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KMMS > RE Pharm > Flashcards

RE Pharm Flashcards

1
Q

Biguanides (METFORMIN) mechanism of action

A

Stimulates AMPK (AMP-activated protein kinase), which activates insulin signalling and increases insulin-dependent glucose uptake. This leads to:

  • a reduction in gluconeogenesis
  • increased insulin receptor expression
  • increased levels of Glucagon-like peptide 1 (GLP1) and - inhibition of synthesis of glucose, lipids, and protein
  • stimulation of glucose uptake and FA oxidation
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2
Q

Which class of drug is recommended for patients with insulin resistance?

A

Biguanides (Metformin)

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3
Q

What are the common and rare side effects of Biguanides (Metformin)?

A

Common: GI- mainly bloating and diarrhea. 5% of patients are intolerant to the medication. Headaches. B12 deficiency due to reduced absorption- risk increases with duration of therapy

Uncommon: Hypoglycaemia (but can be seen with combination therapy)

Rare side effects include:

- LACTIC ACIDOSIS
    - Haemolytic anaemia
- Cholestatic jaundice
- Allergic pneumonitis
- Leucocytoclastic vasculitis
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4
Q

Contraindications for Biguanides (Metformin)

A
  • Acute metabolic acidosis (including lactic acidosis and DKA)
    • eGFR < 30 mL/min/1.73m2 - increased risk of developing lactic acidosis
    • Liver dysfunction
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5
Q

Sulphonylurea (GlicKlazide & Glimpiride) mechanism of action:

A

Blocks potassium ATP channels within beta cells of the pancreas, stimulating insulin secretion

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6
Q

Side effects associated with sulphonylureas (GlicKlazide & Glimepiride)

A

Hypoglycaemia, weight gain, and secondary failure

(NB on secondary failure: Hyperexcitation of beta cells –> excitotoxic reaction –> beta cell apoptosis –> beta cell mass loss –> insulin deficiency)

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7
Q

Key trial data for ______________ showed a decrease in HbA1c by 1-2%, high rates of hypoglycaemia, cardioprotective, and weight gain

A

Sulphonylureas (GlicKlazide & Glimpiride)

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8
Q

Contraindications to sulphonylureas (GlicKlazide & Glimepiride)

A
  • Ketoacidosis
    • Acute porphyria
    • Caution in elderly (d/t risk of hypoglycaemia), obesity (d/t weight gain) and G6PD deficiency (d/t the way it is metabolised)
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9
Q

SGLT2 inhibitors (Dapagliflozin, Canagliflozin, Empagliflozin) MOA

A
  • Decreases rental tubular glucose reabsorption
    • Lowers glucose without increasing insulin release
    • Diuretic effect
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10
Q

Trials have shown this class of drug reduces HbA1c by 0.6-1.2%, contributes to significant reduction in all-cause mortality, significant reduction in CV mortality, and significant reduction in CV death and hospitalization for heart failure

A

SGLT2 inhibitors (Dapagliflozin, Canagliflozin, Empagliflozin)

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11
Q

Side effects of SGLT2 inhibitors (Dapagliflozin, Canagliflozin, Empagliflozin)

A
  • EUGLYCAEMIC DKA
    • Genital and UT infections
    • Urinary retention
    • Hypotension- d/t diuretic effect
    • Reduced bone density
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12
Q

Contraindications of SGLT2 inhibitors (Dapagliflozin, Canagliflozin, Empagliflozin)

A
  • Patients at risk of DKA

- Cautions in elderly patients, heart failure, CKD

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13
Q

Glucagon-like peptide-1 (GLP-1) agonists (Dulaglutide, Exanatide, Liraglutide, Semaglutide MOA:

A
  • Stimulate insulin release
    • Reduces glucose sensitivity
    • Enhances pancreatic beta cell replication
    • Prevents beta-cells from decline
    • Delayed gastric emptying
    • Inhibition of glucagon secretion
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14
Q

Common and rare side effects of Glucagon-like peptide-1 (GLP-1) agonists (Dulaglutide, Exanatide, Liraglutide, Semaglutide

A

Common:
- GI (nausea and loose stools)
- Hypersensitivity
- Local skin reactions to injection sites
Rare:
- Possible increase in medullary thyroid cancer (therefore contraindicated in high risk individuals)
- Risk of antibody formation- therefore if increased hypersensitivity reaction or lack of improved HbA1c, discontinue GLP1 agonist
- Renal impairment- contra-indicated in chronic kidney failure

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15
Q

Contraindications for Glucagon-like peptide-1 (GLP-1) agonists (Dulaglutide, Exanatide, Liraglutide, Semaglutide

A
  • Diabetic gastroparesis
    • IBD
    • Age >75 years
    • DKA
    • Diabetic retinopathy (Semaglutide)
    • Hx of pancreatitis
    • Severe congestive heart failure
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16
Q

Side effects of insulin therapy

A
  • Hypoglycaemia (accounts for up to 6% of deaths in T1DM patients)
    • Weight gain
    • Reaction at injection site
    • Cancer-risk- non consistent results
    • Cardiovascular risk (? Related to hypoglycaemia?)
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17
Q

Which of the diabetes drugs can reduce weight?

A

GLP-1 agonists (-tides)

Possibly d/t delayed gastric emptying leading to N/V –> reduced appetite.

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18
Q

Which diabetes drug enhances insulin signalling in insulin-dependent and insulin-independent pathways?

A

Biguanides (Metformin)

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19
Q

Starting dose of Metformin is _____ mg QD with largest meal

Titrate every two weeks by 500 mg until they achieve __ gram BID

A

500 mg

1 gram

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20
Q

DM2 management:

If HbA1c rises to ____ mmol/mol on lifestyle interventions alone, offer standard- release _________.

A

48

Metformin

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21
Q

DM2 management (first intensification):

If Hba1c rises to ____ mmol/mol with Metformin alone, consider dual therapy with either Metformin and
_________ or Metformin and ________.

A

58 mmol/mol

Metformin + sulfonylurea (GlicKlazide) OR
Metformin + SGLT (-flozins)

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22
Q

DM2 management:
If Metformin therapy is contraindicated or otherwise not tolerated, the patient can start on either a __________ or ___________.

A 
Sulphonylurea (GlicKlazide) OR
SGLT inhibitor (-flozin)
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23
Q

DM2 management (second intensification):

If Hba1c rises to _____ mmmol/mol on dual therapy, consider triple therapy with:
Metformin + Suphonylurea + ________
Or Metformin + Sulphonylurea + ___________

Alternatively, it may be appropriate to start _______-based therapy at this stage

A

58

SGLT inhibitor

GLP1 agonist

Insulin

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24
Q

First line/gold standard insulin regimen for treatment of T1DM?

A

Basal-bolus insulin regimen or multi-daily injection (MDI) therapy

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25
Q

This is a pre-mixed insulin which is 30% short acting insulin and 70% intermediate acting insulin.
Rarely used in type 1
Requires a consistent daily routine that includes three meals a day.
Risk of hypo or hyperglycemia if not consistent with meals

A

Pre-mixed insulin regime (e.g. Novomix)

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26
Q

Most widely prescribed anti-thyroid medication in the UK. MOA is to inhibit thyroid peroxidase, thereby reducing production of T4 and T3

A

Carbimazole

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27
Q

MOA of Propylthiouracil?

A

Inhibits TPO- reducing production of T4 and T3. Also reduces peripheral conversion of T4 into T3

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28
Q

Managment of hyperthyroidism:

Start with a high dose of ____________ (most widely prescribed in UK) or Propylthiouracil. Reduce dose as thyroid function settles. Course of therapy: 18-24 months.

When patient is euthyroid with med tx, then ______________ therapy is indicated.

Last resort treatment option is surgery (only when patient is euthryoid after course of medication)

A

Carbimazole

I 131 radioiodine therapy

29
Q

Management of hypothyroidism:

Start patient on __________. TSH is used as a marker for dose. Average starting dose is ~100-150 mcg QD. (LOWER STARTING DOSE IN 65+ and/or ISCHAEMIC HEART DISEASE). Slowly increase in order to reach equilibrium.

A

Levothyroxine

30
Q

Management of adrenal crisis:

Intravenous ___________
IV fluids
Hypoglycaemia management

(Remember in Addison’s the patient has low sodium and HIGH potassium levels)

A

hydrocortisone

31
Q

In primary adrenal insufficiency, mineralcorticoid replacement needs initiating as soon as daily glucocorticoid dose <50mg/24 hours. Treat with __________ 100 mcg

A

fludrocortisone

32
Q

A medication called _________ is used to treat __________ insufficiency

A

hydrocortisone

adrenal

33
Q

Emergency injection kits for patients with primary adrenal insufficiency consist of what medication?

A

100mg of hydrocortisone phosphate for I.M injection

34
Q

A person with Addison’s disease will require (more/less) of their usual medication when they are ill.

A

more- need for cortisol increases in times of stress and infection

35
Q

Hyperphysiologic doses of steroids such as hydrocortisone, prednisolone, or dexamethasone lead to negative feedback on the pituitary and hypothalmus –> atrophy of the z.fasiculata and z.reticularis of the adrenal glands (z.glomerulosa is spared d/t RAAS system). Therefore, _________ the dose of exogenous steroids in order to discontinue treatment is essential in order to avoid an adrenal crisis.

A

tapering

36
Q

Another corticosteroid (in additon or instead of hydrocortisone) to treat Addison’s disease

A

Fludrocortisone acetate

37
Q

Testosterone MOA:

Androgen target cells generally convert testosterone into ____ before it binds to the androgen receptor

A

DHT

38
Q

Low muscle mass and strength, low BMD, low libido and sexual functioning are effects of low _________

A

testosterone

39
Q

Combined hormonal contraceptives (CHCs) containing a fixed amount of an oestrogen and a progestogen in each active tablet are termed ‘‘__________.” Those with varying amounts of the two hormones are termed ‘__________.’

A

monophasic

multiphasic

40
Q

First line contraceptive offered for women without significant contraindications (uncontrolled BP, previous hx of thromboembolism, clotting disorder, or migraine with aura)

A

Cost effective MONOPHASIC combined hormonal contraceptive.

41
Q

What two classes of drugs can interfere with the metabolism of CHC’s?

A

antibiotics and anti-epileptics

42
Q

MOA of estrogen in CHC’s

A

suppresses ovulation

43
Q

MOA of progesterone in CHC’s

A

Can suppress ovulation.
Also create a hormonally-driven barrier for sperm to enter the uterine cavity. Decreases cilia activity in uterine tube, slowing down transport of the egg. Increases volume and thickness of cervical mucous, and thins the endometrium

44
Q

Sustained high levels of estrogen and progesterone __________ feedback to the pituitary and hypothalamus, ________ production of FSH and LH.

A

negatively

suppressing

45
Q

Most methods of hormonal contraception are effective immediately if started on days _______ of the cycle.

A

1-5

46
Q

Adverse effects of combined hormonal contraceptives (CHC’s)

  • most common
  • rare, but serious
A

most common: breast tenderness, weight gain, bloating, changes in libido and mood, irregular bleeding

rare, but serious: CH is associated with a small increase in breast cancer during use and in the 5 years afterwards. Also associated with increased risk of cervical cancer during use and in 10 years afterwards. Risk of venour thromboembolism. Smoking increases risk of clotting events.

47
Q

Contraindications for CHC’s (4 absolute, 5 relative)

A

Age: Not to be used in women over 50 (progesterone-only preferred)
Weight: Use with caution if BMI >30
Smokers: Smokers at increased risk of clotting events
Family history of blood clots
First 6 weeks of breastfeeding

ABSOLUTE CONTRAINDICATIONS:

  • Uncontrolled BP
  • Previous history of thromboembolism
  • Clotting disorder
  • Migraine with aura
48
Q

Benefits of CHC’s

A
  • Predictable bleeding patterns
  • Decreases heavy menstrual bleeding and pain
  • Decreased risk of ovarian, colorectal, and endometrial cancer
  • Rapid return to fertility when discontinued
  • Can be used to decrease menopausal symptoms in PERI menopausal women <50
49
Q

Progesterone-only contraception is available as….

A

POP (mini-pill), injection, implant, IUS

50
Q

Most suitable type of hormonal contraception immediately after childbirth?

A

Progesterone-only

51
Q

What type of hormonal contraception can be recommended for women with a history of thromboembolic events?

A

Progesterone only

52
Q

Which type of hormonal contraceptive is associated with decreased bone mineral density?

A

Progesterone injection

53
Q

How are POPs administered?

A

Taken daily at the same time with no hormone-free interval

54
Q

Which type of hormonal contraception increases the risk of ectopic pregnancy?

A

IUS (Mirena coil)

55
Q

Which type of contraceptive is licensed for providing the progesterone part of HRT for 4 years?

A

IUS (Mirena coil)

56
Q

Contraindication of IUS (Mirena coil)

A

breast cancer

57
Q

First line choice for emergency contraception?

A

IUD (copper coil)

58
Q

Hormonal form of emergency contraception that can delay ovulation by up to 5 days, including after an LH surge. Licensed for use within 120 hours of unprotected intercourse

A

Ulipristal acetate

59
Q

Second-line (hormonal) choices for emergency contraception

A

Ulipristal acetate

Levonorgestrel

60
Q

MOA: Delays or prevents follicular rupture and ovulation. Licensed for use within 72 hours of unprotected intercourse.

A

Levonorgestrel

61
Q

Adverse effects/risks associated with IUS

A

Risk of perforation, migration, and infection, Increased risk of ectopic pregnancy if patient does become pregnant with IUS

62
Q

What type of HRT regimen is appropriate for women under the age of 50 who are still menstruating (without any risk factors)?

A

Combined, cyclical HRT

63
Q

What type of HRT is appropriate for a post-menopausal woman without any risk factors?

A

Combined, continuous HRT

64
Q

Unopposed estrogen-only HRT increases the risk of what conditions?

A

endometrial hyperplasia and malignancy

65
Q

Mifepristone MOA

A

Progesterone antagonist

66
Q

Mifepristone indications/uses

A

Termination of pregnancy. Can be used at home if gestation is < 10 weeks, or in clinical setting thereafter

67
Q

Misoprostol MOA

A

prostaglandin analogue; binds to myometrial cells to cause strong myometrial contractions leading to expulsion of tissue. This agent also causes cervical ripening with softening and dilation of the cervix.

68
Q

Misoprostol uses/indications

A

For medical management of miscarriages to soften and dilate the cervix. Stimulates the myometrium to contract.
Can also be used to induce labour in later stages of pregnancy.

KMMS (58 decks)

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