CH6: ENDO DRUGS Flashcards
vasopressin
- antidiuretic hormone
- treatment used for limited time = trauma/pituitary surgery
- doses are tailored to produce slight diuresis every 24 hours & avoid water intoxication.
desmopressin
- potent analogue of vasopressin
- no vasoconstriction
- more potent & longer DOA compared to vasopressin
- post-op/unconscious = injection
- maintenance = PO/ intranasal
- 2nd line can be used as nocturnal enuresis
side effects of desmopressin
- hyponatremia (risk of convulsions if not fluid restricted)
- fluid retention
- D/V
- headache
- stomach pain
tolvaptan
- ADH/vasopressin antagonist
- avoid rapid treatment = CNS effects
demeclocycline
- ADH antagonist
- blocks the renal tubular effect of ADH
what are the drug interactions of ADH antagonists
- lamotrigine
- chlorpromazine
- drugs that can cause hyponatraemia = carbamazepine
name corticosteroids (high to low activity)
Dexamethasone (HIGHEST)
Betamethasone
Fludrocortisone
Prednisolone
Hydrocortisone (LOWEST)
name mineralocorticoid (high to low activity)
Fludrocortisone (HIGHEST)
Hydrocortisone
Prednisolone (LOWEST)
fludrocortisone (indications & side effects)
- HIGH glucocorticoid activity
- Minimal anti-inflammatory effect
- High fluid retention
- IND: postural hypotension, septic shock from adrenal insufficiency
- SE:
-> Loss of sodium & water = hypertension
-> hypokalaemia & hypocalcaemia
what are the main side effects of glucocorticoids?
- diabetes
- muscle wasting
- osteoporosis
- GI ulceration and perforation
What are the side effects of all corticosteroids
‘ACHING BOSOM’
Adrenal suppression
Cushing syndrome, cataracts
Hyperglycaemia, hyperlipidaemia
Infections, insomnia
Nervous system; Psychiatric reactions
Glaucoma, GI ulcers
Blood pressure (hypertension)
Osteoporosis
Skin lining
Obesity
Muscle wasting
advise in managing side effects of corticosteroids
- Px lowest effective dose for the shortest duration
- Single dose in the morning = reduce suppression
- Alternate day dose = reduce suppression
- intermediate use with short courses
Name a MILD potency topical corticosteroid drug
hydrocortisone
Name a MODERATE potency topical corticosteroid drug
clobetasone
Name a POTENT topical corticosteroid drug
betametasone
Name a VERY POTENT topical corticosteroid drug
clobetasol
are corticosteroids appropriate for pregnancy/breastfeeding patients?
- generally safe
- monitor for fluid retention
ketoconazole
- cortisol inhibiting drug = tumor based cushing syndrome
- monitor for hepatotoxicity signs; jaundice, dark urine, pale stool, anorexia, abdominal pain, itching, N/V
Name the bisphosphonate drug that has the greatest risk of osteonecrosis of the jaw
Zolendronic acid (IV)
risedronate
- 1st line prevention/treatment for osteoporosis
- PO, can have foods/drinks/other meds after 2 hours of ingestion
- sit upright while taking and for 30 mins after
alendronic acid
- 1st line prevention/treatment for osteoporosis
- PO, have with empty stomach 30 mins before having any food/drinks/other medications
- sit upright while taking and for 30 mins after
side effects of bisphosphonates
- Osteonecrosis of;
- jaw = greater risk with IV bisphos. counsel on dental hygiene. Report; dental pain, swelling and immobility.
- auditory canal = rare but more likely in long term patients. Counsel on ear pain, discharge and infection - Oesophageal reactions =
- STOP use if dysphagia or experiencing new/worsening of heartburn.
- Take with full glass of water while standing and stay upright to reduce risk - Atypical femoral fractures
- report hip/thigh/groin pain
- rare but more likely with long term pts.
strontium
- severe treatment of post-menopausal osp and male osp
- used in pts with high risk of fractures
- MoA: stimulates bone formation & reduces bone resorption
- initiated by specialists
side effects of strontium
- increased risk of CVD; MI and VTE (baseline assessments and 6-12 mo)
- severe allergic reactions: DRESS
DRESS starts with; rash, swollen glands, fever, increased WBC and can affect the liver, kidney and lungs - consult GP and stop use immediately once development of a RASH
counselling advice for taking strontium
- avoid food/drinks 2 hours after/before ingestion
especially Ca/Al/Mg based antacids.
indication of raloxifene
used for secondary prevention and treatment of vertebral fractures in post-meno osteoporosis
indication of teriparatide
used for the treatment of post-menopausal osteoporosis
- increases Ca2+ levels and reduces PO4+ levels by negative feedback
indication for calcitriol
vitamin D3
used for the treatment of post-menopausal osteoporosis
calcitonin is not recommended because?
risk of malignancy with long term use
examples of natural oestrogen
- oestradiol
- oestrone
- oestriol
examples of synthetic oestrogen
- ethinyloestradiol
- mestranol
examples of progestogens
- norethisterone
- levonorgestrel
- desogestrel
clonidine
- antihypertensives
- not 1st line
- has lots of SE
- CI: CVD events
tibolone
- treatment for post-menopause
- increases the risk of endometriosis cancer
- increases the risk of stroke by 2.2 x in 1st year
- NOT to use in the peri-menopausal phase
indications for ethinylestradiol
- Short term treatment of oestrogen deficiency
- Osteoporosis prophylaxis if unable to tolerate other drugs
- Female hypogonadism
- Menstrual disorders
- Palliative treatment of prostate cancer
raloxifene
• Treatment and prevention of post-menopausal osteoporosis
• Doesn’t help with vasomotor symptoms
clomifene
• Anti-oestrogen
• Ovulation stimulant
• Used to treat infertility/ absent periods
• Use 6 cycles only- risk of ovarian cancer
• SE: multiple pregnancy
cyproterone
- anti-testosterone
- used in hyper sexuality
- used for metastatic prostate cancers
- MHRA: risk of meningioma (brain tumour)
ulipristal acetate
- progesterone receptor modulator
- Intermittent ulipristal used to treat mod-severe symptoms of uterine fibroids in post-menopausal women where surgery unsuitable/ failed
- Also used as EHC
metformin
- 1st line treatment for T2DM
- Biguanide class
- MoA= increases insulin sensitivity via GLUT
what are the cautions/ CI of metformin
- DKA
- Contrast media
- Surgery/ anaesthesia
- renal impairment CrCl <30ml/min
- tissue hypoxia - acute HF, MI, respiratory & liver failure
what are the cautions/ CI of metformin?
- DKA
- Contrast media
- Surgery/ anaesthesia
- renal impairment CrCl <30ml/min
- tissue hypoxia - acute HF, MI, respiratory & liver failure
what are the side effects of metformin?
- reduces Vitamin b12 absorption
- GI disturbances - switch to MR prep
- lactic acidosis: increased risk in renal failure/tissue hypoxia
in what circumstances do we advise to stop the use of metformin
- AKI
- Dehydration
- Nausea
- Vomiting
- Diarrhoea
- Fever
advantages of metformin
- weight neutral
- reduce CV morbidity in long-term use
- does not cause hypoglycaemia unless used with hypo-causing drugs
- cheap
DPP4 inhibitors (examples & MOA)
- Used among 1st line treatment options for T2DM
- MOA: prevents the breakdown of GLP (a hormone that stimulates insulin secretion & inhibits glucagon)
- examples (‘gliptin’)
Sitagliptin, Linagliptin, Vildagliptin
what are the advantages of DPP4-i?
- Can be taken with or without food
- weight neutral
- does not cause hypoglycaemia
what are the side effects of DPP4-i?
- headaches
- GI disturbances
- Pancreatitis = report abdominal pain, stop use
- Vildagliptin - hepatotoxic
(report; abdominal pain, dark urine, fatigue, N/V)
what are the cautions/ CI of DPP4-i?
- Reduce dose in renal impairment (except for linagliptin)
- liver impairment = Vildagliptin
(linagliptin & sitagliptin are liver safe) - Avoid use with GLP-1 agonists
pioglitazone
- Used among 1st line treatment options for T2DM
- MoA: PPAR agonist, increases insulin sensitivity and reduces hepatic glucose output
what are the advantages of pioglitazone?
- taken with or without food
- does not cause hypoglycemia
what are the side effects of pioglitazone?
- bladder cancer (report if having urinary problems)
- heart failure if on insulin
- bone fractures: caution in elderly = increased risk of falls
- liver toxicity: monitor LFTs, and report signs of toxicity. Stop if jaundice
caution & CI of pioglitazone
- CI in bladder cancer/hematuria
- CI in HF
- CI in DKA
- Caution in CVD
- if continued use when HbA1c levels have reduced to 0.5% within the last 2-3 months
name the combination of anti-diabetic drugs that are NOT recommended to be taken together on a triple therapy
pioglitazone + Dapaglipflozin (SGLT-2i)
sulfonylurea (SU)
- Used among 1st line treatment options for T2DM
- MOA: stimulates insulin sensitivity
- e.g. gliclazide, glipizide, tolbutamide, glibenclamide (LA) and glimepiride (LA)
advantages of sulfonylurea
- taken with or without food
- SU short acting - Pts with renal impairment/ elderly
- potent
- cheap
- target HbA1c levels are 7% (53 mmol/mol)
side effects of sulfonylurea
- cause hypoglycaemia = to avoid skipping meals
- Avoid driving
- LA SU- increases prolonged hypoglycaemia effect esp in elderly
- Weight gain
- Jaundice
- hypersensitivity = skin rash
- hyponatremia = glipizide or glimepiride
CI/ cautions of sulfonylurea
- CI in DKA or porphyria
- Renal/liver failure= increase risk of hypoglycaemia
- SU-induced hypo- = visit the hospital
- Avoid LA SU in elderly
what are the drug interactions with sulfonylurea
- warfarin & ACE i = hypoglycemia
- NSAIDs (reduce renal excretion)
what are the drug interactions with sulfonylurea?
- warfarin & ACE i = hypoglycemia
- NSAIDs (reduce renal excretion)
name the drug that is to be AVOIDED to use with sulfonylurea
meglitinides (e.g. Repaglinide
Nateglinide)
SGLT2-i (MOA, examples)
- Used for T2DM if SU is CI/not tolerated
- MOA: reduces glucose absorption & increases glucose urine output.
- e.g. empagliflozin, canagliflozin and dapagliflozin
what are the advantages of SGLT2-i?
- weight loss
- reduces CVD risk (esp empagliflozin and canagliflozin)
- taken with or without food
- does not cause hypoglycemia
side effects of SGLT2-i
- polyuria
- polydipsia
- genital/urinary infection (Fourier’s gangrene)
- associated with DKA
- hypotension = increases risk of falls in elderly
- increases the risk of lower limb amputation (report leg ulcers when using canagliflozin)
- correct hypovolemia before starting
cautions/CI of SGLT2-i
- CI in DKA = stop treatment
- Monitor ketones and renal function
- CI in liver failure
- Avoid in renal impairment = dehydration
- Caution use with diuretics as it can cause hypovolemia or hypotension
GLP-1 agonists (MOA, examples)
‘ides’
- Used in triple therapy with metformin + SU
examples; Exenatide (S/C) BD before large meals, MR = OW
Liraglutide (S/C) anytime
Lixisenatide (S/C) anytime
Dulaglutide (S/C) OW
Semaglutide (ORAL OD/ S/C OW)
MoA: Slows gastric emptying
Suppresses glucagon secretion
Increases insulin secretion
advantages of GLP 1 agonists
• Weight loss (feeling full)
• CVD benefit with liraglutide)
side effects of GLP 1 agonist
• GI side effects
- Can cause dehydration
• Risk of pancreatitis- report severe persistent abdominal pain =stop
• Liraglutide: gall bladder disorders
name the drugs of GLP 1 agonists that affect the absorption of oral drugs
Lixisenatide and exenatide affect the absorption of oral drugs so take 1 hour before oral or 4 hours before for S/C
CI/ cautions of GLP 1 agonist
• Do not use with DPP-4I
• MHRA: DKA: Reports of DKA when insulin reduced/ stopped too quick
• GI disease (exenatide/ lixisenatide/ liraglutide)
• Oral semeglutide needs to be taken on empty stomach and 30 mins before other meds/ food. GI SE may reduce after 1 month. Interacts with thyroxine so monitor thyroid levels.
• Review after 6 months, continue if HbA1c reduced by 1%/11mmol/mol and weight loss by 3% of initial wt
• Use contraception
• Do not administer after meal
acarbose
MOA: Delays starch and sucrose absorption
Dose: 50mg daily increased to TDS then to 100mg TDS if necessary. Max 200mg TDS
advantages of acarbose
• Low risk of hypo
• Weight loss
• Take when having meals- allows flexibility (chew with 1st bite or take before with water)
side effects of acarbose
• GI side effects- antacids don’t help, flatulence improves with time but diarrhoea = reduce/ withdraw
• Liver failure (rare): monitor LFT’s
CI/ cautions of acarbose
• GI disorders e.g., hernia, IBD/ surgery
• Liver failure
• CrCl <25ml/min
• Treat hypoglycaemia with GLUCOSE not sucrose
• Monitor liver function
MEGLITINIDES
MOA: Stimulates insulin secretion
Rapid onset and short DOA.
E.g:Repaglinide
Nateglinide
advantages of meglitinides
• Sulphonylurea alternative
• Variable meal pattern (take 30 mins before, max QDS (if pt has 4th meal)
side effects of meglitinides
• May cause hypoglycaemia
• Weight gain
• Hypersensitivity reactions e.g., skin rashes
CI/ cautions of meglitinides
• Repaglinide as monotherapy or used with metformin – not with any others
• Nateglinide cannot be used with SU
• Renal failure
• Severe liver failure (increased risk of hypo)
• DKA
• If they skip a meal, must OMIT dose.
• Rapid onset and short DOA
• If stress: stop treatment and replace with insulin
rapid-acting (insulin analogues)
- Onset, DoA, examples and when to take it
- Onset: 15 mins
- DoA: 2-5 hours
- Examples: Lispro (Humalog I), Aspart (Novo rapid/ fiasp) and glulisine
- Taken immediately before meals, discourage after meals.
- A better option than soluble - as it improves glycemic control and protects against nocturnal hypoglycaemia.
Soluble short-acting (human insulin)
- Onset, DoA, examples and when to take it
- Onset: 30-60 minutes
- DoA: 9 hours
- Examples: Humulin S and actrapid
- Take 15-30 mins before meals
- Can be given via IV in emergencies such as DKA
Intermediate insulin
- Onset, DoA, examples and when to take it
- Onset: 1-2 hours (peaks at 3-12 hours)
- DoA: 11-24 hours
- Examples: Isophane (Humulin I)
- Given to patients who experience hyperglycaemia overnight/morning
- Given before bed
Long-acting insulin
- Onset, DoA, examples and when to take it
- Onset: 2-4 days (no peak)
- DoA: 36 hours
- Examples: Glargine (Lantus), Detemir (Levemir) and Degludec (Tresiba)
- Given to patients who experience hyperglycemia during the day or night
- Given before bed
Levothyroxine
- 1st line treatment for hypothyroidism
- MHRA warning: some patients want to remain brand specific, Perform TFT’s if this occurs
If persistent symptoms, consider maintaining or same brand - Take 30-60 mins before breakfast/ other caffeine containing food/ medication
Monitoring requirements for levothyroxine
• Every 3 months until stable TSH
• Then yearly
• Monitor T4 if symptomatic
• Baseline ECG
Liothyronine
- more rapid & potent compared to levothyroxine
(20-25mcg = 100mcg of Levo) - Not routinely offered
- Ideal in hypothyroid emergencies
- Brand specific – non UK brands not bioequivalent
Briefly explain the metabolism effect of initial dose of levothyroxine
Initial dosage: if metabolised too quickly => excess dosage => hyperthyroid symptoms
Reduce dose OR withhold for 1-2 days then restart at lower dose
Briefly explain the use of levothyroxine in pregnancy
• Advise delaying conception until stable on levothyroxine
• TFT’s may be inaccurate in pregnancy so use trimester related reference ranges
Diazoxide
- Tx for chronic hypoglycaemia
- Dx: Initially 5 mg/kg daily in 2–3 divided doses, adjusted according to response; maintenance 3–8 mg/kg daily in 2–3 divided doses.
- monitor FBCs (WBC and platelets), blood pressure
- CI: established or unstable CVD
