B3 Flashcards
Chlorpromazine
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
Domperidone
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
Metoclopramide
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.
Perphenazine
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)
List 3 histamine (H1) antagonists for anti-emetic therapy
Cyclizine
Cinnarizine
Promethazine
Cyclizine
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
Cinnarizine
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
Promethazine
A phenothiazine
MoA: Promethazine is a H1-antagonist with anticholinergic, sedative, and antiemetic effects and some local anaesthetic properties
Hyoscine
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
Ondasetron
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
Where does hyoscine act?
Vestibular apparatus
Where do histamine, dopamine, and muscarinic antagonists act?
CTZ
Where does 5HT antagonists (ondansetron) act?
Gut to CTZ + Vomiting centre
Where does benzodiazepines (perphenazine) act?
Higher cortical centres to vomiting centre
Esomeprazole
Omeprazole
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
Ranitidine
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
Magnesium trisilicate
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)
Misoprostol
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
Amoxicillin
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
Clarithromycin
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.
Metronidazole
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.
Thalidomide
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
Orlistat
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
The total cholesterol to HDL-C ratio is a strong predictor of what?
Coronary artery disease and high ratios are associated with higher risk of disease
What is atorvastatin?
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
Bezafibrate
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
