CPT Flashcards
(473 cards)
1
Q
What is the definition of a clinical trial?
A
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.
2
Q
What is the purpose of a clinical trial?
A
To provide reliable evidence of treatment efficacy and safety.
3
Q
What are the recommendations for phase I trials?
A
Give the drug to one volunteer at a time.
Give the drug slowly.
Make sure that pre-clinical studies predict safe doses in humans.
4
Q
What method can users in phase IV clinical trials use to report intervention side effects?
A
The Yellow Card reporting site.
5
Q
What is a non-randomised clinical trial?
A
Where one patient group is allocated a new treatment and another patient group is allocated the standard treatment, where the allocation is known.
6
Q
What are historical control comparisons, and what are the drawbacks of this?
A
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.
7
Q
How is randomisation done and why is it done?
A
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.
8
Q
What are open label trials and what are they more prone to?
A
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.
9
Q
State some examples where blinding may be difficult.
A
Surgical procedures - sham surgeries.
Psychotherapy vs anti-depressants.
Alternative medicines, such as acupuncture.
Lifestyle interventions.
Prevention programmes.
10
Q
What is allocation concealment?
A
The lack of knowledge as to whether the next person is to be allocated the new or old treatment.
11
Q
What are the purposes of:
- Allocation concealment.
- Randomisation.
- Blinding.
State what they prevent and when they should be implemented.
A
12
Q
What are inclusion and exclusion criteria, and what do they both relate to?
A
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.
13
Q
What is the primary outcome used for?
A
Working out how large the study needs to be.
14
Q
What are some baseline data that should be compared against?
A
Age.
Sex.
Socioeconomic status.
Ethnicity.
BMI.
Disease burden/ comorbidities.
Occupational exposure.
15
Q
What is pharmacogenetics?
A
The differences in effects that drugs have between different people.
16
Q
What state must a drug be in to produce a response?
A
It must be free - unbound.
17
Q
What are ‘me too’ and repurposed drugs?
A
‘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.
18
Q
Other than IV, if a drug has poor bioavailability, what method of absorption can be used?
A
Sprays or inhalation.
19
Q
What does first pass metabolism consist of?
A
Metabolism in the gut lumen, gut wall, liver and lungs - before reaching the systemic circulation.
20
Q
What are modified release preparations?
A
Manipulation of the absorption of a drug to help have more prolonged therapeutic effects and reduce the numbers of doses required.
21
Q
What is bioequivalence?
A
Compounds of biochemical similarity, sharing the same active ingredients, that produce the same therapeutic effects.
22
Q
What types of drugs do the following molecules bind to:
- Albumin.
- Globulins.
- Lipoproteins.
- Glycoproteins.
A
Albumin - acidic drugs.
Globulins - hormones.
Lipoproteins - basic drugs.
Glycoproteins - basic drugs.
23
Q
As the drug is metabolised more, what happens to the volume of distribution?
A
It decreases, as more drug will become free and shift to the plasma.
24
Q
Where, within the liver, are CYP450s found the most?
A
Smooth endoplasmic reticulum of the hepatocytes.
25
In which half life is the greatest amount of drug removed?
The first half life, it is half of the greatest concentration of drug.
26
What is the equation for calculating half life?
Half life = (0.693 x Vd) / Clearance.
27
How many half lives are required to reach a stead state of plasma concentration of the drug?
4 to 5.
28
How do we calculate maintenance dose?
MD = [ (clearance x the steady state concentration) / bioavailability ] x dose interval.
29
How do we calculate the loading dose?
LD = steady state concentration x volume of distribution.
30
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.
31
What is blood pressure?
The driving force to perfuse organs with blood - force per unit area acting on vessels.
32
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.
33
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.
34
What is emergency hypertension?
Hypertension where treatment is required immediately:
- SBP > 180mmHg.
- A DBP > 120mmHg with clinical signs.
35
What is the target blood pressure for a patient with a high urine albumin to creatine ratio?
< 130/ 80 mmHg.
36
What are the 3 stages of hypertension?
37
Who are pre-hypertensive interventions mainly aimed at and what are they?
Patients in their early-mid 40s, classed as pre-hypertensive.
38
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.
39
How is angiotensin I converted to angiotensin II in the absence of ACE?
Chymases.
40
How does bradykinin cause vasodilation?
Increases in NOS/ NO and PGI2 levels.
41
When should ACEi not be used (contraindications)?
Renal artery stenosis.
AKD.
Pregnancy.
Idiopathic angioedema.
CKD.
42
What are the antihypertensive choice in patients with low renin?
Calcium channel blockers, particularly dihydropyridines.
43
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.
44
Why should amlodipine not be used with simvastatin?
It increases the plasma concentration of simvastatin, increasing its effect.
45
What are phenylalkylamines?
Class IV anti-arrhythmic agents that prolong action potentials, increasing the refractory periods.
46
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.
47
When is labetalol given?
Pregnancy and hypertensive emergencies.
48
What is an example of an alpha-adrenoceptor blocker?
Doxazosin.
49
Why are diuretics given in decompensated liver disease?
There are low levels of albumin, so are given to prevent oedema.
50
What are the adverse effects of thiazides/ thiazide-like diuretics?
Hyperuricaemia.
Hyperglycaemia.
Erectile dysfunction.
Increased LDL and triglyceride levels.
Hyperclacaemia.
Hypokalaemia.
51
What are the contraindications of thiazides/ thiazide-like diuretics?
Addison’s disease.
Hypercalcaemia.
Hyponatraemia.
Refractory hypokalaemia.
Gout.
52
What are the important drug interactions of thiazides/ thiazide-like diuretics?
Alcohol.
Amlodipine.
53
What are the adverse effects of loop diuretics?
Dehydration.
Hypotension.
Hypokalaemia.
Hyponatraemia.
Hyperuricaemia.
Arrhythmias.
Tinnitus - ototoxicity.
Increased cholesterol and triglycerides.
54
What are the contraindications of loop diuretics?
Hypokalaemia.
Hyponatraemia.
Gout.
Hepatic encephalopathy.
55
What are the important drug interactions of loop diuretics?
Aminoglycosides (ototoxic).
Digoxin and lithium (kidney damage).
56
What are the adverse effects of potassium-sparing diuretics?
Hyperkalaemia.
Potential arrhythmias.
57
What are the contraindications of potassium-sparing diuretics (ENaC)?
Addison’s disease.
Anuria.
Hyperkalaemia.
58
What are the important drug interactions of potassium-sparing diuretics (ENaC)?
Other K+-sparing drugs.
ACEi.
Adrenoreceptor blockers.
59
What is an example of a potassium-sparing diuretic (ENaC)?
Amiloride.
60
What are the adverse effects of mineralocorticoid receptor agonists?
Gynaecomastia.
Hyperkalaemia.
Severe cutaneous adverse reactions.
61
What are the contraindications of mineralocorticoid receptor agonists?
Addison’s disease.
Anuria.
Hyperkalaemia.
62
What are the important drug interactions of mineralocorticoid receptor agonists?
Alcohol.
Amiloride.
ACEi.
Angiotensin receptor blockers.
63
What are the two types of ADH antagonists?
Tolvaptan.
Lithium.
64
What are the potential interactions of the following?
65
How can CKD affect delivery of diuretics?
Damage to epithelial cells means OAT transporters are defective.
66
What are the aims of treatment of chronic heart failure?
67
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.
68
What type of drug is valsartan?
Angiotensin II receptor blocker.
69
How does ivabradine help heart failure patients?
Blocks the HCN channels, slowing heart rate.
70
How does hydralazine/ nitrate combinations help patients with heart failure?
Venodilation and arteriodilation, reducing preload and afterload.
71
What is used in the treatment of acute heart failure?
IV loop diuretics.
Nitrates.
Sympathomimetic inotropes.
72
What concentration of potassium is required for spironolactone to no longer be recommended in the 4th level of hypertension treatment?
4.5mmol/L.
73
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.
74
Where in the nephron is potassium re-absorbed from when given thiazides?
The collecting ducts, through ROMK channels.
75
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.
76
Which class of antihypertensives may cause harm if breastfeeding and therefore should be avoided?
Thiazide diuretic - indapamide.
77
What is pharmacovigilance?
The science and activities relating to the detection, assessment and preventing of adverse effects or any other possible drug-related problems.
78
What is the most common clinical adverse event?
Adverse drug reactions.
79
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).
80
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.
81
What is thalidomide used for today?
Treating cancer and leprosy.
82
How many international adverse drug reactions would be enough to withdraw a drug, now?
10 cases.
83
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.
84
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.
85
What is pharmacogenomics?
The effects the genome has on the way a person reacts to a drug, with small individual effects of the genes.
86
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.
87
What factors contribute to interindividual variability drug responses?
88
What are the different pharmacokinetic and pharmacodynamic genetic variability?
89
What gene and CYP450 is responsible for the use and metabolism of warfarin?
VKOR gene - warfarin inhibits vitamin K epoxide reductase.
CYP2C9.
90
What proportions of cholesterol are synthesised in the body and come from the diet?
75% synthesised in the body.
25% coming from the diet.
91
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.
92
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.
93
What is done before prescribing statins?
A full lipid profile is performed - HDL, non-HDL and triglycerides.
94
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.
95
What is the nocebo effect?
Being aware of negative drug interactions increases the risk of experiencing the negative side effects.
96
What drug class is associated with photosensitivity?
Fibric acid derivatives/ fibrates.
97
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.
98
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%.
99
Why is ezetimibe taken orally?
It is a pro-drug that requires hepatic metabolism.
100
What are some drug-drug interactions of ezetimibe?
Ciclosporins.
Fibrates - gall stones.
101
What can statin + ezetimibe do?
Reduce CKD risk.
Improve CVD prevention.
102
How does bempedoic acid work?
ATP-citrate lyase inhibitor, decreasing cholesterol synthesis.
103
What conditions is bempedoic acid used to treat, and how?
Primary hypercholesterolaemia or mixed dyslipidaemia.
It is given with ezetimibe.
104
Why are there fewer muscle side effects with bempedoic acid?
It is a prodrug that is activated exclusively in the liver.
105
What are the side effects of bempedoic acid?
Hyperuricaemia.
Anaemia.
Pain in the extremities.
106
What are the contraindications of bempedoic acid?
Pregnancy.
Breastfeeding.
107
What are the drug-drug interactions of bempedoic acid?
Slows the excretion of many drugs, increasing statins.
108
What type of drug is inclisiran?
State its mechanism of action.
siRNA - inhibits the hepatic translation of PCSK9 so less is produced.
109
What is the target for those being treated for secondary CVD prevention?
< 1.8mmol/L LDL-C.
< 2.5mmol/L non-HDL-C.
110
What CVD preventing drug class is associated with angioedema?
Cholesterol absorption inhibitors - ezetimibe.
111
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.
112
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.
113
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.
114
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.
115
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.
116
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.
117
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.
118
How do class IV anti-arrhythmics work, in the ventricles?
Blocks the L-type calcium channels, prolonging the plateau phase, thus the action potential.
119
Give 1 example of class 3, and 2 examples of class 4 anti-arrhythmics.
Class 3 - amiodarone.
Class 4 - verapamil and diltiazem.
120
Which antiarrhythmics cause QT prolongation?
Class 1A.
Class III.
Repolarisation is prolonged.
121
What can be the consequence of QT prolongation?
They can be pro-arrhythmic - they can cause EADs.
122
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.
123
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.
124
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
125
When should flecainide not be used?
In structural heart disease, such as MI, as it increases the risk of arrhythmias.
126
When should class II anti-arrhythmics not be used?
In asthmatics.
In combination with diltiazem/ verapamil, as it can cause asystole.
127
When should class IV anti-arrhythmics not be used?
Heart failure with reduced ejection fraction.
128
What are the side effects of amiodarone?
Lung fibrosis.
Heptotoxicity.
Optic neuritis.
Thyroid toxicity.
Peripheral neuropathy.
129
What is usually done for younger, healthier patients, before amiodarone is given?
DC cardioversion - shocking the heart.
130
What are the two main pathways of arrhythmias?
Generating abnormal impulses.
Conducting impulses abnormally.
131
What are the different methods of rhythm control?
Felcainide.
Amiodarone.
Sotalol.
Cardioversion.
132
When would you use rhythm control generally?
Younger patients.
133
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.
134
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.
135
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.
136
What are the side effects of the COCP?
Menstrual irregularities
Breast tenderness.
Mood disturbances.
137
What are the disadvantages of the POP?
No STI protection.
User dependent.
Menstrual irregularities.
Increased risk of ectopic pregnancy.
138
What are some early consequences of oestrogen deficiency?
139
What are some intermediate consequences of oestrogen deficiency?
140
What are some late consequences of oestrogen deficiency?
141
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.
142
What is the first-line treatment option for urogenital symptoms?
Low-dose vaginal oestrogen cream.
143
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.
144
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.
145
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.
146
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.
147
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.
148
What are the different effects of tamoxifen at the oestrogen receptors of the:
- Breast.
- Bone.
- Hypothalamus.
- Endometrium.
149
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.
150
What drug type is uliprital acetate?
A selective progesterone receptor modulator.
151
What is the function of ulipristal acetate?
Emergency contraception - inhibiting/ delaying ovulation via suppression of the LH surge.
152
What are two types of incretins?
GLP-1.
GIP.
153
What is the half-life of insulin?
5 minutes.
154
How could an SVT be terminated non-invasively?
Carotid sinus massage.
Valsava manoeuvre.
155
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.
156
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.
157
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.
158
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.
159
What is the normal pattern of insulin release?
Biphasic.
160
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.
161
How is soluble insulin given in emergencies?
As an IV infusion.
162
How do insulin analogues differ from soluble insulin?
They have changes in a few amino acids, changing its pharmacokinetics (absorption and distribution).
163
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.
164
What are the contraindications for giving metformin?
State the drug class it falls under.
Biguanides.
Alcohol intoxication.
If eGFR < 30mL/min.
165
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.
166
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.
167
What molecule can help insulin be taken orally?
SNAC - improves some oral bioavailability but a very large dose is required.
168
Fill in the following table:
169
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.
170
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.
171
What are the components of Virchow’s triad?
172
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.
173
What is the secondary action of prostacyclin?
Stabilises inactive GP IIb and GP IIIa receptors.
This prevents a fibrin clot from forming.
174
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.
175
What are some platelets granules?
ADP.
Thromboxane A2.
Serotonin.
Platelets activation factor.
Thrombin.
176
What drug types are used to treat arterial thrombi?
Antiplatelets.
Fibrinolytic drugs.
177
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.
178
What are the two doses of aspirin given?
Low-non-analgesic dose of 75mg.
Loading doses of 300mg for ACSs.
179
At higher doses, what are the additional functions of aspirin?
Inhibits endothelial prostacyclin:
- Improving vascular health.
- Analgesia.
180
What is the metabolism of aspirin?
Absorbed by passive diffusion and then hepatic hydrolysis to salicylic acid.
181
What are the side effects of aspirin?
GI irritation.
GI bleeding - peptic ulceration.
Haemorrhage - stroke.
Hypersensitivity.
182
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.
183
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.
184
What are the drug-drug interactions of aspirin?
Other anti-platelets and anticoagulants - increasing the risk of bleeding.
185
What is given to close the ductus arteriosus?
Ibuprofen.
186
When is aspirin used?
187
What should be given with aspirin in long-term use?
Proton pump inhibitor, to decrease the risk of peptic ulcers.
188
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.
189
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.
190
What are the side effects of ADP receptor antagonists?
Bleeding.
GI upset - dyspepsia and diarrhoea.
Rare - thrombocytopenia.
191
What are the contraindications of ADP receptor antagonists?
High bleed risk patients.
Hepatic/ renal impairment.
192
What are the drug-drug interactions of clopidogrel and ticagrelor, respectively?
Those that interact with CYP 2C19:
- Omeprazole (PPI).
- Ciprofloxacin.
- Erythromycin.
- Some SSRIs.
Ticagrelor - can inhibit and induce CYPs.
They should BOTH be used in caution with other antiplatelets and anticoagulants, as well as NSAIDs.
193
What are some indications for ADP receptor antagonists?
Clopidogrel - stroke and TIA if unable to take aspirin.
Prasugrel - with PCI.
194
What is an example of a phosphidiesterase inhibitor and what are their actions?
Dipyridamole.
Inhibits cellular reuptake of adenosine, increasing the concentration, inhibiting platelet aggregation via adenosine A2 receptors.
Inhibits phosphodiesterase, preventing cAMP degradation, inhibiting expression of GPIIb and GPIIIa.
195
What are the side effects of phosphodiesterase inhibitors?
Vomiting.
Diarrhoea.
196
What are the drug-drug interactions of phosphodiesterase inhibitors?
Antiplatelets.
Anticoagulants.
Adenosine.
197
When are phosphodiesterase inhibitors used?
Secondary prevention of ischaemic strokes and TIAs.
Prophylaxis of thromboembolism following valve replacement.
Stroke, in a modified release preparation.
198
What is an example of a glycoprotein IIb/ IIIa inhibitor and what is the mechanism of action?
Abciximab - monoclonal antibody.
It blocks the binding of fibrinogen and von Willebrand factor to the receptors.
199
What is the side effect and drug-drug interactions of abciximab?
Bleeding - there is a >80% reduction in aggregation of platelets.
Other anti-platelets and anticoagulants.
200
What are 2 fibrinolytic drugs and what are their mechanism of action?
State the action of tranexamic acid.
Streptokinase and alteplase - stimulates the conversion of plasminogen to plasmin, to cause fibrinolysis.
Tranexamic acid - decreases plasminogen levels.
201
When is alteplase used?
Alteplase:
- Acute ischaemic stroke less than 4.5 hours from the initiation of symptoms.
- PE.
- Following acute STEMI diagnosis.
Streptokinase can also be used here but can only be used once as it is immunogenic.
202
What are the side effects and drug-drug interactions of fibrinolytics?
Bleeding.
Antiplatelets and anticoagulants.
203
When should PCI be used in acute STEMI situations?
Within 12 hours of onset of symptoms, and can be delivered within 120 minutes of when fibrinolytics could have been given.
204
What is the negative consequence of PCI?
How can this be reduced.
Reperfusion injury - increased ROS and calcium.
Vagal stimulation.
205
What is incidence?
A rate measure for the number of new cases of a particular disease arising in a population at risk in a certain period of time.
206
What is point prevalence?
All cases existing in a given population at a given time.
207
What is period prevalence?
All the cases of disease existing in a given population over a given period of time.
208
What is a risk ratio?
Ratio of risk in group A vs group B.
RR = R exposed / R unexposed.
209
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).
210
What is an absolute risk?
The risk of acquiring a given disease over a given period of time.
211
What is an absolute risk difference?
The absolute risk in an exposed group - the absolute risk in an unexposed group.
212
What is a p-value?
The chance of getting a result if the null hypothesis was true - if it was only due to chance.
213
What is a statistically significant p-value?
Less than 0.05, where there is sufficient evidence that the null hypothesis can be rejected.
214
What does a smaller and larger p-value mean?
The smaller the p-value, the stronger the evidence against the null hypothesis, the less likely the outcome is due to chance.
The larger the p-value, the weaker the evidence against the null hypothesis, the greater the outcome is due to chance.
215
What is the issue with p-values?
They give no indication as to the size of the effect.
They give no range of uncertainty around the effect that is estimated.
The statistically significant value of 0.05 may be easy to generate - it depends on the null hypothesis - and there is little difference between 0.049 and 0.051.
If there are problems with the design of the study, such as bias, a low p-value can still be achieved.
216
What is a confidence interval?
A range of values for which one is confident that the true value lies within.
217
What is a statistically significant confidence interval for relative risk and absolute risk?
For relative risk, the confidence interval does not include 1.
For absolute risk, the confidence interval does not include 0.
218
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.
219
What is the initial therapy for treatment of an acute coronary syndrome?
MONA:
- Morphine and metoclopramide.
- Oxygen.
- Nitrates.
- Aspirin (and second line).
220
At what concentrations would potassium and glucose be added to the IV fluids in diabetic ketoacidosis?
Potassium - below 5.5 mmol/L.
Glucose - below 14mmol/L.
221
Which hypoglycaemic agent can be cardioprotective?
SGLT 2 inhibitors.
222
What is primary and secondary research?
Primary research is individual studies.
Secondary research are literature reviews, utilising individual studies.
223
What are narrative reviews?
A literature review of primary studies that has a broad scope, and:
- Implicit assumptions.
- Opaque methodology.
- Non-reproducible.
They are subjective and biased.
224
What are systematic reviews?
Literature reviews of primary studies that are aimed to answer a specific question, and:
- Explicit assumptions.
- Transparent methodology.
- Reproducible.
- Objective and unbiased.
225
What is a meta-analysis?
A quantitive synthesis of results of two or more primary studies that address the same hypothesis in the same way.
226
What are the explicit inclusion and exclusion criteria of systematic reviews?
Types of studies.
Types of participants.
Types of interventions.
Types of outcome measures.
227
How are the studies from systematic reviews found?
Through systematic searches and through the grey literature - conferences and PhD theses.
228
What is an appraisal of studies?
Reviewing the results of the search to select relevant and valid studies.
229
When appraising results, what should be done?
Two reviewers performing screening, extraction and risk of bias assessments.
230
By publishing the protocol in advance, what characteristics does this make systematic reviews?
Explicit.
Transparent.
Reproducible.
231
What is the purpose of meta-analysis?
To facilitate the synthesis of a large number of study results.
To systematically collate study results.
To reduce problems of interpretation due to variation in sampling.
To quantify effect sizes and their uncertainty as a pooled estimate.
232
What is the quality criteria of meta-analyses?
A formal protocol, specifying:
- Compilation of complete set of studies.
- Identification of common variable or category definition.
- Standardised data extraction.
- Analysis incorporating for sources of variation.
233
How are pooled estimate odds ratios performed?
Odds ratios and their 95% confidence intervals are calculated for all studies in the meta-analysis.
The studies are then weighted according to their size, thus their uncertainty of their odds ratio.
234
What are some problems with meta-analysis?
Heterogeneity between studies.
Variable quality of the studies.
Publication bias in the selection of the studies.
235
What is heterogeneity between studies, and what causes it?
The difference in observed effects in studies being greater than the expected amount by chance.
It is caused by methodological heterogeneity and clinical heterogeneity.
236
What is methodological and clinical heterogeneity?
Methodological - differences in methods, such as study designs.
Clinical - differences in patients, interventions and outcomes.
237
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.
238
What two things can be done to rectify heterogeneity between studies?
Describe them.
Fixed effect model - assumes that studies are estimating exactly the same true effect size.
Random effects model - incorporates heterogeneity by assuming that studies are similar, but not the same, allowing for a true mean effect to be calculated.
239
What are the weighting and confidence intervals like between fixed effect and random effect models?
Weighting is more equal in random effect models.
Confidence intervals are wider in random effect models.
240
How can heterogeneity be explained?
Sub-group analysis:
- Study characteristics; year of publication, length to follow up, etc.
- Participant profiles; males, females, children, adults, etc.
241
What can the variable quality of data be due to?
Poor study design.
Poor design protocol.
Poor protocol implementation.
242
How can variable quality studies be approached?
A basic quality standard can be formed with studies only included if they satisfy the criteria.
Scoring each study for its quality and incorporating this into the weighting, or using sub-group analyses.
243
What are the quality of studies assessed on?
Allocation methods.
Blinding.
Patient attrition.
Appropriate statistical analysis.
More than one assessor.
244
How can publications bias be identified?
Checking meta-analysis protocol for the method of identification of studies, including unpublished studies.
Plotting the results of identified studies against a measure of their size, using a funnel plot.
Using statistical tests.
245
What are some pro-inflammatory and anti-inflammatory cytokines?
Pro-inflammatory:
- IL-1.
- IL-6.
- TNF-alpha.
- Metalloproteinases.
Anti-inflammatory:
- IL-4.
- Neuropeptides.
- TGF-beta.
246
What joints of the hands are predominantly affected in rheumatoid arthritis?
Metacarpophalangeal joints.
Proximal interphalangeal joints.
247
What can be seen in blood tests of patients with rheumatoid arthritis?
Anti-CCP antibodies.
Serum rheumatoid factor.
248
What is the mechanism of action of corticosteroids?
Prevent IL-1 and IL-6 production from macrophages.
Inhibit all stages of T-cell activation.
249
What is azathioprine used for?
SLE.
Vasculitis.
Inflammatory bowel disease.
Atopic dermatitis.
Bulbous skin disease.
250
What must be done before giving azathioprine and why?
TPMT activity test must be performed first as it is highly polymorphic, and so if absent, the active metabolite 6-MP can build up and cause myelosuppresion.
251
How does azathioprine work?
Cleaved to 6-MP, which inhibits DNA and RNA synthesis.
252
What are the adverse effects of azathioprine?
Bone marrow suppression.
Increased risk of malignancy.
Increased risk of infection.
Hepatitis.
253
What are two types of calcineurin inhibitors, and what are they used for?
Ciclosporin and tacrolimus.
They are used in:
- Transplants.
- Atopic dermatitis.
- Psoriasis.
- Lupus patients who want to get pregnant.
254
What are the side effects and drug-drug interactions of calcineurin inhibitors?
Renal toxicity.
Drug-drug interactions with cytochrome P-450.
255
What is the mechanism of action of ciclosporin and tacrolimus, respectively?
Ciclosporin binds to cyclophilin protein, preventing calcineurin activating T-helper cells, thus, decreasing IL-2 production.
Tacrolimus binds to tacrolimus-binding protein, preventing calcineurin activating T-helper cells, thus, decreasing IL-2 production.
256
What is mycophenolate mofetil used for?
Transplantation.
Maintenance for lupus nephritis and vasculitis.
257
What is the mechanism of action of mycophenolate mofetil?
Inhibits inosine monophosphate dehydrogenase, impairing B- and T- cell proliferation.
258
What are the adverse drug reactions of mycophenolate mofetil?
Myelosuppression.
Nausea.
Vomiting.
Diarrhoea.
259
How does cyclophosphamide work, as a chemotherapy agent?
Alkylating agent, cross-linking DNA preventing replication, suppressing T-cell and B-cell activity.
260
What is cyclophosphamide used for?
Lymphoma.
Leukaemia.
Solid cancers.
Lupus nephritis.
Wegener’s granulomatosis.
261
Explain the pharmacodynamics of cyclophosphamide.
It is a pro-drug, converted in the liver to 4-hydroxycyclophosphamide via cytochrome P-450.
262
What is the toxic metabolite of cyclophosphamide?
State the contra-indications of this and how it is treated.
Acrolein.
It can lead to haemorrhagic cystitis, which is treated with aggressive hydration and Mesna.
263
What are the side effects of cyclophosphamide?
Increased risk of bladder cancer, lymphoma and leukaemia.
Infertility, which increases in risk as age does.
264
What is methotrexate used for?
Rheumatoid arthritis - prevents joint damage.
Malignancy.
Psoriasis.
Crohn’s disease.
Can be given in ectopic pregnancies before the fallopian tube ruptures.
265
How does methotrexate work in treating rheumatoid arthritis arthritis?
Inhibits accumulation of adenosine.
T-cell activation is inhibited.
Suppression of intracellular adhesion molecule expression by T-cells.
266
How is methotrexate given?
Orally, but with a poor bioavailability.
If it causes nausea, then it is given subcutaneously.
Weekly dosing.
Folic acid is given with.
267
What are the side effects of methotrexate?
Mucositis.
Bone marrow suppression.
Hepatitis.
Cirrhosis.
Pnemonitis.
Increased infection risk.
Teratogenic.
Abortifacient.
268
What is sulfasalazine given for?
Relieving pain and stiffness in rheumatoid arthritis.
Fighting infection.
Safe in pregnancy.
269
How does sulfasalazine work?
T-cell inhibition and apoptosis.
Inhibits T-cell production of IL-2.
Reduced neutrophils chemotaxis and degranulation.
270
What are the adverse effects of sulfasalazine?
Myelosuppression.
Hepatitis.
Rash.
Nausea, vomiting and abdominal pain.
271
What are the effects of blocking TNF-alpha?
Reduced inflammation.
Reduces angiogenesis, by decreasing VEGF.
Decreases joint destruction - bone resorption and cartilage breakdown - by decreasing metaloproteinases.
272
How does rituximab work?
Binds to CD20 proteins on B-cells causing apoptosis.
273
What is rituximab used for?
Rheumatoid arthritis, lupus and vasculitis patients.
274
What are the effects of PGE2?
GI mucosal protection.
Inhibits gastric acid secretion from parietal cells.
Uterine contraction.
275
What are the effects of PGI2?
Prostacyclin:
- Inhibits platelets aggregation.
- Vasodilation.
276
What are the effects of TXA2?
Platelet aggregation.
Vasoconstriction.
277
What are the GI side effects of NSAIDs?
Dyspepsia.
Nausea.
Peptic ulceration.
Bleeding.
Perforations.
Exacerbations of inflammatory bowel disease.
278
Why do the GI side effects of NSAIDs occur?
Decreased mucus and bicarbonate secretions.
Increased acid secretion.
Decreased mucosal blood flow.
279
What are the GI contraindications for NSAIDs?
Elderly.
Prolonged use.
Smoking.
Alcohol.
History of peptic ulcer.
Helicobacter pylori infections.
280
What are the drug-drug interactions of NSAIDs, that can cause GI complications?
Aspirin.
Glucocorticoid steroids.
Anticoagulants.
281
What are the renal side effects of NSAIDs?
Hypernatraemia.
Hypertension.
Exacerbation of renal failure.
282
What are some contra-indications of NSAIDs relating to renal function?
CKD.
Heart failure.
283
What are some drug-drug interactions of NSAIDs, relating to renal function?
ACEi.
ARBs.
Diuretics.
284
State why the renal side effects of NSAIDs occur with certain DDIs?
NSAIDs inhibit the vasodilation of the afferent arteriole.
ACEI/ ARBs decrease angiotensin II production, preventing vasoconstriction of the efferent arteriole.
There is decreased perfusion pressure to the glomerulus, thus, decreasing the GFR.
285
State some general possible contra-indications of NSAID use.
286
State some indications for NSAID use.
287
What are the effects of NAPQI and what levels can cause irreversible damage?
Cell necrosis and apoptosis.
150mg/ kg.
288
How does activated charcoal work?
Prevents absorption within the gut, and so can only be given in paracetamol overdoses in acute situations.
289
Which prostaglandin is particularly inhibited by celecoxib or etoricoxib?
State how.
PGI2, by inhibition of the COX2 enzyme.
290
What is the definition of pain?
An unpleasant sensory and emotional experience, associated with or resembling actual or potential tissue damage.
291
What kind of damage do nociceptors detect?
Chemical or physical damage.
292
What are the two types of pain fibres?
Sate the anatomical difference between the two.
A-delta.
C-fibres.
The A-delta are myelinated primary sensory neurones, but the c-fibres are unmyelinated.
293
What types of pain do a-delta and c-fibres detect?
A-delta - sharp pain as they are fast transmitting.
C-fibres - burning pain as they are slow transmitting.
294
At what level can pain be blocked, and where does this occur?
At the synapse between the primary and secondary sensory neurones, in the dorsal horn of the spinal cord.
295
What are the two pathways that the secondary sensory neurones can take, and what are their effects?
They can travel to the thalamus, where tertiary sensory neurones project to the cortex to perceive physical pain - sensory dimension of pain.
They can travel to the limbic system to perceive emotional pain - affective dimension.
296
What are the components of the pain gate?
The a-delta/ c-fibres are excitatory at the secondary sensory neurone cell body.
There are descending modulations from upper centres of the CNS, which are predominantly inhibitory to the secondary sensory neurone cell body.
Mechanoreceptors, stimulated by rubbing, can excite inhibitory sensory neurones, which inhibit the cell body of secondary sensory neurones.
297
What do inhibitory interneurones release onto the secondary sensory neurone cell body?
GABA.
Enkephalins (endorphin type).
298
What do the descending modulations release onto the inhibitory interneurone cell body?
Noradrenaline.
Serotonin.
299
Apart from within the cerebrum, where in the CNS can have a modulators role in pain?
Periaqueductal grey of the midbrain.
Reticular formation of the medulla.
300
How can the periqueductal grey area influence addiction?
It contains dopaminergic neurones that release dopamine when mu-receptors are stimulated, which can lead to euphoria and addiction.
301
What are some endogenous ligands that bind to mu-opioid receptors?
Beta-endorphins.
Endomorphins.
Dynorphins.
Enkephalins.
302
What CYP converts some codeine to morphine?
CYP2D6.
303
What are the indications for opiods?
Analgesia.
Cough suppression - antitussive.
Dyspnoea.
Anaesthetic.
Anti-diarrhoea.
Palliative.
304
What are the different pharmacodynamics of the following:
- Morphine.
- Fentanyl.
- Codeine.
Morphine - less lipid-soluble so has a slower onset and longer duration.
Fentanyl - highly lipid soluble so has a fast onset, but a short duration. It is typically given as a patch.
Codeine - pro-drug, which 5-10% is converted to morphine by CYP2D6.
305
What are the adverse effects of therapeutic opioids?
Constipation.
Drowsiness.
Dysphoria (dissatisfaction).
Euphoria.
Flushing.
Headache.
Hyperhidrosis.
Miosis (pupil constriction).
Nausea.
Respiratory depression.
Itching.
Urinary retention.
306
What are the contraindications of therapeutic opioids?
Comatose patients.
Head injury and/or raised ICP.
Respiratory depression.
Paralytic ileus.
Asthmatics.
Pregnancy.
307
What are the drug-drug interactions of therapeutic opioids?
CNS depressants.
Benzodiazepines.
Opioid containing drugs, reducing gut motility.
CYP450 inducers or inhibitors.
Opioid receptor antagonists.
308
Why can methadone be used in overdose?
It is more lipophilic than morphine.
It has a longer duration so only needs to be given once per day.
Also has some NMDA receptor antagonism.
309
What is the issue with opioid tolerance in opioid use disorder?
A much greater volume of drug is required to elicit analgesia, but the risk of respiratory depression increases with the increase in drug dose.
310
Why do withdrawal effects occur, and what are these?
Excess of normal neuronal activity, due to increased level of baseline cAMP.
Insomnia.
Anxiety.
Excessive sweating.
Enlarged pupils.
Tachycardia.
Tachypnoea.
Diarrhoea.
311
What are controlled drugs?
Drugs that have their manufacture, supply and possession limited.
312
How are controlled drug classes and schedules divided?
Classes based on harmfulness when misused, ranked A-C.
Schedules - dictates how drugs are produced, sourced and stored; how they are prescribed and what records are kept.
313
What are the difference between schedule 1 and 2-5 drugs?
Schedule 1 drugs are not used medicinally.
314
What class and schedule do opioids sit in?
Class A-C.
Schedule 2, 3 and 5.
315
What is the outcomes of the action of inhaled corticosteroids?
Modifies transcription of proteins via nuclear receptors:
- Reducing mucosal inflammation.
- Widens airways.
- Reduces mucous synthesis.
316
What are the mechanisms of action of inhaled corticosteroids?
Gene activation:
- Increase beta-2 receptors.
- Anti-inflammatory mediators.
- Inhibit arachidonic acid release.
Gene repression:
- Decreased inflammatory mediators; interleukins, chemokines and cytokines.
317
What are the pharmacokinetics of inhaled corticosteroids?
Poor bioavailability as they are lipophilic.
Slow dissolution in bronchial fluid.
High affinity for glucocorticoid receptors.
Metabolised by the liver.
318
What are the fast and short acting, fast and long acting, and the slow and long acting beta-2 agonists?
Fast and short acting - salbutamol and terbutaline.
Fast and long acting - formoterol.
Slow and long acting - salmeterol.
319
What are the side effects of beta-2 agonists?
Tachycardia.
Palpitations.
Anxiety.
Tremor.
Increased glycogenolysis.
Increased renin secretion.
Supraventricular tachycardia (decreased refractory period at the AVN).
320
What are the contraindications of LABAs?
Have to be prescribed with inhaled corticosteroids as without, it can mask airway inflammation, near-fatal and fatal asthma attacks.
321
What GPCRs do leukotriene receptor antagonists work at?
CysLT1.
322
What are the side effects of montelukast?
Headaches.
GI disturbances.
Dry mouth.
Hyperactivity.
323
What are leukotrienes released by and what do they cause?
Mast cells and eosinophils.
Bronchoconstriction.
Increased mucous production.
Oedema.
324
What contraindications are there for leukotriene receptor antagonists?
Neuropsychiatric reactions.
325
What is the drug class and actions of tiotropium?
Long acting muscarinic antagonist.
Blocks vagally mediated contraction of airway smooth muscle.
326
What are the side effects of tiotropium?
Dry mouth.
Urinary retention.
Dry eyes.
327
What is the mechanism of action of theophylline?
Adenosine receptor antagonist, inhibits phosphodiesterase, decreasing bronchoconstriction.
328
What are the contraindications and drug-drug interactions of theophylline?
Narrow therapeutic index, and can cause arrhythmia.
CYP450 inhibitors.
329
What is the drug class of theophylline?
Methylxanthine group.
330
What is given for apnoea of prematurity?
Caffeine.
331
What is given for life-threatening asthma?
Oxygen.
Nebulised salbutamol.
Oral steroids - hydrocortisone/ prednoisolone.
Nebulised ipratroium.
IV magnesium sulphate/ aminophylline.
332
What are the 5 tasks of COPD management?
Confirm diagnosis.
Smoking cessation.
Breathlessness score.
Vaccination.
Medication.
333
What is given in acute exacerbations of COPD?
Nebulised salbutamol, and/or ipratropium.
Oral steroids.
Antibiotics - broad spectrum if more severe, narrow if less.
334
What happens if the inhaled substance is too large or too small?
Too large - deposited in mouth and oropharynx.
Too small - inhaled to alveoli and then exhaled.
335
What happens if the inhaled substance is too fast or too slow?
Too fast - deposits in the throat.
Too slow - deposits in the mouth.
336
What is the function of alginic acids and what is an example?
Increases stomach viscosity and reduces reflux.
Sodium alginate.
337
What are the side effects of alginates and antacids - Mg and Al?
Magnesium salts - diarrhoea.
Aluminium salts - constipation
338
What are the contraindications of alginates and antacids?
Na+ and K+ containing preparations - renal failure.
High sucrose - type II diabetes mellitus.
339
What are the drug-drug interactions of alginates and antacids?
Increased urine alkalinity can increase aspirin excretion.
340
What are the side effects of proton pump inhibitors?
Can mask symptoms of gastrointestinal-oesophageal cancer.
Osteoporosis.
341
What are the drug-drug interactions of proton pump inhibitors?
Reduced clopidogrel action.
Increased effects of warfarin and phenytoin.
342
What is an example of a H2-receptor antagonist?
Famotidine.
Ranitidine.
343
What are the side effects of H2 receptor antagonists?
Diarrhoea.
Headache.
344
What are the contradinications of H2 receptor antagonists inhibitors?
Mask gastro-oesophageal cancer.
Renal impairment.
345
What is the mechanism of action of aminosalicylates?
State what they are used to treat.
Release 5-aminosalsylic acid, having a topical action at the colon.
They are first line treatment for ulcerative colitis.
346
Give 2 examples of aminosalicylates and how they differ in their indication.
Mesalazine - UC.
Sulfasalazine - rheumatoid arthritis.
347
What are the side effects of aminosalicylates?
GI disturbances - nausea, dyspepsia, leukopenia.
348
What are the contraindications of aminosalicylates?
Hypersensitivity reactions.
349
What is vomiting?
Involuntary, forceful expulsion of gastric contents through the mouth.
350
What are the inputs to the vomiting centre and what receptors reside here?
Higher cortical centres.
Vestibular nuclei.
Vagal afferents.
Chemotherapy trigger zone.
NK1, mAChR, H1, 5HT2.
351
What stimulates the higher cortical centres to stimulate the vomiting centre?
Pain.
Repulsive sights.
Smell.
Emotional factors.
352
What are the side effects, contraindications and drug-drug interactions of hyoscine hydrobromide (mAChRa)?
SE - sedation, constipations, dizziness, dry mouth, visual problems and confusion.
CI - elderly, glaucoma.
DDIs - anti-psychotics.
353
What are the side effects and contraindications of H1 antagonists?
SE - sedation, dry mouth, urinary retention, blurred vision.
CI - epilepsy, glaucoma, urinary retention, children and elderly patients.
354
What are some examples of sedating and non-sedating H1-antagonists?
Sedating - cyclizine, promethazine, diphenhydramine (Benadryl), chlorphenamine, cinnarizine.
non-sedating - cetrizine, fexofendaine, loratidine.
355
Who is motion sickness seen in most frequently, and what practical methods can be done to prevent it?
Women, children and those that have migraines.
Hydration, sitting at the front of the vehicle, and distractions.
356
What things can stimulate the chemotherapy trigger zone?
Drugs - chemotherapy, opioids, NSAIDs, general anaesthetics.
Metabolites - uraemia, DKA, Addison’s disease, hyperthyroidism.
Toxins - bacteria and viral.
1st trimester of pregnancy.
Brain lesions.
357
What are the effects of metoclopramide (D2 RA) peripherally?
Cholinergic agonists:
- Increases gastric emptying.
- Increased tone of LOS.
- Increased amplitude of gastric contractions.
- Decreased tone of pylorus for gastric emptying.
- Increased peristalsis.
358
What are the side effects and contraindications of metoclopramide (D2 antagonist)?
Side effects - depression, diarrhoea, drowsiness, hypotension, galactorrhoea, dystonia and Parkinsonism.
Contraindications - post-GI surgery, GI obstruction, GI perforations, GI haemorrhage.
359
What are the side effects and contraindications of domperidone (D2 antagonist)?
SE - dry mouth, long QT and VT, galactorrhoea, loss of libido.
CI - over 60 years old.
360
What are the side effects and contraindications of haloperidol (anti-psychotic D2 antagonist)?
SE - parkinsonism, movement disorders, long QT, arrhythmias, constipation and dry mouth.
CI - Parkinson’s disease, CVD, diabetes, myasthenia gravis.
361
What are the side effects and contraindications of the -zines (anti-psychotic D2 antagonist)?
Prochlorperzine, chlopromazine, levomepromazine.
SE - drowsiness, dry mouth, movement disorders, Parkinsonism, long QT, urinary retention.
CI - elderly, Parkinson’s disease, CVD, diabetes, myasthenia gravis.
362
What are the side effects and contraindications of NK-1 receptor antagonists?
SE - constipation, headache and asthenia (weakness).
CI - acute porphyrias (blood disorders).
363
What are NK-1 RAs good for?
Chemotherapy - delayed emesis.
Anxiolytic and antidepressant properties.
364
What are corticosteroids good for?
Perioperative nausea and vomiting.
Chemotherapy.
Palliation.
365
What are the side effects and contraindications of corticosteroids?
SE - insomnia, osteoporosis, weight gain, appetite stimulation, increase blood sugars, Cushing syndrome.
CI - osteoporosis, diabetes mellitus, peptic ulcer.
366
What are the side effects and contraindications of cannabinoids?
SE - confusion, depression, drowsiness, dizziness, movement disorders, psychosis, tremor, visual impairment.
CI - elderly, heart disease, psychiatric disorders.
367
What is an example of and the use of cannabinoids?
Nabilone.
Chemotherapy.
368
What can be given for pregnancy-induced vomiting?
369
What can be given for the following:
- acute emetic chemotherapy.
- delayed chemotherapy-induced nausea and vomiting.
- anticipatory nausea and vomiting.
Acute - serotonin antagonists, like ondansetron.
Delayed - aprepitant or dopamine antagonists, like metoclopramide.
Anticipatory - lorazepam.
370
What are the side effects and contraindications of 5-HT3 antagonists?
SE - constipation, headache, elevated liver enzymes, long QT syndrome, dystonia and Parkinsonism.
CI - aubacute abdominal obstruction, susceptible to long QT.
371
How do bulk-forming laxatives work?
Polysaccharide polymers that are not digested, promoting peristalsis, improving faecal consistency.
372
What are the side effects and contraindications of codeine?
SE - paralytic ileus, constipation, nausea and vomiting, reduced respiratory rate, sedation, addiction/ withdrawal syndrome.
CI - impaired respiratory function, adrenocortical insufficiency, elderly.
373
What is the mechanism of action of loperamide?
Specific to mu-opioid receptors in the myenteric plexus:
- Decreases tone of longitudinal and circular smooth muscle.
- Reduced peristalsis but increased segmental contractions.
- Decreased colonic mass movement, by suppressing the gastrocolic reflex.
374
What are the side effects and contraindications of loperamide?
SE - headache, nausea, drowsiness, dizziness and dry mouth.
CI - abdominal pathologies, children less than 12.
375
What anti-emetic can be given for a raised intra-cranial pressure?
Dexamethasone.
376
What is the mechanism of action and clearance of nitrofurantoin?
Affects bacterial protein, DNA and RNA synthesis.
50% is excreted unchanged in the urine.
377
What are the adverse drug effects of nitrofurantoin?
Orange urine.
Pulmonary fibrosis.
Hepatic disorders.
Peripheral neuropathy.
Haematological - anaemia, thrombocytopenia, agranulocytosis.
378
What is the mechanism of action of trimethoprim?
Folate antagonist - inhibits bacterial dihydrofolate reductase; inhibiting nucleic acid and protein synthesis.
379
What are the adverse drug reactions of trimethoprim?
Teratogenicity in the first trimester.
380
What are some examples of, and the mechanism of action of aminoglycosides?
Vancomycin, streptomycin, gentamicin.
Inhibits protein synthesis by binding to the 30s subunit.
381
What are some indications for and the adverse drug reactions of gentamicin?
Sepsis.
Otitis externa.
Meningitis.
Pneumonia.
Biliary tract infections.
Prostatitis.
Nephrotoxicity and ototoxicity.
382
Why do aminoglycosides need to be monitored?
They have a narrow therapeutic window, and as they are renally excreted, impairment can cause toxicity.
383
What are some drug-drug interactions of trimethoprim?
Methotrexate.
They are both folate antagonists, and so can cause severe bone marrow suppression.
384
When should antibiotic prescriptions be reviewed?
Following a senior review of the patient.
Following a change in the clinical condition.
Daily, on the ward round.
Following receipt of relevant investigations/ cultures.
385
What antibiotics should be given in pneumonia patients on the basis of the following CURB-65 scores:
- 0-1.
- 2.
- 3-5.
0-1 - amoxicillin.
2 - amoxicillin, and clarithromycin if atypical pathogen suspected.
3-5 - Co-amoxiclav IV and clarithromycin.
386
What is the MOA of clarithromycin?
Protein synthesis inhibitor.
387
What is the MOA of aciclovir?
Inhibits viral DNA polymerase.
Metabolites can be incorporated into the replicating DNA, causing chain termination.
388
What are some examples of beta-lactams?
Penicillins.
Cephalosporins.
Carbapenems.
Monobactams.
389
What is the MOA of quinolones?
Inhibit DNA gyrase.
390
Which antibiotics inhibit 50s subunits?
Macrolides.
Clindamycin.
Linezolid.
Streptogramins.
Chloramphenicol.
391
Which antibiotics inhibit 30s subunits?
Aminoglycosides.
Tetracyclines.
Tigecycline.
392
What are some endogenous anti-coagulants?
Antithrombin III.
Protein C.
Protein S.
393
What ion is an important co-factor in the clotting cascade?
Calcium.
394
How do heparins increase the activity of antithrombin III?
They cause a conformational change, activating it.
395
What are some contra-indications of heparins?
Clotting disorders.
GI ulcer.
Renal impairment.
396
What are some drug-drug interactions of heparins?
Other anti-thrombotic drugs.
ACEi/ ARB/ K+-sparing drugs - hyperkalaemia.
397
If a patient can take a DOAC, when would warfarin be preferentially used?
Heart valve replacement - bio-prosthetic and some mechanical.
398
When should warfarin not be taken?
Pregnancy - crosses the placenta and is teratogenic in the 1st trimester.
Early postpartum.
Haemorrhagic stroke.
399
What are the contraindications for DOACs?
Dabigatran - low creatinine clearance < 30ml/min.
Pregnancy.
Breastfeeding.
400
Which antibiotic class are vitamin K absorption inhibitors?
Cephalosporins.
401
How does the body adapt in IPD to prevent symptoms?
Increased turnover of dopamine.
Upregulation of receptors.
402
What non-motor manifestations can levodopa help to inhibit?
Mood changes.
Sleep disorders.
403
How does dopamine treatment differ from physiological levels of dopamine?
Levodopa has a short half-life of 2 hours and so there are fluctuations of dopamine levels in the blood.
This differs from physiologically, as dopamine levels are kept constant.
404
What are some peripheral dopa decarboxylase inhibitors and what are they combinations of?
State why they in combinations form.
Co-careldopa - levodopa and carbidopa.
Co-beneldopa - levodopa and benserazide.
The inhibitors have no action without levodopa as their function is the increase the amount of levodopa reaching the brain.
405
How can levodopa be given?
Standard dosage tablets.
Controlled release preparations.
Dispersible madopar.
406
What are the side-effects of levodopa?
Nausea.
Hypotension.
Psychosis - schizophrenic-like, hallucinations.
Tachycardia.
407
What are some long term motor effects of levodopa?
Dyskinesia - abnormal positioning of limbs.
Dystonia - spasms.
Freezing.
Choreoathetosis - excess involuntary movements.
408
What are some examples of COMT-inhibitors?
State the function of these drugs.
Entacapone.
Opicapone.
Prolongs the motor response to levodopa.
409
Give an example for the following types of dopamine receptor agonists:
- Non-ergot.
- Patch.
- Subcutaneous.
Non-ergot - ropinirole, pramipexole.
Patch - rotigotine.
Subcutaneous - apomorphine.
410
What is punding?
Compulsive arrangement.
411
What is given for patients with severe motor fluctuations?
Apomorphine.
It can be given as a bolus for freezing.
It can be given as a continuous infusion.
412
Give some examples of monoamine oxidase B inhibitors, and what symptoms improvement they provide.
Selegiline.
Rasagaline.
Safinamide.
Prolongs action of levodopa, smoothing out the motor response.
413
What are some examples of anticholinergics?
Trihexyphenidydyl.
Orphenadrine.
Procyclidine.
414
What are the side effects of anticholinergics?
Confusion.
Drowsiness.
415
What is given for levodopa-induced dyskinaesia?
State its side effects.
Amantadine - hallucinations, confusions.
416
What is the criteria for deep brain stimulation surgery?
Highly dopamine responsive.
Has significant side effects with levodopa.
No psychiatric illness.
417
What can be seen if there is sudden withdrawal of L-Dopa?
Severe akinetic mutism - complete rigidism.
Life threatening neuroleptic malignant syndrome.
418
What are the symptoms of neuroleptic malignant syndrome?
Confusion.
Rigidity.
Fever.
Autonomic dysregulation.
419
What happens if there is sudden withdrawal of dopamine agonists?
Dopamine agonists withdrawal syndrome:
- Neuropsychiatric symptoms = agitation, panic, anxiety, depression and fatigue.
- Autonomic symptoms = orthostatic hypotension, perspiration.
420
When should pyridostigmine be given?
An hour before eating as the peak is an hour to 120 minutes.
421
What dictates how a seizure presents?
Where the uncontrolled signalling occurs.
422
What is post-tetanic potentiation?
Synaptic plasticity - modifying and forming new synapses.
Increased neurotransmitter release, following increased action potential firing.
Factor that can help cause seizures.
423
What are some risk factors for epilepsy?
Premature brith.
Complicated febrile seizures.
Genetic conditions.
Head trauma, infections and tumours.
Cerebrovascular disease.
Dementia and neurodegenerative disorders.
Very young or old.
424
What do the following terms means
- Prodrome.
- Aura.
- Ictal.
- Post-ictal.
Prodrome - early signs or symptoms that a seizure may occur in a number of hours or days.
Aura - focal awareness seizure leading to secondary generalised.
Ictal - during a seizure.
Post-ictal - begins as a seizure subsides, with symptoms such as confusion, fatigue, headache, anxiety, frustration or embarrassment, muscles aches and pains, injury, and lack of consciousness.
425
What are the adverse effects, warnings and contraindications and DDIs of carbamazepine?
AE - dizziness, skin rash, eosinophilia, leukopenia, hyponatraemia.
CIs - teratogenic, bone marrow depression, AV conductions issues, HLA-B*1502 allele (SJS).
DDIs:
- CYP3A4 inducer, so decreased COCP effect, increased warfarin metabolism.
- CYP3A4 inhibitors = clarithromycin, diltiazem; decrease carbamazepine effect.
426
What are the adverse effects, warnings and contraindications and DDIs of phenytoin?
AEs - dizziness, skin rash, visual disturbance, gingival hyperplasia, arrhythmias.
CIs - teratogenic, acute porphyrias, bone marrow suppression, SJS allele.
DDIs - COCP and certain antibiotics decreased effectiveness as its an inducer.
427
Why does phenytoin need to have its plasma concentration measured?
It has zero order kinetics and has a very narrow therapeutic window, so can have unpredictable plasma concentrations.
428
What are the adverse effects, warnings and contraindications and DDIs of sodium valproate?
AEs - hepatotoxic, appetite stimulant, alopecia, thrombocytopenia.
CIs - teratogenic.
DDIs - increases lamotrigines conc. hepatotoxicity with phenytoin.
429
What are the adverse effects, warnings and contraindications and DDIs of lamotrigine?
AEs - aggression, agitation, hypersensitivity.
CIs - long half life.
DDIs - sodium valproate increases its concentration. Phenytoin and OCP decreases its concentration.
430
How does levetiracetam work?
Synaptic vesicle protein 2A inhibitor.
431
What are the adverse effects, warnings and contraindications and DDIs of levetiracetam?
AEs - anxiety, drowsiness, dizziness.
CIs - prolongs QT interval.
DDIs - CNS depressants.
432
What are the adverse effects, warnings and contraindications and DDIs of benzodiazepines?
AEs - ataxia, depression, drowsiness, hypotension, muscle weakness, sleep disorders.
CIs - respiratory depression.
DDIs - CNS depressants.
433
State the process of treatment of status epilepticus.
Continue down each step after 5-10 minutes passes:
- IV lorazepam.
- 2nd IV lorazepam.
- Levetricaetam/ phenytoin/ sodium valproate.
- Alternative to the prior given.
- Barbiturates/ general anaesthesia.
434
What are the 3 categories of AEDs?
1 - must maintain the same brand/ generic (carbamazepine and phenytoin).
2 - clinical judgement and patient consultation as to whether switches can be made.
3 - swap between generics and brands applicable.
435
What is the main concern with neuroleptic malignant syndrome?
Rhabdomylosis - rigidity and fever disposition for it.
436
Why are multiple cycles of chemotherapy typically needed?
Some neoplastic cells are dormant, and so cannot be killed until they are out of this phase.
Allows for the bone marrow cells to recover between the cycles.
437
Describe the process of volatile anaesthesia administration to a patient?
They are produced at a liquid, but are vaporised by agonist-specific vaporisers, allowing the patients to inhale them.
438
What is ‘anaesthesia’ a combination of?
Analgesia.
Hypnosis - loss of consciousness.
Depression of spinal reflexes.
Muscle relaxation.
439
What bodily functions are lost from first to last?
Memory.
Consciousness.
Movement.
Cardiovascular collapse.
440
What does a low blood:gas, and oil:gas partition mean?
Low blood:gas - fast induction and recovery from general anaesthetic.
Low oil:gas - less lipophilic so less potent.
441
Which general anaesthetics bind to NMDA receptors?
Ketamine.
Xenon.
N2O.
Argon.
442
State some general anaesthetics which act on the GABAa receptors.
Chloroform.
Halothane.
Fluoroxene.
443
What are the changes in the brain circuitry seen in the use of general anaesthesia?
Reticular formation depressed - decreased arousal.
Hippocampus depressed - impaired memories.
Brainstem depressed - respiratory and cardiovascular depression.
Spinal cord dorsal horn depressed - analgesia and motor neuronal activity.
444
What nerves do local anaesthetics block and when?
Small myelinated nerves, blocking nociception and sympathetic afferents.
They are use dependent, meaning they preferentially block the VGSCs that are firing more frequently.
445
What is a nerve block?
Where local anaesthetic or an opioid is inserted into a nerve plexus.
446
What are some different drug therapies for cancer treatment?
Cytotoxic chemotherapy.
Tyrosine-kinase inhibitors.
Monoclonal antibodies.
CDK4/6 inhibitors.
Immune checkpoint inhibitors.
mTOR inhibitors.
PARP inhibitors.
447
What are the 5 phases of the cell cycle and what happens in each of them?
448
What is the growth fraction?
State how this can affect treatment.
The proportion of cells dividing at any given time.
The greater the growth fraction, the more responsive the tumour will be to chemotherapy.
Tumour are heterogenous and so not all cells are dividing at the same time, meaning that cycles of chemotherapy need to be given.
449
What determines the growth fraction?
The tumour size.
The greater the tumour size, the lower the growth fraction.
The smaller the tumour size, the greater the growth fraction.
450
Chemo therapies target the DNA of a neoplastic cell. How does this kill the cancer?
The damage to DNA means that the cell cannot undergo repair and so the cell undergoes apoptosis.
451
What are the properties of cancer?
Evade apoptosis.
Self-sufficient growth factors.
Insensitivity to anti-growth factors.
Tissue invasion and metastasis.
Limitless replicative potential.
Sustained angiogenesis.
452
Where do the following chemotherapies target in life of a cancer cell:
- Intercalating agents.
- Alkylating agents.
- Spindle poisons.
- Antimetabolites.
IA - inhibit DNA transcription and duplication.
AA - damages DNA itself.
SP - inhibits mitosis.
AM - inhibits DNA synthesis.
453
What phases of the cell cycle do the following cytotoxic agents work at:
- Antibiotics.
- Antimetabolites.
- Vinca alkaloids.
- Mitotic inhibitors.
- Taxoids.
- Alkylating agents.
Abx - G1, S, G2.
Am - S phase.
VA - M phase.
MI - M phase.
T - G1 and M phase.
AA - all phases.
454
What are monofunctional and bifunctional alkylating agent?
Monofunctional - the alkyl group forms covalent bonds with 1 DNA strand.
Bifunctional - the alkyl group forms covalent bonds with both DNA strands.
455
What is the reactive intermediate of alkylating agents?
Carbonium ion - a carbon atom with only 6 electrons in the outer shell.
456
What is the difference between the mechanism of action of cisplatin and oxaliplatin?
Cisplatin - forms inter- and intra-strand adducts, inhibiting DNA synthesis.
Oxaliplatin - forms bulky platinum adducts which is more effective in inhibiting DNA synthesis.
457
What chemotherapies are worst for hair loss?
State which causes minimal loss.
Doxorubicin.
Vinca alkaloids.
Cyclophosphamide.
Platinums.
458
What are some skin toxicities that bleomycin causes?
Hyperkeratosis.
Hyperpigmentation.
Ulcerated pressure sores.
459
Other than bleomycin, which chemotherapies can cause hyperpigmentation?
Busulphan.
Doxorubicin.
Cyclophosphamide.
Actinomycin D.
460
Which chemotherapies can cause cardio-myopathies and which can cause arrhythmias?
Cardio-myopathies = doxorubicin and cyclophosphamide.
Arrhythmias = cyclophosphamide and etoposide.
461
What chemotherapies can cause pulmonary fibrosis?
Bleomycin.
Mitomycin C.
Cyclophosphamide.
Melpalan.
Chlorambucil.
462
Describe the chemotherapy bear.
463
What are some DDIs of capecitabine?
Warfarin.
St John’s Wort.
Grapefruit juice.
464
What are some DDIs of vincristine and methotrexate?
Vincristine - itraconazole (neuropathy).
Methotrexate - penicillin and NSAIDs.
465
What are the different aims of chemotherapy treatment?
Neoadjuvant - make the surgery easier to perform.
Adjuvant - after surgery to reduce relapse risk.
Palliative - treat or prevent symptoms without a curative intent.
Primary - first line treatment for cancer with curative intent.
Salvage - chemotherapy for relapsed disease.
466
What are the ‘undesirable’ side effects of loperamide and chlorpromazine that are exploited for their use in clinical practice?
Loperamide - an opioid that causes constipation.
Chlorpromazine - an anti-muscarinic that has antipsychotic sedation.
467
What should be co-prescribed with chemotherapies and methotrexate, due to their common side effects?
Chemotherapies - anti-emetics.
Methotrexate - folic acid.
468
What is the drug class and mechanism of action of phenobarbital?
Barbiturate.
Agonises the GABAa receptors.
469
When should N-acetylcysteine be given to patients taking paracetamol, without an overdose?
Hepatic necrosis.
CYP inducers, including alcohol.
Low hepatic reserves of glutathione.
470
For what drugs should activated charcoal be continued to be given to, for up to 36 hours?
Benzodiazepines.
Phenobarbital.
471
What should be given for aspirin overdose?
Sodium bicarbonate - increasing the pH leads to alkaline diuresis, removing the salicylate.
472
What is the MOA of chelating agents, and what should they be used for?
They form complexes with the poison, reducing the concentration of the free drug.
Cyanide, lead, iron salts.
473
What does STOPP-START stand for?
Screening tool of older people’s prescriptions.
Screening tool to alert to right treatment.
