Top 100 Drugs (Part 1) Flashcards
What is acne?
Acne is a common skin condition that affects most people at some point. It causes spots, oily skin and sometimes skin that’s hot or painful to touch.
What are the common indications of tetracyclines?
1) Acne Vulgaris, particularly where there are inflammed papules, paustules and/or cysts
2) Lower respiratory tract infections (including infective exacerbations of COPD), pneumonia and atypical pneumonia
3) Chlamydia infection, including pelvic inflammatory disease
4) Other infections such as typhoid, anthrax, malaria and lyme disease
What is the spectrum of activity for tetracyclines?
Tetracyclines have a relatively broad spectrum of activity against many gram positive and gram negative organisms, including chlamydia, mycoplasma and spirochaetes. However, their utility may be limited by increasing bacterial resistance.
What is the mechanism of action of tetracyclines?
- Tetracyclines inhibit bacterial protein synthesis
- They bind to the ribosomal 30s subunit found specifically in bacteria.
- This prevents binding of tRNA to mRNA, which prevents addition of new amino acids to growing polypeptide chains.
Is tetracycline action bacteriostatic or bactericidal?
Inhibition of protein synthesis is bacteriostatic (stops bacterial growth), which assists the immune system in killing and removing bacteria from the body.
When were tetracyclines discovered?
1945 and have been widely used since
Increasing bacteria resistance to tetracyclines is a concern, list one common mechanism of bacteria resistance to tetracylclines?
A common mechanism is an efflux pump, which allows bacteria to pump out tetracycline, preventing cytoplasmic accumulation.
Does tetracycline have a high risk or a low risk of C.difficile infection?
Compared to other broad-spectrum antibiotics - there is a lower risk for c.difficile with tetracyclines
What are the most common side effects of tetracyclines?
- nausea, vomiting
- Diarrhoea
- Oesophageal irritation
photosensitivity (exaggerated sun burns) - Discolouration and/or hypoplasia of tooth enamel in children
- ulcer and dysphagia
Rare but serious adverse effects include:
- hepatoxicity
- intracranial hypertension - causing headache and visual disturbance
Does tetracyclines have cross-reactivity with penicillins?
No - as antibiotic structure are different with penicillins or other B-lactam antibiotics.
Can tetracyclines be prescribed during pregnancy?
NO - as tetracyclines bind to teeth and bones during fetal development, infancy and early childhood and so should not be prescribed during pregnancy, breastfeeding or for children under 12 years of age.
Can tetracyclines be used in renal impairment?
Yes but they should be used with caution in renal impairment as their antianabolic effects can raise serum urea and reduced excretion can increase the risk of adverse effects.
Is there any important interactions for tetracycline?
Tetracyclines bind to divalent cations. They should therefore not be given within 2 hours of calcium, antacids or iron, which will prevent antibiotic absorption.
Tetracycline and warfarin??
Tetracyclines can enhance the anticoagulant effect on warfarin by killing gut bacteria that synthesise vitamin K.
What is the primary form of administration for tetracyclines?
Primarily available as oral administration.
What are the two most common drugs of tetracyclines?
Doxycycline and Lymecycline
What is the usual dose of doxycycline?
200mg on the first day then then 100mg orally daily
What is the usual dose of lymecycline?
408mg-816mg orally 12-hourly
What does the duration of treatment depend on?
The indication it is being used for
What is the usual duration of tetracycline use for infective exacerbation of COPD?
5-7 days
What is the usual duration of lymecycline for acne?
8 weeks
Can tetracyclines be taken lying down?
No - should be swallowed whole with plenty of water while sitting or standing to stop them getting stuck in the oesophagus where they may cause ulceration.
What should a patient do if a rash occurs when taking tetracyclines?
ensure they have no allergy to tetracyclines. Warn them to seek medical advice if a rash or other unexpected symptoms develop. If an allergy develops during treatment, give the patient written and verbal advice not to take this antibiotic in the future and make sure that the allergy is clearly documented in the patient’s medical records.
Should tetracyclines be taken with food?
yes can be taken with food to avoid upset stomach and should be taken while sitting or standing up.
What foods or nutrients should be avoided while taking tetracyclines?
Should avoid indigestion remedies and medicines containing zinc, iron or calcium 2 hours before and after taking the antibiotic.
What warning about sunlight needs to be given with tetracyclines?
During treatment they should protect their skin from sunlight, even on cloudy days.
Clinical Tip - What is Demeclocycline known to increase in the blood?
Serum sodium concentrations in patients with syndrome of inappropriate antidiuretic hormone (SIADH). It appears to do this by blocking the binding of antidiuretic hormone (ADH) to its receptor, although the mechanism is poorly understood.
What are other non-antibiotic properties of tetracyclines?
Other non-antibiotic properties of tetracyclines, including anti-inflammatory, immune-modulating and neuroprotective effects, are being tested in clinical trials and may lead to new therapeutic applications in the future.
Which drug classes are used in acute coronary syndrome (ACS)?
ACE inhibitor, Antiplatelet drugs (ADP-receptor antagonists) Aspirin, B-blockers, Fibrinolytic drugs, heparins and fondaparinux, nitrates, opioids, Statins
List a few ACE inhibitors?
Ramipril Lisinopril Enalapril Perindopril Catopril Fosinopril Imidapril Quinapril Trandolapril
What are the common indications of Angiotensin converting enzyme (ACE) inhibitors?
1) Hypertension: for the first- or second-line treatment of hypertension, to reduce the risk of stroke, myocardial infarction and death from cardiovascular disease.
2) Chronic heart failure: for the first-line treatment of all grades of heart failure, to improve symptoms and prognosis.
3) Ischaemic heart disease: to reduce the risk of subsequent cardiovascular events such as myocardial infarction and stroke.
4) Diabetic nephropathy and chronic kidney disease (CKD) with proteinuria: to reduce proteinuria and progression of nephropathy.
What is the mechanism of action of ACE inhibitors?
- ACE inhibitors block the action of angiotensin converting enzyme, to prevent the conversion of angiotensin I to angiotensin II.
- angiotensin II is a vasoconstrictor ands stimulates aldosterone secretion.
- Blocking its action reduces peripheral vascular restriction (afterload), which lowers blood pressure (BP).
- It particularly dilates the efferent glomerular arteriole, which reduces intraglomerular pressure and slows the progression of CKD.
What does reduction in aldosterone levels caused by ACE inhibitors promote?
Promotes sodium and water excretion. This can help reduce venous return (pre-load), which has a beneficial effect in heart failure.
What are the common side effects of ACE inhibitors?
- Hypotension (particularly after the first dose)/ dizziness
- persistent dry cough (due to increased levels of bradykinin, which is inactivated by ACE).
- Hyperkalaemia (because a lower aldosterone level promotes potassium retention). Can cause or worsen renal failure
Rare important idiosyncratic side effects include:
Angioedema;
Anaphylactoid reactions
Which patients should ACE inhibitors be avoided in?
- Renal artery stenosis
- Acute kidney injury
- in women who are or could be pregnant
- women who are breastfeeding
_Although ACE inhibition is potentially valuable in some forms of ▴CKD, lower doses should be used and the effect on renal function monitored closely.
Which route of administration is common for ACE inhibitors?
Oral route
Can ACE inhibitors be taken with food?
Can be taken with or without food.
What time of day is it best to take first dose of Ace inhibitor?
Night - before bed to reduce symptomatic hypotension.
(Profound hypotension may occur following the first dose of an ACE inhibitor, particularly in patients on other diuretics, such as loop diuretics, and those with restricted salt and water intake).
(In addition, it can sometimes be advisable to omit the diuretic dose that precedes the first dose of the ACE inhibitor.)
What OTC product should people taking ACE inhibitors be wary of taking?
OTC anti-inflammatories such as ibuprofen due to risk of kidney damage.
Monitoring of ACE inhibitors?
Monitor efficacy - measure blood pressure reduced symptoms of breathless in heart failure etc.
- Check electrolytes and renal function before starting treatments
- Repeat these 1-2 weeks into treatment and after increasing the dose.
When should ACE inhibitors be stopped due to which abnormal monitoring paramters?
In the absence of other causes, the ACE inhibitor should be stopped if the serum creatinine concentration rises more than 30% or the estimated glomerular filtration rate (eGFR) falls more than 25%. If serum potassium rises above 5.0 mmol/L, stop other potassium-elevating and nephrotoxic drugs.
Do ACE inhibitors need titrating or can a high dose be used initially?
You should start at a low dose and titrate up gradually.
List three ADP-receptor antagonists (Antiplatelets)?
- Clopidogrel
- ticagrelor
- prasugrel
What the the common indications of ADP-receptor antagonists (antiplatelets)??
1) For treatment of acute coronary syndrome (ACS), usually in combination with aspirin, where rapid inhibition of platelet aggregation can prevent or limit arterial thrombosis and reduce subsequent mortality.
2) To prevent occlusion of coronary artery stents, usually in combination with aspirin.
3) For long-term secondary prevention of thrombotic arterial events in patients with cardiovascular, cerebrovascular and peripheral arterial disease, alone or in combination with aspirin.
How do thrombotic events occur?
when platelet-rich thrombus forms in atheromatous arteries and occludes the circulation.
What is the mechanism of ADP-rector antagonists?
These drugs prevent platelet aggregation and reduce the risk of arterial occlusion by binding irreversibly to adenosine diphosphate (ADP) receptors (P2Y12 subtype) on the surface of platelets.
As this process is independent of the cyclooxygenase (COX) pathway, its actions are synergistic with those of aspirin.
What the important adverse effects of ADP-receptor antagonsits?
Most common effect is bleeding, which can be serious, particularly if gastrointestinal, intracranial or following a surgical procedure.
- GI upset
- Dyspepsia, abdominal pain and diarrhoea
Rarely, antiplatelet agents can affect platelet numbers as well as function, causing thrombocytopenia.
What are the contraindications of ADP-receptor antagonists?
Antiplatelet drugs should not be prescribed for people with significant active bleeding and may need to be stopped 7 days before elective surgery and other procedures.
Which patients should ADP-receptor antagonists be used with caution?
patients with renal and hepatic impairment especially as these patients have an increased risk of bleeding.
What important interactions is there with clopidogrel, the mechanism?
- Clopidogrel is a pro-drug that requires metabolism by hepatic cytochrome P450 (CYP) enzymes to its active form to have an antiplatelet effect.
- Its efficacy may be reduced by CYP inhibitors by inhibiting its activation.
What are relevant examples of drugs that may inhibit the activation of clopidogrel dur to CYP450 inhibition?
Omeprazole, ciprofloxacin, erythromycin, some antifungals and some selective serotonin reuptake inhibitors.
What should be prescribed if gastroprotection with a proton pump inhibitor (e.g. with aspirin use) is required for patients taking clopidogrel?
lansoprazole or pantoprazole are preferred over omeprazole as they are considered less likely to inhibit clopidogrel activation.
Is Prasugrel a pro-drug?
Yes it is also a pro-drug but it is less susceptible to interactions.
Is ticagrelor a pro-dug?
No it is not, but it interacts with CUP inhibitors (which may increase the risk of toxicity) and inducers (which may reduce efficacy).
What does co-prescription with other anti-platelet drugs or anticoagulants e.g. heparin or NSAIDs, increase the risk of?
Increases the risk of bleeding
Out of the 3 ADP-receptor antagonists which is the most used drug?
Clopidogrel is the most commonly used example in this class.
How long does low doses of clopidogrel take to have their full antiplatelet effect?
Require up to a week.
What should be prescribed if a rapid effect of clopidogrel is needed?
prescribe a loading dose, normally 300mg orally for ACS (Acute Coronary Syndrome), in the once only section of the drug chat before commencing a regular maintenance dose of 75mg orally daily.
Following the insertion of a drug-eluting coronary stent, how long should dual antiplatelet therapy be continued?
for 12 months to reduce the risk of stent thrombosis and should not be discontinued prematurely without prior discussion with a cardiologist.
Should clopidogrel be given before or after food?
Can be given with or without food.
Before starting therapy what should be checked?
Check that the patient does not have any active bleeding. Explain that if bleeding does occur while on treatment it might take longer than usual to stop. Patients should report any unusual or sustained bleeding to their doctors.
Does clopidogrel act reversibly or irreversibly?
Clopidogrel acts irreversibly - binds to ADP-receptors on platelets irreversibly. It therefore takes the lifespan of a platelet (around 7 to 10 days) for its antiplatelet effect to wear off.
how many days before elective surgery should clopidogrel be stopped?
7 days before elective surgery or other invasive procedures, unless the risk of stopping clopidogrel exceeds the risk of continuing.
What may patients taking clopidogrel require in an emergency case?
Platelet infusion to help stop bleeding
What kind of drug is Aspirin?
Aspirin is an antiplatelet also an NSAID
What are the common indications of Aspirin?
1) For treatment of acute coronary syndrome (ACS) and acute ischaemic stroke, where rapid inhibition of platelet aggregation can prevent or limit arterial thrombosis and reduce subsequent mortality.
2) For long-term secondary prevention of thrombotic arterial events in patients with cardiovascular, cerebrovascular and peripheral arterial disease.
Historically, aspirin was used to control mild-to-moderate pain and fever, although other NSAIDs are now usually preferred for this indication.
When do thrombotic events occur?
When platelet-rich thrombus forms in atheromatous arteries and occludes the circulation.
What is the mechanism of action of Aspirin?
Aspirin irreversibly inhibits cyclooxygenase (COX) to reduce production of the pro-aggregatory factor thromboxane from arachidonic acid reducing platelet aggregation and the risk of arterial occlusion.
Does the antiplatelet effect of aspirin occur at high or low doses?
Occurs at low doses and lasts for the lifetime of a platelet (which does not have a nucleus to allow synthesis of new COX)
What are the side effects of aspirin?
- most common adverse effect is GI irritation
- ## serious effects include peptic ulceration and haemorrhage and hypersensitivity reactions including bronchospasm.
What does regular use of high dose aspirin cause?
Tinnitus
Aspirin overdose is life-threatening, what are the clinical features?
Features include:
- Hyperventilation
- hearing changes
- metabolic acidosis
- confusion
- followed by convulsions
- cardiovascular collapse and respiratory arrest
What is the age restriction for aspirin?
Should not be given to children aged 16 years due to the risk of Reye’s syndrome.
What is Reye’s syndrome?
A rare but life threatening illness that principally affects the liver and brain.
Which people should not take aspirin?
People with aspirin hypersensitivity i.e. who have had bronchospasm or other allergic symptoms triggered by exposure to aspirin or another NSAID.
- Aspirin should be avoided in the third trimester of pregnancy when prostaglandin inhibition may lead to premature closure of the ductus arteriosus.
Is aspirin contraindicated in asthma?
No, Aspirin is not routinely contraindicated in asthma.
Which people should aspirin be used with caution?
- Those with peptic ulceration
- Gout - as it may trigger an acute attack
Can aspirin be used with other antiplatelet therapy?
Yes, aspirin acts synergistically with other antiplatelet agents such as clopidogrel but there is an increased risk of bleeding. CAUTION IS REQUIRED.
Can aspirin be used rectally?
Yes and in higher doses too
What is the dose of Aspirin in ACS? (Acute coronary syndrome)
Initially as a once only loading dose of 300mg followed by a regular dose of 75mg daily.
What is the dose of acute ischaemic stroke?
300mg aspirin daily for 2 weeks
What is the dose of aspirin for long term prevention of thrombosis?
After an acute event for secondary prevention prescribe a low dose aspirin 75mg daily.
What is the dose of aspirin required for pain?
Much higher doses of aspirin are required for the treatment of pain, with a maximum daily dose of 4 g, taken in divided doses.
What should be co-prescribed with aspirin for gastro-protection?
PPI such as omeprazole 20mg daily - for people who are at increased risk of GI complications
What are the risk factors for increased risk of GI complications when taking aspirin?
- Age over 65 years old
- previous peptic ulcer disease
- co-morbidities (such as cardiovascular disease, diabetes) and concurrent therapy with other drugs with GI side effects, particularly NSAIDs and prednisolone.
How should oral aspirin be taken what advice to give?
To minimise gastric irritation, aspirin should be taken after food.
Enteric coated tablets may help further, but are associated with slower absorption and are therefore not suitable for use in medical emergencies or for rapid pain relief.
- warn patients to look out for indigestion or bleeding symptoms and report these to their doctor if they occur.
In the UK is aspirin licensed for use in primary prevention of cardio vascular disease (i.e. in patients who have not previously had an event)?
No it is not licensed for primary prevention.
The reason is that large-scale randomised-controlled trials and meta-analyses have found that the absolute risk of serious vascular events in this group is low (around 1/500), and any potential benefits of low-dose aspirin are offset by the increased risk of serious bleeding (around 1/1000).
List as many B-Blockers?
ACEBUTOLOL ATENOLOL BETAXOLOL BISOPROLOL FUMARATE CARVEDILOL CELIPROLOL ESMOLOL LABETALOL LEVOBUNOLOL METOPROLOL TARTRATE NADOLOL NEBIVOLOL PHENOXYBENZAMINE HYDROCHLORIDE PINDOLOL PROPRANOLOL SOTALOL TIMOLOL MALEATE
Which B-Blockers are selective?
ACEBUTOLOL ATENOLOL ATENOLOL WITH Bisoprolol NIFEDIPINE BETAXOLOL CELIPROLOL CO-TENIDONE ESMOLOL HYDROCHLORIDE METOPROLOL TARTRATE NEBIVOLOL
What are the common indications of B-blockers?
1) Ischaemic heart disease: to improve symptoms and prognosis associated with angina and acute coronary syndrome (ACE).
2) Chronic heart failure: bisoprolol and carvedilol are used to improve prognosis.
3) Atrial fibrillation (AF): to reduce the ventricular rate and, in paroxysmal AF, to maintain sinus rhythm.
4) Supraventricular tachycardia (SVT): as an option in patients without circulatory compromise to restore sinus rhythm.
5) Hypertension: although not indicated for initial therapy, β-blockers may be used when other medicines (e.g. calcium channel blockers, ACE inhibitors, thiazide diuretics) are insufficient or inappropriate.
What are the important side effects of B-blockers?
can cause fatigue
- cold extremities
- headaches
- GI disturbance (e.g. nausea)
- sleep disturbances and nightmares
- can cause impotence in men
Where are B1 and B2-adrenoreceptors located?
β1-adrenoreceptors are located mainly in the heart, whereas β2-adrenoreceptors are found mostly in smooth muscle of blood vessels and airways.
What is the mechanism of action of B-blockers?
Via the B1 receptor, B-blockers reduce force of contraction and speed of contraction in the heart.
This relieves myocardial ischaemia by reducing cardiac work and oxygen demand, and increasing myocardial perfusion.
How do B-blockers help in heart failure?
They improve prognosis in heart failure by ‘protecting’ the heart from chronic sympathetic stimulation.
How do B-blockers help in AF?
They slow the ventricular rate in AF mainly by prolonging the refractory period of the atrioventricular (AV) node.
Through the same effect they may terminate SVT if this is due to a self-perpetuating (‘re-entry’) circuit that takes in the AV node.
How do b-blockers help in hypertension?
In hypertension, β-blockers lower BP through a variety of means, one of which is by reducing renin secretion from the kidney, since this is mediated by β1-receptors.
Which patients should beta blockers be avoided in?
In patients with asthma as beta blockers can cause life-threatening bronchospasm and should be avoided. This effect is mediated by blockade of B2-adrenoreceptors in the airways.
- Also should be avoided in patients with haemodynamic instability
- also contraindicated in heart block
Can B-blockers be used safely in COPD patients?
Yes although it is prudent to choose a B-blocker that is relatively B1-selective (e.g. bisoprolol, metoprolol), rather than on-selective (e.g. propranolol, carvedilol).
When Beta-blockers are used in heart failure what about the dose should we be aware of?
In heart failure beta blockers should be started at a very low dose and increased slowly, as they may initially impair cardiac function.
What about Beta blockers and use in hepatic failure?
Can be used with caution but require dosage reduction significantly
Can Beta-blockers be used with diltiazem?
β-blockers must not be used with ✗non-dihydropyridine calcium channel blockers (e.g. verapamil, diltiazem), except in specialist practice. This combination can cause heart failure, bradycardia and even asystole
Which indication is b-blocker dose the lowest?
Dosage varies according to the drug and the indication – the starting dose in heart failure is lower than that for ischaemic heart disease or hypertension.
It is generally best to start at the lowest dosage listed in the BNF for that indication.
Which b-blocker is available as IV if rapid effect is required?
Intravenous preparations (e.g. of metoprolol) are available for use when rapid effect is necessary.
What should patients with heart failure who are starting on a beta blocker be made aware of?
Warn patients with heart failure about the risk of initial deterioration in their symptoms, and advise them to seek medical attention if this occurs.
What should patient with obstructive airways disease who are using beta blocker be made aware of?
Warn patients with obstructive airways disease to stop treatment and seek medical advice if they develop any breathing difficulty.
When using Beta blockers in ischemic heart disease what resting heart rate should be aimed for?
In ischaemic heart disease, aim for a resting heart rate of around 55–60 beats/min).
Give examples of fibrinolytic drugs?
Altepase
Streptokinase
Tenecteplase
Urokinase
What are the common indications of fibrinolytic drugs?
1) In acute ischaemic stroke, alteplase increases the chance of living independently if it is given within 4.5 hours of the onset of the stroke.
2) In acute ST elevation myocardial infarction, alteplase and streptokinase can reduce mortality when they are given within 12 hours of the onset of symptoms in combination with antiplatelet agents and anticoagulants. However, primary percutaneous coronary intervention (where available) has largely superseded fibrinolytics in this context.
3) For massive pulmonary embolism (PE) with haemodynamic instability fibrinolytic drugs reduce clot size and pulmonary artery pressures, but there is no clear evidence that they improve mortality.
What are fibrinolytic drugs also known as?
AKA Thrombolytic drugs
What is the mechanism of action of fibrinolytic drugs?
Fibrinolytic drugs, also known as thrombolytic drugs, catalyse the conversion of plasminogen to plasmin, which acts to dissolve fibrinous clots and re-canalise occluded vessels.
This allows reperfusion of affected tissue, preventing or limiting tissue infarction and cell death and improving patient outcomes.
What are the common indications of fibrinolytic drugs?
- nausea and vomiting
- bruising around the injection site and hypotension
What adverse reactions of fibrinolytics require to stop treatment?
Serious bleeding, allergic reaction,
cardiogenic shock,
cardiac arrest
What may serious bleeding caused by finbrinolytics require treatment with?
With coagulation factors and antifibrinolytic drugs e.g. tranexamic acid, but this is usually avoidable as fibrinolytic drugs have a very short half life.
What can reperfusion of infarcted brain or heart tissue lead to ?
Cerebral oedema and arrhythmias, respectively
What are the contraindications of fibrinolytics drugs?
There are many contraindications to thrombolysis, which are mostly factors that predispose to ✗bleeding, including: recent haemorrhage; recent trauma or surgery; bleeding disorders; severe hypertension; and peptic ulcers.
