TOP 100 DRUGS (1-5)

Question 1

01 Acetylcysteine indication

Answer 1

1. As the antidote for paracetamol poisoning.
2. To help prevent renal injury due to radiographic contrast material
   (contrast nephropathy).
3. To reduce the viscosity of respiratory secretions (acting as a
   mucolytic) .

Question 2

01 Acetylcystine MOA (paracetemol OD)

Answer 2

In therapeutic doses, paracetamol is metabolised mainly by conjugation
with glucuronic acid and sulfate. A small amount is converted to
N-acetyl-p-benzoquinone imine (NAPQI), which is hepatotoxic. Normally,
this is quickly detoxified by conjugation with glutathione. However, in
paracetamol poisoning, the body’s supply of glutathione is overwhelmed
and NAPQI is left free to cause liver damage.

Acetylcysteine works
mainly by:
- replenishing the body’s supply of glutathione.
- antioxidant effects, which may contribute to its
the effect in preventing contrast nephropathy
- If acetylcysteine is brought into contact with mucus, it
causes it to liquefy. For patients who have tenacious respiratory
secretions (e.g. in bronchiectasis), this may aid sputum clearance.

Question 3

01 Acetylcystine side effects

Answer 3

• IV large dose anaphylactoid reaction (presenting with nausea, tachycardia,
  rash and wheeze) involves histamine release independent of IgE
  antibodies.
• to settle anaphalaxis:
  stop acetylcysteine, give an antihistamine ± a bronchodilator then it is
  usually safe to restart acetylcysteine, but at a lower rate of infusion.
• When administered in nebulised form as a mucolytic, acetylcysteine may
  cause bronchospasm. Therefore, a bronchodilator (e.g. salbutamol)
  should usually be given immediately beforehand.

Question 4

01 Acetylcysteine contraindications and warning

Answer 4

• History of an anaphylactoid reaction to acetylcysteine does not
  contraindicate its use in future,
• There are no significant adverse drug interactions with acetylcysteine.

Question 5

01 Acetylcycstine Perscription

Answer 5

paracetamol poisoning: weight-adjusted doses are
given as an IV infusion with three components (total infusion time 21
hours).

contrast nephropathy, you
should consult local guidelines as dosing instructions may not be given
in the BNF.

The usual dose is 600–1200 mg orally 12-hrly for 2 days,
beginning the day before the procedure.

For use in tenacious
respiratory secretions, a typical dose is 2.5–5 mL of acetylcysteine
10% solution by nebuliser every 6 hours

Question 6

01 Acetylcysteine monitoring

Answer 6

In the treatment of paracetamol poisoning, patients should be monitored
clinically for signs of anaphylactoid reaction. T

he international normalised
ratio (INR),
serum alanine aminotransferase (ALT) activity creatinine

concentration should be measured at presentation and on completion of
the acetylcysteine.

(The INR is the most sensitive marker of ongoing liver
injury and recovery of liver function in this situation.)

Question 7

02 Activated Charcoal Indications

Answer 7

1. A single dose of activated charcoal may be used to reduce
   absorption of certain poisons (including some drugs in overdose)
   from the gut.
2. Multiple doses of activated charcoal may also be used to increase
   the elimination of certain poisons.

Question 8

02 Activated Charcoal MOA

Answer 8

Van der Waals (weak intermolecular) forces are responsible for the
mechanism of action of activated charcoal.

Molecules are adsorbed onto the surface of the charcoal as they travel through the gut, reducing their absorption into the circulation.

However, activated charcoal is only useful in cases where the poison ingested is likely to be
adsorbed onto it.

The affinity of a substance for activated charcoal is
determined by its ionic status and its solubility in water.

Weakly ionic,
hydrophobic substances (e.g. benzodiazepines, methotrexate) are
generally well adsorbed to activated charcoal. (strongly ionic and hydrophilic substances (e.g. strong acids/bases, alcohols, lithium
and iron) are not adsorbed.)

Activated charcoal can also increase the elimination of certain
poisons. multiple doses
of activated charcoal can be used to maintain a steep concentration
gradient of the poison (high in the circulation, low in the gut),
encouraging diffusion out of the circulation and hastening the elimination of
the drug. This is sometimes referred to as ‘gut dialysis’.

Of note, charcoal is ‘activated’ during preparation through chemical processes, including blasting it with steam or hot air. These processes increase the surface area of the charcoal particles by increasing pore
size. With a surface area around 1000 m2
/g, a lot of poison can be
adsorbed!

Question 9

02 Activated Charcoal

• warnings
• side effects
• interactions

Answer 9

serious complications:
pneumonitis, bronchospasm and airway obstruction, precipitate intestinal obstruction. H

common side effects: black stools and vomiting.

not to be used in patients with a reduced level of consciousness, unless their airway is first protected by
endotracheal intubation.

caution if persistent vomiting/risk of aspiration., reduced GI motility.

Activated charcoal prevents absorption of many drugs taken therapeutically as well as those taken in overdose.

Question 10

02 Activated Charcoal Perscription

Answer 10

single dose of activated charcoal to reduce absorption is recommended only for patients presenting within 1 hour of ingestion of a clinically significant amount of a substance that is adsorbed
by charcoal.

For drugs that delay gastric emptying (e.g. aspirin,
opioids, tricyclic antidepressants), charcoal can be administered up to 2
hours following ingestion.

Activated charcoal should be prescribed on
the once-only section of the drug chart at a dose of 50 g orally (or by nasogastric tube if the patient is intubated).

When using multiple doses
of activated charcoal (potential situations include significant overdose with carbamazepine, quinine, or theophylline – but seek advice), you should prescribe 50 g of activated charcoal to be administered 4-hrly.

• Pre-emptive treatment with an antiemetic and a laxative may be advisable.*
• usually given with 250mL of water which the patient drinks (unconscious NG tube)

no monitoring needed

Question 11

03 Adenosine indication

Answer 11

a first-line diagnostic and therapeutic agent in supraventricular
tachycardia (SVT)

Question 12

03 Adenosine MOA

Answer 12

Agonist of adenosine receptors on cell surfaces.

In the heart, activation of these G protein-coupled receptors induces a number of effects, including reducing the frequency of spontaneous
depolarisations (automaticity) and increasing resistance to depolarisation
(refractoriness).

In turn, this transiently slows the sinus rate, conduction
velocity, and increases atrioventricular (AV) node refractoriness.

Many forms of SVT arise from a self-perpetuating electrical (re-entry) circuit that takes in the AV node.

Increasing refractoriness in the AV node breaks the re-entry circuit, which allows normal depolarisations
from the sinoatrial (SA) node to resume control of heart rate
(cardioversion). Where the circuit does not involve the AV node (e.g. in atrial flutter), adenosine will not induce cardioversion.

However, by
blocking conduction to the ventricles, it allows closer inspection of the atrial rhythm on the ECG. This may reveal the diagnosis. The duration of
effect of adenosine is very short because it is rapidly taken up by cells
(e.g. red cells). Its half-life in plasma is less than 10 seconds.

Question 13

03 Adenosine

- adverse effects

Answer 13

• induce bradycardia (interferes with SA and AV nodes) and even asystole
• deeply unpleasant sensation for the patient (sinking feeling in chest and breathlessness, impending doom)

warnings:
- do not admit if pt will not tolerate transient bradycardia
(hypotension, coronary ischaemia, or decompensated heart failure.)

• can induce bronchospasm (avoid in COPD, asthma, heart transplant)

Dipyridamole blocks cellular uptake of adenosine, which prolongs and potentiates its effect: the dose of adenosine should be halved.

Theophylline, aminophylline and caffeine are competitive antagonists of adenosine receptors and reduce its effectiveness.

Patients who have taken
these drugs respond poorly and may require higher doses.

Question 14

03 Adenosine Perscription

Answer 14

Given IV once-only section of drug chart. the initial dose is 6g IV = 12mg

if central line= lower (3mg)

*large bore cannula (18 gauge green or bigger as proximal as possible e.g anterior cubital fossa.

rapid injection then flushes with 20mL of 0.9% sodium chloride.

the effect will be evident 10-15 seconds then dissipate over 30-60 seconds.

*very close monitoring, continuous cardiac rhythm strip, recorded for subsequent
examination.

Question 15

04 Adrenaline indications

Answer 15

1. cardiac arrest (ALS)
2. anaphylaxis
3. injected directly into the tissue to induce local vasoconstriction. (endoscopy to control mucosal bleeding)
4. prolong anaesthesia: mixed with local anaesthetic
   drugs (e.g. lidocaine) to prolong local anaesthesia.

Question 16

04 Adrenaline MOA

Answer 16

• potent agonist of the α1, α2, β1 and β2 adrenoceptors. multitude of sympathetic (‘fight or flight’) effects.
• vasoconstriction of vessels
  supplying skin, mucosa and abdominal viscera (mainly α1-mediated);
• increases in heart rate, force of contraction and myocardial excitability β1)
• vasodilatation of vessels supplying the heart and muscles (β2).

cardiac arrest: redistribution of
blood flow in favour of the heart is desirable,

β2 receptors: bronchodilatation and suppression of inflammatory mediator release from mast cells. (use in anaphylaxis)

Question 17

04 Adrenaline

• side effects
• warning
• contraindications

Answer 17

• anxiety, tremor, headache and palpitations.
• It may also cause angina, myocardial infarction and
  arrhythmias, particularly in patients with existing heart disease.

to induce local vasoconstriction- caution in patients with heart disease.

if used for anaesthetic- DO NOT use in end artery (poor collateral supply: fingers and toes (tissue necrosis)

Important interactions: β-blocker, adrenaline may
induce widespread vasoconstriction, because its α1-mediated
vasoconstricting effect is not opposed by β2-mediated vasodilatation.

Question 18

04 Adrenaline perscription

Answer 18

cardiac arrest (shockable)
1mg adrenaline IV after the third shock and repeated every 3-5 mins  (1mg in 10mL solutation) followed by flush (10mL of 0.9% NaCl)

not shockable (asystole or pulseless electrical activity), adrenaline 1 mg IV is given as soon as IV access is available, and then repeated every
3–5 minutes. 

anaphylaxis: 500 micrograms (0.5mL of 1:1000) (1mg in 1ML)?
IM, repeated after 5 minutes if necessary. anterolateral aspect of the thigh halfway between the knee and hip.

local anaesthetic to induce local vasoconstriction 1:200,000 (5 micrograms/mL)

Question 19

05 Aldosterone Antagonist indications

Answer 19

1. Ascites and oedema due to liver cirrhosis: spironolactone is the first-line diuretic.
2. Chronic heart failure: of at least moderate severity or arising within 1 month of myocardial infarction, usually as an addition to a β-blocker
   and an ACE inhibitor/angiotensin receptor blocker.
3. Primary hyperaldosteronism: for patients awaiting surgery or forwhom surgery is not an option.

Question 20

05 Aldosterone Antagonist MOA

Answer 20

• aldosterone is a mineralocorticoid that is produced in the adrenal cortex and acts on mineralocorticoid receptors in the distal tubules of the kidney to increase the activity of luminal epithelial sodium channels (ENaC). This
  increases the reabsorption of sodium and water (which elevates blood
  pressure) with the by-product of increased potassium excretion.

Aldosterone antagonists inhibit the effect of aldosterone by
competitively binding to the aldosterone receptor. This increases sodium and water excretion and potassium retention. Their effect is
greatest in primary hyperaldosteronism or when circulating aldosterone
is increased, e.g. in cirrhosis

Question 21

05 Aldosterone antagonist

• side effects
• warning
• contraindications

Answer 21

adverse effect:
hyperkalaemia- muscle weakness, arrhythmias and
even cardiac arrest.

• Spironolactone causes gynaecomastia
• liver impairment and jaundice
• Stevens–Johnson syndrome (a T cell-mediated
  hypersensitivity reaction)

contraindication:
- renal impairment, - hyperkalaemia
- Addison’s disease (who
are aldosterone deficient).

pregnancy:
can cross the placenta during pregnancy and appear in breast milk so should be
avoided where possible in pregnant or lactating women.

risk of hyperkalaemia if on potassium-elevating drugs, including ACE inhibitors and
angiotensin receptor blockers

Question 22

05 Aldosterone antagonist persription

Answer 22

prescribed for regular administration, generally as a single daily dose.

typical starting dose of
spironolactone is 100 mg daily for ascites compared to 25 mg daily forheart failure.

Spironolactone is also available as a combined preparation with a thiazide or loop diuretic. take with food.