporosis (any reason).
• Osteogenesis Imperfecta
• Pagets
• Indicated for a maximum of 10 years.
• 5 years → do bone scan → another 5 years
• IV agents can be also used for Hypercalcemia of malignancy
• S/E
• Osteonecrosis of mandible
• Phossy jaw
• Actinomyces → Discharging sinuses
• Radiotherapy
• Bisphosphonates
• Highly toxic to esophagus.
• Prevention of Esophagitis:
• Take empty stomach.
• Take with full glass of water.
• Remain upright for 30 min.
• Prolonged use (5-7 years)
• ↓↓ osteoclastic activity (below osteoblastic activity)
• → Atypical Fractures around the hip
• NEXT step: Do Xray, NOT DEXA
• Drug Holiday: 
• to avoid Atypical fractures
• Temporarily stop using bisphosphonates (1-2 years)
• switch to other drugs (e.g., Teriparatide)

3. Estrogen and SERM
• Decreased estrogen causes post-menopausal osteoporosis.
• Actions of Estrogen:
• Bone → Prevent resorption.
• Blood → Increased HDL/LDL Ratio.
• Breast → Increased Risk of Carcinoma.
• Endometrium → Increased Risk of Carcinoma.
• Liver → Increased Clotting Factors → Thromboembolism.
• Not preferred for treatment of post-menopausal osteoporosis.
• Raloxifene:
• Selective estrogen receptor modulator (SERM).
• Agonist action on ER in bone, blood, liver;
• antagonistic action on breast, endometrium.
• Used in post-menopausal osteoporosis.
• Reduces only vertebral # risk
• (Bisphosphonates reduce both vertebral and non vertebral)
• Additional Benefits:
• Increased HDL.
• Decreased Breast and Endometrial carcinoma risk.
• Major S/E:
• Thromboembolism.
• Tamoxifene → ↑ endometrial cancer risk

4. Denosumab:



• Monoclonal antibody → ⛔ RANK ligand.
• ⛔ osteoclastic activity and bone resorption.
• Mnemonic: Rank (RANK L) nu anserich Dinosaur (Denosumab) nte adth vidum → Clash cheyyan (Clast)

Drugs Stimulating Osteoblasts

Teriparatide:

• Fraction of parathyroid hormone (PTH 1-34)
• Intermittent low-dose PTH (Teriparatide) → stimulates osteoblast activity more than osteoclasts → bone formation.

• Used for osteoporosis treatment.

• Only anabolic agent for new bone formation

• Black box warning
• Use < 2 yrs
• ↑ risk of osteosarcoma
• Avoid in patients with increased risk of osteosarcoma
• Paget's disease
• Unexplained elevated ALP
• Open Epiphysis
• Prior radiation to skeleton

• Candidates
• Women with osteoporotic #
• Men with Primary or hypogonadal Osteoporosis
• Intolerant to other therapy

• Not effective orally
• OD subcutaneously

• Recommended for maximum 2 years.

• Treatment should be preceded or followed by bisphosphonates.

NOTE: PTH Action on Bone Cells

• PTH does NOT act directly on osteoclasts.

• Osteoclasts lack PTH receptors.

• PTH acts on osteoblasts → they release RANKL & M-CSF.

• These stimulate osteoclast differentiation and activation → ↑ bone resorption.

Drugs with Dual Action

• Stimulate osteoblast and inhibit osteoclast.

• Strontium ranelate and romosozumab.

• Romosozumab is a monoclonal antibody against sclerostin.

• Mnemonic: Romans (Romosumab) had Strong (Strontium) Bones

Oral Contraceptive Pills (OCPs):

Classification by Ethinyl Estradiol (EE) Dosing

• High dose: EE ≥ 50 mcg

• Low dose: EE = 30-35 mcg

• Very low dose: EE < 20 mcg

• Minimum effective dose: EE = 10 mcg

Non-Contraceptive Uses of OCP's

1. Irregular cycles: OCP is Drug of Choice (DOC)

2. Decrease blood loss in:
• Fibroids
• Adenomyosis
• Abnormal Uterine Bleeding (AUB)

3. DOC for:
• Primary dysmenorrhea
• Endometriosis (minimal to mild)
• Hirsutism
• Acne
• Hyperandrogenism

4. Manage premenstrual syndrome (PMS)
• OCPs are used but
• DOC for PMS: Fluoxetine (SSRI)

5. Progesterone in OCP's thickens cervical mucus, decreasing chances of:
• Pelvic Inflammatory Disease (PID)
• Sexually Transmitted Disease (STD)
• Ectopic pregnancy

• Most common PID with OCP use: Chlamydia

• Most common vaginitis with OCP use: Candidiasis

OCP's and Cancers

• Increases Risk
1. Hepatic adenomas
2. Breast cancer in perimenopausal females
3. Cervical cancer (Reversible risk)

• Decreases Risk
• Mnemonic: OCP → ↓ CEO cancer
1. Endometrial cancer
• Due to endometrial thinning and anovulation
2. Colorectal cancer
3. Ovarian cancer
• Due to anovulation
4. Ovarian cyst
5. Benign breast disease

• No Effect
• Liver cancer

Absolute Contraindications for OCP's (WHO Category 4)

• Mnemonic: Banks Have Various Schemes To Provide Home Loans During May
• Known/suspected breast cancer
• Uncontrolled hypertension (Severe ≥160/110)
• (Medically controlled hypertension in non-smoking female of any age is not a contraindication)
• Undiagnosed vaginal bleeding
• Smoker ≥35 years of age
• Known/suspected thromboembolism
• History of
• Cerebrovascular Accident (CVA)
• Myocardial Infarction (MI)
• Conditions predisposing to it
• malignancy,
• lupus anticoagulant present
• prolonged immobility due to trauma or surgery
• Family history of idiopathic thromboembolism in parent or sibling
• Pregnancy or history of peripartum cardiomyopathy
• Severe hypercholesterolemia, hypertriglyceridemia
• Presently impaired liver function/liver cancer/acute or chronic cholestatic liver disease
• Diabetes with vasculopathy
• Migraine with aura
• Also contraindicated in:
• Breastfeeding
• Post-partum females (<21 days)

Note on OCPs

• 1 pill/day

• Start between Day 1 and Day 5 of menstrual cycle

• Maintain high levels of estrogen and progesterone for 21 days

• Stoppage: Fall in estrogen + progesterone levels induces menses
• Day of menses is the new Day 1 for the next cycle

• Most common side effect:
• Irregular/Breakthrough Bleeding
• Most common with low-dose pills
• Due to less estrogen

• Elective surgery with anticipated immobilization:
• OCPs stopped 4 weeks prior.

• Return of fertility
• ≤ 3 months → Rapid

Mala N, Mala D: 

• Ethinylestradiol 30 mcg + Levonorgestrel 0.15 mg.
• 21 hormonal pills + 7 ferrous fumarate (Iron) tablets.
• EE → FF

• Mala N:
• Mnemonic: N → Nation → Free
• Free of cost, by GOI.

• Mala D:
• Mnemonic: D → Delivery
• Home delivery contraceptive by ASHA worker.

Missed Pill

Non-Contraceptive Benefits of OCPs (BENEFITS)

• O: Decreased Ovarian cyst (DOC for PCOD).

• B: Decreased Benign Breast Disease.

• E: Decreased Endometriosis.

• N: Decreased Neoplasia (Endometrial and ovarian cancers).

• E: Decreased Ectopic pregnancy.

• F: Decreased Fibroid.

• I: Decreased Iron deficiency Anemia.

• T: Decreased Premenstrual Tension Syndrome.

• S: Decreased Skeletal Disease (Osteoporosis).

Side Effect

• Increased Risk of:
• Cervical Cancer (Reversible)
• Breast Cancer.

• Decreased Risk of:
• Endometrial Cancer.
• Ovarian Cancer.

Polycystic Ovarian Disease (PCOD)

• OCPs are DOC for regulating menstrual cycle.

• Metformin used to reverse insulin resistance.

• Ovulation inducers used to induce ovulation.
• Aromatase inhibitors (e.g., Letrozole) is DOC.
• Clomiphene citrate can also be used.

POP

• Used where Combined OCPs cannot be used.

• Contains LNG.

• OCP of choice in lactation

• Taken every day of the month.

• No pill-free interval.

• Each pack = 28 pills (all active, no placebo).

Missed POP Pill

• Should be taken at the same time, daily.

• Delay in taking POPs:
• Backup method x 48 hrs, if > 3h late.

Vomiting/Severe Diarrhea

• If within 2 hours of pill intake → treat as missed pill.

Emergency Contraceptives: LOCUM

• Mnemonic:
• Ulli → Stone → Cent
• 30 → 50 → 60

• Drugs not used as emergency contraceptives:
• POP
• MIRENA
• Misoprost
• Minipill

• M/C MOA:
• Delayed ovulation.

• MOA of IUCD:
• Inhibits fertilization and implantation.

• Most effective hormonal EC:
• Ulipristal.

• Order of Effectiveness:
• Cu T (most effective) > Ulipristal > Mifepristone > LNG.

• Most effective when given:
• < 72 hours of unprotected sexual intercourse
• (Can be given up to 5 days after).

• If patient vomits after taking EC:
• Repeat EC.