B11

Question 1

Folic acid

Answer 1

A DNA precursor

MoA: Folic acid, is converted to tetrahydrofolic acid and methyltetrahydrofolate by dihydrofolate reductase. Tetrahydrofolic acid and methyltetrahydrofolate are transported across cells by receptor-mediated endocytosis, as they are required to maintain normal erythropoiesis, synthesize purine and thymidylate nucleic acids, interconvert amino acids, methylate tRNA, and generate and use formate.

Use: Folate deficiencies and megaloblastic anaemia

Question 2

What is flucloxacillin and ampicillin?

Answer 2

Penicillin beta-lactam antibiotic (transpeptidase inhibitor)

Question 3

Tetracycline and gentamicin are broad spectrum antibiotics.

What do they inhibit?

Answer 3

Tetracycline: 30S inhibitor
Gentamicin: 30S/50S inhibitor

Question 4

Tetracycline

Answer 4

30S inhibitor

Tetracycline is a short acting antibiotic that inhibits translation, thereby inhibiting bacterial growth.

MoA: It passively diffuses into the bacteria through the porin channels. Once inside the bacteria it blocks protein synthesis by binding to the bacterial 30S ribosomal subunit and blocking incoming tRNA from binding to the ribosome acceptor site. It also binds to some extent to the bacterial 50S ribosomal subunit and may alter the cytoplasmic membrane causing intracellular components to leak from bacterial cells. This binding to the ribosomal unit is reversible.

Note: Tetracycline is rarely used now, it is much more common to prescribe doxycycline

Question 5

Gentamicin

Answer 5

30S/50S inhibitor

MoA: Gentamicin is a broad-spectrum aminoglycoside antibiotic, useful for infections involving Gram-negative bacteria, such as Pseudomonas, Acinetobacter, and Enterobacter. Aminoglycosides bind to the bacterial 30S ribosomal subunit, inhibiting protein synthesis.

Use: Used to treat mycobacteria (TB) and gram positive infections.

SE: SIgnificant ear and kidney damage.

Question 6

Ampicillin

Answer 6

Penicillin beta-lactam antibiotic (transpeptidase inhibitor)

MoA: Its anti-bacterial effects occur via inhibition of cell wall synthesis. Ampicillin binds to penicillin binding proteins (PBPs), and therefore inhibits the last stage of cell wall synthesis leaving the bacteria venerable to cell lysis.

Ampicillin is also stable against hydrolysis by a variety of beta-lactamases, (penicillinases, cephalosporinases and extended spectrum beta-lactamases)

Use: Ampicillin is used in the treatment of gram-positive bacterial infections.

Question 7

Fucloxacillin

Answer 7

Penicillin beta-lactam antibiotic (transpeptidase inhibitor)

MoA: The bactericidal activity of Flucloxacillin anti-bacterial action is derived from inhibition of cell wall synthesis. This inhibition occurs via inhibition of penicillin binding proteins located in the cell wall, which prevents the last stage of bacterial cell wall synthesis. Cell lysis can then occur via bacterial cell wall autolytic enzymes (autolysins).

Uses: treatment of bacterial infections caused by susceptible, usually staphylococcus aureus.

Note: Flucloxacillin is also stable against hydrolysis by a variety of beta-lactamases, (penicillinases, cephalosporinases and extended spectrum beta-lactamases).

Question 8

Sodium valproate

Answer 8

An anti-convulsant. It’s a fatty acid (GABA receptor agonist).

MoA:
♣ Increasing gamma-aminobutyric acid (GABA) levels in the brain through inhibition of enzymes that catabolise GABA
♣ Altering the properties of voltage dependent sodium channels
♣ Act as a histone deacetylase inhibitor

Use: It is used as an anti-epileptic drug (more commonly than carbamazepine) and still used as a mood stabiliser

Question 9

Ethanol

Answer 9

MoA:
♣ Ethanol binds directly to the receptors for acetylcholine, serotonin, GABA, and the NMDA receptors
♣ The sedative effects of ethanol are mediated through binding to GABA receptors & glycine receptors (alpha 1 and 2 subunits). It also inhibits NMDA receptor functioning
♣ Has an anti-infective role as it acts as a dehydrating agent that disrupts the osmotic balance across cell membranes

Question 10

What is fomepizole used for?

Answer 10

It’s the first line treatment for methanol/ethylene glycol poison

Question 11

Cocaine

Answer 11

An anaesthetic (topical anaesthesia) and vasoconstrictor

NA reuptake inhibitor/sodium channel blocker

MoA: Produces anaesthesia by inhibiting excitation of nerve endings or by blocking conduction in peripheral nerves. This is achieved by reversibly binding to and inactivating sodium channels, which are necessary for the depolarization of nerve cell membranes and subsequent propagation of impulses along the course of the nerve.

Use: Cocaine is the only local anaesthetic with vasoconstrictive properties. This is a result of its blockade of norepinephrine reuptake in the autonomic nervous system.

Question 12

Lithium

Answer 12

MoA: Li+ can displace K+, Na+ and even Ca2+, in several critical neuronal enzymes and neurotransmitter receptors.

Lithium’s therapeutic action may be due to several effects, ranging from inhibition of enzymes such as glycogen synthase kinase 3, inositol phosphatases, or modulation of glutamate receptors

Use: Bipolar disorder by counteracting both mania and depression

Question 13

Thalidomide

Answer 13

Thalidomide is an immunomodulatory agent can also have anti-angiogenic effects

MoA: Immune modulation is due to changes in the concentration of TNF, whilst it can also affect VEGF leading to its effects on the blood vessels. It has teratogenic effects on humans

Question 14

Testosterone

Answer 14

Steroid sex hormone (androgen hormone receptor agonist)

MoA: Free testosterone (T) is transported into the cytoplasm of target tissue cells, where it can bind to the androgen receptor, or can be reduced to 5α-dihydrotestosterone (DHT) by the cytoplasmic enzyme 5α-reductase. DHT binds to the same androgen receptor with greater affinity than T, so it has 2.5 times higher androgenic potency of T.

The T-receptor or DHT-receptor complex undergoes a structural change that allows it to move into the cell nucleus and bind directly to specific nucleotide sequences of the chromosomal DNA. The areas of binding are called hormone response elements (HREs), and influence transcriptional activity of certain genes, producing the androgen effects.

Question 15

Somatropin

Answer 15

Somatropin is a synthetic human growth hormone (hGH) that stimulates skeletal growth at the epiphyseal plates at the ends of a growing bone in paediatric patients with growth failure.

MoA: hGH binds to the human growth hormone receptor, causing dimerization and activation of a JAK2 mediated cell signalling pathway.

Use: Dwarfism and growth failure

Question 16

Oxytocin

Answer 16

MoA: Oxytocin has specific receptors on the uterus which once activated, increase intracellular Ca2+, activate myosin’s light chain kinase, and therefore causing muscle contraction. In addition, Oxytocin after labour is associated with lactation.

Use: It is used in delivery and immediately post-partum to stimulate uterine smooth muscle contraction.

Note: In men oxytocin is thought to be involved in movement of sperm, and the production of testosterone. The effects of elevated or low levels of oxytocin are not understood.

Question 17

Desogestrel / Etonogestrel / Levonorgestrel

Answer 17

Synthetic versions of progesterone. Progesterone nuclear hormone receptor agonist.

MoA: They work by binding to the progesterone and oestrogen receptors present on the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary.

Once bound to the receptor, progestins like desogestrel will slow the frequency of release of gonadotropin releasing hormone (GnRH) from the hypothalamus and blunt the pre-ovulatory LH (luteinizing hormone) surge, and maintain the high levels of progesterone.

Use: Oral Contraceptive Pill, alone or in combination with oestrogen and in high dose (levonorgestrel) for emergency contraception.

Question 18

Ethinylestradiol

Answer 18

A synthetic derivative of the natural oestrogen oestradiol

Class: A oestrogen nuclear hormone receptor agonist

MoA: Both Ethinylestradiol and Oestradiol interact with the oestrogen receptor (Erα or Erβ) present on female organs, breasts, hypothalamus, and pituitary gland.

Note:

• Too much oestradiol has been linked to acne, constipation, loss of sex drive and depression.
• Too little oestradiol, retards bone growth and development.
• In men, proper oestradiol levels help with bone maintenance, nitric oxide production and brain function.

Question 19

Dinoprostone

Answer 19

Prostaglandin E2 (prostaglandin receptor agonist)

MoA: Direct myometrial stimulation, but the exact mechanism is unknown.

Use: As a prescription drug, it is used as a vaginal suppository, to induce cervical ripening and labour.