203 Core Drugs

Question 1

Core Drug : Insulin
What class of drug? 
Mechanism? 
Indication? 
Side effects?

Answer 1

Indication - Diabetes mellitus
Insulin lowers blood glucose by stimulating peripheral glucose uptake primarily by skeletal muscle cells and fat, and by inhibiting glucose production and release by the liver.
Indication - Diabetes (Net effect is to cause hypoglycemia and increase fuel storage in muscle, fat tissue and liver), also Diabetic ketoacidosis (DKA)
Side effects - Hypoglycemia may occur

Question 2

Short acting Insulin

Answer 2

Short-acting insulin begins to lower blood glucose levels within 30 minutes, so you need to have your injection 30 minutes before eating. It has its maximum effect two to five hours after injection and lasts for six to eight hours.

Question 3

Long acting Insulin

Answer 3

Long acting insulins will be injected either once or twice daily

Question 4

Mixed Insulin

Answer 4

Mixed or combination insulins are where a shorter acting insulin is combined with a longer acting insulin. On the plus side, this can mean less injections and can help to make dosages simpler.

Question 5

Core Drug : Gliclazide
What class of drug? 
Mechanism? 
Indication? 
Side effects?

Answer 5

Gliclazide is a type of medicine known as a sulfonylurea - it increases the amount of insulin that your pancreas makes
Gliclazide is a medicine used to treat type 2 diabetes
Primary mechanism of action- stimulates endogenous insulin release

Question 6

Are Sulfonylureas orally active?

Answer 6

All orally active

All bound to plasma protein (90-99%)

Question 7

Primary mechanism of action of sulfonylureas

Answer 7

stimulates endogenous insulin release

Question 8

Core Drug : Metformin
What class of drug?
Mechanism?
Indication?

Answer 8

Biguanides
Metformin - oral antihyperglycemic
Biguanides do not stimulate insulin release or cause hypoglycemia - biguanides appear to increase glucose uptake in muscle and decrease glucose production by liver.
- The exact mechanism is unknown but does involve primarily suppression of hepatic glucose production through gluconeogenesis
- Increases insulin sensitivity
- Enhances peripheral glucose uptake
- Increases fatty acid oxidation via decreasing insulin-induced suppression of fatty acid oxidation
- Decreases glucose absorption from GI tract

Question 9

Mechanism of action of Biguanides

Answer 9

The exact mechanism is unknown but does involve primarily suppression of hepatic glucose production through gluconeogenesis

• Increases insulin sensitivity
• Enhances peripheral glucose uptake
• Increases fatty acid oxidation via decreasing insulin-induced suppression of fatty acid oxidation
• Decreases glucose absorption from GI tract

Question 10

What drugs increase insulin sensitivity

Answer 10

metformin - Biguanides

Question 11

Core Drug : Pioglitazone
What class of drug?
Mechanism?
Indication?

Answer 11

Glitazones (thiazolidinediones)
Pioglitazone now only one remaining approved
Activate peroxisome proliferator-activated receptor-y(PPARy)
In presence of endogenous or exogenous insulin glitazones will
Decrease gluconeogenesis, glucose output, and triglyceride production in liver
Increase glucose uptake and utilization in skeletal muscle
Increase glucose uptake and decrease fatty acid output in adipose tissue
Cause differentiation of adipocytes
Monotherapy or with other anti-diabetic medications
Used for T2 diabetes - Type 2 diabetes mellitus (alone or combined with metformin or a sulfonylurea, or with both, or with insulin)

Question 12

Adverse effects and toxicity 
of biguanides (e.g. metformin)

Answer 12

metformin produces lactic acidemia only rarely
more frequent in patients with renal impairment
nausea, abdominal discomfort, diarrhea, metallic taste, anorexia more common
vitamin B12 and folate absorption decreased with chronic metformin
myocardial infarction or septicemia mandate immediate stoppage (associated renal dysfunction)

Question 13

Metformin contraindications

Answer 13

hepatic disease
past history of lactic acidosis (any cause)
cardiac failure
chronic hypoxic lung disease - causes metabolic acidosis

Question 14

Glitazones (thiazolidinediones) - example

Answer 14

Pioglitazone - now only one remaining approved

Question 15

Adverse effects and drug interactions - Glitazones

Answer 15

fluid retention (promotes amiloride-sensitive sodium ion reabsorption in renal collecting ducts) causing, edema, mild anemia 
dose-related weight gain safety in pregnancy and lactation not determined
do not cause lactic acidosis, even in patients with renal impairment
Liver damage may require regular blood tests
Pioglitazone subject to interactions due to liver metabolism - may lower oral contraceptives levels containing ethinyl estradiol and norethindrone

Question 16

Core Drug : Levothyroxine
What class of drug? 
Mechanism? 
Indication? 
Adverse effects?

Answer 16

Levothyroxine is used to treat thyroid deficiency. It can be used to suppress TSH secretion in the treatment of some thyroid tumours. It can be given by mouth or by injection.
Adverse effects
At excessive doses: palpitations, arrhythmias, diarrhoea, insomnia, tremor, weight loss.

Question 17

Levothyroxine

Answer 17

Levothyroxine is used to treat thyroid deficiency. It can be used to suppress TSH secretion in the treatment of some thyroid tumours. It can be given by mouth or by injection.
Oral Bioavailability - 100%
Protein binding - > 99% Metabolism = Metabolised in liver by glucoronidation
Half-life - 7 days approx
Excretion- 20-40% excreted in urine
Standard maintenance dose: 50-100 μg/day

Question 18

Core Drug : Carbimazole
What class of drug? 
Mechanism? 
Indication? 
Adverse effects?

Answer 18

Carbimazole is used to treat hyperthyroidism. Carbimazole is a pro-drug, after absorption it is converted to the active form, methimazole which prevents peroxidase iodinating the tyrosine residues on thyroglobulin, hence reducing the production of the thyroid hormones T3 and T4.
Adverse effects
Rashes and pruritus are common which can often be treated with antihistamines. The most serious rare side effect is neutropenia and agranulocytosis. Teratogenic.

Question 19

Core Drug : Propylthiouracil
What class of drug? 
Mechanism? 
Indication? 
Adverse effects?

Answer 19

Propylthiouracil (PTU) is used to treat hyperthyroidism (including Graves’ disease) by inhibiting thyroperoxidase, which normally acts in thyroid hormone synthesis. PTU also acts by inhibiting tetraiodothyronine deiodinase which converts T4 to T3. Drug of choice to treat hyperthyroidism in first trimester.
Adverse effects
Rashes and pruritus are common which can often be treated with antihistamines. Its notable side effects include a risk of agranulocytosis and risk of serious liver injury, including liver failure and death.

Question 20

Which antithyroid drug is teratogenic?

Answer 20

carbimazole

Question 21

Combined hormonal contraceptives (CHC)

Answer 21

Available as tablets (COC), transdermal patches (CTP), and vaginal rings (CVR).
Highly user-dependant methods where the failure rate if used perfectly (i.e. correctly and consistently) is less than 1%.
Certain factors such as the person’s weight, malabsorption including diarrhoea and vomiting (COC only), and drug interactions (enzyme inducing drugs) may contribute to contraceptive failure.
Prescriptions of up to 12 months’ supply for CHC initiation or continuation may be appropriate to avoid unwanted discontinuation and increased risk of pregnancy.
Should not be continued beyond 50 years of age as safer alternatives exist.

Question 22

Benefits of Combined Hormonal Contraception

Answer 22

Reduced risk of ovarian, endometrial and colorectal cancer;
• Predictable bleeding patterns
• Reduced dysmenorrhoea and menorrhagia;
• Management of symptoms of polycystic ovary syndrome (PCOS), endometriosis and premenstrual syndrome;
• Improvement of acne;
• Reduced menopausal symptoms;
• Maintaining bone mineral density in peri-menopausal females under the age of 50 years.

Question 23

Risks with Combined Hormonal Contraception

Answer 23

Breast cancer and cervical cancer associated with current or recent use of CHC is
small, but is greater than that with progestogen-only or non-hormonal contraception.
Venous and arterial thromboembolism
CHC is associated with a 3- to 3.5-fold increase in VTE risk compared with non-use of CHC.
Absolute risk of VTE during use of CHC is estimated by the European Medicines Agency to be between 5 and 12 per 10 000 women per year of use compared to 2 per 10 000 non-CHC users per year.
NB VTE risk is lower during CHC use than during pregnancy and the postpartum period.214–221 By reducing rates of unplanned pregnancy, CHC use lowers the overall rate of VTE in the population in comparison to populations without access to effective contraception.
VTE events that do occur during use of CHC, approximately 1% are fatal
n Levonorgestrel (LNG), norethisterone (NET) and norgestimate COC are associated with a lower risk of venous thromboembolic events than COC containing newer progestogens, the combined transdermal patch and the combined vaginal ring.
COC containing higher EE (ethinylestradiol) doses may be associated with greater risk of arterial thrombotic events than lower EE doses.

Question 24

Oral progestogen-only contraceptives

Answer 24

Alter cervical mucus to prevent sperm penetration and may inhibit ovulation in some women;
oral desogestrel-only preparations consistently inhibit ovulation and this is their primary mechanism of action.
Progestogen-only contraceptives offer a suitable alternative to combined hormonal contraceptives when oestrogens are contra- indicated.

Question 25

Parenteral progestogen-only contraceptives

Answer 25

Medroxyprogesterone acetate (Depo-Provera®, SAYANA PRESS®) is a long-acting progestogen given by injection;
- At least as effective as the combined oral preparations
- Prolonged action, it may be used as a short-term or long-term contraceptive for
women
- Delayed return of fertility and irregular cycles may occur after discontinuation of treatment but there is no evidence of permanent infertility.
- Norethisterone enantate (Noristerat®) is a long-acting progestogen given as an oily injection which provides contraception for 8 weeks; it is used as short-term interim contraception e.g. before vasectomy becomes effective.
- Etonogestrel-releasing implant (Nexplanon®) is also available.
- Highly effective long-acting contraceptive, consisting of a single flexible rod that is inserted subdermally into the lower surface of the upper arm and provides contraception for up to 3 years. Local reactions such as bruising and itching can occur at the insertion site. The contraceptive effect of etonogestrel is rapidly reversed on removal of the implant

Question 26

Intra-uterine progestogen-only device (mirena)

Answer 26

Mirena®, Jaydess® and Levosert® release levonorgestrel directly into the uterine cavity.
Licensed for contraception and some licensed for the treatment of menorrhagia
Effects - prevention of endometrial proliferation, thickening of cervical mucus, and suppression of ovulation in some women (in some cycles), the intra-uterine system itself may contribute slightly to the contraceptive effect.
Return of fertility after removal is rapid and appears to be complete.
Advantages over copper intra-uterine devices - improvement in any dysmenorrhoea and a reduction in blood loss; possible reduced pelvic inflammatory disease

Question 27

Emergency contraception

Answer 27

Hormonal emergency contraceptives (includes levonorgestrel and ulipristal acetate) should be offered as soon as possible after unprotected intercourse if a copper intra-uterine device is not appropriate or is not acceptable to the patient; either drug should be taken as soon as possible after unprotected intercourse to increase efficacy. Hormonal emergency contraception administered after ovulation is ineffective.
Levonorgestrel is effective if taken within 72 hours (3 days) of unprotected intercourse and may also be used between 72 and 96 hours after unprotected intercourse [unlicensed use], but efficacy decreases with time.
n Ulipristal acetate is effective if taken within 120 hours (5 days) of unprotected
intercourse. Ulipristal acetate has been demonstrated to be more effective than levonorgestrel for emergency contraception

Question 28

… … should be considered as the first-line hormonal emergency contraceptive for a woman who has had unprotected intercourse 96–120 hours ago (even if she has also had unprotected intercourse within the last 96 hours). It should also be considered first line for a woman who has had unprotected sexual intercourse within the last 5 days if it is likely to have taken place during the 5 days before the estimated day of ovulation.

Answer 28

Ulipristal acetate should be considered as the first-line hormonal emergency contraceptive for a woman who has had unprotected intercourse 96–120 hours ago (even if she has also had unprotected intercourse within the last 96 hours). It should also be considered first line for a woman who has had unprotected sexual intercourse within the last 5 days if it is likely to have taken place during the 5 days before the estimated day of ovulation.

Question 29

It is possible that a higher body-weight or BMI could reduce the effectiveness of oral emergency contraception, particularly …; if BMI is greater than 26 g/m2 or body-weight is greater than 70 g, it is recommended that either ulipristal acetate or a double dose of levonorgestrel [unlicensed indication] (see Emergency contraception under levonorgestrel) is given. It is unknown which is more effective.

Answer 29

It is possible that a higher body-weight or BMI could reduce the effectiveness of oral emergency contraception, particularly levonorgestrel; if BMI is greater than 26 g/m2 or body-weight is greater than 70 g, it is recommended that either ulipristal acetate or a double dose of levonorgestrel [unlicensed indication] (see Emergency contraception under levonorgestrel) is given. It is unknown which is more effective.

Question 30

Ulipristal acetate is effective if taken within 120 hours (5 days) of unprotected
intercourse. Ulipristal acetate has been demonstrated to be more effective than … for emergency contraception.

Answer 30

Ulipristal acetate is effective if taken within 120 hours (5 days) of unprotected
intercourse. Ulipristal acetate has been demonstrated to be more effective than levonorgestrel for emergency contraception.

Question 31

HRT - HRT replaces the hormones that a woman’s body no longer produces because of the ….

Answer 31

HRT replaces the hormones that a woman’s body no longer produces because of the menopause.

Question 32

HRT hormones

Answer 32

The 2 main hormones used in HRT are:

oestrogen – types used include estradiol, estrone and estriol
progestogen – either a synthetic version of the hormone progesterone (such as dydrogesterone, medroxyprogesterone, norethisterone and levonorgestrel), or a version called micronised progesterone (sometimes called body identical, or natural) that is chemically identical to the human hormone

Question 33

HRT involves either taking both of these hormones (combined HRT) or just taking oestrogen (oestrogen-only HRT).

Answer 33

HRT involves either taking both of these hormones (combined HRT) or just taking oestrogen (oestrogen-only HRT).

Question 34

HRT is given to who?

Answer 34

For the treatment of menopausal symptoms where the risk:benefit ratio is favourable, in fully informed women.
For women with early menopause until the age of natural menopause (until age 52), even if they are asymptomatic.

Question 35

Core Drug : mifepristone
What class of drug? 
Mechanism? 
Indication? 
Adverse effects?

Answer 35

Mifepristone is a cortisol receptor blocker used to treat Cushing’s syndrome, and to terminate pregnancies up to 70 days gestation. (Mifepristone, also known as RU-486, is a medication typically used in combination with misoprostol to bring about an abortion during pregnancy.)
It is a progestational and glucocorticoid hormone antagonist.
Adverse effects - Nausea, vomiting, diarrhea, weakness, or dizziness may occur.

Question 36

Core Drug : misoprostol
What class of drug? 
Mechanism? 
Indication? 
Adverse effects?

Answer 36

Misoprostol is a synthetic prostaglandin - medication - used to used to prevent and treat stomach ulcers, start labor, cause an abortion, and treat postpartum bleeding due to poor contraction of the uterus.
For abortion it is best administered following an initial dose of mifepristone
It is not inherently unsafe if medically supervised, but 1% of women will have heavy bleeding requiring medical attention, some women may have ectopic pregnancy, and the 12% of pregnancies that continue after misoprostol failure are more likely to have birth defects and are usually followed up with a more effective method of abortion

Question 37

Termination of pregnancy - medication

Answer 37

mifepristone, misoprostol