Pharmacology Flashcards
N-acetylcysteine
List its common indications and mechanism
Common indications:
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).
Paracetamol is usually metabolised to a hepatotoxic metabolite nut glutathione detoxifies it. In poisoning with paracetamol, the glutathione is overwhelmed. Acetylcysteins kicks in here and replenishes the stores of gluethione. It also has antioxidant effects which may prevent contrast nephropathy.
May cause bronchospasm so give salbutamol before.
What is the most sensitive marker for ongoing liver injury? I.e. monitoring liver damage after paracetamol toxicity
The INR!
Activated Charocal
Common indications:
1) Single dose may reduce absorption of certain poisons and drugs
2) Multiple doses to actually increase elimination of certain poisons
Van der waals (weak intermolecular) forces are responsible for the action of this as the molecules are adsorbed onto the surface of the charcoal as they travel through the gut. This affinity to the charcoal therefore depends on the ionic status and solubility in water. Weakly ionic hydrophobic substances such as benzodiazepines and methotrexate are generally well adsorbed to the activated charcoal. Iron is strongly ionic and hydrophilic therefore will not be adsorbed.
The elimination works as the charcoal can adsorb substances back into the gut by diffusion as we are maintaining a low concentration in the gut and high in the circulation. The multiple doses make a steep concentration gradient of poison (gut dialysis).
SE: black stools and vomiting
Single dose only given if presenting within 1hr of ingestion unless they have ODd on a drug that delays gastric emptying in which case up to two hours.
Mix AC with water and drink. If unconscious intibate and give via NGT.
Adenosine
First line diagnostic and therapeutic agent in SVT.
Adenosine receptor agonist. Reduces automaticity frequency and increases refractoriness - slows sinus rate, conduction velocity and increases AVN refractoriness.
Many SVTs arise from re-entry circuit than involves the AVN, and because adenosine increases AVN refractoriness, this circuit is broken so the SAN can take control. If the circuit does not involve AVN as in atrial flutter then adenosine will not induce cardioversion but it will still block conduction to ventricles and therefore we can see the atrial rhythm closely on ECG which may help diagnosis.
Half life in plasma less than 10 seconds as the RBCs eat it up!
SE: asystole and bradycardia as it bashes the SAN and AVN - impending doom feeling to patient. Short lived due to half life.
Avoid in suspected bronchospasms as asthma COPD, and those who wont tolerate bradycardia as hypotension and coronary ischaermia.
Caffeine is a competitive antagonist of adenosine receptors and reduces its effect.
Continuous ECG monitoring is a must.
Always given IV Continuous
Adrenaline (epinephrine)
Common indications:
1) Cardiac arrest - part of ALS
2) Anaphylaxis
3) Injected locally into tissue for local vasoconstriction
Adrenaline is a very potent agonist of α1, α2, β1 and β2
adrenoceptors - vasoconstricts skin, mucosal, abdominal visceral vessels. makes heart pump faster and harder. it actually vasodilated the vessels supplying the heart - yay! - great for cardiac arrests.
Additional effects are bronchodilation and suppression of Histamine release from mast cells.
Dangerous drug - anxiety, tremor, headache, palpitations, can cause angina, MI and arrhythmias - esp. if previous heart disease
No contraindications to use in cardiac arrest and anaphylaxis.
In patients receiving treatment with a β-blocker, adrenaline may
induce widespread vasoconstriction, because its α1-mediated
vasoconstricting effect is not opposed by β2-mediated vasodilatation.
During CPR for cardiac arrest, 1mg Adrenaline is given after third shock to shockable rhythm (VF and Pulseless VT) - then given after every cycle of CPR.
Anaphylaxis - use half dose of cardiac arrest - do not give IV in this case unless cardiac arrest also occurs.
In cardiac arrest adrenaline is given from pre filled syringe.
Screw cost of drug in this case
Amiodarone
Used in wide range of tachyarrhythmias including AF, atrial flutter, SVT and refractory VF. Generally used when electrical cardioversion are ineffective or inappropriate.
It blocks sodium, calcium and potassium channels and antagonizes α- and β-adrenergic receptors. These effects reduce automaticity (spontaneous depolarisation) and increases refractoriness, including AVN. This interference of AVN reduces ventricular rate in AF and atrial flutter.
It also increases chance of cardioversion to sinus rhythm.
It can also be used for prevention of VT due to the drugs effect in suppressing automaticity across the ventricles.
SE: due to iodine content of drug it is structurally similar to thyroid hormone - causes thyroid abnormalities includin hypo and hypoer.
VERRRRRYYYY long half life - make take months to be eliminated after stopping.
Avoid in those with severe hypotension, heart block and active thyroid disease.
It is given for VF or pulseless VT immediately after the
third shock in the Advanced Life Support algorithm
Aldosterone antganonists
Common indications:
1) Ascites and oedema due to liver cirrhosis - spironolactone is first line diuretic (it is an aldosterone antagonist)
2) CHF - of at least moderately severity or arising within 1 month of MI, usually as an addition to a beta blocker and ACEi/ARB
3) Primary hyperaldosteronism – when patient awaiting surgery or patients who can’t have surgery to reat their hyperaldosteronism.
Competitively bind to the aldosterone receptor increasing sodium and water excretion, and potassium retention.
Contraindicated in patients with severe renal impariemtn, hyperkalaemia, Addison’s (aldosterone defcient).
Takes severeal days to kick in so loop/thiazide given in combination initially.
Alginates and antacids
Used in GORD and dyspepsia
Most often taken as compound preparations containing an alginate with one o more antacids such as sodium bicarbonate.
Antacids buffer stomach acid whilst alginates increase viscosity of stomach contents thereby reducing reflux.
After reacting with stomach acid, a layer/raft is formed which barriers off the acid from the GOJ.
Magnesium salts can cause diarrhoea.
Aluminium salts can cause constipation
Antacids can reduce serum concentrations of
many drugs, so the doses should be taken at different times. This
applies to ACE inhibitors, some antibiotics (e.g. cephalosporins,
ciprofloxacin and tetracyclines), bisphosphonates, digoxin, levothyroxine
and proton pump inhibitors.
Take after meal, before bedtime, when symptoms occur.
Identify food drink triggers, and stop smoking, raise head of bed.
Allopurinol
Used to protect acute attacks of gout, to prevent uric acid and calcium oxalate renal stones and to prevent hyperuricaemia and tumour lysis syndrome associated with chemotherapy.
Xanthine oxidase inhibitor. Xanthine oxidase usually metabolises purines to uric acid. Inhibiting this lowers uric acid levels –> less chance of uric acid stones in joints/kidneys.
SE include rask, SJS, TEN.
Warning: azathioprine needs xanthine oxidase enzyme to be broken down. If you give allopurinol you are inhibitng this enzyme and therefore azathioprine levels can build up to toxic levels.
When starting
allopurinol for gout, NSAID or colchicine treatment should also be
prescribed and continued for at least a month after serum uric acid
levels return to normal to avoid triggering an acute attack. Although
allopurinol should not be started during an acute attack of gout, patients
who are already on it should continue to take it. Where allopurinol is
used as part of cancer treatment, it should be commenced before
chemotherapy.
Which drugs can precipitate gout?
Treatment with thiazide or loop diuretics increases serum uric acid
concentrations and can cause gout. Low-dose aspirin inhibits renal excretion of uric acid
and can trigger acute attacks of gout. Always consider drug-induced gout as a cause of
new-onset joint pain in patients taking these medicines.
Alpha blockers
Used to improve BPH symptoms. e.g. tamsulosin and doxazosin
Highly selective for α1-adrenoceptor. These are found mainly in SM, including blood vessels and urinary tract (bladder neck and prostate in particular).
Stimulating of α1-adrenoceptor induces contraction - blocking induces relaxation which is why there is symptomatic relief - tamsulosin makes the prostate relax helping reduce obstruction.
α1-adrenoceptor blockers also cause vasodilatation and a fall in BP
Adverse effects include dizziness, syncope and postural hypotension.
Aminoglycosides
Good for severe infections, particularly Gram -ve (inc. pseudomonas aueroginosa)
Used in:
1) Severe sepsis where source is unidentified
2) Pyelonephritis and complicated UTI
3) Biliary and other intra-abdo sepsis
4) Endocarditis
Aminoglycosides irreversibly bind to robosobes in bacteria thereby inhibiting protein synthesis.
They work on Gram -ve aerobic bacteia, staph and mycobacteria.
Strep and anaerobic bacteria are not affected by this class of antibiotic as it enters the bacteria via oxygen dependent transport system which strep and anaerobes do not have. Hence, they have innate resistance.
REMEMBER THAT THIS DRUG CAUSES OTO AND NEPHRO TOXICITY- damages hair cells in inner ear. Caution in paeds/elderly.
Aminoglycosides can impair neuromuscular transmission so should not be
given to people with myasthenia gravis unless absolutely necessary.
Cannot be given orally as they are highly polarised so will not cross lipid membranes.
List of aminoglycosides:
Amikacin
Gentamicin
Kanamycin
Neomycin
Streptomycin
Tobramycin
Aminosalicyclates
1) Mesalazine is first like for mild-moderate UC. Sulfasalazine is alternative but mostly been replaced by mesalazine
2) Sulfasalazine is one of several options for RA, used as DMARD
Antiinflamm. and immunosuppressive effects.
Mesalazine has no role in treating RA.
In men sulfasalazine causes oligospermia whch is reversible.
Avoid in aspirin allergic as these drugs are also salicyclates.
Ace inhibitors
Indications:
1) HTN
2) CHF
3) IHD
4) Diabetic nephropathy and CKD with proteinuria (reduces proteinuria and progression of the nephropathy)
ACEi block action of ACE which converts angiotensin I to angiotensin II. Angiotensin II is a vasoconstrictor and stimulates aldosterone therefore blocking it from being produced with an ACE inhibitor reduces peripheral vascular resistance (afterload), which lowers BP.
Also dilates efferent glomerular arteriole, which reduces intraglomerular pressure slowing progression of CKD
Common side effecs are a persistent dry cough and hypotension. Hyperkalaemia can occur as less aldosterone means less potassium is excreted..
Start on low dose and titrate up. For safety, check electrolytes and renal function
before starting treatment. Repeat these 1–2 weeks into treatment and
after increasing the dose.
Examples are lisinopril and ramipril.
