Miscellaneous lectures Flashcards
describe the mode of action of Carbamazepine
- Sodium channel blocker
- Strong hepatic enzyme inducer (CYP3A4)
- Hepatic metabolism
- Auto-induction (over weeks-months) of liver enzymes can fall by 50%.
- Also used for neuropathic pain.
- Use slow release preparation - better tolerability
describe some of the side effects of Carbamazepine
- Dose dependent - diplopia (double vision), ataxia (loss of full control of bodily movements), sedation, fatigue.
- Hyponatraemia - SIADH (SIADH-syndrome of antidiruetic hormone release) : increases ADH release.
- Idiosyncratic (unpredictibly) - bone marrow suppression, hypersensitivity, hepatic derangement, rash.
describe some of the interactions with Carbamazepine
Beware with other sodium channel blockers - compounding of side effects.
describe the mode of action of Phenytoin
Sodium channel blocker
describe some of the side effects of Phenytoin
P= P450 interactions H = Hirsutism - abnormal growth of hair on woman's face or body E = Enlarged gums N = Nystagmus - involuntary movement of the eyes Y = Yellow-browning of the skin T = Teratogenic O = Osteomalacia - softening of bones - vitamin D deficiency I = Interferes with folate metabolism, leads to anaemia N = Neuropathies: vertigo, ataxia, headaches
describe some of the interactions of phenytoin
Hepatic enzyme inducer.
Phenytoin conc. increased with use of enzyme inhibitors.
Phenytoin conc. can be reduced by carbamazepine and antacids. (i.e. other enzyme inducers)
90% protein bound. Valproate displaces & inhibits metabolism - Increases free phenytoin and toxicity.
Reduced effect of warfarin, anticonvulsants e.g. carbamazepine, oral contraceptive.
describe the mode of action of Sodium Valproate
Multiple modes of action: Sodium/calcium channel blocker, GABA, Glutamate
describe the side effects of Sodium Valproate
Teratogenicity is the major issue in young women.
Valproate side effects Appetite increase and weight gain Liver failure Pancreatitis Reversible hair loss Oedema Ataxia Teratogenicity, tremor, thrombocytopenia Encephalopathy (confusion as elevated ammonia)
spells valproate
describe the interactions of Sodium Valproate
- Antidepressants (reduced anticonvulsant effect) – SSRIs, TCAs, MAOIs
- Antimalarials (reduced anticonvulsant effect) – mefloquine, chloroquine
describe the mode of action of Levetiracetam
Seen as a number one choice for most seizure types.
Acts via SV2A ligand - blocks synaptic vesicle release
Rapid and complete absorption. Little effect from food.
Renal excretion as unchanged drug.
describe the side effects of Levetiracetam
Few side effects and no significant interactions.
Common side effects: irritability, anxiety, fatigue, dizziness, behavioral changes and rarely psychosis.
Rare hepatic failure.
describe the interactions of Levetiracetam
Few side effects and no significant interactions.
describe the mode of action of Lamotrigine
Similar to other sodium channel modulators.
Safer to fetus in terms of congenital malformation. - still not completely safe
describe side effects of Lamotrigine
Well tolerated typically
Idiosycratic rash/Stevens-Johnson syndrome can be fatal .
Rash incidence minimized by slow titration. Stop if develop rash.
Other side effects:
- Insomnia
- Less cognitive effects
describe the interactions with Lamotrigine
Interactions with OCP (oral contraceptive pill), other AEDs
describe the mode of action of Topiramate
Multiple modes of action: Sodium/calcium channel blocker, GABA, Glutamate
Enzyme inducer and inhibitor.
describe the side effects of Topiramate
Side effects: sedation, anorexia, and weight loss, psychiatric. Word finding difficulties.
Rare side effects: kidney stones, and acute angle closure glaucoma.
Teratogenic- avoid in young women if possible.
describe AED (Anti-epileptic drug) Hypersensitivity syndrome
Rare. Potentially fatal (10%)
First 1-8 weeks of exposure.
Rash, temps, tender nodes, hepatitis (50% mortality), eosinophilia, pharyngitis, organ failure.
Aromatic AEDs Phenytoin/Carbamazepine show Cross reactivity.
what is status epilepticus
describe its treatment
New operational definition: 5 minutes of continuous seizure activity, of briefer seizures with no recovery of consciousness in between times.
On time with decent doses:
- T = 5mins : 4 mg Lorazepam. Repeat once at 10-15m. (max 0.1mg/kg)
- T = 15m : Phenytoin 20mg/kg. 50mg/min. Slower if contraindicated/elderly. - T = 15m : Anaesthetic drugs in ICU with EEG monitoring.
Benzodiazepines:
- Different benzodiazepines used in status epilepticus.
- Diazepam, Midazolam, Lorazepam - lorazepam is the best
- GABA agonists
- Multiple routes
- IV most definitive. IM in pre hospital status epilepticus.
- Pharmacokinetics of lorazepam make it drug of choice.
what 3 things increase and what 1 thing decreases the action of the proton pump in the stomach and the control of acid secretion
increase:
- acetylcholine
- histamine
- gastrin
decrease:
- prostaglandin
what is a peptic ulcer and what causes it
Defect in the gastric or duodenal mucosa
Due to an imbalance in the peptic acid secretion and gastroduodenal mucosal defence
how are peptic ulcers treated
- Remove gastric irritants especially NSAIDs
- Test and treat for H Pylori infection
- 1st Line – Proton pump inhibitors
- 2nd Line – H2 antagonist
Must investigate anyone at increased risk of gastric carcinoma as treatment may mask early symptoms.
describe how antacids work in treating peptic ulcers
Produce symptomatic relief by raising gastric pH and reducing proteolytic activity.
Most are ALUMINIUM and MAGNESIUM SALTS often in combination.
Sodium bicarbonate is a rapidly acting antacid but is well absorbed and can cause a metabolic alkalosis, sodium and water retention and renal stone formation.
what is the ending for proton pump inhibitors and give 2 examples
-prazole
Omeprazole
Lansoprazole
Pantoprazole
Esomeprazole
describe the mode of action and clinical indications and some adverse drug reactions of omeprazole
mode of action:
Targeted irreversible proton pump inhibitor
Clinical Indications:
- Peptic ulcer disease (PUD)
- Reflux oesophagitis (GORD)
ADRs:
- GI disturbance e.g. nausea, vomiting, abdominal pain, flatulence, diarrhoea, constipation
- Headache
Important ADRs:
- Increased risk of Clostridium difficile infection,
- electrolyte disturbance: Hyponatraemia, Hypomagnesaemia,
- Hepatitis, Interstitial nephritis, Blood disorders – leucopenia, leucocytosis, pancytopenia, thrombocytopenia,
- Observational studies suggest small increase in risk of community acquired and hospital acquired pneumonia
- Observational studies have also suggested a small increase risk in developing CKD
name some of the interactions of omeprazole
Slight variation between different PPIs
Warfarin (Omeprazole and esomeprazole are weak CYP450 enzyme inhibitors, therefore they can increase anticoagulant effect)
Clopidogrel (Pro-drug) (Omeprazole and esomeprazole are weak CYP450 enzyme inhibitors reduce antiplatelet effect)
what is the ending for Histamine2 Receptor Antagonists
name 2
- tidine
Cimetidine
Ranitidine
what is the mode of action, clinical indications, adverse effects and interactions of cimetidine
Mode of Action:
Competitive antagonist at the H2 receptor in gastric parietal cells.
Clinical Indications:
2nd line agent for peptic ulcer disease and reflux oesophagitis.
Adverse Effects:
Diarrhoea, confusion, gynaecomastia.
Interactions:
A potent inhibitor of cytochrome P450 dependent metabolism.
what is the mode of action, clinical indications, adverse effects and interactions of ranitidine
Mode of Action:
Competitive antagonist at the H2 receptor in gastric parietal cells.
Clinical Indications:
2nd line agent for peptic ulcer disease and reflux oesophagitis.
Adverse Effects:
Diarrhoea, fewer than cimetidine.
Interactions:
A mild inhibitor of cytochrome P450 dependent metabolism, of little clinical importance.
how would you treat a helicobacter infection
- PPI (or H2 blocker)
- Clarithromycin
- Amoxicillin (or Metronidazole if penicillin allergic)
- Triple therapy for 7 days
when should you do an urgent upper GI endoscopy
- Acute bleeding suspected
- Chronic bleeding / Fe def Anaemia
> Upper and Lower as 10% dual pathology - Weight loss
- Dysphagia
- Persistent vomiting
- Anyone with unexplained, persistent dyspepsia
>Especially if 55+ years
briefly describe how you would manage nausea
- identify underlying causes and correct these if you can
- treat the symptoms
> anti-emetics selected according to the inferred underlying mechanisms - prevent nausea
> anti-emetic regimen if nausea prolonged
> prevent constipation - if one agent not completely effective then review, add another or replace it
name three anti-emetics
Metoclopramide - Anti-dopamine agent
Ondansetron - 5HT3 antagonist
Cyclizine - Antihistamine
