PHARM - Osteoporosis, Thyroid, Diabetes

Question 1

non-pharmacological Tx for osteoporosis

Answer 1

• manage risk factors e.g. lack of sunlight, smoking, alcohol
• physical exercise to strengthen bones and muscles
• Ca2+ and vit D supplementation (limited evidence for Ca2+ supplement, only use if insufficient dietary intake)

Question 2

when should you consider osteoporosis Tx?

Answer 2

• presence or Hx of osteoporotic fracture
• BMD T score < -2.5

Question 3

3 things to take into consideration BEFORE pharmacological Tx of osteoporosis

Answer 3

• exclude a secondary cause e.g. malabsorption, hyperthyroidism
• evaluate risk factors e.g. diet, physical activity, smoking
• fall prevention: balance training, medication management etc.

Question 4

2 classes of drugs for osteoporosis + e.g.s

Answer 4

• antiresorptive agents (prevent breakdown of bone) e.g. bisphosphonates, denosumab, oestrogen, SERMs
• bone anabolic agents (stimulate bone formation) e.g. human PTH (teriparatide)

Question 5

bisphosphonates
- MOA
- indication
- A/Es
- e.g.s

Answer 5

• MOA: toxic to osteoclasts = decreased resorption
• indication: 1st line Tx for postmenopausal osteoporosis
• A/Es: jaw osteonecrosis, atypical fractures, flu-like symptoms if IV
• e.g. alendronate

Question 6

strategies to avoid GIT upset and increase bioavailability with oral bisphosphonates and why could this be problematic?

Answer 6

• prevent GIT upset: don’t chew, drink with a full glass of water, stay upright for 30-60 mins afterwards
• bioavailability: separate from other meds, take on an empty stomach, take early in the morning
• could be problematic due to low compliance in elderly ppl

Question 7

how long should bisphosphonates be taken for and why?

Answer 7

• 5-10 yrs (oral) or 3-6 years (IV) and then have a drug holiday since benefits maintained for 12 months after discontinuation
• monitor BMD and restart medication if necessary

Question 8

denosumab
- MOA
- indication
- mode of administration
- A/Es

Answer 8

• MOA: binds to RANKL on osteoblasts = inhibits RANK receptor on osteoclasts = reduced number and resorptive function of osteoclasts
• indicated in osteoporosis, only when bisphosphonates aren’t appropriate
• 6-monthly subcutaneous injection
• A/Es: risk of vertebral fracture on withdrawal, must continue forever or replace w/ bisphosphonate

Question 9

oestrogen + SERMs
- MOA
- A/Es

Answer 9

• MOA: inhibits osteoclasts and promotes osteoblast action
• A/Es: risk of thromboembolism (both) or breast cancer (oestrogen only) = therefore not used for osteoporosis

Question 10

teriparatide (PTH) for osteoporosis
- MOA
- indications
- A/E

Answer 10

• MOA: PTH paradoxically stimulates osteoblasts at low doses = increased bone formation
• indications: only if very high Fx risk and all other osteoporosis Tx contraindicated
• A/E: treatment restricted to 18 months due to potential risk of sarcoma, hypercalcaemia, hyperuricaemia

Question 11

compare carbimazole and propylthiouracil
- what do they do?
- which one is first line
- which has a longer duration of action

Answer 11

• both are thionamides used for the Tx of Graves’ disease
• propylthiouracil also reduces peripheral conversion of T4 > T3
• carbimazole = 1st line, whereas propylthiouracil used if intolerant OR 1st trimester of pregnancy
• carbimazole has a longer duration of action

Question 12

thionamides
- MOA
- indication
- A/Es
- e.g.s

Answer 12

• MOA: inhibit iodine binding to tyrosine on thyroglobulin = decreased T3/T4 synthesis
• indication: Graves’ disease or prior to thyroidectomy
• A/Es: can cross placenta and enter milk (congenital hypothyroidism = goitre, cretinism), rashes, headaches, nausea, jaundice, agranulocytosis
• e.g. carbimazole (1st line) and propylthiouracil (if intolerant or in 1st trimester of pregnancy)

Question 13

agranulocytosis

Answer 13

• A/E of thionamides
• reduced granulocytes e.g. neutrophils > immunocompromised Pts more susceptible to infection (= fever, mouth ulcers, sore throat, rash)
• rare, rapid onset but can be reversible if treated quickly

Question 14

why can the effect of thionamides take a few weeks to kick in? what can we do in the meantime

Answer 14

• they decrease thyroid hormone synthesis but the thyroid has stores of hormones which can take weeks to deplete
• in the meantime, symptomatic Tx e.g. non-selective B blockers for tachycardia (B1), tremors and agitation (B2)

Question 15

excess iodide
- MOA
- indication
- A/Es
- C/I

Answer 15

• MOA: high dose inhibits T3/T4 secretion due to -ve feedback to prevent toxicity, decrease vascularity and gland size
• indication: short-term Tx of hyperthyroidism or prior to thyroidectomy
• A/Es: may worsen Sx, allergic
• C/I: pregnancy + breastfeeding, autonomous thyroid tissue

Question 16

what can be done to treat hyperthyroidism if pharmacological Tx doesn’t work? + A/Es

Answer 16

• destroy thyroid cells w/ surgery or oral radioactive iodine
• A/Es: Pt left radioactive temporarily, N&V

Question 17

issue with treating hyperthyroidism

Answer 17

• can develop reactive HYPOthyroidism due to loss of thyroid cells (e.g. radioactive iodine, surgery), iodine deficiency or Hashimoto’s thyroiditis (autoimmune)

Question 18

hypothyroidism first line Tx
- A/Es
- 2nd line

Answer 18

• first line: oral T4 (thyroxine) = longer duration of action than T3
• A/Es: risk of angina, arrhythmias, CHF, osteoporosis in elderly Pts so start w/ small dose
• 2nd line: IV T3 for speed e.g. myxoedema coma

Question 19

main Tx for T1DM + diff types

Answer 19

• subcutaneously injected insulin (not oral b/c poor bioavailability), trying to replicate normal physiological action
• basal insulin = long acting for between meals inc. overnight
• bolus insulin = short/intermediate acting for mealtime
• can use combined short/intermediate acting syringe for compliance

Question 20

endogenous vs exogenous insulin
- onset of action
- where is it cleared by?

Answer 20

• endogenous: rapid action, mostly cleared by liver
• exogenous: subcutaneous admin = slow absorption and onset, mostly cleared renally

Question 21

3 methods of injecting insulin

Answer 21

• syringe
• portable pen injectors
• continuous subcutaneous insulin infusion (CSII) pump using pre-programmed and user-programmed insulin delivery

Question 22

metformin
- MOA
- indications
- A/Es
- C/I

Answer 22

• MOA: increases tissue sensitivity to insulin and stops gluconeogenesis (doesn’t cause production of insulin = no hypoglycaemia)
• indications: ALL T2DM Pts unless not tolerated or contraindicated
• A/Es: weight loss (h/w may be good considering they’re probs obese anyway), nausea, diarrhoea
• C/I: renal issues

Question 23

when would you need to use additional therapies on top of metformin for T2DM?

Answer 23

• if HbA1c is significantly (>1.5%) above target, OR if the Pt has other risk factors for CVD/CKD

Question 24

two additional diabetes drugs w/ benefit for CVD/renal disease

Answer 24

• CVD or CKD: GLP-1 agonist or SGLT2 inhibitor
• CHF: SGLT2 inhibitor

Question 25

GLP-1 (glucagon-like peptide) agonist - class - method of administration - MOA - indications - A/Es - e.g.

Answer 25

- incretin mimetic - injected - MOA: mimic effects of GLP-1 to promote insulin release - indications: T2DM with risk of atherosclerotic CVD or CKD - A/Es: hypoglycaemia (when combined w/ sulphonylurea or insulin), N/V/D, abdominal pain - e.g. dulaglutide

Question 26

sodium-glucose cotransporter 2 (SGLT2) inhibitors - MOA - indications - A/Es - e.g.

Answer 26

- prevent reabsorption of glucose in PCT = decreased BP and BGL - indications: T2DM with risk of CKD, CHF or atherosclerotic CVD - A/Es: heavy glycosuria (increased risk of UTI/candidiasis), hypotension, weight loss, risk of hypoglycaemia (when combined with sulphonylurea or insulin) - e.g. dapagliflozin

Question 27

additional medications to use on top of metformin if HbA1c is still significantly (>1.5%) above target

Answer 27

- DPP-4 inhibitor - sulphonylurea (or if metformin contraindicated due to renal disease) - a-glucosidase inhibitor - pioglitazone

Question 28

DPP-4 inhibitor - MOA - indication - A/Es - e.g.

Answer 28

- MOA: prevent breakdown of GIP and GLP-1 = increased insulin and decreased glucagon release - T2DM in conjunction with metformin if HbA1c is still significantly (>1.5%) above target - A/Es: hypoglycaemia (when combined w/ sulphonylurea or insulin), headache, MSK pain - e.g. sitagliptin

Question 29

sulphonylurea - MOA - indication - A/Es - e.g.

Answer 29

- MOA: block ATP- sensitive K+ channels = K+ stays in the cell = depolarisation = stimulate insulin release (needs functioning B-cells) - T2DM in conjunction with metformin if HbA1c is still significantly (>1.5%) above target - A/Es: hypoglycaemia, weight gain (appetite stimulation) - e.g. gliclazide

Question 30

a-glucosidase inhibitor (rare) - MOA - indication - A/Es - e.g.

Answer 30

- MOA: slows postprandial metabolism of complex CHO into glucose - T2DM in conjunction with metformin if HbA1c is still significantly (>1.5%) above target, useful when postprandial BGL are high despite dietary changes - A/E: flatulence, diarrhoea - e.g. acarbose

Question 31

pioglitazone (rare) - MOA - indication - A/Es

Answer 31

- MOA: binds to PPAR-Y = increased GLUT4 = increased glucose uptake and sensitivity to insulin - T2DM in conjunction with metformin if HbA1c is still significantly (>1.5%) above target, if unable to tolerate other antidiabetics (b/c less effective) - A/Es: fluid retention, bladder cancer, Fx risk, long term safety unsure

Question 32

why might type 2 diabetics need to be started on insulin after some time?

Answer 32

- B-cell exhaustion occurs > glycaemic control gets even worse = need insulin