Top 100 drugs (Not finished) Flashcards
1
Q
What is the common indication for adenosine?
A
As a first-line diagnostic and therapeutic agent in supraventricular tachycardia (SVT).
2
Q
What is the mechanism of action of adenosine in cardioversion (allowing the depolarisations from the SA node to resume normal control of the heart)?
A
Adenosine is an agonist of adenosine receptors on cell surfaces. In the heart, activation of these GPCRs induces a number of effects: reducing the frequency of spontaneous depolarisations (automaticity) and increaseing resistance to depolarisation (refractoriness). In turn, this transiently slows the sinus rate, conduction velocity, and increases atrioventricular node refractoriness. Increasing the refractoriness in the AV node breaks the re-entry circuit, which allows normal depolarisations from the SA node to resume normal control of heart rate.
3
Q
What is the mechanism of action of adenosine in atrial flutter?
A
Does not induce cardioversion, however by blocking conduction to the ventricles. It allows closer inspection of the atrial rhythm on the ECG. Which may reveal the diagnosis.
4
Q
What are the important adverse effects of adenosine?
A
It interferes with the function of the SA and AV nodes so adenosine can induce bradycardia and even asytole (flat line). Sinking feeling, impending doom, breathlessness.
5
Q
What type of patients are especially sensitive to the effects of adenosine?
A
Those who have had a heart transplant.
6
Q
Which patients should not be administered adenosine?
A
Those who cannot tolerate the transient bradycardic effects, hypotensive patients, those with coronary ischaemia or decompressed heart failure. As adenosine may also induce bronchospasm it should be avoided in those such as people with asthma or copd or may be suceptible.
7
Q
Why would we avoid adenosine in a COPD patient?
A
As adenosine may also induce bronchospasm it should be avoided in those such as people with asthma or copd or may be suceptible.
8
Q
What is the interaction between adenosine and dipyridamole?
A
Dipyridamole (is a medication that inhibits blood clot formation when given chronically and causes blood vessel dilation when given at high doses over a short time) blocks cellular uptake of adenosine, which prolongs and potentiates the effects of adenosine.The adenosine dose should be halved.
9
Q
What is the interaction between adenosine and theophylline, aminophylline and caffeine?
A
Theophylline, aminophylline and caffeine are all competitive antagonists of adenosine receptors and may reduce its effect - may require higher doses.
10
Q
How is adenosine given and at what doses? where would it be found on the drug chart?
A
IV, once-only section, 6mg IV or 12mg in selected cases.
11
Q
What are the three main indications for Aldosterone antagonists?
A
- Ascities 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 a MI, usually as an addition to a B-blocker and an ACEI/ATRB.3. Primary hyperaldosteronism for patients awaiting surgery or for those who surgery is not an option.
12
Q
What are the two common examples of aldosterone antagonists?
A
Spironolactone + epleronone
13
Q
What is the first - line diuretic for ascities and oedema due to liver cirrhosis?
A
Spirinolactone
14
Q
What is the place in the heart failure therapy of an aldosterone antagonist?
A
Moderate severity heart failure or heart failure within 1 month of a MI.Used in addition to a B-blocker and an ACEi/ATRB
15
Q
When are aldosterone antagonists used in the treatment of primary hyperaldosteronism?
A
While awaiting surgery or when surgery is not an option.
16
Q
Where is aldosterone produced and what is its mechanism of action?
A
Mineralcorticoid produced in the adrenal cortex which acts on mineralcorticoid 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 elavates blood pressure and heartload) with the by-product of increased potassium excretion.
17
Q
What is the by-product of the increased sodium and water retention caused by aldosterones? (electrolyte)
A
Increased potassium excretion = hypokaleamia
18
Q
What is an important adverse effect of aldosterone antagonists?
A
Hyperkalaemia (aldosterone can cause hypokalaemia).But also liver impairment, jaundice and Stevens-Johnson syndrome which is a T-cell mediated hypersensitivity reaction.
19
Q
What are the symptoms of hyperkalaemia caused by aldosterone antagonists?
A
Muscle weakness, arrhythmias and even cadiac arrest.
20
Q
What is the most common reason males stop taking spironolactone?
A
Gynaecomastia + impotence. These are benign and reversible and may abate on dose reduction.
21
Q
Aldosterone antagonists such as epleronone and spironolactone are contraindicated in which patient groups? [4]
A
- Severe renal impairment2. Hyperkalaemia 3. Addisons disease (aldosterone deficient) 4. Aldosterone antagonists can cross placenta and appear in breast milk so should be avoided in pregnant/breast feeding women when possible.
22
Q
The combination of an aldosterone antagonist with ACE inhibitors and aniotensin receptor blockers increases the risks of what?
A
Hyperkaleamia.
23
Q
Epleronone is an aldosterone antagonist which is only licensed for the treatment of
A
heart failure, spironolactone: acities/oedema due to liver cirrhosis, primary hyperaldosteronism + heart failure.
24
Q
What are the typical starting doses for spironolactone in the treatment of ascities and heart failure?
A
Ascities: 100mg dailyHeart failure: 25mg daily.
25
Which aldosterone antagonist is also available as a combined preparation with a thiazide or loop diuretic?
Spironolactone: Lasilactone 20mg/50mg capsules: furosemide (LD).CO-FLUMACTONE: Hydroflumethiazide
26
When should spironolactone generally be taken?
With food.
27
What monitoring is needed for Aldosterone antagonists?
Efficacy: patient reporting and clinical findings i.e. reduction in ascities or blood pressure.Safety: renal function and serum K+ concentration due to risk of renal impairment and hyperkalaemia.
28
Why should spironolactone be prescribed instead of epleronone?
A month of spironolactone = £1.50, epleronone = £40 as it is still protected by patent.
29
Why is spironolactone usually precribed alongside a loop or thiazide diuretic?
It is a relatively weak diuretic that takes several days to start having an effect.
30
In the treatment of ascities due to chronic liver failure, spironolactone and furosemide are generally used together in a ratio of what?
5:1 eg spironolactone 200mg, furosemide 40mg.
31
What are the common indications of alpha-blockers?
1. First-line medical option to improve symptoms in benign prostatic hyperplasia, which lifestyle changes are insufficient. [5alpha-reductase inhibitors may be added in selected cases, surgical treatment is also an option - especially if evidence of urinary tract damage]2. As an add-on treatment in resistant hypertension, when other medicines (eg CCB, ACEI, thiazide diuretics) are insufficient.
32
Why is the term alpha blocker not the most accurate when describing drugs such as doxazosin, tamsulosin and alfuzosin?
They are highly selective for the alpha-1 adrenoreceptor which are found mainly in smooth muscle, including blood vessels and the urinary tract. Stimulation induces contraction; blockade induces relaxation. Alpha-blockers therefore cause vasodilation and a fall in blood pressure, and reduced resistance to bladder outflow.
33
What is the mechanism of action of doxazosin, tamsulosin and alfuzosin in the treatment of BPH and resistant hypertension?
They are highly selective for blocking the alpha-1 adrenoreceptor which is found mainly in smooth muscle, including blood vessels and the urinary tract. The blockade induces relaxation and a fall in blood pressure, and reduced resistance to bladder outflow.
34
What are the important adverse effects of alpha-blockers?
Predictably from their effects on vascular tone, alpha-blockers can cause postural hypotension, dizziness and syncope.
35
When are the adverse effects of alpha-blockers most prominent?
After the first dose - similar to ACE inhibitors and angiotensin receptor blockers.
36
In what patients should alpha blockers not be used in?
In those patients with existing postural hypotension.
37
What are the important interactions with regard to the use of alpha blockers?What adjustments to a patients existing medicines regime may need to be made?
Combining anti-hypertensive drugs results in additive blood pressure lowering effects. In order to avoid pronounced first-dose hypotension, we may need to omit doses of one or more existing anti-hypertensive drugs on the day the alpha blocker is started. This is particularly the case for B-blockers, which inhibit the reflex tachycardia that forms part of the compensatory response to vasodilation.
38
What is the main difference between the licensing for Doxazosin and Tamsulosin?
Doxazosin is licensed both for BPH and hypertension, tamsulosin is only licensed for BPH - this is because it has a less pronounced blood pressure lowering effect.
39
What is the typical starting dose for Doxazosin for both BPH and hypertension?
1mg daily and increased at 1-2 weeks intervals according to response.
40
When is the best time to take doxazosin, at least initially?
Because of the pronounced blood pressure lowering effect of doxazosin, it is best taken at bedtime, at least initially.
41
Why might we introduce an alpha blocker at an earlier stage in the hypertension treatment pathway for a man?
They may also have BPH and thus an alpha blocker could relieve symptoms of both with the use of a single drug.
42
Why would we use modified release forms of alpha blockers?
There is little convincing evidence that MR forms are any more effective than standard-release forms and since they are taken at the same frequency (daily) they do not improve convenience for patients. As they are branded products they are more expensive for the NHS.
43
Long acting nitrates are used for what?
Isosorbide nitrate is used for the prophylaxis of angina where a beta blocker and/ or a ccb has been insufficient or not tolerated
44
What are intravenous nitrates used for?
IV nitrates are used in the treatment of pulmonary oedema usually in combination with furosemide and oxygen
45
What are short acting nitrates used for?
Treatment of acute angina and the chest pain associated with acute coronary syndrome
46
What is the mechanism of action of nitrates?
Nitrates are converted to nitric oxide (NO) which increases cGMP synthesis and reduces intracellular calcium in smooth muscle cells causing them to relax and a reduction in cardiac preload and ventricular filling.
47
What are the important adverse effects of nitrates?
They are vasodilator so can cause: flushing, headaches, lightheadedness and hypotension. Sustained nitrate use can cause tolerance thus a nitrate free period overnight needs to be adhered to: take morning and afternoon
48
In who should the use of nitrates be contraindicated?
Patients with severe aortic stenosis as can cause cardiovascular collapse. Patients with haemodynamic instability such as hypotension.
49
What is an important prescribing issue when dealing with prescriptions for generic modified release isosorbide mononitrate?
It must be prescribed by brand are there are important differences between preparations.
50
What are the practical communication points regarding a prescription for nitrates?
Patient may develop headache when starting nitrates but normally passes.Patient should use sublingual GTN before tasks that normally bring on their angina. Due to the risks of postural hypotension, it is a good idea to advise them to sit down and rest before and for 5 minutes after taking sublingual GTN.Due to the risk of tolerance, doses should be taken morning and afternoon with twice daily isosorbide mononitrate.
51
What are the major interactions to be aware of with nitrate drugs?
Contraindicated in patients using phosphodiesterase inhibitors such as sildenafil, as they enhance and prolong the hypotensive effect of nitrates.Nitrates should also be used with care in patients on antihypertensive medication as they may precipitate hypotension.
52
What are the common indications for aspirin use?
1. Treatment of ACS and acute ischaemic stroke - where the rapid inhibition of platelet aggregation can prevent or limit arterial thrombosis and reduce mortality.2. Secondary prevention of thrombotic arterial events in patients with cardiovascular, cerebrovascular and peripheral arterial disease.3. As an alternative to warfarin and novel anticoagulants to reduce the risk of intracranial thrombus and embolic stroke in AF 4. Mild to moderate pain relief and fever.
53
What is the mechanism of action of aspirin?
Aspirin irreversibly inhibits COX to reduce the production of the pro-aggregatory factor thromboxane from arachidonic acid, reducing platelet aggregation and the risk of arterial occlusion.The antiplatelet effect of aspirin occurs at low doses and lasts for the lifetime of the platelet as they do not have Nuclues and thus no ability to synthesis New COX.
54
What are the important adverse effects of aspirin?
GI upset but more serious include gastrointestinal ulceration, bronchospasm etc. In regular high dose aspirin therapy tinnitus can occur.ASPIRIN is life threatening in overdose: hyperventilating, metabolic acidosis, confusion followed by convulsions, cardiovascular collapse and respiratory arrest.
55
Why should aspirin not be given to people under the age of 16?
There is the risk of Reye’s syndrome, a rare but life threatening illness that principally affects the liver and brain.
56
Can aspirin be used by people with asthma?
Yes, but it should not be taken by people with aspirin hypersensitivity.
57
Can aspirin be used safely in pregnancy?
Aspirin should not be used in the third trimester or pregnancy because prostaglandin inhibition may lead to premature closure of the ductus arteriosus.
58
Can someone taking allopurinol use aspirin?
Aspirin should be avoided in people with gout as it can precipitate an attack.
59
What are the main interactions for aspirin?
Aspirin acts synergistically with other antiplatelet agents which can cause increased risk of bleeding so caution must be used when using it with clopdigrel, warfarin etc,
60
What are the common indications for clopidogrel?
1. Treatment of acute coronary syndrome, where rapid inhibition of platelet aggregation can prevent or limit arterial thrombosis and mortality.2. To prevent occlusion of coronary artery stents3. For long term secondary prevention of thrombotic arterial events in patients with cardiovascular, cerebrovascular and peripheral arterial disease. 4. To reduce the risk of intracardiac thrombus and embolic stroke in atrial fibrillation where warfarin and novel oral anticoagulants are contraindicated.
61
How does clopidogrel inhibit platelet aggregation?
Clopidogrel binds irreversibly to adenosine diphosphate (ADP) receptors ( the p2712 subtype) n the surface of platelets. As this process is independent of the cyckoxygenase pathway, it’s actions are synergistic with those of aspirin.
62
What are the main risks of clopidogrel use?
Bleeding in the GI tract and thrombocytopenia
63
Who should clopidogrel not be used in?
Anyone with active bleeding and may need to be stopped 7 days before elective surgery. It should also be used with caution in patients with renal and hepatic impairment.
64
Why may clopidogrel efficacy be reduced by cytochrome p450 inhibitors such as omeprazole, erythromycin, ciprofloxacin, some antifungals and SSRIs?
Clopidogrel is a pro drug that requires metabolism by hepatic p450 enzymes to be activated.
65
Why is omeprazole not first line for GI protection in patients taking clopidogrel?
Clopidogrel is a pro drug which needs activation by hepatic metabolism via p450 enzymes and omeprazole is a cyp450 enzyme inhibitor which can lead to reduced levels of clopidogrel. Lansoprazole and pantoprazole are preferred
66
Why must clopdigrel be stopped 7 days before elective surgery?
It acts irreversibly on the ADP surfacer receptor therefore the effect lasts for the lifespan of the platelet 7-10 days.
67
What are the clinical indications for the use of loop diuretics?
Relief of breathlessness in acute pulmonary oedema in conjunction with 02 and nitrates (IV).Symptomatic relief of fluid overload in chronic heart failure.Symptomatic relief of fluid overload in other oedematous states, eg renal failure, liver failure, where they may be given in conjunction with other diuretics
68
How do loop diuretics work? (2)
Act on the ascending limb of the loop of Henle. They inhibit the Na+/K+/2Cl-co-transporter which is the protein responsible for transporting sodium, potassium and chloride ions from the tubular lumen into the epithelial cell. Water then follows by osmosis. Inhibiting this process has a potent diuretic effect. In addition, loop diuretics also cause dilution of capacitance veins.In acute heart failure, this reduces preload and improves contractile function of the overstretched heart muscle.
69
Why, when taken chronically, can loop diuretics worsen gout?
They inhibit Uric acid excretion.
70
Why can loop diuretics cause practically any low electrolyte state?
Inhibiting the Na+/K+/2Cl- co transporter increases urinary losses of sodium, potassium, and chloride ions. Indirectly, this also increases excretion of magnesium, calcium and hydrogen ions.
71
How can loop diuretics, at high doses lead to hearing loss and tinnitus?
A similar sodium potassium chloride co transporter to the one they inhibit in the ascending limb of the loop of henle is present in the ear and is responsible for regulating endolymph composition.
72
In who are loop diuretics contra indicated?
Patients with severe hypovolemia or dehydration.
73
In who should the use of loop diuretics only be used with caution?
Patients at risk of hepatic encephalopathy (where hypokalaemia can cause or worsen coma.Those with severe hypokalaemia and or hyponatraemia.Taken chronically, loop diuretics have the potential to affect uric acid excretion and worsen gout.
74
What are two examples of loop diuretics?
Furosemide and bumetanide.
75
Loop diuretics have the potential to affect drugs that are excreted by the kidneys. What are 3 drugs/drug classes that this is clinically relevant to?
Lithium levels are increased due to reduced excretion. The risk of digoxin toxicity is increased due to the diuretic associated hypokalaemia.The ototoxicity and nephrotoxicity of aminoglycosides can be increased.
76
In the context of severe fluid overload, why might furosemide be given via IV?What could be an alternative and why?
The proportion of furosemide absorbed from the gut, its bioavailability, is highly variable both between and within individuals.In cases of severe fluid overload this is particularly the case, presumably due to gut wall oedema. This can be circumvented by using it via IV but not always desirable. Bumetanide has a more predictable BA and may be a better choice. 1mg of bumetanide is the equivalent of 40mg furosemide.
77
What is the dose equivalence between furosemide and bumetanide?
1mg bumetanide = 40mg furosemide
78
When should oral maintenance doses of a loop diuretic, such as furosemide or bumetanide, be taken and why?
In the morning and with a second in the afternoon if needed to avoid causing nocturia
79
What is the most important patient counselling point for loop diuretics?
Will make them pee more so should not be taken at night.
80
How does warfarin treatment differ regarding tissue heart valve replacement and mechanical heart valve replacement?
Short term after tissue replacement. Long-term after mechanical.
81
Why is warfarin not used for the prevention of ARTERIAL thrombosis?
Myocardial infarction, thrombotic stroke etc are driven by platelet aggregation, which are prevented by anti-platelet agents such as aspirin and clopidogrel.
82
How does warfarin work?
Warfarin inhibits hepatic production of vitamin-k dependent coagulation factors and co factors.Vitamin k must be in its reduced form for the synthesis of coagulation factors.It is then oxidised and then reactivated by vitamin k epoxide reductase. Warfarin inhibits vitamin k epoxide reductase, preventing the reactivation of vitamin k and hence coagulation factor synthesis.
83
Who should not take warfarin?
Those with active bleeding, those with at immediate risk of haemorrhage, people with liver diseases are less able to metabolise the drug and thus are at an increased risk of overanticoagulation.Warfarin should not be used in the first trimester because it can cause fetal malformations and should not be used towards term as it can cause maternal haemorrhage at delivery.
84
How do many antibiotics cause an increase in anticoagulation in warfarin patients?
Many antibiotics can increase anticoagulation in patients on warfarin by killing gut flora which synthesises vitamin K
85
What effect do cytochrome p 450 inhibitors have on the metabolism of warfarin?
Cytochrome p 450 inhibitors decrease warfarin metabolism and this increase the risk of bleeding. Relevant examples include fluconazole, macrolides and protease inhibitors.
86
What effect do cytochrome p 450 inducers such as phenytoin, rifampicin and carbamazepine have on the metabolism of warfarin?
Increase it and thus increased risk of clots occurring.
87
Warfarin is taken orally once-a-day. The dose is 5-10 mg on day one with a lower dose used for patients who are elderly lighter and increased risk of bleeding due to interacting medicines for example.How are subsequent warfarin doses calculated?
INR.
88
After starting warfarin it takes several days for full anticoagulation to be achieved.Patients requiring immediate Anticoagulation are normally started on warfarin and what other drug?
Heparin as it has a fast onset of action. Heparin is with drawn one full anticoagulation with warfarin is achieved.
89
Single episode of VTE requires treatment with warfarin of what duration?
Treatment may last for between three and six months. Lifelong warfarin may be required for recurrent VTE or for cardiac disease.
90
When is warfarin normally taken and why?
Warfarin is normally taken around 6 PM every day for consistent effects on the INR in the following morning
91
What is the INR?
This is the prothrombin time as a person on warfarin divided by that of a non-wharf a nice control person.
92
What is the INR target of a patient with AF or in VTE?
2.0-3.0
93
What are the costs of warfarin?
Warfarin costs about 1 pound per month but the associated monitoring costs at this. Novel oral anticoagulants such as The bigger tram and River rocks are banned have a similar efficacy to warfarin slightly better safety profiles and require less intensive monitoring however they are more expensive and this cost is likely a barrier to the NHS adopting them
94
How is digoxin used in AF and atrial flutter?
Digoxin is used in atrial flutter and AF to reduce the ventricular rate.However, a beta blocker of a non-dihydropyridine calcium channel blocker is usually more effective.
95
When is digoxin used in severe heart failure?
Third line treatment in people who are already taking an ACEi, beta blocker and either an aldosterone antagonist Or an angiotensin receptor blocker.It is used at an earlier stage in patients with co-existing AF.
96
How does digoxin work? What is it’s mechanism of action?
Digoxin is negatively chronotopic. This means it reduces the heart rate. Digoxin is ask positively inotropic, this means it increases the force of the heart contraction. So it has the effect of slowing the heart rate down and increasing the force with which it beats.
97
What is the therapeutic effect of digoxin in treating atrial flutter and atrial fibrillation?
Via an indirect route involving increased vagal (parasympathetic) tone. This reduces conduction at the atrioventricular node, preventing some impulses from being transmitted to the ventricles, thereby reducing the ventricular rate.
98
How does digoxin work in heart failure?
In heart failure, digoxin has a direct effect on myocytes via inhibition the sodium potassium ATPase pumps, causing sodium to accumulate in the cell. As the cellular extrusion of calcium ions requires low sodium levels intracellularly, elevation of the intracellular sodium causes calcium ions to accumulate in the cell, increasing the contractile force.
99
How is digoxin eliminated?
Renally, so the dose needs to be reduced in renal impairment.
100
Certain Electrolyte abnormalities increase the risk of the jocks in toxicity, Which of these disturbances is probably the most important? Why?
Potassium disturbance is probably the most important as digoxin competed with potassium to bind the sodium potassium ATPase pump, thus when serum potassium levels are low, more digoxin can bind at the pump and thus more therapeutic effect is seen which can cause toxicity.
101
What are the main side effects of digoxin? Less serious and serious.
Bradycardia, gastrointestinal upset, rash, dizziness and even visual disturbances ( blurred or yellow vision).Serious: a wide range of arrhythmia can be caused by digoxin and these may be life threatening.
102
What is the common indication for nicorandil?
Prevention and treatment of chest pain in people with STABLE angina. The first choice treatments for stable angina are beta blockers and CCB, individually or in combination. Nicorandil (or a long -acting nitrate) may be used if these drugs are insufficient or not tolerated.
103
What is the mechanism of action of nicorandil?
Nicorandil causes both arterial and venous vasodilation through its action as a nitrate. (NO = more GMP= more CA leave cell, more relaxation). IT also works by activating K+-ATP channels. Efflux of K+ through activated K+-ATP channels leads to hyperpolarisation of the cell membrane and subsequent inactivation of voltage-gated Ca2+ channels, the net effect is a decrease in free intracellular calcium.
104
What are the unwanted effects of nicorandil use?
Vasodilation causes flushes, dizziness and headache. Nicorandil can also cause nausea, vomting and hypotension. Less frequently it can cause GI, skin or mucosal ulceration which responds to withdrawal of treatment.
105
What are the warnings associated with nicorandil usage?
Not to be used in patients with poor left ventricular function, hypotension or pulmonary oedema. This is because it can worsen these conditions. As wth nitrates, the hypotensive side effects of nicorandil are significantly enhanced by phosphodiesterase inhibitors (e.g. sildenafil) and they should not be prescribed together.
106
How is nicorandil inititated?
It is started at a low dose of 5-10mg twice daily and increased to 20-30mg twice daily as the patient becomes tolerant of the vasodilatory adverse effects.
107
What are the two indications for the use of dipyridamole?
1. In cerebrovascular disease for secondary prevention of stroke.Dipyridamole is currently first-line therapy following a transient ischaemic attack, and second-line therapy following an ischaemic stroke where clopidogrel is contraindicated or not tolerated. Should usually be given with aspirin but monotherapy is possible if aspirin not used. 2. To induce tachycardia during a myocardial perfusion scan in the diagnosis of ischaemic heart disease.
108
What are the antiplatelet mechanisms of action of dipyridamole?
The end effect is an increase in intra-platelet cyclic adenosine monophosphate (cAMP) that inhibits platelet aggregation, reducing the risk of arterial occlusion. Its vasodilatory effects are due to blocking the cellular uptake of adenosine, prolonging its effect on blood vessels to produce vasodilation.
109
How does dipyridamole produce vasodilation?
Blocks cellular uptake of adenosine, prolonging its effect on blood vessels to produce vasodilation. Its antiplatelet effects are due to an increase in intra-platelet adenosine monophosphate (cAMP) that inhibits platelet aggregation, reducing the risk of arterial occlusion.
110
What are the important adverse effects of dipyridamole?
They relate to its vasodilatory (headache, flushing, dizziness, GI symptoms) and antiplatelet effects (increased bleed risk, and rarely thrombocytopenia).
111
Why should dipyridamole be used with caution in patients with ischaemic heart diease, aortic stenosis and heart failure?
It causes vasodilation and tachycardia that can exacerbate these conditions.
112
What are the important interactions with dipyridamole?
Dipyridamole + other antiplatelets/anticoagulants = increased sick of bleeding.Prolongs the effects of adenosine.
113
Current evidence is strongest for the use of what form and strenght of dipyridamole?
mr 200MG BD, should be taken with food and not crushed but swallowed whole.
114
When is amiodarone used?
In the management of tachyarrhythmias, including AF, atrial flutter, supraventricular tachycardia, ventricular tachycardia and refractory ventricular fibrillation. It is generally only used when other therapeutic options (drugs or electrical cardioversion) have been ineffective or not tolerated.
115
How does amiodarone work?
Amiodarone has many effects on myocardial cells, including blockade of sodium, calcium and potassium channels and antagonism of alpha and beta adrenergic receptors.
116
When taken chronically amiodarone can have a number of adverse effects such as:
Pneumonitis (lungs)Bradycardia, AV block (heart)Hepatitis (liver)Photosensitivity and grey discolouration (skin)Thyroid abnormalities due to its high iodine content and structural similarities to thyroid hormone.
117
In what patients whould amiodarone be avoided?
Patients with severe hypotension, those with heart block and those with any active thyroid disease.
118
What are the most important drug interactions with amiodarone?
Amiodarone increases the plasma concentrations of:Digoxin VerapamilDiltiazem This may increase the risk of bradycardia, AV block and heart failure. The doses of these drugs should be halved if amiodarone is initiated.
119
When is atropine used?
First-line in the management of severe or symptomatic bradycardia to increase heart rate.
120
When is hyoscine butylbromide used?
1. First-line for IBS due to antispasmodic effect2. End of life to reduce copious respiratory secretions.
121
How do antimuscarinic drugs achieve their actions?
Atropine, hyoscine butylbromide, glycopyrronium bind to the muscarinic receptor and act as competive inhibitors of acetylcholine. Stimulation of the muscarininc receptors brings about a range of parasympathetic 'rest and digest' effects. By blocking the receptor, antimuscarinics have the opposite effects: they increase heart rate and conduction, reduce smooth muscle tone and peristaltic contraction, including in the fut and urinary tract. They reduce secretions from glands in the respiratory tract and gut.
122
What are the adverse effects of drugs such as atropine, hyoscine butylbromide and glycopyrronium?
As they are antimuscarinic they have predictable side effects of tachycardia, dry mouth and constipation. By reducing destrusor muscle activity, they can cause urinary retention in patients with benign prostatic hypertrophy. The occular effects may cause blurred vision. Atropine has central effects so can cause drowsiness and confusion, particularly in the elderly.
123
In which patients should antimuscarinics be used with caution?
In patients susceptible to angle-closure glaucoma, in whom they can precipitate a dangerous rise in intraocular pressure. They should generally be avoided in patients at risk of arrhythmias unless the indication for use is bradycardia.
124
What is the main clinical difference between atropine and glycopyrronium?
Glycopyrronium does not cross the BB and hence causes less drowsiness but it is not widely available on hospital wards.
125
What are the indications for amlodipine use?
First line in over 55 or black as step 1 hypertension management, also see nifedipine to a lesser degree
126
All calcium channel blockers can be used to control symptoms in people with what? What is the main alternative?
Stable angina, beta blockers being the main alternative
127
Diltiazem and Verapamil are used to control cardiac rate in people with what’s?
supraventricular arrhythmia including supraventricular tachycardia, atrial flutter and atrial fibrillation
128
How do calcium channel blockers work in hypertension management?
CCBS decrease calcium entry into vascular and cardiac cells, reducing intracellular calcium concentration. This causes relaxation and vasodilation in arterial smooth muscle, lowering arterial pressure.
129
How do ccbs function in the management of stable angina?
In the heart, ccbs reduces myocardial contractility, they suppress cardiac contraction, particularly across the atrioventricular node, slowing the ventricular rate. Reduced cardiac rate, contractility and afterload reduce myocardial oxygen demand, preventing angina.
130
CCBs can be divided into what?
Two classes:Dihydropyridines, such as amlodipine and nifedipine which are relatively selective for the vasculature.Non-dihydropyridines such as verapamil and diltiazem which are more selective for the heart. Verapamil is the most cardio selective with diltiazem having some effect on vessels.
131
Which ccb is most cardioselective?
Verapamil, diltiazem has some effect on the vasculature.
132
What are the common side effects of amlodipine and nifedipine?
Ankle swelling, flushing, headache and palpitations which are caused by vasodilation and compensatory tachycardia.
133
What are the common side effects of verapamil?
Constipation and less often, but more seriously heart block, cardiac failure and bradycardia.
134
What are the common side effects of verapamil?
Because it has mixed cardio selective and vascular effects it can cause ankle oedema, flushing, headache, plalpitaitons, constipation, bradycardia, heart block and cardiac failure.
135
Why should verapamil and diltiazem be used in caution in people with poor left ventricular function?
Their use can precipitate or worsen heart failure. They should also generally be avoided in people with AV nodal conduction delay in whom they can provoke complete heart block.
136
Why should amlodipine and nifedipine be avoided in patients with unstable angina?
Vasodilation causes a reflex increase in contractility and tachycardia, which increases myocardial oxygen demand.
137
Non-dihydropyridine calcium channel blockers such as verapamil and diltiazem should not be prescribed with what drug class?
Beta blockers unless under specialist treatment.
138
Why should non-dihydropyridine calcium channel blockers such as verapamil and diltiazem not be prescribed alongside beta blockers?
Both drug classes are negatively inotropic and chronotropic, and together may cause heart failure, bradycardia and even asystole.
139
Why must longer-acting preparations of nifedipine and diltiazem be prescribed by brand?
Different modified release preparations may not be bioequivalent.
140
What is the first choice agent for pharmacological VTE prophylaxis in hospital inpatients and for the initial treatment of deep vein thrombosis and pulmonary embolism?
Low molecular weight heparin (LMWH) such as enoxaparin, dalteparin, fondaparinux, unfractionated heparin etc.
141
LMWH or fondaparinux are part of first line therapy to improve revascularisation and prevent intracoronary thrombus progression in what condition?
ACS: acute coronary syndrome.
142
How do low molecular weight heparins work?
They preferentially inhibit factor Xa.
143
How does unfractionated heparin work?
UFH activates antithrombin that, in turn, inactivates clotting factor Xa and thrombin.
144
Do LMWH and UFH use require laboratory monitoring?
Only UFH as LMWH have a more predictable effect.
145
What is fondaparinux?
Fondaparinux is a synthetic compound that is similar to heparin. it inhibits factor Xa only. It appears to have a similar efficacy to LMWH and has become the anticoagulant of choice in the treatment of ACS in many hospitals across the UK.
146
What are the main important adverse effects of heparins?
Bleeding is the main one, funnily enough. Injection site reactions.Rarely: heparins may cause a dangerous syndrome characterised by low platelet count and thrombosis (heparin-induced thrombocytopenia), this immune reaction is less likely with LMWH and fondaprinux than UFH.
147
In major bleeding associated with heparin therapy, what can be given to reverse anti-coagulation?
Protamine, this is also effective for UFH but much less so for LMWH. It is ineffective against fondaparinux.
148
What are the indications for gabapentin and pregabalin? (4)
1. Focal epilepsies - usually as an addon treatment when other antiepileptic drugs provide inadequate control as monotherapy. 2. Neuropathic pain; pregabalin in particular is recommended as a second-line option in painful diabetic neuropathy (after duloxetine) and as a first-line option in other painful neuropathies. 3. Gabapentin is used in migraine prophylaxis.4. Pregabalin is used in generalised anxiety disorder.
149
How do gabapentin and pregabalin work?
Despite being a closely related structural analogue of GABA (the major inhibitory neurotransmitter), gabapentins mechanism of action is due to binding to voltage-sensitive calcium channels, where it presumably prevents the inflow of calcium ions and therefor inhibits neurotransmitter release: interfering with synaptic transmission and reducing neuronal excitability. Pregabalin is a structural analogue of gabapentin and presumably has a similar mec of action.
150
What are the main side effects of gabapentin and pregabalin?
There are more well tolerated than other AEDs: main side effects are transient drowsiness, dizziness and ataxia which will usually improve over the first few weeks of treatment.
151
When should doses of pregabalin and gabapentin be reduced?
Renal impairment as they are renally excreted.
152
What are the important drug interactions with gabapentin and pregabalin?
Very few, sedative effect may be enhanced when used alongside benzo's/other sedating drugs.
153
What are the practical prescribing points wrt pregabalin and gabapentin?
To improve tolerability, they are started at low doses and increased over subsequent days and weeks to reach a dose that strikes the optimal balance between benefits and side effects.
154
What is the only indication of the Z-drugs?
Short term treatment of insomnia which is debilitating or distressing.
155
What is the mechanism of action of Z-drugs? What is it similar to?
Similar mechanism of action to benzodiazepines, despite being chemically distinct. Their target is the GABA type A receptor which is a chloride channel that opens in response to binding by GABA - the main inhibitory neurotransmitter in the brain. Opening the channel allows chloride to flow into the cell, making the cell more resistant to depolarisation. Z-drugs, like BZs potentiate the effect of GABA leading to a widespread depressant effect on synaptic transmission.
156
What are the important adverse effects of Z-drugs?
Daytime sleepiness, rebound insomnia upon stopping. Zopiclone can cause taste disturbance. Zolpidem can cause GI upset. Prolonged use of Z-drugs beyond 4 weeks can cause dependence and withdrawal symptoms upon stopping.
157
In who should Z-drugs be used with caution?
Elderly as more susceptible to drugs with central nervous system effects.Should not be prescribed for people with obstructive sleep apnoea or those with respiratory muscle weakness or respiratory depression.
158
What are the main interactions to be away of with Z-drugs?
Z-drugs enhance the sedative effect of alcohol, antihistamines and benzos.They also enhance the hypotensive effect of antihypertensive medications. Z-drugs are metabolised by CYP450 enzymes so P450 inhibitors such as macrolides can enhance sedation, while P450 inducers such as phenytoin and rifampicin can impair sedation.
159
What is the interaction between Z-drugs and phenytoin and rifampicin?
Impaired sedation due to action as P450 inducers leading to increased metabolism of z-drugs
160
What is the interacton between macrolides and Z-drugs?
Enhanced sedation due to macrolides inhibiting P450 metabolism of Z-drugs.
161
What are the clinical indications for first generation (typical) antipsychotics? (4)
1. Urgent treatment of severe psychomotor agitation that is causing dangerous or violent behaviour, or to calm patients to permit assessment. 2. Schizophrenia, particularly when the metabolic side effects of 2nd gen are likely to be problematic. 3. Bipolar disorder, particularly in acute episodes of mania or hypomania. 4. Nausea and vomiting, particularly in the palliative care setting.
162
How do antipsychotic drug works?
They block post-synaptic dopamine D2 receptors.
163
D2 blockade of what pathway is probably the main determinant of antipsychotic effect by antipsychotic drugs?
The mesolimbic/mesocortical pathway which runs between the midbrain and the limbic system/frontal cortex.
164
Blockade of D2 receptors in what zone are responsible for the use of antipsychotics in nausea and vomiting?
D2 receptors in the chemoreceptor trigger zone.
165
What are the main drawbacks of the first generation antipsychotics? What causes this?
D2 blockade of the nigrostriatal pathway causes extrapyramidal side effects: acute dystonic reactions are involuntary parkinsonian movements or muscle spasms; akathisia is a state of inner restlessness; and neuroleptic malignant syndrome is rare but life-threatening. Tardive dyskinesia occurs after months or years of treatment.
166
What other side effects of first generation antipsychotics exist? (other than movement side effects)
Drowsiness, hypotension, QT-interval prolongation, ED and hyperprolactinaemia due to tuberhohypophyseal D2 blockade (menstrual disturbance, galactorrhoea and breast pain).
167
Why should antipsychotics ideally be avoided in dementia patients?
They may increase the risk of death and stroke. Also should ideally be avoided in possible in parkinson patients due to their extrapyramidal side effects.
168
Why should amiodarone/macrolifes not be used alongside first gen antipsychotics?
They all prolong the QT interval.
169
Prochlorperazine, haloperidol and chlorpromazine are examples of
First gen antipsychotics.Chlorpromazine has most sedative effect.
170
What first gen antipsychotic is also licensed for the treatment of intractable hiccups?
Haloperidol.
171
What is the first line treatment for focal seizures, with and without secondary generalisation and for primary generalised seizures?
Carbamazepine - apparent mech of action is inhibiting neuronal sodium channels.
172
What is the first line treatment of trigeminal neuralgia to control the pain, and reduce the frequency and severity of attacks?
Carbamazepine.
173
When can carbamazepine be used in bipolar disorder treatment?
An option for prophylaxis in patients resistant to or intolerant or other medication.
174
How is carbamazepine believed to work in the treatment of Epilepsy, trigeminal neuralgia and bipolar disorder?
Mechanism of action is not fully understood. Believed to inhibit neuronal sodium channels, stabilising membrane potentials and reducing neuronal excitability.This may inhibit the spread of seizure activity in epilepsy, control neuralgic pain by blocking synaptic transmission in the trigeminal nucleus and stabilise mood in bipolar disorder by reducing electrical ‘kindling’ in the temporal lobe and limbic system.
175
What are the most common side effects of carbamazepine?
Dose-related are GI upset and neurological effects (dizziness and ataxia).
176
Carbamazepine hypersensitivity affects about what percentage of people taking the drug? How does it manifest?
10%, manifests as a mild maculopapular skin rash.
177
Can carbamazepine be used in pregnancy?
Carbamazepine exposure in utero is associated with neural tube defects, cardiac and urinary tract abnormalities and cleft palate. Women with epilepsy planning pregnancy should discuss treatment with a specialist and start taking high-dose folic acid supplements before conception.
178
Why does carbamazepine interact with warfarin, oestrogens and phenytoin?
Carbamazapine induces cytochrome p450 enzymes, reducing plasma concentration and efficacy of drugs that are metabolised by these enzymes. Carbamazepine itself is metabolised by these enzymes, so its concentration and adverse effects are increased by cytochrome p450 inhibitors such as macrolides.
179
The efficacy of all AEDs is reduced by seizure lowering drugs such as
SSRIs, TCAs, antipsychotics and tramadol
180
The serum concentration and adverse effects of carbamazepine are increased by what?
cytochrome p450 inhibitors such as macrolides, as carbamazepine is metabolised by CYP450 enzymes.,
181
Can carbamazepine be prescribed generically?
Yes but as bioavailability can differ between formulations it isnt recommended.
182
What is the primary indication for the use of nitrofurantoin?
Uncomplicated lower urinary tract infection (UTI), as a first-line antibiotic (alternatives being amoxicillin and trimethoprim).
183
Why is nitrofurantoin particularly suited to the treatment of UTI?
1. It is effective against the common causative agents 2. It reaches therapeutic concentrations in urine through renal excretion3. It is most bactericidal in acidic environments such as urine.
184
How does nitrofurantoin work?
It is reduced in bacterial cells by nitrofuran reductase. Its active metabolite damages bacterial DNA and causes cell death. Nitrofurantoin is active against the gram-ve (e.coli) and gram+ve (s. saprophyticus) that commonly cause UTIs
185
What are the main side effects of nitrofurantoin?
Red/brown urine. GI upset. Hypersensitivity. Chronic pulmonary reactions.Hepatitis. Peripheral neuropathy. Haemolytic anaemia.
186
Who should not be prescribed nitrofurantoin?
Pregnant women towards term.Babies in the first 3 months of life. Patients with renal impairment as impaired excretion increases toxicity and reduces efficacy due to lower urinary drug concentrations.
187
When should nitrofurantoin be taken?
With food or milk to minimise GI effects.
188
Why would nitrofurantoin not be suitable for complicated UTIs or pyelonephritis?
Tissue concentrations of nitrofurantoin are very low, a suitable alternative would be co-amoxiclav with gentamicin.
189
For the treatment of an acute UTI, what is the typical dosage regimen of nitrofurantoin?
50-100mg qds for 3 days for women, up to 7 days for men.
190
What are the 4 indications for metronidazole use?
1. Antibiotic-associated colitid caused by C.diff which is a Gram+ve anaerobe. 2. Oral infections/aspiration pneumonia caused by Gram-ve anaerobes from the mout.3. Surgical and gynaecological infections caused by Gram-ve anaerobes from the colon, for example B. fragilis. 4. Treatment of protozoal infections including: trichomonal vaginal infection, amoebic dysentery, giardisis.
191
How does metronidazole work?
Metronidazole enters bacterial cells by passive diffusion.In anaerobic bacteria, reduction of metronidazole generates a nitroso free radical which binds to bacterial DNA, reducing synthesis and causing widespread damage, DNA degradation and cell death. As aerobic bacteria are not able to reduce metronidazole in this way they are resistant to its use.
192
What are the important adverse effects with one-off an chronic metronidazole use?
One-off: GI upset such as nausea and vomiting and immediate and delayed hypersensitivity reactions. Chronic: neurological effect such as peripheral and optic neuropathy, seizures and encephalopathy.
193
In what patients whould metronidazole doses be reduced?
Those with severe liver disease as its metabolised by hepatic CYP450 enzymes.
194
Metronidazole can treat what protozoal infections? (3)
Trichomonal vaginal infectionAmoebic dysenteryGiardisis
195
Why should metronidazole not be used at the same time as alcohol?
Metronidazole inhibits the enzyme acetaldehyde dehydrogenase, which is responsible for clearing the intermediate alcohol metabolite acetaldehyde from the body. A disulfiram-like reaction, including flushing, headache, nausea and vomiting can occur if alcohol and metronidazole are combined.
196
What is the interaction between warfarin and metronidazole?
Metronidazole has some inhibitory effect on cytochrome p450 enzymes, reducing metabolism of warfarin - increasing the risk of bleeds.
197
What is the interaction between phenytoin and metronidazole?
Metronidazole can inhibit the CYP450 metabolsim of phenytoin leading to an increased risk of phenytoin toxicity.
198
What effect does metronidazole have on lithium?
Increased risk of lithium toxicity
199
When is vancomycin used to treat gram-positive infection, e.g. endocarditis ?
When the infection is severe and/or penicillins cannot be used due to resistance (MRSA) or allergy
200
When is vancomycin used in the treatment of antibiotic associated colitis?
When it is caused by C.diff infection and usually only second-line where metronidazole is ineffective or poorly tolerated.
201
How does vancomycin work?
Vancomycin works by inhibiting the growth and cross-linking of peptidoglycan chains, inhibiting synthesis of the cell wall of gram+ve bacteria. It has specific activity against gram+ve aerobic and anaerobic bacteria and is inactive against most gram-ve bacteria, which have a different (lipopolysaccharide) cell wall structure.
202
What is the spectrum of activity of vancomycin?
Works against gram+ve aerobic and anaerobic bacteria and is inactive against most gram-ve bacteria due to different cell wall structures.
203
What is the most common adverse effect of vancomycin administration?
Pain and inflammation of the vein, thrombophlebitis, at the infusion site.
204
What is red man syndrome?
If vancomycin is infused rapidly, it can cause anaphylactoid reactions described as 'red man syndrome' .
205
Other than red man syndrome, what else can IV vancomycin cause?
1. renal failure/nephrotoxicity2. ototoxicty - with tinnitus and hearing loss3. blood disorders - neutropenia and thrombocytopenia.
206
There is an increased risk of ototoxicty and.or nephrotoxicity when vancomycin is prescribed with what?
1. Aminoglycosides2. Loop diuretics3. Ciclosporin
207
Antibiotic treatment with vancomycin may be required for several weeks for patients with severe or deep-seated infection e.g. what? (2)
Endocarditis OROsteomyelitis
208
For C. difficile colitis, vancomycin must be given via what route?
Oral, typically 125mg 6-hourly for 10-14 days.
209
For C. difficile colitis, vancomycin is given orally for how long?
Oraly, typically 125mg 6-hourly for 10-14 days
210
Why should patients takint vancomycin be advised to report any ringing in the ears or change in hearing during treatment.
ototoxicityWhich is reversible only if treatment is stopped promptly.
211
Vancomycin plasma concentrations should be above what level to be therapeutic?
10mg/L to be therapeutic but below 15mg/L to minimise toxicity.
212
Vancomycin plasma concentrations should be kept below what level to reduce toxicity?
10mg/L to be therapeutic but below 15mg/L to minimise toxicity.
213
What are the common indications for aminoglycoside antibiotics?
Severe infections, particularly those caused by Gram-negative aerobes (including P. aeruginosa). 1. Severe sepsis, including where the source is unidentified. 2. Pyelonephritis and complicated urinary tract infection. 3. Biliary and other intra-abdominal sepsis. 4. Endocarditis Aminoglycosides lack activity against streptococci and anaerobes so should be combined with penicillin and/or metronidazole when the organism is unknown.
214
Why should aminoglycosides be combined with penicillin and/or metronidazole when treating severe infections where the causative agent is unknown?
Aminoglycosides lack activity against streptococci and anaerobes so should be combined with penicillin and/or metronidazole when the organism is unknown.
215
How do aminoglycosides work?
They bind irrerversibly to bacterial ribosomes (30s subunit) and inhibit protein synthesis. They are bactericidal (kill bacteria).
216
Why do streptococci and anaerobic bacteria have innate aminoglycoside resistance?
Aminoglycosides enter bacterial cells via an oxygen-dependent transport system. Streptococci and anaerobic bacteria do not have this transport system.
217
How can the addition of penicillin to aminoglycoside therapy result in more uptake of aminoglycosides into bacterial cells?
Penicillins weaken bacterial cell walls.
218
What are the most important adverse effects of aminoglycosides?
1. Nephrotoxicity 2. Ototoxicity
219
Apart from nephrotoxicity and ototoxicty, what are the less important adverse effects of aminoglycosides?
Amioglycosides accumulate in renal tubular epithelial cells and cochlear and vestibular hair cells where they trigger apoptosis and cell death. Alopecia.
220
As aminoglycosides can impair neuromuscular transmission they should not be given to what patient group unless absolutely necessary?
Myasthenia Gravis
221
Ototoxicity is more likely with aminoglycosides if they are co-prescribed with what drugs?
Loop diuretics: furosemide. Vancomycin.
222
Nephrotoxicty is more likely if aminoglycosides are co-prescribed with what drugs? (4)
1. Ciclosporin2. Platinum 3. Cephalosporins4. Vancomycin
223
Why are aminoglycosides such as gentamicin and amikacin not given orally?
They are highly polarised molecules and do not cross lipid membranes. In severe infections, parenteral aminoglycosides are usually given as a once daily IV infusion.
224
The dose of aminoglycosides to be used is calculated how?
Using the patients ideal weight if obese and renal function.
225
For aminoglycoside therapy, the plasma drug concentration is usually measured how long after the first dose?
18-24 hours
226
The safe plasma concentraion of gentamicin is what?
<1mg/ml
227
Why are quinolones usually reserved as second or third-line treatment options?
Due to the emergence of rapid resistance and an associated with c.diff infection.
228
What are quinolones used for?
Normally second or third-line options for:1. UTI2. Severe GI infection such as Shigella, Campylobacter. 3. LRTI (moxifloxacin, levofloxacin). 4. Ciprofloxacin is the only oral antibiotic in common use with against P. aeruginosa. Moxifloxacin and levofloxacin do not have this property.
229
How do quinolones work?
They kill bacteria by inhibiting DNA synthesis. Particularly active against aerobic Gram-negative bacteria, which explains their utilit in treatment of urinary and gastrointestinal infections.
230
Which quinolones are better against Gram-positive organisms?
Moxifloxacin and levofloxacin are newer quinolones with enhanced activity against Gram-positive organisms. They can therefore be used to treat LRTI, which may be caused by either Gram-positive or Gram-negative organisms.
231
What are the side effects associated with quinlones? (4)
1. Neurological effects: lowered seizure threshold, hallucinations. 2. Inflammation and rupture of muscle tendons. 3. Quinolones (particularly moxifloxacin) prolong the QT interval and therefore increase the risk of arrhythmias. 4. They promote C.diff colitis.
232
Quinolones should not be taken at the same time as what?
Antacids, calcium etc due to chelation with them
233
Ciprofloxacin inhibits certain CYP450 enzymes, increasing the risk of toxicity with some drugs. What is one notable example?
Theophylline.
234
Co-prescription of what drug class increases the risk of seizures with quinolones?
NSAIDs
235
Co-prescription of what drug with quinolone increases the risk of tendon rupture?
Prednisolone
236
Quinolones should be prescribed with caution in patients taking other drugs that prolong the QT interval such as what? (5)
1. Amiodarone 2. Antipyschotics 3. Quinine4. Macrolide antibiotics5. SSRIs
237
What are the three common indications for a macrolide antibiotic?
1. In the treatment of respiratory and skin and soft tissue infections as an alternative to a penicillin when this is contrainidicated by an allergy. 2. In severe pneumonia, added to a penicillin to cover atypical organsims including Legionella pneumophilia and Mycoplasma pneumoniae. 3. Eradication of Helicobacter pylori in combination with a proton pump inhibitor and either amoxicillin or metronidazole. (also azithromycin for chlamydia)
238
Macrolides are used in the eradication of H.pylori in combination with what other drugs?
A PPI and amoxicillin/metronidazole
239
How do macrolides work?
They inhibit bacterial protein synthesis by binding to the 50S subunit of the bacterial ribosome and block translocation. They are bacteriostatic not bactericidal meaning they stop bacteria growth but do not kill bacterial populations.
240
Which macrolides have increased activity against Gram-negative bacteria, particularly Haemophilus influenzae?
The newer synthetic macrolides like azithromycin and clarithyromycin have better Gram-negative activity than the original erythromycin.
241
Adverse reactions are more common to what macrolide antibiotic?
Erythro. Macrolides are irritant causing nausea, vomting, abdo pain and diarrhoea when taken orally and thrombophlebitis when given IV.
242
What adverse reactions can occur with macrolide use?(Other than the usual N+V, abdominal pain, diarrhoea etc)
1. Antibiotic-associted colitis2. Cholestatic jaundice (liver abnormalities)3. Prolongation of the QT interval (predisposing to arrythmias)4. Ototoxicity (at high doses)
243
Which macrolides inhibit CYP450 enzymes and which dont?
Clarithyro and erythro do, azithro doesnt.
244
Because of the effect of the macrolides Clarithyromycin and Erythromycin to inhibit CYP450 enzymes, interactions with with common drugs are possible? (2)
1. Increased anticoagulation due to inhibiting the breakdown/metabolism of warfarin. 2. Increases risk of myopathy when given with statins.
245
Macrolides should be prescribed with caution in patients taking other drugs that prolong the QT interval such as what? (5)
1. Amiodarone2. Antipsychotics3. Quinine 4. Quinolone antibiotics 5. SSRIs
246
In patients with lower respiratory tract infections (LRTI), macrolides should generally only be added to penicillin treatment when?
If there is evidence of pneumonia e.g. consolidation on the chest X-ray. Macrolides are required to cover penicillin-resistant atypical organisms. e.g. Legionella pneumophila and mycoplasma pneuomonia that cause pneumonia but do not cause other LRTI such as COPD exacerbations.
247
What is the indication for metformin?
T2D, as first line medication for control of blood glucose, used alone or in combination with other oral drugs or insulin.
248
What is the mechanism of action of metformin?
Metformin is a biguanide that lowers blood glucose by increasing the sensitivity of cells to insulin. It suppresses hepatic glucose production (glycogenolysis and gluconeogenesis), increases glucose uptake and utilization by skeletal muscle and suppresses intestinal glucose absorption. It does not stimulate pancreatic insulin secretion and therefore does not cause hypoglycemia.It reduces weight loss, which can prevent worsening of insulin resistance and slow deterioration of diabetes mellitus.
249
Why does metformin not cause hypoglycemia?
It does not stimulate pancreatic insulin secretion, it works by suppressing hepatic glucose production (glycogenolysis and gluconeogenesis), increases glucose uptake and utilization by skeletal muscle and suppresses intestinal glucose absorption.
250
What is the most common side effect of metformin and how can it be overcome?
Causes GI upset, can be overcome by taking with or after food or by changing to MR release formulation.The GI upset can contribute to weight loss in patients taking metformin. Lactic acidosis is a rare adverse effect associated with metformin use, which can be fatal if left untreated.
251
In what cases is metformin contraindicated?
Metformin is excreted unchanged by the kidney, therefore it is contraindicated in severe renal impairment and a dose reduction is required for patients with moderate renal impairment. Metformin should be withheld where there is acute kidney injury, e.g. in sepsis, shock, or dehydration or severe tissue hypoxia. Metformin should be withheld during acute alcohol intoxication, when it may precipitate lactic acidosis, and be used with caution in chronic alcohol overuse, where there is a risk of hypoglycaemia.
252
What do prednisolone, thiazide-like and loop diuretics have in common?
All elevate blood glucose, and hence oppose the actions and reduce the efficacy of metformin.
253
Why should patients be advised to tell a doctor that they are taking metformin before having an X-ray or operation?
Metformin must be withheld before and for 48 hours after injection of IV contrast media (e.g. for CT scans, coronary angiography) when there is an increased risk of renal impairment, metformin accumulation and lactic acidosis.
254
Why can insulin and sulphonylureas worsen diabetes mellitus over the long term?
Insulin is an anabolic hormone, it and drugs which increase insulin secretion (e.g. sulphonylureas) cause weight gaine, which can worsen diabetes mellitus in the long term.
255
What are the two indications for oestrogens and progestogens?
1. For hormonal contraception in women who require highly effective and reversible contraception, particularly if they may also benefit from its other effects, such as imporved acne symptoms with oestrogens. 2. For hormone replacement therapy (HRT) in women with early menopause (when it is given until 50 years of age) and those who have distressing menopause symptoms.
256
An improvement in acne symptoms is a benefit of treatment with which hormonal contraception?
Oestrogens.
257
How do oestrogens and progesterones work as contraception?
Luteinising hormone (LH) and follicle-stimulating hormone (FSH) control ovulation and ovarian production of oestrogen and progesterone. In turn, oestrogen and progesterone exert predominantly negative feedback on LH and FSH release. In hormonal contraception, an oestrogen (such as ethinylestradiol) and/or progestogen (e.g. desogestrel) are given to suppress LH/FSH release and hence ovulation.
258
What type of contraception is ethinylestradiol? How does it work as a contraception?
Ethinylestradiol is an oestrogen and works to suppress LH/FSH and hence ovulation.
259
What type of contraception is desogestrel?
Desogestrel is a progestogen.
260
Oestrogens and progestogens also have effects outside of the ovary, what are these?
Effects on the cervix and endometrium may contribute to their contraceptive effect (this is especially important in progestogen only pills). Some cause reduced menstrual pain and bleeding, and improvements in acne (oestrogens).
261
All forms of oestrogens and progestogens are contraindicated in patients with what?
Breast cancer
262
Why should combined hormonal contraception be avoided in patients at an increased risk for VTE? what would constitute being 'at an increased risk for VTE'?
The oestrogens in the combined hormonal contraceptive products double the risk of venous thromboembolism, VTE, but the absolute risk remains low. A past VTE or a known thrombogenic mutation would constitute an increased risk for VTE.
263
All forms of combined hormonal contraceptives should be avoided in those with cardiovascular disease, such as what?
If Age >35 years; cardiovascular risk factors; migraine with aura, heavy smoking history.
264
Concurrent use of Rifampicin may reduce the efficacy of the hormonal contraceptive, particularly progestogen-only forms. Why is this?
Rifampicin = cytochrome p450 inducer, increased metabolism. Most other antibiotics are fine to use.
265
When can COC pills be started in a womans cycle?
COC pills can be started at any day of the cycle. If this is within the first 6 days, no additional contraception is needed. If it is beyond day 6, a barrier method should be used or sex avoided for the first 7 days.
266
What are the three indications of allopurinol?
1. To prevent acute attacks of gout2. To prevent uric acid and calcium oxalate renal stones.3. To prevent hyperuricaemia and tumour lysis syndrome associated with chemotherapy.
267
What is allopurinol? How does it work?
Allopurinol is a xanthine oxidase inhibitor. Xanthine oxidase metabolises xanthine (produced from purines) to uric acid. Inhibition of xanthine oxidase lowers plasma uric acid concentrations and reduces precipitation of uric acid in the joints or kidneys.
268
What are the important adverse effects of allopurinol?
The most common side effect is a skin rash, which may be mild or may indicate a more serious hypersensitivity reaction such as Stevens-Johnson syndrome or toxic epidermal necrolysis. Drug hypersensitivity syndrome is rare.Starting allopurinol can trigger or worsen an acute attack of gout.
269
When should the dose of allopurinol be reduced?
Allopurinol is metabolised in the liver and excreted by the kidney. The dose should therefore be reduced in patients with severe renal or hepatic impairment.
270
What are the important drug interactions with allopurinol? (3)
1. The cytotoxic drug mercaptopurine and its pro-drug azathioprine require xanthine oxidase for metabolism. When allopurinol is prescribed with these drugs, it inhibits their metabolism and increases the risk of toxicity. 2. Co-prescription of allopurinol with amoxicillin increases the risk of skin rash.3. Allopurinol and ACEi or thiazides increases the risk of hypersensitivity reactions.
271
Why does allopurinol increase the risk of mercaptopurine/azathioprine toxicity?
The cytotoxic drug mercaptopurine and its pro-drug azathioprine require xanthine oxidase for metabolism. When allopurinol is prescribed with these drugs, it inhibits their metabolism and increases the risk of toxicity.
272
When starting allopurinol for gout, what other treatment should be prescribed and for how long, to avoid triggering an acute gout attack?
When starting allopurinol for gout, NSAID or colchicine treatment should also be prescribed and continued for at least one month after serum uric acid levels return to normal to avoid triggering an attack.
273
Where allopurinol is used as part of cancer treatment, when should it be commenced?
Before chemotherapy.
274
When should allopurinol be taken?
Allopurinol should be taken after meals and patients should be encouraged to maintain good hydration with fluid intake of 2-3 litres daily.
275
What should be done to allopurinol treatment if a rash develops?
Stopped, recommenced cautiously once the rash resolves.
276
What are the two aminosalicylates commonly prescribed?
Mesalazine: first line in treatment of mild-moderate ulcerative colitis.Sulfasalazine: one of the several options for management of rheumatoid arthritis, in which it is used as a disease-modifying antirheumatic drug (DMARD), usually as part of combination therapy.
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What is the common indiaction for mesalazine?
First line treatment in mild-moderate ulcerative colitis.
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What is the indication for sulfasalazine?
One of the several options for the management of RA, usually as part of combination therapy.
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How do aminosalicylates such as mesalazine and sulfasalazine work in Ulcerative colitis?
They work by releasing 5-aminosalicylic acid (5-ASA), which has both anti-inflammatory and immunosuppressive effects and appears to act topically on the gut rather than systemically. For this reason, 5-ASA preparations are designed to delay delivery of the active ingredient to the colon.
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What does sulfasalazine consist of?
Sulfasalazine consists of a molecule of 5-ASA linked to sulfapyridine. In the colon, bacterial enzymes break this link and release the two molecules.Sulfapyridine has no beneficial effect in UC but does cause Side effects. However, it does have a probably beneficial role in RA.
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Does mesalazine have a role in RA?
No.
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What side effects can sulfasalazine cause in men?
A reversible decrease in the number of sperm (oliospermia).
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What are the main side effects of mesalazine and suflasalazine?
Mes tends to have less then sulf but both can cause GI upset and headache as well as rare but serious blood abnormalities (leucopenia, thrombocytopenia) and renal impairment.
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What are the interactions between lactulose and omeprazole with 5-ASA drugs?
Omeprazole (PPI) can alter gastric pH and cause Asacol MR (mesalazine) to be released prematurely. LActulose can alter pH of stool and may prevent 5-ASA release in the colon.
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What monitoring accompanies oral mesalazine usage?
For safety, renal fucntion should be checked in patients receiving oral mesalazine, and full blood count and liver profile monitored in patients recieving sulfasalazine.
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What is the only indication for naloxone?
The treatment of opioid toxicity associated with respiratory and/or neurological depression.
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How does naloxone work?
Naloxone binds to opioid receptors (particularly the pharmacologically-important opioid mu-receptors) where it acts as a competitive antagonist. It has little or no effect in the absence of an exogenous opioid. However, if an opioid is present, naloxone displaces it from its receptors and, in so doing, it reverses its effects. In opioid toxicity, this is used to restore an adequate level of consiousness and respiratory rate.
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What are the important adverse effects of naloxone?
Where naloxone is administered to reverse opioid toxicity in an opioid-dependent individual, an opioid withdrawal reaction may be precipitated. This presents with pain (if the opioid was being taken for its analgesic effect), restlessnes, nausea and vomiting, dilated pupils, and cold, dry skin with piloerection (cold turkey). Naloxone has no other significant adverse effects.
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What are the indications for topical corticosteroids (glucocorticoids)?
Used in inflammatory skin conditions e.g. eczema, to treat disease flares or to control chronic disease where emollients alone are ineffective.
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How do corticosteroids have their effects on skin?
Corticosteroids have immunosuppresant, metabolic and mineralcorticoid effects. Where they are applied topically, effects are mostly limited to the site of application.
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What are the adverse effects of corticosteroids?
Adverse effects are uncommon with mild or moderately potent topical corticosteroids (hydrocortisone 0.1-2.5% is mild). However potent (betamethasone valerate 0.1% is potent) and very potent topical corticosteroids can cause local adverse effects such as skin thinning, striae (stretch marks), telangiectasia (Telangiectasia is a condition in which widened venules (tiny blood vessels) cause threadlike red lines or patterns on the skin) and contact dermatitis.
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Half a finger tip unit is enough cream or ointment to cover what corresponding region of space?
one palm size
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What are emollients used for?
Dry skin disorders, they work by replacing water content in dry skin. They contain oils or paraffin-based products that help to soften the skin and can reduce water looss by protecting against evaporation from the skin surface.Many can be used as a soap substitute (as soap is drying to the skin).
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Why can emollients exacerbate acne vulgaris and folliculitis?
By blocking pores and hair follicles.
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What is the main adverse effect of emollients?
They cause greasy skin but this is integral to their therapeutic effect.
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What is the main risk of using parafin-based emollients where the oil content is high (>50%)?
They are a significant fire hazard and if accumulation into bedding or clothing occurs become a significant fire risk.
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When is loperamide used?
Antimotolity drug used as symptomatic treatment for diarrhoea, usually in the context of irritable bowel syndrome or viral gastroenteritis.
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How does loperamide work?
Loperamide is pharmacologically similar to pethidine. However, unlike pethidine, it does not penetrate the central nervous system so has no analgesic effects. It is an agonist of the mu-opioid receptors in the gastrointestinal tract. This increases non-propulsive contractions of the gut smooth muscle but reduces propulsive (peristaltic) contractions. As a result, transit of bowel contents is slowed and anal sphincter tone is increased. Slower gut transit also allows more time for water absorption, which in the context of water diarrhoea) has a desirable effect in hardening the stool. Other opioids (e.g. codeine phosphate) have similar effects but less reason to use them.
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What are the important adverse effects of loperamide?
Loperamide is a safe drug with few adverse effects, these are mostly GI, predictable from its mech of action: constipation, abdominal cramping and flatulence.
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In whom should loperamide be avoided?
In acute ulcerative colitis where inhibition of peristalsis may increase the risk of megacolon and perforation. Also if there is a possibility of C.diff colitis, particularly if in patients who develop diarrhoea in association with broad spectrum antibiotics.
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What are the interactions of loperamide?
None of clinical significance
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Can loperamide syrup be purchased OTC?
Nope. POM only.
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Why would a hospital patient who develops diarrhoea not be prescribed loperamide immediately?
Due to the risk of inhibiting peristalsis in C.diff colitis, should wait until there is a better idea of the aetiology of the condition such as a positive viral PCR and/or negative c.diff toxin test.
304
Antimuscarinics such as _____ ___________ are first line treatment for what syndrome?
Hyoscine butylbromide and IBS, they are used for their antispasmodic effect.
305
What is the mechanism of action of antimuscarinics in IBS?
Antimuscarinic drugs bind to the muscarinic receptor, where they act as a competitive inhibitor of acetylcholine. Stimulation of the muscarinic receptor brings about a wide range of parasympathetic 'rest and digest' effects, by blocking these receptors they cause increased heart rate and conduction, reduced smooth muscle tone and peristaltic contraction.
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In whom should antimuscarinics be used with caution?
Patients susceptible to angle-closure glaucoma, in whom they can precipitate a dangerous rise in intraocular pressure. Also generally be avoided in patients at risk of arrhythmias (eg those with significant cardiac disease) unless the indication for use is bradycardia.
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What type of antidepressant drug can lead to more pronouced side effects of antimuscarinic drugs such as atropine, hyoscine butylbromide and glycopyrronium?
TCAs such as amitriptyline.
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What are metoclopramide and domperidone?
Dopamine D2-receptor antagonists, antiemetics.
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What is the mechanism of action of metoclopramide and domperidone?
The D2 receptor is the main receptor in the chemoreceptor trigger zone (CTZ) which is the area responsible for sensing emetogenic substances in the blood (e.g. drugs). Also dopamine is an important neurotransmitter in the gut, where it promotes relaxation of the stomach and lower oesophageal sphincter and inhibits gastroduodenal coordination. Drugs that block D2 receptors therefore have a prokinetic effect - promoting gastric emptying - which contributes to their antiemetic action.
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Why is domperidone often preffered to metoclopramide?
Domperidone does not cross the blood brain barrier thus does not cause extrapyramidal side effects. The chemoreceptor trigger zone is largely outside the blood-brain barrier.
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Metoclopramide can cause extrapyramidal side effects via the same mechanisms as what other type of drugs?
Anti-pscyhotic
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What is the most common side effect of d2-antagonist anti-emetics?
Diarrhoea
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The extrapyramidal side effects of metoclopramide are more common when?
Parkinsons patients, young adults and children and so should not be used in these patient groups.
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Why might a patient be on both a proton pump inhibitor/H2-receptor antagonist and metoclopramide?
For patients with gastro-oesophageal reflux disease that does not respond to conventional treatment with a proton-pump inhibitor and/or a H2-receptor antagonist, metoclopramide can be considered as an add-on treatment. its effects on the lower oesophageal sphincter and gastric emptying may improve the patients symptoms.
315
What is the first-line symptomatic treatment of dry eye conditions including keratoconjunctivitis sicca and sjorgens syndrome?
Ocular lubricants like artificial tears
316
What are the main differences between Hypromellose, Viscotears and Lacri-lube?
Hypromellose solution retained for least amount of time. Viscotears (carbomer) the gel stays in the eye longer than the solution and Lacri-lube ointment stays on the eye the longest but can cause blurred vision (white soft parafin).
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What are latanprost and bimatoprost?
They are prostaglandin analogues used in eye drops to lower intraocular pressure in open-angle glaucoma and ocular hypertension.
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Why are prostaglandin analogues, such as latanoprost and bimatoprost preffered over topical beta-blockers for the treatment of glaucoma?
They cause fewer systemic side effects
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How do prostaglandin analogues such as latanoprost and bimatoprost work?
They reduce intraocular pressure by increasing outflow of aqueous humour via the uveoscleral pathway. The exact mechanism for this is uncertain. Elevated intraocular pressure is a risk factor for open-angle glaucoma. Glaucoma is characteristed by progressive optic nerve damage associated with visual field loss and eventually blindness.
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What side effect of prostaglandin analogues can affect about one in three people?
Bimatoprost and latanoprost can cause a permanent change in eye colour by increasing the amount of melanin in stromal melanocytes of the iris.
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When is it best to administer latanoprost eye drops?
Best to do so in the evening.
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What is advice that should be given regarding all eye drops?
The patient should gently compress the medial canthus (nasal corner) of the eye for about 1 minute, immediately after instilling the drop. This reduces systemic absorption of the drug.
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What is xalatan?
Branded latanoprost
