Steroids, drugs acting on 🦴 Flashcards
Hydrocortisone
Least glucocorticoid effect, so t1/2 is just 8-12 hr
Effects:
Glucocorticoids x1
Mineralocorticoid x1
Prednisolone and
Methyl prednisolone
1. Prednisolone: • Adding double bone to hydrocortisone • Oral • GC x4 & MC x0.8 2. Methyl prednisolone: • IV • GC x5 & MC x0.8
Fludrocortisone
Add F to hydrocortisone GC x15, but MC *150 Most potent MC in MC receptor But aldosterone has max M/C activity and it is a pure MC with MC x500
Steroids with bone double bond and F
Pure GC like: 1. Triamcinolone: • GC x5 • t1/2 12-36 hr 2. Betamethasone & Dexamethasone (most potent): • GC x30 • Both have max GC effect • t1/2 36-72 hr
Combining propionate, valerate & butyrate with clobetasol steroid
🔼 lipids solubility ➡️ topical use Potency depends on: 1. Formulation Ointment 🧴 > cream 2. Functional group Most potent topical steroid: clobetesol propionate
Combining dipropionate functional group with steroids (like beclomethasone)
Inactivates steroids
Inhalation route
Activated in lung by esterase ➡️ 🔽 risk of oropharyngeal candidiasis
Steroids effects
1. Glucose Lemon on stick, 🔼 DM 2. Musculoskeletal 3. GIT: gastric ulcer 🔼 4. Ocular 5. Skin & hair: thinning 6. 🤰: surfactant, … 7. Bone marrow 8. CNS: 🔼 psychosis,… 9. Anti-neoplastic effects: ALL, NHL
Steroids and glucose & GIT
- 🔽GLUT-4 ➡️ 🔼insulin ➡️ 🅱️HSL ➡️ 🅱️ lipolysis ➡️:
• Thinning of limbs due to muscle breakdown
• Buffalo 🦬 hump and trunkal obesity
Lemon 🍋 on stick appearance - Insulin resistance ➡️ 🔼DM
- GIT:
🅱️ PG synthesis ➡️ 🔼 gastric ulcer
Steroids and musculoskeletal system
- Osteoporosis
- Growth retardation in children
- Myopathy
Steroids and 👁
Use:
Topically for inflammation like uveitis, optic neuritis, choroiditis
CI: HSV keratitis
can cause irreversible clouding of cornea
S/E:
1. Topical: glaucoma
2. Systemic: cataract
Steroids and 🤰
- Maturation of surfactant in premature labor:
• Dexamethasone: DoC
6 mg 12 hourly, 4 doses
• Betamethasone: best drug (less risk of peri ventricular leukomalacia of newborn)
12 mg 24 hourly, 2 doses - Dexamethasone used in 🤰 with congenital adrenal hyperplasia baby to prevent virilisation
Dexamethasone is preferred during pregnancy for fetal lung maturation, but not
prednisolone
Prednisolone is converted to its inactive form prednisone by placental 11-βHSD. Immature
fetal lung cannot activate prednisone into prednisolone.
Dexamethasone is a poor substrate for placental 11-βHS resulting in its poor placental
metabolism along with low maternal protein binding. Thus, there is an increased transfer
of dexamethasone across the placenta to the foetus. Hence it is preferred
Steroids on skin/hair, CNS and bone marrow
Skin/hair: Thinning of both ➡️ bruises and striae Bone marrow: 🔼 RBC & neutrophil ➡️ 🔽rest CNS: Neuropsychiatric effects: psychosis, depression, insomnia
Steroids and immunomodulatory and anti-inflammatory effects
mechanisms
- 🅱️ production of inflammatory mediators:
IL-1, IL-6, TNF-α - 🔼 production of anti-inflammatory mediators:
Annexin-1, IL-10 - Lymphocytes:
apoptosis and redistribution
Steroids and immunomodulatory and anti-inflammatory effects
side effects, contraindications and uses
S/E: opportunistic infections CI: Active infection except H. influenza meningitis Uses: autoimmune and inflammatory disorders
Mechanism of bone 🦴 resorption
- PTH / interleukin / vit D3 stimulates osteoblast
- Osteoblasts using its RANK ligand stimulates RANK receptor of osteoclast
- Structural change in bone leading to ruffled borders
Mechanism of bone material deposition
- Bone resorption ➡️:
• BMP (🦴 morphogenic protein)
• PG
• IGF-1 - They stimulates osteoblasts which rush to site of bone damage
- Induced bone formation
📝: activated osteoclasts secrete sclerostin which 🅱️ this process
Treatment of osteoporosis
1. Inhibit 🦴 resorption: • Denosumab: 🅱️ RANK • Bisphasphonates: apoptosis • SERMs like raloxifene • Salcatonin 2. Stimulate 🦴 formation: • PTH analogues • Anti-sclerostin Mab 3. Does both: strontium ranelate
Denosumab
RANK ligand mab
sc route for 3-5 years
Uses:
1. Drug resistant post-menopausal osteoporosis
2. Giant cell tumour
3. Hypercalcemia associated with malignancy/ hyperparathyroidism
4. Prevention of 🦴 metastasis in prostate cancer
Denosumab
side effects
- Osteoporosis of jaw (contradictory)
- Femur fracture
- Dermatitis
- 2° cancer
- Pancreatitis
Bisphosphonates
Mechanism and examples
Induces apoptosis of osteoclasts Drugs: 1. Oral: Alendronate: glucocorticoid induced Risendronate Ibadronate 2. Parenteral: Zoledronate: longest acting and most potent Pamidronate
Bisphosphanates
properties, pharmacokinetics and contraindications
All drugs 🔽 risk of vertebral and non-vertebral fractures except ibadronate which 🔽 risk of cerebral fractures only
Oral drugs reduce food absorption ➡️
They are taken on empty stomach
CI: renal failure
Bisphosphonates
uses
- DoC for osteoporosis
duration: 3-5 years
t1/2: 10 years - Glucocorticoid induced osteoporosis:
alendronate - DoC for Paget’s disease
- DoC for hypercalcemia of malignancy and hyperthyroidism
Preferred drug is zoledronate
Bisphosphonates
side effects
1. Esophagitis: oral drugs Take the drug with full glass of water and not lie down for at least 30 min 2. Osteonecrosis of jaw max with zoledronate 3. Hypocalcemia: max with bisphosphonates (esp zoledronate) faster with salcatonin 4. Seizure (hypocalcemia) 5. Femoral chalk stick fracture
SERM
selective estrogen receptor modulator wrt 🦴
- Raloxifene:
• Rx and prophylaxis of post-menopausal osteoporosis
• S/E: thrombosis, hot flushes - Bazedoxifene:
Prophylaxis of post menopausal osteoporosis (along with estrogen) in patients with intact uterus
Salcatonin
Calcitonin analogue Uses: 1. SC for Paget’s disease 2. IN for prophylaxis of osteoporosis 3. Analgesic effect in vertebral fracture S/E: 1. Fastest drug to cause hypocalcemia 2. 🔼 risk of liver cancer (but 🔽 risk of breast cancer)
PTH analogues
drugs and mechanism
Teriparatide: PTH analogue
Abolaparatide: PTH related peptide analogue
Mechanism:
Bone resorption (transient hypercalcemia) ➡️ 🔼 bone formation (supplement Ca2+)
PTH analogues
uses
Uses: SC
- Osteoporosis of hypogonadism in post-menopausal 👱🏽♀️ and 👨🦰
- Severe osteoporosis (in 🔼 risk of fracture)
- Bisphosphonate induced femoral chalk stick fracture
PTH analogues
side effects
1. Osteosarcoma (🕋 ⚠️) CI in Paget’s disease Max duration of therapy: 2 yr 2. Hypotension 3. Pneumonia
Strontium ranelate
Strontium resembles Ca2+
Mechanism:
1. Movies into bone matrix ➡️ 🔼 bone formation
2. Osteoclasts can’t remove strontium ➡️ 🔽 bone resorption
Use: osteoporosis
Plicamycin
Aka mithramycin Inhibits bone resorption Uses: 1. Paget’s disease 2. Hypercalcemia
Romosuzumab
FDA approved in 2019
Anti-sclerostin mab ➡️ 🔼 🦴 formation
Uses:
Osteoporosis in post menopausal female with high risk of fracture
Inhalational steroids has less systemic side effects, even though most of drug enters
GIT
After reaching the GIT, steroids will undergo high first pass metabolism in liver, so the
minimum amount of drug only will reach the systemic circulation. Inhalational steroids like
beclomethasone have very short t1/2 after they enter blood, so the systemic toxicity is
reduced
Glucocorticoids are administered before thyroid in cases of initiation of therapy for
panhypopitutarism
Thyroid hormones increase the metabolism of cortisol. So glucocorticoids are administered
before thyroid hormone replacement to avoid acute adrenal insufficiency
