Miscellaneous lectures

Question 1

describe the mode of action of Carbamazepine

Answer 1

• 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

Question 2

describe some of the side effects of Carbamazepine

Answer 2

• 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.

Question 3

describe some of the interactions with Carbamazepine

Answer 3

Beware with other sodium channel blockers - compounding of side effects.

Question 4

describe the mode of action of Phenytoin

Answer 4

Sodium channel blocker

Question 5

describe some of the side effects of Phenytoin

Answer 5

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

Question 6

describe some of the interactions of phenytoin

Answer 6

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.

Question 7

describe the mode of action of Sodium Valproate

Answer 7

Multiple modes of action: Sodium/calcium channel blocker, GABA, Glutamate

Question 8

describe the side effects of Sodium Valproate

Answer 8

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

Question 9

describe the interactions of Sodium Valproate

Answer 9

• Antidepressants (reduced anticonvulsant effect) – SSRIs, TCAs, MAOIs
• Antimalarials (reduced anticonvulsant effect) – mefloquine, chloroquine

Question 10

describe the mode of action of Levetiracetam

Answer 10

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.

Question 11

describe the side effects of Levetiracetam

Answer 11

Few side effects and no significant interactions.

Common side effects: irritability, anxiety, fatigue, dizziness, behavioral changes and rarely psychosis.

Rare hepatic failure.

Question 12

describe the interactions of Levetiracetam

Answer 12

Few side effects and no significant interactions.

Question 13

describe the mode of action of Lamotrigine

Answer 13

Similar to other sodium channel modulators.

Safer to fetus in terms of congenital malformation. - still not completely safe

Question 14

describe side effects of Lamotrigine

Answer 14

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

Question 15

describe the interactions with Lamotrigine

Answer 15

Interactions with OCP (oral contraceptive pill), other AEDs

Question 16

describe the mode of action of Topiramate

Answer 16

Multiple modes of action: Sodium/calcium channel blocker, GABA, Glutamate

Enzyme inducer and inhibitor.

Question 17

describe the side effects of Topiramate

Answer 17

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.

Question 18

describe AED (Anti-epileptic drug) Hypersensitivity syndrome

Answer 18

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.

Question 19

what is status epilepticus

describe its treatment

Answer 19

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.

Question 20

what 3 things increase and what 1 thing decreases the action of the proton pump in the stomach and the control of acid secretion

Answer 20

increase:

• acetylcholine
• histamine
• gastrin

decrease:
- prostaglandin

Question 21

what is a peptic ulcer and what causes it

Answer 21

Defect in the gastric or duodenal mucosa

Due to an imbalance in the peptic acid secretion and gastroduodenal mucosal defence

Question 22

how are peptic ulcers treated

Answer 22

• 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.

Question 23

describe how antacids work in treating peptic ulcers

Answer 23

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.

Question 24

what is the ending for proton pump inhibitors and give 2 examples

Answer 24

-prazole

Omeprazole
Lansoprazole
Pantoprazole
Esomeprazole

Question 25

describe the mode of action and clinical indications and some adverse drug reactions of omeprazole

Answer 25

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

Question 26

name some of the interactions of omeprazole

Answer 26

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)

Question 27

what is the ending for Histamine2 Receptor Antagonists name 2

Answer 27

- tidine Cimetidine Ranitidine

Question 28

what is the mode of action, clinical indications, adverse effects and interactions of cimetidine

Answer 28

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.

Question 29

what is the mode of action, clinical indications, adverse effects and interactions of ranitidine

Answer 29

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.

Question 30

how would you treat a helicobacter infection

Answer 30

- PPI (or H2 blocker) - Clarithromycin - Amoxicillin (or Metronidazole if penicillin allergic) - Triple therapy for 7 days

Question 31

when should you do an urgent upper GI endoscopy

Answer 31

- 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

Question 32

briefly describe how you would manage nausea

Answer 32

- 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

Question 33

name three anti-emetics

Answer 33

Metoclopramide - Anti-dopamine agent Ondansetron - 5HT3 antagonist Cyclizine - Antihistamine