Inflammation: drugs Flashcards
NB finish for migrane
First generation antihistamines
Mepyramine, Promethazine
Not very selective, actions in CNS cause drowsiness
Second generation antihistamines
Terfenadine (prodrug, metabolised to its active form fexofenadine)
More selective, couldn’t cross BBB
Withdrawn due to cardiac toxicity
Terfenadine toxicity
Metabolised to fexofenadine by 3A4 isoform of cytochrome P450
3A4 isoform may be inhibited by e.g ketoconazole, grapefruit juice
If not metabolized sufficiently, can affect heart via block of HERG channel (Kv11.1) -> torsade de pointes, hence long QT interval, potentially fatal arrythmia
Third-generation antihistamines
Loratidine, Fexofenadine
Fewer CNS effects, not action on heart
Fexofanadine has a much lower affinity for Kv11.1 than Tetrafenadine
Dimenhydrinate (Dramamine)
CNS-penetrant antihistamine used to treat motion sickness
Prevention of mast cell degranulation
Salbutamol, salmeterol, sodium cromoglycate
Salbutamol
B2 adrenergic agonist
Inhibit degranulation of mast cells
Used in asthma- cause direct bronchodilation
Salmeterol
B2 adrenergic agonist
Longer acting than salmeterol
Inhibit degranulation of mast cells
Used in asthma- cause direct bronchodilation
Sodium cromoglycate
Blocks mast cell Ca2+ channels and so inhibits degranulation (exocytosis from mast cells)
Cimetidine (tagamet)
H2 selective receptor antagonist- reduces gastric acid secretion.
Used to treat gastric ulcers
Ranitidine (Zantac)
H2 selective receptor antagonist- reduces gastric acid secretion.
Used to treat gastric ulcers
Omeprazole
Proton pump inhibitor (reduces gastric acid secretion)
Clarithromycin
Antibiotic used to treat helicobacter pylori
Treatment for peptic ulcers
Metronidazole
Antibiotic used to treat helicobacter pylori
Treatment for peptic ulcers
Ecallantide (Kalbitor)
Kallikrein inhibitor (mimics an antibody binding domain)
Kallikrein is a protease, cleaves high-molecular weight kininogen (blood) to bradykinin, or low-molecular weight kininogen (tissues) to kallidin.
Treatment of hereditary angioedema (rare acute inflammatory condition caused by low levels of C1-INH, characterised by episodes of severe, often painful swelling)
Asprin
Non selective COX inhibitor
Anti-thrombotic at low doses
Irreversible. Donates acetyl group to a serine near the binding site of COX enzymes. Product is salicylate, a reversible competitive COX inhibitor, but [ ] probably not high enough to have much effect.
Side effects specific to asprin: salicylate poisoning, Reye’s syndrome, hypersensitivity reactions
Ibuprofen
Reversible, non-selective COX inhibitor
Paracetamol
Non-selective COX inhibitor. Little anti-inflammatory action
Celecoxib
COX-2 selective inhibitor
Rofecoxib
COX-2 selective inhibitor
Withdrawn because of increased incidence of MI
Ondansetron
5-HT3 antagonist
Anti-emetic
Metoclopramide
D2 antagonist
Anti-emetic
Phenothiazines
D2 antagonists
Anti-emetics
Scopolamine
Muscarinic antagonist
Anti-emetic
Mepyramine
H1 antagonist
Anti-emetic
Triptans e.g sumatriptan
Class of 5-HT1D antagonists
Used to control migrane. Remarkably effective in suppressing migrane- mechanism not known but implicates 5-HT in origin of migrane
Ergotamine
Non-specific 5-HT1 agonist used to control migrane
Preventative measures for migrane
Valproic acid
B-adrenoceptor blockers
Ca2+ channel blockers
Treatment of peptic ulcers
Older treatments: antacids, cholinergic blockade, vagotomy.
Newer strategies (often combined):
- H2 selective antagonists e.g cimetidine, ranitidine
- PPIs e.g omaprazole
- Eradication of H.pylori e.g clarithromycin, metronidazole
Side effects of NSAIDS
Pharmacological strategies to reduce gastrotoxic effects (8)
Nephropathy, prolonged gestation, GI damage, ulceration, bleeding, anaemia.
Pharmacological strategies to reduce gastrotoxic effects:
- Enteric coating: reduces topical damage
- NSAID prodrug: minimises level of action at gastric mucosa
- NSAID + NO: slow release of gastroprotective NO
- NSAID + misoprostol: PG substitute
- NSAID + PPI: prevents acid secretion
- NSAID + vitamin C: antioxidant effect
- Selective COX 2 inhibitor: COX 1 still active
- Inhibition of COX and 5-LOX: prevents leukotriene formation
