P3

Question 1

Chlorpromazine

Answer 1

Phenothiazine based antipsychotic

A dopamine antagonist for anti-emetic therapy

MoA: Chlorpromazine’s antipsychotic actions are due to long-term adaptation by the brain to blocking dopamine receptors. Chlorpromazine has several other actions and therapeutic uses, including as an antiemetic and in the treatment of intractable hiccup

Question 2

Domperidone

Answer 2

A dopamine antagonist for anti-emetic therapy

MoA: Domperidone inhibits the dopamine receptor (D2 + D3) in the chemoreceptor trigger zone, located just outside the blood brain barrier.
Domperidone also acts as a gastrointestinal emptying (delayed) adjunct and peristaltic stimulant

Question 3

Metoclopramide

Answer 3

Dopamine receptor antagonist for anti-emetic therapy

MoA: It raises the threshold of activity in the chemoreceptor trigger zone and decreases the input from afferent visceral nerves. Metoclopramide can also inhibits gastric smooth muscle relaxation produced by dopamine, therefore increasing cholinergic response of the gastrointestinal smooth muscle

Use: Decrease reflux in oesophagus by increasing the resting pressure of the lower oesophageal sphincter and improves acid clearance from the oesophagus by increasing amplitude of oesophageal peristaltic contractions.

Question 4

Perphenazine

Answer 4

A dopamine antagonist for anti-emetic therapy

Use: It’s anti-emetic effect is due predominantly to blockage of the dopamine D2 neurotransmitter receptors in the chemoreceptor trigger zone and vomiting centre.

Note: Perphenazine is also used to treat psychosis (e.g. in people with schizophrenia and the manic phases of bipolar disorder)

Question 5

List 3 histamine (H1) antagonists for anti-emetic therapy

Answer 5

Cyclizine
Cinnarizine
Promethazine

Question 6

Cyclizine

Answer 6

Apiperazine-derivative antihistamine

MoA: Histamine (H1) antagonists for anti-emetic therapy

Use: Cyclizine is antiemetic agent used in the prevention and treatment of nausea, associated with motion sickness. Additionally, it has been used in the management of vertigo in diseases affecting the vestibular apparatus. Its mechanism of action is not understood, but it possesses anticholinergic, antihistaminic, central nervous system depressant, and local anaesthetic effects

Question 7

Cinnarizine

Answer 7

Antihistamine and a calcium channel blocker

MoA: Cinnarizine inhibits dopamine D2 receptors, histamine H1 receptors, muscarinic acetylcholine receptors, and also vascular smooth muscle contraction via by blockage of L-type and T-type voltage gated calcium channels

Question 8

Promethazine

Answer 8

A phenothiazine

MoA: Promethazine is a H1-antagonist with anticholinergic, sedative, and antiemetic effects and some local anaesthetic properties

Question 9

Hyoscine

Answer 9

A muscarinic antagonist for anti-emetic therapy

MoA: It is thought ACh plays an important role in communication between the vestibular system and the vomiting centre.

Acts at the vestibular apparatus!

Therefore, by blocking this communication there is a reduction in the activity of the vomiting centre and a reduction in nausea. However, as Scopolamine also may work directly on the vomiting centre its precise mechanism of action is unclear. Scopolamine works best before the onset of motion sickness

Question 10

Ondasetron

Answer 10

5-HT3 receptor antagonist

Serotonin (5-HT) antagonists for anti-emetic therapy

MoA: Ondansetron is a selective serotonin 5-HT3 receptor antagonist with low affinity for dopamine receptors. The serotonin 5-HT3 receptors are located on the nerve terminals of the vagus in the periphery, and centrally in the CTZ. The antiemetic activity of the drug is via inhibition of 5-HT3 receptors present both centrally (CTZ) and peripherally (GI tract). This inhibition of 5-HT3 receptors in turn inhibits the visceral afferent stimulation of the vomiting centre, and serotonin activity in the CTZ

Question 11

Where does hyoscine act?

Answer 11

Vestibular apparatus

Question 12

Where do histamine, dopamine, and muscarinic antagonists act?

Answer 12

CTZ

Question 13

Where does 5HT antagonists (ondansetron) act?

Answer 13

Gut to CTZ + Vomiting centre

Question 14

Where does benzodiazepines (perphenazine) act?

Answer 14

Higher cortical centres to vomiting centre

Question 15

Esomeprazole

Omeprazole

Answer 15

PPIs

MoA: Proton pump inhibitors target gastric acid secretion by specific inhibition of the H+/K+-ATPase in the gastric parietal cell. This inhibition block transport of H+ ions into the stomach lumen and therefore increases the pH of the stomach contents

Question 16

Ranitidine

Answer 16

Competitive histamine H2 antagonist

MoA: Ranitidine is a competitive inhibitor of histamine on parietal cells in the stomach, decreasing acid production.

It is an example of an inverse agonists rather than a true receptor antagonists.

Rantidine reduces stomach acid by blocking histamine binding and reduce the effect of other substances that promote acid secretion (such as gastrin and acetylcholine) on parietal cells.

Use: Peptic ulcer treatment

Question 17

Magnesium trisilicate

Answer 17

An antiacid

MoA: Antacids can neutralise gastric acid and reduce acid delivery to the duodenum

Use: They might be useful for treatment against peptic ulcers (PPIs are much more likely to be used)

Question 18

Misoprostol

Answer 18

A prostaglandin mimetic

MoA: Misoprostol inhibits gastric acid secretion by binding to the prostaglandin receptor on the parietal cell. This receptor inhibits the activity of adenylate cyclase, reducing cAMP levels, and the downstream protein kinase activity. This reduces the availability of the proton pump at the surface reducing acid secretion

Use: The treatment and prevention of stomach ulcers induced by NSAIDs

Question 19

Amoxicillin

Answer 19

Beta-actam antibiotic

Amoxicillin is active against wide range of Gram-positive, and a limited range of Gram-negative organisms

Note: Amoxicillin is susceptible to degradation by β-lactamase-producing bacteria, and so may be given with clavulanic acid to increase its susceptibility. Amoxicillin can be combined with clavulanic acid, a β-lactamase inhibitor, to overcome bacterial antibiotic resistance mediated through β-lactamase production

MoA: Binds to penicillin-binding protein 1A (PBP-1A) located inside the bacterial cell well. This inactivation of PBP-1A prevents the cross-linking of two linear peptidoglycan strands, inhibiting bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins

Question 20

Clarithromycin

Answer 20

Macrolide antibiotic

MoA: Clarithromycin penetrates the bacteria cell wall and reversibly binds to RNA of the 50S subunit of the bacterial ribosome, blocking translocation of aminoacyl transfer-RNA and polypeptide synthesis. Clarithromycin also inhibits the hepatic microsomal CYP3A4 isoenzyme and P-glycoprotein, an energy-dependent drug efflux pump.

Question 21

Metronidazole

Answer 21

Nitroimidazole antibacterial and antiprotozoal

MoA: Unionized metronidazole is taken up by anaerobic bacteria, and is then reduced to its active form. This reduced metronidazole then covalently binds to DNA, disrupting its helical structure, inhibiting bacterial nucleic acid synthesis and resulting in bacterial cell death

Use: Used against protozoa such as Trichomonas vaginalis, amebiasis, and giardiasis. Metronidazole is extremely effective against anaerobic bacterial infections and is also used to treat Crohn’s disease, antibiotic-associated diarrhea, and rosacea. Metronidazole is a prodrug.

Question 22

Thalidomide

Answer 22

An immunomodulatory agent can also have anti-angiogenic effects.

MoA: Not well understood, but it is thought that its 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 23

Orlistat

Answer 23

Lipase inhibitor

Reversible inhibitor of gastric and pancreatic lipases

MoA: The inactivated enzymes cannot hydrolyse triglycerides into absorbable free fatty acids and monoglycerides.

Use: Weight loss. At the recommended therapeutic dose, orlistat inhibits dietary fat absorption by approximately 30%. As some vitamins are fat soluble, there absorption can be affected and as such orlistat should be taken with fatty meals, and a multivitamin tablet containing these vitamins (D E K and beta-carotene

Question 24

The total cholesterol to HDL-C ratio is a strong predictor of what?

Answer 24

Coronary artery disease and high ratios are associated with higher risk of disease

Question 25

What is atorvastatin?

Answer 25

A selective, competitive HMG-CoA reductase inhibitor.

MoA: HMG-CoA reductase converts HMG-CoA to mevalonate in the cholesterol biosynthesis pathway. This results in a subsequent decrease in hepatic cholesterol levels, stimulating upregulation of hepatic LDL-C receptors, and therefore increasing hepatic uptake of LDL-C. As a consequence serum LDL-C concentrations are reduced.

Use: Reduces CV morbidity and mortality by reducing total cholesterol it reduces the risk of cardiovascular morbidity and mortality. Atorvastatin has a long half-life and hepatic selectivity, which gives it greater LDL-lowering potency than other HMG-CoA reductase inhibitors

Question 26

Bezafibrate

Answer 26

Anti-lipemic agent

An agent that prevents or counteracts the accumulation of fatty substances in the blood.

Use: It’s an antilipemic agent that lowers cholesterol and triglycerides via activation of triglyceride lipases (lipoprotein lipase and hepatic lipoprotein lipase) and reduction of cholesterol biosynthesis.

Note: Bezafibrate can cause a significant decrease in elevated plasma fibrinogen levels

Elevated fibrinogen is an important risk-factor, in the development of atheroma due to its role in blood flow and viscosity, and in thrombus development and lysability