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.
What must be excluded before treatment with fibrinolytic (Hint-involves a scan?)
intracranial haemorrhage must be excluded with a computed tomography (CT) scan before treatment.
Can streptokinase be used twice on same patient?
✗Previous streptokinase treatment is a contraindication to repeat dosing (although other fibrinolytics can be used), as development of antistreptokinase antibodies can block its effect.
Which drugs when taken with fibrinolytics increase the risk of haemorrhage?
Anticoagulants and antiplatelet agents
Which drug class interacts with fibrinolytics to increase the risk of anaphylactoid reactions?
ACE inhibitors
Who should fibrinolytics be prescribed by?
Fibrinolytic drugs should be prescribed only by clinicians with expertise in their use.
What does the dose of fibrinolytic drug vary on?
The dose varies depending on the indication, timing from the onset of symptoms and the patient’s weight.
Which formulations are fibrinolytics available in?
They are available as injectable preparations only
Are fibrinolytics given as IV?
Given first as a bolus dose, followed by an IV infusion.
Where (which setting) would you expect finbrinolytics to be administered in?
Fibrinolytic drugs should be administered in a high dependency area such as the emergency department, hyperacute stroke unit or coronary care unit, by staff with expertise in their use
How is altepase given?
Alteplase comes as a powder, which is reconstituted with sterile water (also provided in the package), and then either given directly as an IV bolus injection or diluted further in 0.9% sodium chloride and given as an IV infusion.
What should be discussed when deciding to ‘thrombolyse’ (prescribe fibrinolytic therapy)?
the risks and benefits discussed with the patient and next of kin. For example, in acute stroke, explain that part of the brain is being starved of blood and oxygen due to a blocked artery, which will cause long-term damage. Giving a ‘clot-busting drug’ can reduce damage to the brain by dissolving the blood clot and restoring blood flow.
However, it works only if given soon after the onset of the stroke.
With or without treatment people may show some improvement, but symptoms may also get worse and one in three strokes is fatal.
Although the chance of death is increased initially after receiving a clot-busting drug (due to bleeding), after the first week the chances of living independently are increased.
Is consent required to administer fibrinolytic?
For licensed indications, written consent is not essential but verbal consent should be obtained. If neurological impairment prevents consent, treatment can still be given if judged to be in the patient’s best interests.
What monitoring is required with fibrinolytic treatment?
Patients should be monitored in a high dependency area
- vital signs checked every 15 minutes for the first 2 hours.
This should include observation for signs of bleeding,
anaphylaxis,
particularly in the case of acute stroke,
- neurological deterioration
Are fibrinolytic drugs available as both generic and branded products?
Available as only branded products only. Treatment with altepase costs around £300-600 and with streptokinase costs around £80.
What is the clinical tip of fibrinolytics in patients with acute ischaemic stroke?
Likely benefits of thrombolysis diminish rapidly with time.
Compared with untreated patients, the chance of being alive and independent at 6 months is increased by 10% for patients who receive thrombolysis within 3 hours of symptom onset, but by 2% if thrombolysis is performed between 3 and 6 hours
List a few examples of Low molecular weight heparins (LMWH)?
Bemiparin Certoparin Dalteparin Enoxaparin Nadroparin Parnaparin Reviparin Tinzaparin
What are the common indications of heparins and fondaparinux?
1) Heparin, usually low molecular weight heparin (LMWH), is used for primary prevention of deep vein thrombosis and pulmonary embolism (collectively venous thromboembolism, VTE) in hospital inpatients. It is also an option for initial treatment of VTE, until oral anticoagulation (e.g. with warfarin, dabigatran) is established. Fondaparinux and DOACs (e.g. rivaroxaban) are alternatives.
2) Acute coronary syndrome (ACS): Heparin (usually LMWH) or fondaparinux is used with antiplatelet agents to reduce clot progression or maintain revascularisation.
In simple terms what is venous and intracardiac clot formation driven by compared to arterial thrombosis?
In simplistic terms, venous and intracardiac clot formation is driven largely by the coagulation cascade, while arterial thrombosis is more a phenomenon of platelet activation.
What is the mechanism of action of heparins and fondaparinux?
- The coagulation cascade is an amplification reaction between clotting factors that generates a fibrin clot.
- Antithrombin (AT) inactivates clotting factors, particularly factors IIa (Thrombin) and Xa, providing a natural break to the clotting process.
- ## Heparins and fondaparinux act by enhancing the anticoagulant effect of AT.
What about heparins determines their molecular specificity?
The size of heparin molecules determines their molecular specificity.
What does unfractionated heparin (UFH) (large and small molecules) promote?
Promotes inactivation of both factor IIa and Xa.
What about LMWH (low molecular weight heparins) (smaller molecules) what do they promote?
LMWH is more specific for factor Xa.
Is fondaparinux natural or synthetic product?
Fondaparinux is a synthetic pentasaccharide that mimics the sequence of the binding site of heparin to AT and is very specific for factor Xa.
Out of the three (LMWH, UFH and fondaparinux) which has the lower risk of haemorrhage?
Fondaparinux compared to the other two
What are the side effects of heparins and fondaparinux?
- Main adverse effect is haemorrhage
- Bruising or other reactions may occur at the injection site
- hyperkalaemia occurs occasionally due to an effect on adrenal aldosterone secretion.
- Rarely patients may experience a dangerous immune reaction to heparin, characterised by low platelet count and thrombosis (heparin-induced thrombocytopenia - HIT).
Which out of the three (LMWH, UFH and fondaparinux) is HIT (heparin induced thrombocytopenia) more common in?
More common in UFH, less likely with LMWH,
and does not occur with fondaparinux
Who should anticoagulants be used with extra caution in?
With caution in patients at increased risk of bleeding, including:
- clotting disorders
- severe uncontrolled hypertension
- recent surgery or trauma
They should be withheld immediately before and after ▴invasive procedures, particularly lumbar puncture and spinal anaesthesia.
In renal impairment which of the three (LMWH, UFH or fondaparinux) should be used?
Fondaparinux is CI in renal impairment less than 30.
In ▴renal impairment, LMWH and fondaparinux accumulate, so a lower dose or UFH should be used instead.
What form/ route are LMWH usually preferred to be given?
SC
With heparins how are the dosage specified?
In units (never abbreviate this to ‘U’ which can easily be misread as ‘0’), and varies with indication and weight.
What is a typical example of a VTE prophylaxis regimen?
A typical VTE prophylaxis regimen is dalteparin 5000 units SC daily, but you should refer to local protocols.
When may unfractioned heparin be preffered?
UFH may be preferred in renal impairment (e.g. heparin 5000 units SC 12-hrly for VTE prophylaxis) or when rapid onset and offset of anticoagulation is required (when it is given as a variable-rate IV infusion).
Where are heparins and fondaparinux usually adminsterred?
SC injections of these drugs should be given into the SC tissue of the abdominal wall. The arm should not be used because this can cause uncomfortable and disabling bruising.
Usually a daily injection??
What does the patient or their carer need to be trained or aware of?
Will need to be trained in SC injection technique. If this is not possible, administration by a district nurse may be arranged.
What is a major advantage of LMWH and fondaparinux over UFH? (Hint- monitoring requirements)
their anticoagulant effect is sufficiently predictable than UFH which reduces the need for routine laboratory monitoring.
What is measured in selected cases?
Where required in selected cases (e.g. renal impairment, pregnancy), plasma antifactor Xa activity is measured.
What is the target activated partial thromboplastin ratio (APTR) for UFH?
usually 1.5-2.5
UFH has a less predictable effect and, when used to achieve full (‘therapeutic’ as opposed to ‘prophylactic’) anticoagulation, the dosage is titrated against the activated partial thromboplastin ratio (APTR) (usual target 1.5–2.5).
What should be checked/ monitored before starting treatment with heparins/ fondaparinux?
- Full blood count
- baseline clotting
- renal profiles
How many days is considered as pro-longed therapy with heparins?
More than 4 days
WHat should be monitored in pro-longed therapy?
Platelet count
Serum potassium concentration
As the risk of thrombocytopenia and hyperkalaemia increases with duration of therapy
When warfarin is used for VTE treatment, another anticoagulant (…….) may be given alongside it initially? (what is the missing word??)
often LMWH
What is the mechanism/ rationale behind warfarin + LMWH therapy?
LMWH provides ‘bridging anticoagulation’ during the period in which warfarin may be briefly pro-thrombotic (due to its initial inhibition of natural anticoagulants [proteins C and S], before its effect on other clotting factors [II, VII, IX, X] is established). LMWH should be continued for 5 days or until the INR (see Warfarin) is in the therapeutic range, whichever is longer.
List examples of Nitrates?
Glyceryl trinitrate
Isosorbide Mononitrate
Isosorbide Dinitrate
What are the common indications of Nitrates?
1) Short-acting nitrates (glyceryl trinitrate) are used in the treatment of acute angina and chest pain associated with acute coronary syndrome (ACS).
2) Long-acting nitrates (e.g. isosorbide mononitrate) are used for prophylaxis of angina where a β-blocker and/or a calcium channel blocker are insufficient or not tolerated.
3) Intravenous nitrates are used in the treatment of pulmonary oedema, usually in combination with furosemide and oxygen
What is the mechanism of action of Nitrates?
- Nitrates are converted into Nitric Oxide (NO).
- NO increases cyclic gyanosine monophosphate (cGMP) synthesis and reduces intracellular Ca2+in vascular smooth muscle cells, causing them to relax.
- this results in venous, to a lesser extent, arterial vasodilation.
- relaxation of the venous capacitance vessels reduces cardaic preload and left ventricular filling.
These effects reduce cardiac work and myocardial oxygen demand, relieving angina and cardiac failure.
What else can nitrates relieve?
Coronary vasospasm and dilate collateral vessels, improving coronary perfusion. They aslo relax the systemic arteries, reducing peripheral resistance and afterload.
What are most of the antianginal effects of nitrates mediated by the reduction of?
Mainly by the reduction of preload.
What are the side effects of nitrates?
- flushing
- Headaches
- Light-headedness
- hypotension
- sustained use of nitrates can lead to tolerance (with reduced symptom relief despite continued use
how can tolerance of nitrates be reduced?
This can be minimised by careful timing of doses to avoid significant nitrate exposure overnight, when it tends not to be needed.
Which patients are nitrates contraindicated in?
- severe aortic stenosis (in whom they may cause cardiovascular collapse)
- This is because the heart is unable to increase cardiac output sufficiently through the narrowed valve area to maintain pressure in the now dilated vasculature.
- Nitrates should be avoided in patients with haemodynamic instability, particularly hypotension
which drugs in particular should nitrates be avoided in?
Nitrates must not be used with phosphodiesterase (PDE) inhibitors (e.g. sildenafil) because these enhance and prolong the hypotensive effect of nitrates.
which patients should nitrates be used with caution with?
Used with caution in patients taking antihypertensive medication, in whom they may precipitate hypotension.
What route is GTN usually given?
In patients with stable angina, glyceryl trinitrate (GTN) is prescribed to be taken sublingually as tablets or spray for immediate relief of chest pain.
What is the half life of GTN?
GTN has a plasma half-life of <5 minutes, so has a very quick onset and offset of action.
In patients with ACS or heart failure how form of GTN is prescribed?
GTN is prescribed as a continuous IV infusion
what is the half-life of isosorbide mononitrate?
4-5 hours and is prescribed two to three times daily as immediate release tablets for the prevention of recurrent angina.
What other formulations is isosorbide mononitrate available in?
- modified release tablets
- transdermal patches
(prescribed once daily)
When prescribing modified release tabs of isosorbide mononitrate what is important to be aware of?
should be prescribed by brand name, since there are important differences between preparations.
What should be advised about postural hypotension to patients on nitrates?
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 GTN.
When nitrates are administered intravenously what should be measured frequently?
blood pressure should be monitored frequently, and the infusion rate adjusted to ensure the systolic blood pressure does not drop below 90 mmHg.
How long do GTN tablets last once package is opened?
8 weeks
For those who use nitrates less (infrequent symptoms) which may be a better choice? Tablets or sprays?
Sprays
What is Tachyphylaxis?
The term used for tolerance to nitrates - where frequent use of nitrates can lead to tolerance, which can reduce efficacy.
how can patients avoid tacyphylaxis?
To prevent this, time doses to ensure there is a ‘nitrate-free period’ every day during a time of inactivity, usually overnight.
For example, patients should be advised to take twice-daily ISMN morning and mid-afternoon (rather than evening) to provide a longer (about 18-hour) gap between doses in the afternoon and the following morning.
What about timing of transdermal patches of nitrates, how should they be applied to avoid tacyphylaxis?
Transdermal patches should be applied in the morning and removed at bedtime.
How long does sublingual nitrate spray last for?
Lasts for 20 to 30 minutes.
List some strong opioids?
morphine, oxycodone, fentanyl, buprenorphine, diamorphine, methadone, tramadol, pethidine, pentazocin
What are the common indications of opioids?
1) Rapid relief of acute severe pain, including post-operative pain and pain associated with acute myocardial infarction.
2) Relief of chronic pain, when paracetamol, NSAIDs and weak/moderate opioids are insufficient (‘rung 3’ of the World Health Organization (WHO) pain ladder).
3) Relief of breathlessness in the context of end-of-life care.
4) Relief of breathlessness and anxiety in acute pulmonary oedema, alongside oxygen, furosemide and nitrates.
Give an example of a naturally occurring opioid?
Morphine
Give an example of a synthetic opioid?
Oxycodone
What is the mechanism of action of opioids?
- The therapeutic action of opioids arises from activation of µ receptors in the central nervous system (CNS).
- Activation of these G-protein coupled receptors has several effects that, overall, reduce neuronal excitability and pain transmission.
What effect does opioids have in the medulla?
In the medulla, they blunt the response to hypoxia and hypercapnoea, reducing respiratory drive and breathlessness.
- By relieving pain, breathlessness and associated anxiety, opioids reduce sympathetic nervous system (fight or flight) activity. Thus is myocardial infarction and acute pulmonary oedema they may reduce cardiac work and oxygen demand, as well as relieving symptoms.
Is the safe to use morphine in acute pulmonary oedema?
Although commonly used, the efficacy and safety of morphine in acute pulmonary oedema is not firmly established.
What can opioids cause that is a dangerous side effect?
Opioids can cause respiratory depression by reducing respiratory drive. They may cause euphoria and detachment.
In higher doses, what other depression can opioids cause?
Neurological depression
How do opioids cause nausea and vomiting?
They can activate the chemoreceptor trigger zone, causing nausea and vomiting, although this tends to settle with continued use.
With opioids what’s the reason for pupils constriction?
Pupillary constriction occurs due to stimulation of the Edinger–Westphal nucleus.
What is the mechanism of constipation due to opioid use?
Activation of µ receptors increases smooth muscle tone and reduces motility, leading to constipation.
In the skin what may opioid cause the release of?
May cause the release of histamine, leading to itching, urticaria, vasodilation and sweating.
What can continued use of opioids lead to?
Tolerance (a state in which the dose required to produce the same effect increases over time)
Dependence - becomes apparent on cessation of the opioid, when a withdrawal reaction occurs
Can opioids be used in hepatic and renal impairment?
Most opioids rely on the liver and the kidneys for elimination, so doses should be reduced in ▴hepatic failure and▴ renal impairment and in the ▴elderly.
Can opioids be used in respiratory failure?
Do not give opioids in ▴respiratory failure except under senior guidance (e.g. in palliative care).
Which condition should opioids be avoided in?
Avoid opioids in ▴biliary colic, as they may cause spasm of the sphincter of Oddi, which may worsen pain.
Which other drugs should not be used with opioids?
Opioids should ideally not be used with ▴other sedating drugs (e.g. antipsychotics, benzodiazepines and tricyclic antidepressants). Where their combination is unavoidable, close monitoring is necessary
When treating acute severe pain in high dependency areas, how is morphine usually given for rapid effect?
Given as IV for rapid effect (onset at about 5 minutes).
Intravenous morphine should be given only in high dependency areas as adverse effects may be more pronounced.
It should be given incrementally (1–2 mg every few minutes) to achieve the desired response.
what initial IV dose of morphine is given?
An initial dose of 2–10 mg, tailored to pain, age and other individual factors, is prescribed in the once-only section.
On a general ward what route of administration of morphine is preffered?
IM or SC administration is preffered.
For chronic pain which form of administration of morphine is best?
For chronic pain, the oral route is safest and usually most appropriate.
Initially which form of morphine tablets is preferred for chronic pain?
Immediate-release oral morphine is preferred initially (e.g. Oramorph® 5 mg orally every 4 hours).
Then, having found the optimum dose, this is converted to an modified-release (MR) form (e.g. MST Continus® 15 mg every 12 hours). Alongside regular treatment, ‘breakthrough analgesia’ should be prescribed.
What is the dose of the breakthrough pain (immediate release morphine)?
Prescribe immediate-release morphine at a dose of about One-tenth to one-sixth of the total daily regular dose (e.g. Oramorph® 5 mg 2-hrly) in the as-required section.
Is morphine/ oxycodone preferred to be prescribed by generic or brand name?
For safety reasons, we favour brand name prescribing for strong oral opioids, although local practices may vary.
What advice about nausea and vomiting should be given for patients on opioid treatment?
Explain that nausea usually settles after a few days, but offer an antiemetic (e.g. metoclopramide).
What is treatment for opioid induced constipation?
Constipation is very common; pre-emptive use of a laxative (e.g. senna), along with good hydration, is advisable.
+ osmotic laxative
(Avoid bulk forming laxative for opioid induced constipation)
What advice/ warning about drowsiness needs to be given for patients using opioids?
Advise patients not to drive or operate heavy machinery if they feel drowsy or confused.
What are the features of opioid withdrawal?
The features of opioid withdrawal are the opposite of the clinical effects of opioids: anxiety, pain and breathlessness increase; the pupils dilate; and the skin is cool and dry with piloerection (‘cold turkey’).
Should we think about opioid dependence during end of life care?
do not let this concern deter you from offering opioids for severe or chronic pain, especially in end-of-life care
What step are weak opioids on the WHO ladder?
Weak opioids are on the second ‘rung’ of the WHO pain ladder
Give two examples of a weak opioid?
Codeine and Dihydrocodeine
What are codeine and dihydrocodeine metabolised in the liver to produce?
Metabolised in the liver to produce very small amounts of morphine (codeine) or dihydromorphine (dihydrocodeine). These metabolites, which are stronger agonists of opioid µ (mu) receptors probably account for most of the analgesic effect.
What is the reason why Caucasians may find codeine or dihydrocodeine ineffective?
About 10% of Caucasians have a less active form of the key metabolising enzyme (CYP 2D6), and these people may find codeine and dihydrocodeine largely ineffective.
What is drug class of tramadol?
Tramadol is a synthetic analogue of codeine; it is perhaps best classified as a ‘moderate-strength’ opioid.
How does tramadol work?
Like codeine, tramadol and its active metabolite are µ-receptor agonists.
Unlike other opioids, which other pathways does tramadol affect but other opioids don’t?
receptor agonists. Unlike other opioids, tramadol also affects serotonergic and adrenergic pathways, where it is thought to act as a serotonin and noradrenaline reuptake inhibitor (SNRI). This probably contributes to its analgesic effect.
What are the common side effects of weak opioids?
- nausea
- constipation
- dizziness
- drowsiness
When taken in overdose what can all opioids cause?
All opioids can cause neurological and respiratory depression when taken in overdose.
Does tramadol cause more or less constipation and respiratory depression compared to other opioids?
Tramadol may cause less constipation and respiratory depression than other opioids.
Can codeine/ dihydrocodeine be given intravenously?
Codeine and dihydrocodeine must never be given intravenously, as this can cause a severe reaction similar to anaphylaxis. This is mediated by histamine release, but does not have an ‘allergic’ basis.
Can tramadol be given in epilepsy?
Tramadol lowers the seizure threshold, so is best avoided in patients with ▴epilepsy, and certainly should not be used in those with ✗uncontrolled epilepsy
Which other drugs should tramadol not be given with?
- other sedating drugs such as antipsychotics, benzodiazepines and tricyclic antidepressants
- Tramadol should not be used with other drugs that lower the seizure threshold, such as antipsychotics.
What about tramadol + other serotonergic drugs?
Due to its serotonin-modulating effects, tramadol may increase the risk of serotonin syndrome when taken with other ▴serotonergic drugs (e.g. monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, tricyclic antidepressants, tramadol).
What is the typical dose of tramadol?
50mg orally 4-hourly 9( to maximum 400mg/day)
Whenever an opioid is to be administered regularly, what should we consider?
should consider the need for a laxative (e.g. a stimulant laxative such as senna) to mitigate its constipating effects
How is efficacy of analgesics best established?
Efficacy of analgesics is best established by symptom enquiry and/or with a pain score: e.g. a visual analogue scale. In acute pain, review the response to analgesia 1–2 hours after an oral dose. For chronic pain, schedule a review after 1–2 weeks to assess the need to step up or down the analgesic ladder, to assess side effects, and to consider the need for specialist referral.
What is the therapeutic range of lithium?
0.4-1 mmom/L
What are the indications of lithium?
- prophylaxis and treatment of mania
- depression in bipolar disorder and recurrent unipolar depression
How often should thyroid function be monitored when on lithium?
Every 6 months
When using lithium - caution is required when used with which kind of drugs?
- Those that lower seizure threshold, prolongs QT interval and causes sodium depletion (e.g.thiazide diuretics)
With lithium how long after given a dose should serum lithium be measured?
- 12 hours after the dose - to achieve a concentration of 04.1mmol/L
Lithium target of 0.8-1 mmol/L is recommended for which patients?
for acute episode of mania and for patients who have previously relapsed or have sub syndromal symptoms
How often should lithium concentrations be measured?
Weekly and after every dose change until concentrations are stable
- Then every 3 months thereafter
When on lithium how often should renal function be monitored?
- At baseline and every 6 months thereafter
Can lithium be stopped abruptly, or how should it be stopped?
- Should not be discontinued abruptly,
If to be discontinued, the dose should be reduced gradually over a period of at least 4 weeks (preferably over 3 months)
When is lithium contra indicated?
- CI in addison’s disease
- Cardiac insufficiency
- Dehydration
- F/H of brugada syndrome (Condition that affects your heart)
- low sodium diet
- rhythm disorder
- untreated hypothyroidism
What is the major route of elimination of lithium?
Renal - freely filtered at glomerulus with 80% reabsorbed
What are the side effects of lithium?
- can slow thinking and makes them feel a bit ‘numb’
- nausea
- diarrhoea
- dry mouth and or metallic taste in the mouth
- feeling thirsty (needing to drink more and pee more than usual)
- Slight shaking of the hands (mild tremor)
- Feeling tired or sleepy
- Weight gain (this is likely to be gradual)
What are the signs and symptoms of toxicity of lithium?
Increased GI disturbances
- Visual disturbances
- Polyuria (excessive passing of urine)
- tremor
- Bradycardia
- renal impairment
- seizures
What long-term effects is associated with lithium use?
- associated with thyroid disorders
- Mild cognitive and memory impairment
Do females of child bearing age need to take extra precautions?
Yes - need to use effective contraception
Can lithium be used in pregnancy and breastfeeding?
Should be avoided if possible (Teratogenic in first trimester) and present in breastmilk
What monitoring overall is required of lithium?
- Body weight or BMI
- serum electrolytes
- eGFR
- Thyroid function
(every 6 months)
What advice should be given to patients and carers regarding fluid and diet?
- Maintain adequate fluid intake and avoid dietary changes which reduce or increase sodium intake
Does a higher or lower dose of lithium need to be used in elderly?
A lower dose should be used in the elderly
What regarding changes in preparations of lithium should be noted?
- preparations vary widely in bioavailability, changing the preparation requires the same precautions as initiation of treatment
After how many hours after a dose should lithium be measured?
After 12 hours of taking a dose
What signs of lithium toxicity can indicate renal dysfunction?
- Polyuria (excessive urine)
- Polydipsia (excessive thirst)
When on lithium should patients report signs of hypothyroidism?
Yes as it can indicate toxicity
Weight gain
being sensitive to the cold
fatigue/ tiredness
Can lithium cause AKI?
Yes - in overdose
Which drugs interact with lithium?
- NSAIDs (
- Thiazides (reduce sodium levels)
- Loop diuretics (reduce sodium levels)
ACE inhibitors (reduce sodium levels)
Is there an antidote available for lithium?
No none available
What is the full list of lithium toxicity?
increasing gastro-intestinal disturbances (vomiting, diarrhoea), visual disturbances, polyuria, muscle weakness, fine tremor increasing to coarse tremor, CNS disturbances (confusion and drowsiness increasing to lack of coordination, restlessness, stupor); abnormal reflexes, myoclonus, incontinence, hypernatraemia.
What does signs of intoxication of lithium require?
Withdrawal of treatment
What is the full list of cautions of lithium?
Avoid abrupt withdrawal;
• cardiac disease;
• concurrent ECT (may lower seizure threshold);
• diuretic treatment (risk of toxicity);
• elderly (reduce dose);
• epilepsy (may lower seizure threshold);
• myasthenia gravis;
• psoriasis (risk of exacerbation);
• QT interval prolongation;
• review dose as necessary in diarrhoea;
• review dose as necessary in intercurrent infection (especially if sweating profusely);
• review dose as necessary in vomiting; surgery
Does same brand of lithium need to be maintained?
Yes
Do patients need to be given lithium booklet and alert cards?
Yes (purple colour)
What is written in the lithium booklet?
- Dose of lithium
- your lithium blood levels
- any other blood test results
- Your weight
What are the two types of lithium?
- Lithium carbonate
- Lithium Citrate
It’s important not to change to a different type unless your doctor has recommended it. This is because different types are absorbed differently in the body.
Lithium carbonate comes as regular tablets and slow-release tablets – where the medicine is released slowly over time.
Lithium citrate comes as a liquid. This is usually only prescribed for people who have trouble swallowing tablets .
Can you take lithium with or without food?
Can be taken with or without food
What if someone forgets to take their dose of lithium?
tablets or slow-release tablets – if it’s less than 6 hours since you were supposed to take your lithium, take it as soon as you remember. If it is more than 6 hours, just skip the missed dose and take your next one at the usual time
liquid – if you forget to take a dose, just skip the missed dose and take your next one at the usual time
Can patients on lithium drink alcohol?
Advised not to drink in large amounts especially in hot weather as alcohol has dehydrating effects which can lead to lithium toxicity.
Is lithium an antipsychotic?
No it is not it is known as a mood stabiliser
Summarise the MAO of lithium?
Lithium acutely stimulates the NMDA receptor, increasing glutamate availability in the postsynaptic neuron. After chronic administration, lithium induces NMDA downregulation, this way lithium modulates glutamate neurotransmission. In the previous slides we saw how lithium inhibits excitatory neurotransmission.
What is a key tip to remember about lithium and sodium pair?
The kidney treats lithim and sodium similarly.
So like serum sodium, lithium is also partially reabsorbed.
therefore, this makes lithium sensitive to water and electrolyte balance and is the reason why sodium depletion can significantly elevate lithium reabsorption
S.T.A.N.D makes lithium go up? What does this mean?
Salt - decreased salt intake promotes lithium retention
Thiazide diuretics - induce NA+ loss leading to a compensatory increse in the reabsorption of Na+ and lithium in the proximal tubule
ACE/ARBs - Similar reason above ^^. ACE/ARBs decrease conc of angiotensin II, which is responsible for the reabsorption of NA+ and water
NSAIDs - lower kidney’s internal ability to eliminate lithium thus increasing lithium serum concentrations
Dehydration - causes the body to loose fluids and electrolytes such as NA+
What are the indications of methotrexate?
- Active rheumatoid arthritis
- Severe Crohn’s disease
- Neoplastic diseases
- Severe psoriasis unresponsive to conventional therapy
What is the MAO of methotrexate?
Methotrexate inhibits the enzyme dihydrofolate reductase. essential for the synthesis of purines and pyrimidines.
What are some side effects of methotrexate?
- Myelosuppression (A condition in which bone marrow activity is decreased, resulting in fewer red blood cells, white blood cells, and platelets)
- Mucositis (when your mouth or gut is sore and inflamed)
- Pneumonitis (is a general term that refers to inflammation of lung tissue)
Where is methotrexate primarily excreted?
In the kidneys
Is methotrexate CI in significant renal impairment or hepatic impairment?
Yes in both
What is the anti-dote to methotrexate?
- Folinic acid
Which other drug (anti-folate) can increase the risk of myelosuppression if given with methotrexate?
Trimethoprim
For people on methotrexate what can dyspnoea, cough or fever be a sign of that requires patient to seek medical attention?
Sign of pulmonary toxicity - Discontinue if pneumonitis is suspected
Is it safe to sell aspirin and other NSAIDs OTC for patient taking methotrexate?
- No patients should avoid this
- If given on prescription then the dose of methotrexate should be carefully monitored
Is methotrexate safe to be used in pregnancy?
No it is teratogenic
Is effective contraception required during methotrexate treatment?
Yes - during and for at least 6 months after treatment in men and women
What blood monitoring should be carried out for methotrexate?
- FBC
- Renal function
- Liver functions
How often should methotrexate be monitored?
- before starting treatment
- repeated every 1-2 weeks until therapy stabilised
- thereafter patients should be monitored every 2-3 months
Which symptoms should patients be advised to report?
- Any signs suggestive of infection such as sore throat
or signs of blood disorders such as bruising and mouth ulcers),
Liver toxicity - nausea, vomiting, abdominal discomfort, dark urine)
Respiratory effects (Shortness of breath)
What is the recommended frequency of administration of methotrexate?
- Taken once weekly
What advice about vaccines should be given to patients on methotrexate?
- Recommend to the patient to obtain an annual flu vaccine but live vaccines should be avoided
Why should NSAIDs and penicillins be avoided in patients taking methotrexate?
Excretion reduced by NSAIDs and therefore increased risk of toxicity
There is an increased risk of haematological toxicity when methotrexate is given with which drugs?
- Trimethoprim
- Sulfamethoxazole (Co-trimoxazole)
Which indication can methotrexate (intrathecally route) be used in only?
- Chemotherapy
What are the signs of methotrexate toxicity?
Bone marrow suppression
signs include sore throat, bruising, mouth
ulcers. Gastro intestinal toxicity. Liver toxicity signs include nausea,
vomiting, yellowing of the skin and whites of the eyes, fatigue, loss of
appetite.
What signs can indicate gastro-intestinal toxicity for patients taking methotrexate?
Manufacturer advises withdraw treatment if stomatitis or diarrhoea develops—may be first sign of gastro-intestinal toxicity
