CPT Flashcards
What is the definition of a clinical trial?
Any form of planned experiment which involves patients and is designed to elucidate the most appropriate method of treatment for future patients with a given medical condition.
What is the purpose of a clinical trial?
To provide reliable evidence of treatment efficacy and safety.
What are the recommendations for phase I trials?
Give the drug to one volunteer at a time.
Give the drug slowly.
Make sure that pre-clinical studies predict safe doses in humans.
What method can users in phase IV clinical trials use to report intervention side effects?
The Yellow Card reporting site.
What is a non-randomised clinical trial?
Where one patient group is allocated a new treatment and another patient group is allocated the standard treatment, where the allocation is known.
What are historical control comparisons, and what are the drawbacks of this?
Compare a group of patients who had the standard treatment, previously, with a group of patients receiving a new treatment.
Selection is often less defined and less rigorous.
The groups are often treated differently.
Potential bias/ confounders.
Unable to control for confounders.
There may be differences in healthcare over time.
May not have sufficient information.
How is randomisation done and why is it done?
Using 3rd parties , such a computer generated lists.
Sequentially numbering sealed envelopes.
It is done to reduce confounding - the greater the sample size, the fewer the differences between the groups due to chance.
What are open label trials and what are they more prone to?
They are trials where there is knowledge for which participant is receiving the treatment.
They are more prone to:
- Performance bias; patient altering the behaviour or the clinician altering their treatment.
- Information bias; investigator altering their approach to making measurements.
State some examples where blinding may be difficult.
Surgical procedures - sham surgeries.
Psychotherapy vs anti-depressants.
Alternative medicines, such as acupuncture.
Lifestyle interventions.
Prevention programmes.
What is allocation concealment?
The lack of knowledge as to whether the next person is to be allocated the new or old treatment.
What are the purposes of:
- Allocation concealment.
- Randomisation.
- Blinding.
State what they prevent and when they should be implemented.
What are inclusion and exclusion criteria, and what do they both relate to?
Inclusion criteria relates to the ability to find the people with desired characteristics for a study.
Exclusion criteria relates to the ability to prevent certain people with certain characteristics from entering a study.
These criteria relate to the generalisability of the study.
What is the primary outcome used for?
Working out how large the study needs to be.
What are some baseline data that should be compared against?
Age.
Sex.
Socioeconomic status.
Ethnicity.
BMI.
Disease burden/ comorbidities.
Occupational exposure.
What is pharmacogenetics?
The differences in effects that drugs have between different people.
What state must a drug be in to produce a response?
It must be free - unbound.
What are ‘me too’ and repurposed drugs?
‘Me too’ - drugs that have had the molecular structure changed very slightly but still produce the same or very similar effects.
Repurposed drugs are drugs that were previously used for something but now have alternative therapeutics.
Other than IV, if a drug has poor bioavailability, what method of absorption can be used?
Sprays or inhalation.
What does first pass metabolism consist of?
Metabolism in the gut lumen, gut wall, liver and lungs - before reaching the systemic circulation.
What are modified release preparations?
Manipulation of the absorption of a drug to help have more prolonged therapeutic effects and reduce the numbers of doses required.
What is bioequivalence?
Compounds of biochemical similarity, sharing the same active ingredients, that produce the same therapeutic effects.
What types of drugs do the following molecules bind to:
- Albumin.
- Globulins.
- Lipoproteins.
- Glycoproteins.
Albumin - acidic drugs.
Globulins - hormones.
Lipoproteins - basic drugs.
Glycoproteins - basic drugs.
As the drug is metabolised more, what happens to the volume of distribution?
It decreases, as more drug will become free and shift to the plasma.
Where, within the liver, are CYP450s found the most?
Smooth endoplasmic reticulum of the hepatocytes.
In which half life is the greatest amount of drug removed?
The first half life, it is half of the greatest concentration of drug.
What is the equation for calculating half life?
Half life = (0.693 x Vd) / Clearance.
How many half lives are required to reach a stead state of plasma concentration of the drug?
4 to 5.
How do we calculate maintenance dose?
MD = [ (clearance x the steady state concentration) / bioavailability ] x dose interval.
How do we calculate the loading dose?
LD = steady state concentration x volume of distribution.
Why is a buprenorphine-naloxone combined treatment given orally?
Buprenorphine is a partial agonist so inhibits withdrawal symptoms.
Naloxone has a poor bioavailability so will only inhibit buprenorphine if it is injected.
What is blood pressure?
The driving force to perfuse organs with blood - force per unit area acting on vessels.
What are autacoids, and how do they work?
State some examples.
Locally acting compounds that have an action on the endothelium or vascular smooth muscle.
Bradykinin and nitric oxide.
How can hyperinsulinaemia and hyperglycaemia lead to hypertension?
Endothelial dysfunction and increased reactive oxidative species can lead to reduced nitric oxide signalling, so less vasodilation.
What is emergency hypertension?
Hypertension where treatment is required immediately:
- SBP > 180mmHg.
- A DBP > 120mmHg with clinical signs.
What is the target blood pressure for a patient with a high urine albumin to creatine ratio?
< 130/ 80 mmHg.
What are the 3 stages of hypertension?
Who are pre-hypertensive interventions mainly aimed at and what are they?
Patients in their early-mid 40s, classed as pre-hypertensive.
What are the effects of AT1 receptor activation?
Vasoconstriction.
Stimulation of aldosterone which acts at distal renal tubules.
ADH release.
Cardiac and vascular muscle cell growth.
How is angiotensin I converted to angiotensin II in the absence of ACE?
Chymases.
How does bradykinin cause vasodilation?
Increases in NOS/ NO and PGI2 levels.
When should ACEi not be used (contraindications)?
Renal artery stenosis.
AKD.
Pregnancy.
Idiopathic angioedema.
CKD.
What are the antihypertensive choice in patients with low renin?
Calcium channel blockers, particularly dihydropyridines.
What is significant about amlodipine and nimodipine?
Amlodipine has a long half life.
Nimodipine is selective for cerebral vascular use, so is used to treat subarachnoid haemorrhage.
Why should amlodipine not be used with simvastatin?
It increases the plasma concentration of simvastatin, increasing its effect.
What are phenylalkylamines?
Class IV anti-arrhythmic agents that prolong action potentials, increasing the refractory periods.
Why are people of Black African or African Caribbean descent given calcium channel blockers, first line?
They have an increased risk of angioedema (so not ACEi) and have lower renin levels.
When is labetalol given?
Pregnancy and hypertensive emergencies.
What is an example of an alpha-adrenoceptor blocker?
Doxazosin.
Why are diuretics given in decompensated liver disease?
There are low levels of albumin, so are given to prevent oedema.
What are the adverse effects of thiazides/ thiazide-like diuretics?
Hyperuricaemia.
Hyperglycaemia.
Erectile dysfunction.
Increased LDL and triglyceride levels.
Hyperclacaemia.
Hypokalaemia.
What are the contraindications of thiazides/ thiazide-like diuretics?
Addison’s disease.
Hypercalcaemia.
Hyponatraemia.
Refractory hypokalaemia.
Gout.
What are the important drug interactions of thiazides/ thiazide-like diuretics?
Alcohol.
Amlodipine.
What are the adverse effects of loop diuretics?
Dehydration.
Hypotension.
Hypokalaemia.
Hyponatraemia.
Hyperuricaemia.
Arrhythmias.
Tinnitus - ototoxicity.
Increased cholesterol and triglycerides.
What are the contraindications of loop diuretics?
Hypokalaemia.
Hyponatraemia.
Gout.
Hepatic encephalopathy.
What are the important drug interactions of loop diuretics?
Aminoglycosides (ototoxic).
Digoxin and lithium (kidney damage).
What are the adverse effects of potassium-sparing diuretics?
Hyperkalaemia.
Potential arrhythmias.
What are the contraindications of potassium-sparing diuretics (ENaC)?
Addison’s disease.
Anuria.
Hyperkalaemia.
What are the important drug interactions of potassium-sparing diuretics (ENaC)?
Other K+-sparing drugs.
ACEi.
Adrenoreceptor blockers.
What is an example of a potassium-sparing diuretic (ENaC)?
Amiloride.
What are the adverse effects of mineralocorticoid receptor agonists?
Gynaecomastia.
Hyperkalaemia.
Severe cutaneous adverse reactions.
What are the contraindications of mineralocorticoid receptor agonists?
Addison’s disease.
Anuria.
Hyperkalaemia.
What are the important drug interactions of mineralocorticoid receptor agonists?
Alcohol.
Amiloride.
ACEi.
Angiotensin receptor blockers.
What are the two types of ADH antagonists?
Tolvaptan.
Lithium.
What are the potential interactions of the following?
How can CKD affect delivery of diuretics?
Damage to epithelial cells means OAT transporters are defective.
What are the aims of treatment of chronic heart failure?
What is Sacubitril and what is its effects?
Neprilysin inhibitor - inhibits natriuretic inactivating enzyme, increasing the effects of ANP and BNP, as well as preventing the breakdown of bradykinin.
This causes natriuresis and vasodilation.
What type of drug is valsartan?
Angiotensin II receptor blocker.
How does ivabradine help heart failure patients?
Blocks the HCN channels, slowing heart rate.
How does hydralazine/ nitrate combinations help patients with heart failure?
Venodilation and arteriodilation, reducing preload and afterload.
What is used in the treatment of acute heart failure?
IV loop diuretics.
Nitrates.
Sympathomimetic inotropes.
What concentration of potassium is required for spironolactone to no longer be recommended in the 4th level of hypertension treatment?
4.5mmol/L.
What tests should be carried out prior to treating a hypertensive pregnant woman?
HELLP syndrome:
- FBC for haemolysis.
- LFTs for elevated liver enzymes.
- Platelets for low platelets.
U&Es and proteinuria for kidney function.
Where in the nephron is potassium re-absorbed from when given thiazides?
The collecting ducts, through ROMK channels.
What is the target blood pressure for hypertensive pregnant women, and how frequently should it be measured?
< 135/85 mmHg.
Should be measured twice a week.
Which class of antihypertensives may cause harm if breastfeeding and therefore should be avoided?
Thiazide diuretic - indapamide.
What is pharmacovigilance?
The science and activities relating to the detection, assessment and preventing of adverse effects or any other possible drug-related problems.
What is the most common clinical adverse event?
Adverse drug reactions.
What was thalidomide introduced for, and what were the contraindications for this?
As a sedative and hypnotic effects, and then for morning sickness in pregnancy.
Its isomer, (s)-enantiomer, is teratogenic and causes limb malformations (phocomelia).
What lessons were learnt from thalidomide?
There needs to be adequate testing.
Government regulations.
Reporting systems.
Implications of unfounded claims.
Most medicine cross the placenta.
Avoidance of unnecessary drug use during pregnancy.
What is thalidomide used for today?
Treating cancer and leprosy.
How many international adverse drug reactions would be enough to withdraw a drug, now?
10 cases.
Why are some ADRs not found in clinical trials?
The numbers of people enrolled are low so it is harder for low-frequency adverse events or long-term side effects to be seen.
What is pharmacogenetics?
A single/ small number of genes that affect the way a person reacts to a drug, with large individual effects of the genes.
What is pharmacogenomics?
The effects the genome has on the way a person reacts to a drug, with small individual effects of the genes.
What is precision medicine and how is it useful?
The use of the genome and other clinical and diagnostic information to help treat a patient.
It helps predict and prevent disease.
More precise diagnoses are made.
Personalised and targeted interventions.
Patients are more involved in their healthcare.
What factors contribute to interindividual variability drug responses?
What are the different pharmacokinetic and pharmacodynamic genetic variability?
What gene and CYP450 is responsible for the use and metabolism of warfarin?
VKOR gene - warfarin inhibits vitamin K epoxide reductase.
CYP2C9.
What proportions of cholesterol are synthesised in the body and come from the diet?
75% synthesised in the body.
25% coming from the diet.
What does the aggression of the treatment of high cholesterol depend on?
The total CVD risk and willingness to comply with medication and lifestyle changes.
What is primary and secondary CVD prevention?
Primary prevention - interventions for individuals at high risk of CVD.
Secondary prevention - interventions for individuals who already have cardiovascular disease.
What is done before prescribing statins?
A full lipid profile is performed - HDL, non-HDL and triglycerides.
What are the targets of statin treatment for primary and secondary prevention of CVD?
Primary - >40% reduction in non-HDL-cholesterol at 3 months.
Secondary:
- LDL 2.0mmol/L or less
- non-HDL cholesterol levels of 2.6mmol/L or less.
What is the nocebo effect?
Being aware of negative drug interactions increases the risk of experiencing the negative side effects.
What drug class is associated with photosensitivity?
Fibric acid derivatives/ fibrates.
What are the secondary effects of fabric acid derivatives?
Increased TAG removal from plasma lipoproteins.
Increased fatty acid uptake by the liver.
Increased levels of HDL.
Increased LDL affinity of LDL receptors.
What proportion of cholesterol is prevented from being absorbed in the gut by ezetimibe, and what are some secondary effects?
50%.
Hepatic LDL receptor expression increases.
Decrease in total cholesterol of 15%.
Decrease in LDL of 20%.
Why is ezetimibe taken orally?
It is a pro-drug that requires hepatic metabolism.
What are some drug-drug interactions of ezetimibe?
Ciclosporins.
Fibrates - gall stones.
What can statin + ezetimibe do?
Reduce CKD risk.
Improve CVD prevention.
How does bempedoic acid work?
ATP-citrate lyase inhibitor, decreasing cholesterol synthesis.
What conditions is bempedoic acid used to treat, and how?
Primary hypercholesterolaemia or mixed dyslipidaemia.
It is given with ezetimibe.
Why are there fewer muscle side effects with bempedoic acid?
It is a prodrug that is activated exclusively in the liver.
What are the side effects of bempedoic acid?
Hyperuricaemia.
Anaemia.
Pain in the extremities.
What are the contraindications of bempedoic acid?
Pregnancy.
Breastfeeding.
What are the drug-drug interactions of bempedoic acid?
Slows the excretion of many drugs, increasing statins.
What type of drug is inclisiran?
State its mechanism of action.
siRNA - inhibits the hepatic translation of PCSK9 so less is produced.
What is the target for those being treated for secondary CVD prevention?
< 1.8mmol/L LDL-C.
< 2.5mmol/L non-HDL-C.
What CVD preventing drug class is associated with angioedema?
Cholesterol absorption inhibitors - ezetimibe.
What are the 5 phases of ventricular action potentials?
Phase 0 - VG sodium channels open, an influx of sodium causes rapid depolarisation.
Phase 1 - transient outward efflux of potassium, through VG channels causing slight repolaristion.
Phase 2 - opening of L-type VG calcium channels, an influx of calcium and efflux of potassium causes a plateau.
Phase 3 - L-type VG calcium channels close and VG potassium channels allow for repolarisation.
Phase 4 - resting membrane potential is maintained by the Na+/K+ ATPase.
Explain the 3 phases of the pacemaker action potential.
Phase 4 - HCN channels open, allowing influx of sodium, causing slow depolarisation. T-type calcium channels open.
Phase 0 - L-type calcium channels open, allowing influx of calcium, causing rapid depolarisation.
Phase 3 - voltage-gated potassium channels open and L-type calcium channels close, allowing efflux of potassium and repolarisation.
What are the 3 types of class 1 anti-arrhythmia drugs?
State an example of each.
Class 1A - procainamide.
Class 1B - lidocaine.
Class 1C - flecainide.
How does lidocaine work?
State its effect on an ECG and when it is used.
It blocks the voltage-gated sodium channels, preventing influx of sodium ions, prolonging the upstroke of the action potential.
It slightly prolongs the QRS complex, just enough to prevent additional action potentials to be generated.
It only works in the ventricles, and particularly on damaged heart tissue such as in an MI/ ischaemia. Ventricular arrhythmias.
How does flecainide work differently to lidocaine?
It blocks the voltage gated sodium channels for a longer period of time, prolonging the QRS complex more.
Explain the mechanism and effect that class III anti-arrhythmics have on the action potential and ECG.
Block the voltage-gated potassium channels, causing prolongation of the repolarisation.
QT is prolonged.
How do class IV anti-arrhythmics work, at the SA node?
They block the L-type calcium channels, decreasing the rapid upstroke of phase 0, within the SA node.
How do class IV anti-arrhythmics work, in the ventricles?
Blocks the L-type calcium channels, prolonging the plateau phase, thus the action potential.
Give 1 example of class 3, and 2 examples of class 4 anti-arrhythmics.
Class 3 - amiodarone.
Class 4 - verapamil and diltiazem.
Which antiarrhythmics cause QT prolongation?
Class 1A.
Class III.
Repolarisation is prolonged.
What can be the consequence of QT prolongation?
They can be pro-arrhythmic - they can cause EADs.
What is an example of a cardiac glycoside, what is its action and when is it used?
Digoxin.
It is a positive inotrope and AV node blockade, increasing force of contraction but decreasing heart rate.
It is used in acute heart failure to improve symptoms.
What is an example of a pacemaker current inhibitor, what is its action and when is it used?
Ivabradine.
It blocks HCN channels, slowing phase IV of the action potential, slowing heart rate.
Angina and CVD, as it decreases the demand on the heart, so less ischaemia occurs.
What is adenosine’s method of action and when is it used?
It stimulates A1 adenosine receptors, blocking the conduction of the AV node, so no action potentials pass from the atria to the ventricles for a short period of time.
It is used in supraventricular tachycardia
When should flecainide not be used?
In structural heart disease, such as MI, as it increases the risk of arrhythmias.
When should class II anti-arrhythmics not be used?
In asthmatics.
In combination with diltiazem/ verapamil, as it can cause asystole.
When should class IV anti-arrhythmics not be used?
Heart failure with reduced ejection fraction.
What are the side effects of amiodarone?
Lung fibrosis.
Heptotoxicity.
Optic neuritis.
Thyroid toxicity.
Peripheral neuropathy.
What is usually done for younger, healthier patients, before amiodarone is given?
DC cardioversion - shocking the heart.
What are the two main pathways of arrhythmias?
Generating abnormal impulses.
Conducting impulses abnormally.
What are the different methods of rhythm control?
Felcainide.
Amiodarone.
Sotalol.
Cardioversion.
When would you use rhythm control generally?
Younger patients.
Why is progesterone injected, and how is it excreted?
State how this excretion differs from oestrogen.
The oral bioavailability is low.
It is metabolised in the liver and excreted in the urine, conjugated to glucuronic acid.
Oestrogen is excreted in the urine as glucoronides and sulfates.
What are the advantages of the COCP?
Reliable if taken correctly.
Can relieve menstrual disorders.
Decreased risk of ovarian and endometrial cancer.
Decrease acne severity is some.
What are the disadvantages of the COCP?
State contraindications, too.
User dependent.
No STI protection.
Medication interactions.
Increased risk of CVD, stroke, VTE, breast and cervical cancer.
Contraindications - raised BMI, migraines with aura, breast cancer.
What are the side effects of the COCP?
Menstrual irregularities
Breast tenderness.
Mood disturbances.
What are the disadvantages of the POP?
No STI protection.
User dependent.
Menstrual irregularities.
Increased risk of ectopic pregnancy.
What are some early consequences of oestrogen deficiency?
What are some intermediate consequences of oestrogen deficiency?
What are some late consequences of oestrogen deficiency?
In what form are oestrogens and progesterones given to women for HRT?
State some examples.
Oestrogens are given in their natural form - oestradiol, oestrone and oestriol.
Progesterones are given in their synthetic form - levonorgestrel, medroxyprogesterone, norgestrel, micronised progesterone.
What is the first-line treatment option for urogenital symptoms?
Low-dose vaginal oestrogen cream.
Why are perimenopausal women given sequential HRT?
Because they still have higher levels of oestrogen and so they need cycles to allow for bleeding, to prevent endometrial cancer.
What are the risks associated with the following HRTs:
- Oral.
- Oestrogen and progesterone.
- After the age of 60.
- Oestrogen-only.
Oral - VTE.
Oestrogen and progesterone - breast cancer.
After the age of 60 - coronary heart disease and stroke.
Oestrogen-only - endometrial cancer.
What are bisphosphonates? State when they are given.
A class of drug that reduce bone turnover by decreasing osteoclasts activity.
They are given as prophylaxis of osteoporosis (early menopause), Paget’s disease of the bone and bone malignancy.
What are the pharmacokinetics of bisphosphonates?
Long biological half life, so is taken weekly.
Poor gut absorption.
Absorption affected food so taken on an empty stomach.
What are the ADRs of bisphosphonates? State what is done for these.
Oesophagitis - must be taken sitting upright or stood for 30 minutes after taking.
Hypocalcaemia - can give calcium and vitamin D supplements.
What are the different effects of tamoxifen at the oestrogen receptors of the:
- Breast.
- Bone.
- Hypothalamus.
- Endometrium.
What is the function of raloxifene? State how.
Prevention of osteoporosis in menopause. Agonises oestrogen receptors at the bone, decreasing osteoclast function.
Prevention of breast cancer. Antagonises oestrogen receptors at the breast tissue.
What drug type is uliprital acetate?
A selective progesterone receptor modulator.
What is the function of ulipristal acetate?
Emergency contraception - inhibiting/ delaying ovulation via suppression of the LH surge.
What are two types of incretins?
GLP-1.
GIP.
What is the half-life of insulin?
5 minutes.
How could an SVT be terminated non-invasively?
Carotid sinus massage.
Valsava manoeuvre.
Why should amiodarone be avoided in patients with active thyroid disease?
It is high in iodine and has a similar structure to T3.
This means it can act on thyroid receptors and cause thyrotoxicosis symptoms, but it can also inhibit thyroid hormone release, causing hypothyroidism.
Why can cardioversion be contraindicated with some clotting disorders?
If there is an increased risk of clotting then it should not be used.
This is because cardioversion can displace a clot or cause emboli to form from thrombi.
Why is metaprolol used instead of bisoprolol in acute cases?
It has to be given IV and so has a much faster effect in decreasing the symptoms experienced.
Why does digoxin have a limited effect on rate control during exertion?
Digoxin decreases heart rate by stimulating the vagal control of the heart.
Exercise increases the sympathetic innervation of the heart, overriding the vagal stimulation.
What is the normal pattern of insulin release?
Biphasic.
What are the tests that can confirm diabetic ketoacidosis?
Ketonuria via urine dipstick of ++ or greater.
Ketonaemia > 3mmol/l.
Venous pH < 7.3.
HCO3- < 15mmol/L.
How is soluble insulin given in emergencies?
As an IV infusion.
How do insulin analogues differ from soluble insulin?
They have changes in a few amino acids, changing its pharmacokinetics (absorption and distribution).
What are often the first and second line treatments for type II diabetes mellitus?
First - metformin (modified release if poorly tolerated).
Second - metformin (modified release if poorly tolerated) + an add-on therapy.
What are the contraindications for giving metformin?
State the drug class it falls under.
Biguanides.
Alcohol intoxication.
If eGFR < 30mL/min.
What drug class should not be used in heart failure, when treating type II diabetes?
State why.
Glitazones.
They can cause an increase in fluid retention.
Why can gliflozins cause UTIs and genital infections?
They are SGLT-2 inhibitors, and so there is an increased amount of glucose in the urine.
This can predispose to infections, as it allows bacterial proliferation, particularly in women.
What molecule can help insulin be taken orally?
SNAC - improves some oral bioavailability but a very large dose is required.
Fill in the following table:
What are venous thrombi most associated with and what are their contents?
Stasis of blood and/or damage to the veins.
They have a high red blood cell and fibrin content, with a low platelet count.
What are arterial thrombi most associated with and what are their contents?
Usually forms at the site of atherosclerosis, following a plaque rupture.
Low fibrin content and very high platelet content.
What are the components of Virchow’s triad?
What is PGI2 produced and released by, and what is its function?
Endothelial cells.
It binds to platelet receptors, increasing the concentrations of cAMP, decreasing the calcium content of the platelets, preventing platelet aggregation.
What is the secondary action of prostacyclin?
Stabilises inactive GP IIb and GP IIIa receptors.
This prevents a fibrin clot from forming.
How are platelets activated?
Adhere to damage endothelium and release of platelet granules.
Platelet granules then activate the GP IIb and GP IIIa receptors, allowing fibrinogen to bind.
There is an increase in calcium and decrease in cAMP, and a change in the shape, rendering them fully activated.
It is an amplification sequence.
What are some platelets granules?
ADP.
Thromboxane A2.
Serotonin.
Platelets activation factor.
Thrombin.
What drug types are used to treat arterial thrombi?
Antiplatelets.
Fibrinolytic drugs.
What is an example of a cyclo-oxygenase inhibitor and what is the mechanism of action?
Aspirin.
Inhibits COX-1 mediated production of thromboxane A2, irreversibly reducing platelet aggregation.
What are the two doses of aspirin given?
Low-non-analgesic dose of 75mg.
Loading doses of 300mg for ACSs.
At higher doses, what are the additional functions of aspirin?
Inhibits endothelial prostacyclin:
- Improving vascular health.
- Analgesia.
What is the metabolism of aspirin?
Absorbed by passive diffusion and then hepatic hydrolysis to salicylic acid.
What are the side effects of aspirin?
GI irritation.
GI bleeding - peptic ulceration.
Haemorrhage - stroke.
Hypersensitivity.
What are the contraindications of aspirin?
Reye’s syndrome - avoid in people under the age of 16.
Hypersensitivity.
3rd trimester - premature closure of the ductus arteriosus.
What is Reye’s syndrome and when is there an increased risk of it?
An acute swelling of the brain and liver - encephalopathy and hepatitis.
After a viral infection and taken aspirin, under the age of 16.
What are the drug-drug interactions of aspirin?
Other anti-platelets and anticoagulants - increasing the risk of bleeding.
What is given to close the ductus arteriosus?
Ibuprofen.
When is aspirin used?
What should be given with aspirin in long-term use?
Proton pump inhibitor, to decrease the risk of peptic ulcers.
What are some ADP receptor antagonists, and what are their actions?
Clopidogrel.
Prasugrel.
Ticagrelor.
They inhibit the binding of ADP to P2Y12 receptors, inhibiting the activation of GPIIb and GPIIIa receptors.
They are given orally.
What are some differences between clopidogrel and prasugrel, and ticagrelor?
Clopidogrel and prasugrel are irreversible inhibitors of P2Y12 receptors.
They are pro-drugs that are activated by hepatic metabolism.
Clopidogrel has a slow onset of action, compared to the other two.
Ticagrelor acts reversibly and has active metabolites.
What are some indications for ADP receptor antagonists?
Clopidogrel - stroke and TIA if unable to take aspirin.
Prasugrel - with PCI.
What is a risk ratio?
Ratio of risk in group A vs group B.
RR = R exposed / R unexposed.
What is an odds ratio?
A ratio of odds of an outcome between group A vs group B.
OR = Odds of outcome (exposed) / Odds of outcome (unexposed).
What do each of the 4 lines mean?
From top to bottom:
- Significant effect, favouring the old drug.
- Non-significant effect, favouring the old drug.
- Significant effect, favouring the new drug.
- Non-significant effect, favouring the new drug.
On a forest plot, how can we determine whether it is heterogenous or not?
It is heterogenous if the confidence intervals do not overlap - if the confidence intervals overlap then the studies are homogenous.
What are the side effects and drug-drug interactions of calcineurin inhibitors?
Renal toxicity.
Drug-drug interactions with cytochrome P-450.
State some general possible contra-indications of NSAID use.
State some indications for NSAID use.
What can be given for pregnancy-induced vomiting?
What are the 5 phases of the cell cycle and what happens in each of them?
Describe the chemotherapy bear.
