Q1

What are the pharmacokinetic properties of frusemide?

  • Rapid absorption after oral admin
  • Oral bioavailability 50% (range 10 –100%)
  • Highly protein-bound (>95%)
  • 50% conjugated in kidney & 50% excreted in urine unchanged (tubular secretion)
  • Elimination t1/1.5 – 2 hours
  • Peak effect 30 minutes IV / 1 hour oral

Pass Criteria:

  • Must list 3 properties

What are the site and mechanism of action of frusemide?

  • Actively secreted into lumen of nephron from proximal tubule cells via organic-base pump
  • Inhibits Na+-K+-2Cl transporter in thick ascending limb of loop of Henle thuspreventing resorption of  Na+ & Cl
  • Abolishes counter-current concentrating mechanism leading to a dilute urine

Pass Criteria:

  • Must mention thick ascending limb of loop of Henle and reduced resorption of Na and Cl

What factors determine drug half-life?

  • Electrolyte disturbances – hypokalemiahyponatraemia, hypomagnesaemia, hyperuricaemia
  • Postural hypotension & dizziness
  • Increased LDL & triglycerides, decreased HDL
  • Ototoxicity (high dose IV)
  • Drug interactions

Pass Criteria:

  • Must list
    • Hypokalemia
    • Hyponatremia
    • Hypotension or dizziness
    • PLUS 1 other

Q2

How does frusemide exert its action?

  • Selective inhibition of NaCl reabsorption in the thick ascending loop of Henle

Pass Criteria:

  • Na & loop of Henle

What are the adverse effects of frusemide?
Prompt: Are any other organ systems effected?

  • Hypokalemic Metabolic Alkalosis
  • Ototoxicity
  • Hyperuricemia
  • Hypomagnesemia
  • Allergy: Skin rash, Eosinophilia
  • Interstitial nephritis
  • Hyponatremia

Pass Criteria:

  • 4 adverse effects
    • Including hypokalaemia
    • AND 1 non electrolyte

Q3

How do thiazides exert their diuretic action?

  • Inhibition of NaCl reabsorption in the distal convoluted tubule

What are the adverse effects of thiazides?

  • Hypokalaemic metabolic alkalosis and hyperuricaemia
  • Impaired carbohydrate tolerance
  • Hyperlipidaemia
  • Hyponatraemia
  • Allergic reactions (sulphonamides)
  • Weakness, fatigue, paraesthesia (like carbonic anhydrase inhibitors)

Pass criteria:

  • 3/6 to pass

Q4

What are the pharmacological differences between dexamethasone and hydrocortisone?

  1. 30x greater anti-inflammatory potency
  2. Longer duration of action
  3. No salt retaining activity

In what situations could you use dexamethasone?

  1. Diagnosis – dexa suppression test
  2. Anti inflammatory effect
  3. Croup

Q5

What is the mechanism of action of indirectly acting cholinomimetics?

  • Inhibition of the enzyme acetylcholinesterase thereby increasing the concentration of endogenous acetylcholine in the vicinity of cholinoreceptors
  • Action on both nicotinic and muscarinic receptors.
  • Action on the neuromuscular end plate and autonomic ganglion cells

Pass Criteria:

  • Bold items

What types of indirectly acting cholinomimetics are there? Please give examples.

  • Reversible:
    • Group 1. Alcohols –edrophonium
    • Group 2. Carbamates –neostigmine, physostigmine, pyridostigmine
  • Irreversible:
    • Group 3. Organophosphates –Ecothiophate, insecticides

Pass criteria:

  • Delineate reversible and irreversible groups
  • OR give two well explained examples

What are the cardiovascular effects of these groups of drugs?

  • Both sympathetic and parasympathetic ganglia can be activated
  • Parasympathetic effects generally predominate
  • Bradycardia, decreased CO, decreases contractility, no change or modest decrease in BP.
  • OD may cause tachycardia and hypotension

Pass Criteria:

  • Bold items

Q6

Can you describe the basic mechanism of action of atropine?

  • Anti-cholinergic
  • Anti-muscarinic at all three types of muscarinic receptors
  • No significant nicotinic effect

Pass criteria:

  • Must say anti -muscarinic

What are the therapeutic applications of drugs that block muscarinic receptors?

  • Heart
  • Gut
  • Eye
  • Organophosphate poisoning
  • Parkinsons
  • Motion Sickness
  • Respiratory (IB)
  • Urinary disorders

Pass criteria:

  • Any 4

What are the toxic effects of antimuscarinic overdose?

  • Delirium
  • Hyperpyrexia
  • Mydriasis
  • Tachycardia
  • Dry mouth
  • Urinary retention
  • Dry as a bone
  • Red as a beet

Pass criteria:

  • 5 out of 8

Q7

How are osmotic diuretics handled by the kidney?

  • Freely filtered by glomeruli. Not reabsorbed, causes water retention in the freely permeable sections of the nephron = proximal tubule and descending loop of Henle

What are the clinical uses of Mannitol?

  • IV dose 0.5-1-2 g/kg for raised intracranial pressure.
  • Rarely for intraocular pressure and diuresis in haemolysis or rhabdomyolysis

Pass Criteria:

  • 2/3 mechanisms

What are the toxic effects of Mannitol?

  • Extracellular volume expansion
  • Hypernatraemia

Pass Criteria:

  • At least 1

Q8

List the advantages of eye ointments over eye drops.

  • More stable
  • Less absorption into lacrimal ducts
  • Longer retention time on conjunctival surface
  • Safer with potent drugs
  • Ointment bases provide protection and comfort at night

Pass Criteria:

  • 2 to pass

List by action the types of drugs used topically in the eye.

  • Mydriatics
  • Miotics
  • Cycloplegics
  • Decongestants
  • Antibiotics
  • Antivirals
  • Antiseptics
  • Corticosteroids
  • Local anaesthetics
  • Stains eg. Fluoroscein

Pass Criteria:

  • 4 to pass

List the ideal properties of an ocular local anaesthetic.

  • Quick onset of action ( 10-20 secs. )
  • Useful duration of action ( 10-20 mins )
  • No obvious effects on function or healing
  • No interactions with drugs used concurrently

Pass Criteria:

  • Quick onset and useful duration of action

Q9

What are the medical uses for St Johns Wort?

  • Depression

What are its important drug interactions?

  • Kinetic – CYP inducer (decrease drug effect)
  • Dynamic – inhibits catechol reuptake (potentiates some drug effects)

Q10

What are the clinical uses of H1 antagonists?

Allergic reactions; rhinitis,urticaria, possible role in type I

Motion sickness (best as preventers)

Vestibular disturbance

Nausea and vomiting (esp in pregnancy)

Sedation (mentioned as SFX in book)

Serotonin antagonist (cyproheptadine)

Drug induced Parkinsonism

What are the major adverse effects?

1 Sedation, 2 Antimuscarinic effects, 3 Seizures, 4 Postural hypotension, 5 Drug allergy

What are the significant potential drug interactions?

  • Additive effect with other sedatives
  • Additive effect with Muscarinic and alpha-blocking drugs
  • Grapefruit juice inhibits same p450 group

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