ILA

Question 1

Describe the main stages involved in the formation of an atherosclerotic plaque?

Answer 1

1. Fatty streaks form from young ages
2. Endothelial damage
3. Release of inflammatory chemokines that attracts inflammation cells and increased expressoin of adhesion cells
4. Inflammation
5. Macrophages start coming into the intima and become FOAM CELLS
6. Plaque progression: intermediate lesions (smooth muscle cells, platelets, foam cells, T lymphocytes, pools of extracellular lipid)
7. Fibrous cap forms: smooth muscle cells produce collagen and elastin making it fibrous and forming the cap, necrotic core forms, impeding blood flow (ischaemia)
8. Plaque rupture, exposing collagen, necrotic tissue and basement membrane, small vessels haemorrage = blood coagulation = clotting = occlusion = infarction = myocardial or cerebral

Question 2

Describe the structure of an atherosclerotic plaque?

Answer 2

• Tends to be found at bifurcation points
• Lipid necrotic core, connective tissue, fibrous cap
• Dangers are angina, myocardial or cerebral infection via blockage

Question 3

What are some modifiable risk factors of atherosclerosis?

Answer 3

Smoking > free radicals in cigarette smoke

Sedentary lifestyle > increase risk of diabetes and hyperlipidaemia (endothelial damage) and hypertension

Hypertension > shearing forces damage endothelium and also increased permeablilty to LDLs

High chloesterol > more LDL deposits = more modified macrophages (foam cells)

Diabetes > more bloody sugar = more LDLs attracting more inflammatory properties also causes more lipids

BMI

Question 4

What are some non modifiable risk factors of atherosclerosis?

Answer 4

Family history > genetic component of hyperlipidaemia, hypertension and diabetes

Gender
Age
Ethnicity

Question 5

How does smoking increase the risk of atherosclerosis?

Answer 5

Free radicals in cigarette smoke damage endothelium

CO and nicotine - ROS - oxidises LDL

Increases LDL levels

Makes blood thicker (thrombogenicity) so more tendency to clot

Question 6

What primary prevention measures can be taken for atherosclerosis?

Answer 6

-Take low-dose aspirin to reduce platelet aggregation
-Exercise regularly
-Stop smoking
-Take blood pressure medication (ACE inhibitors, angiotensin II receptor
blockers, beta-blockers, etc.)
-Healthy diet, less salt
-lose weight

Question 7

What secondary prevention measures can be taken for atherosclerosis?

Answer 7

• prescribe aspirin and anti-hypertensive medication
• prescribe exercise
• diet program/ referral?
• regular check-ups
• procedure to widen/bypass affected arteries
• take statins to reduce cholesterol level
• if diabetes then metformin

Question 8

Define anaphylaxis?

Answer 8

Anaphylaxis is a severe, life-threatening, generalised or systemic hypersensitivity reaction.

Characterised by rapidly developing life-threatening airway and/or breathing and/or circulation problems usually associated with skin and mucosal changes.

Question 9

Describe the beta adrenergic receptor activity of adrenaline?

Answer 9

• Stimulation of Beta1-adrenoceptors positive ionotropic and chronotropic effects on the heart
• Reduces oedema and bronchodilates via beta2-adrenoceptors

• Attenuates further release of mediators from mast cells and basophils by increasing
intracellular c-AMP and so reducing the release of inflammatory mediators

Question 10

Describe the alpha adrenergic activity of adrenaline?

Answer 10

• Peripheral vasoconstriction increase in peripheral vascular resistance, increased BP and coronary perfusion via alpha1-adrenoceptors
• Reduction of oedema

Question 11

Why might a second does of adrenaline be required if symptoms do not initially respond or get worse?

Answer 11

Because adrenaline has a short half life and therefore a second dose may be required if the symptoms do not initially respond or get worse

Question 12

What is the recommended treatment for anaphylaxis? (full)

Answer 12

REMOVE THE PRECIPITATING CAUSE e.g. IV antibiotics

Lie flat and raise legs

1. 500 micrograms of adrnaline intramuscularly unless experiences with IV adrenaline > repeat after 5 mins if no better
2. High flow oxygen > increases the alveolar oxygen concentration to over come hypoxia due to bronchospasm, reduced ventilatory effort and interstitial oedema
3. Fluids > help restore circulating volume therefore stroke volume increasing cardiac output
4. Chlorphenamine > antihistamine blocking histamine-1 receptor thus blocking the action of histamine released during anaphylaxis
5. Hydrocortisone > surpresses prostaglandin and leukotrine mediators, inflammatory cell recruitment and migration are inhibited and vasoconstriction reduces leakage from blood vessels

Question 13

What confirmatory blood test will you need to take after an anaphylactic reaction? How will this confirm or refute a diagnosis of anaphyalxis?

Answer 13

Blood test is Mast Cell Tryptase.

Anaphylaxis causes an elevated serum mast cell tryptase.

Question 14

What would the large histamine release in anaphylaxis cause?

Answer 14

Histamine causes vasodilation and increased vascular permeability

This causes anigo-oedema and erythema (redness) to local tissues and therefore swelling

Question 15

Why might someone have a raised heart rate, low bp, and slow capillary refill time?

Answer 15

Vasodilation and increased vascular permeability (therefore oedema) means that there is less fluid in the vessels therefore lower bp (hypotension) and the heart pumps faster to compensate

Question 16

Why might someone what a raised respiratory rate, low oxygen saturation and expiratory wheeze?

Answer 16

Contraction of respiratory smooth muscle surrounding trachea therefore airway constriction would cause all three

Question 17

What cells are involved with anaphylaxis?

Answer 17

Mast cells

Question 18

What antibody is involved in anaphylaxis?

Answer 18

IgE

Question 19

What is the mediator of decreased blood pressure?

Answer 19

Histamine

Question 20

What would be immediate treatment for anaphylaxis be?

Answer 20

ABCDE, adrenaline, oxygen

Question 21

What is the treatment drug for anaphylaxis and describe its mechanism?

Answer 21

= Adrenaline, non-selective agonist of

adrenergic receptors, increases vasoconstriction and bronchodilation

Question 22

What treatments other than adrenaline are given?

Answer 22

Hydrocortisol, oxygen, fluids, antihistamine

Question 23

What are normal values for?
O2
BP
HR

Answer 23

O2 = 95% <
Heart rate = 60-100
BP = 120/80

Question 24

What does ABCDE stand for in relation to anaphylaxis?

Answer 24

Airway 
Breathing 
Circulation 
Disability 
Exposure

Question 25

What would you look for when diagnosing anaphylaxis?

Answer 25

1. Acute onset of illness 2. Life-threatening airway and/or breathing and/or circulation problems 3. Usually skin changes

Question 26

In order to induce anaesthesia quickly what characteristics should a drug have in terms of its protein binding?

Answer 26

Protein binding lowers the free concentration of a drug, ideally the induction drug should have LOW protein binding to enable a high initial plasma concentration If strongly protein bound then plasma concentration of the free drug will be lower

Question 27

In order to induce anaesthesia quickly what characteristics should a drug have in terms of its lipid solubility?

Answer 27

In order to put the patient to sleep quicky the drug should have a high lipid soluablilty in order for it to readily cross the blood brain barrier and reach its site of action

Question 28

Explain in terms of the drug distribution of the intravenous drug why an additional volatile drug needs to be given as soon as the patient is asleep?

Answer 28

With IV drug injection there is a high initial plasma concentration and the drug may rapidly enter well perfused tissue such as brain, liver & lungs… * The drug will continue to enter less well perfused tissues lowering the plasma concentration… * The concentrations in the highly perfused tissues then decrease. * This action is important in terminating some drugs given as a bolus e.g thiopentone produces rapid anaesthesia because of initial high brain concentrations, but is short lived as continued muscle uptake lowers the blood concentration & indirectly the brain concentration

Question 29

What would happen if a second anaesthetic agent was not given?

Answer 29

As the plasma concentratoin of thiopentone decreases the patient will start to wake up

Question 30

In addition to ‘receptors’ what three other drug targets are there?

Answer 30

Enzymes Transporters Ion channels

Question 31

Give an example of a drug that acts on receptors and how it produces its desired effect?

Answer 31

Receptors - muscle relaxants are completive antagonists of acetylcholine at the post synaptic nicotinic receptor. They block the receptor preventing ACh from binding and causing muscle contraction.

Question 32

Give an example of a drug that acts on enzymes and how it produces its desired effect?

Answer 32

Enzymes – Angiotension-converting enzyme (ACE) inhibitors block the conversion of angiotensin I to angiotensin II (a vasoconstrictor) this causes vasodilation which reduces blood pressure.

Question 33

Give an example of a drug that acts on transporters and how it produces its desired effect?

Answer 33

Transporters / carrier proteins – Proton pump inhibitors (lansoprazole) prevent the production of stomach acid (H+) by inhibiting the proton pump mechanism in the parietal cells.

Question 34

Give an example of a drug that acts on transporters and how it produces its desired effect?

Answer 34

Ion channels Calcium channel blockers (nifedipine, verapamil) target the calcium ion channels which leads to arterial vasodilation e.g. coronary arteries and improve coronary artery blood flow helping to relieve angina.

Question 35

Define: bioavailability?

Answer 35

Bioavailability – the amount of drug that reaches the circulation unaltered. Intravenous drugs therefore have high bioavailability (100%) as do intramuscular drugs which are absorbed into the blood stream unaltered. Oral drugs have a bioavailability of less than 100%.

Question 36

Explain this difference in terms of Morphine’s bioavailability and first pass metabolism, and how much more morphine is needed orally?

Answer 36

Morphine when given orally undergoes first pass metabolism where a proportion of the drug is which results in a bioavailability of about 50%. It is metabolised / extracted by the intestine and metabolised by the liver before entering the systemic circulation. This means that the oral dose of morphine is twice the intramuscular morphine e.g. IM dose is 5mg and oral dose is 10mg

Question 37

If a patient has renal failure, a lower than normal dose of morphine is given at longer intervals, why?

Answer 37

Morphine is metabolised in the liver to morphine 6 glucuronide which is more potent than morphine. It is excreted by the kidneys therefore if a patient has renal failure it will not be as readily excreted. This requires the dose and frequency of administration to be reduced.

Question 38

What are the physical properties of the ideal anaesthetic drug?

Answer 38

* Stable in solution * Long shelf life * No pain on intravenous injection * Cheap

Question 39

What are the pharmacokinetic properties of the ideal anaesthetic drug?

Answer 39

Rapid onset – low protein binding and crosses blood brain barrier easily • Rapid clearance and metabolism • No active metabolites

Question 40

What are the pharmacodynamic properties of the ideal anaesthetic drug?

Answer 40

* Minimal cardiovascular and respiratory effects * No histamine release/hypersensitivity/ allergy reactions * Does not make patients feel sick * No hang over effect so patients have a quick recovery.

Question 41

Explain the difference in presentation (signs and symptoms) between an arterial thrombosis and a venous thrombosis?

Answer 41

An AVT would present with a lack of pulse, pale skin, coldness to touch which is completely the opposite to DVT which would present as a hot red limb that would still have a pulse

Question 42

Describe virchows triad?

Answer 42

1. Hypercoaguability of blood 2. Vessel wall injury 3. Stasis of blood

Question 43

Describe the pathophysiology of thrombus development?

Answer 43

1. Protein adsorption onto vessel e.g. fibrinogen, vWF 2. Platelet adhesion/activation 3. Cell deposition and fibrin formation 4. Thrombus formation

Question 44

What blood test would you do to help confirm a diagnosis of DVT and why?

Answer 44

D Dimer D dimer measure the amount of a protein called fibrin d dimer which is produced whenever fibrin is being actively degraded somewhere within the vascular system - therefore levels generally increase after DVT or PE Positive does NOT confirm diagnosis

Question 45

Heparin and warfarin are used in the treatment of DVT. In relation to the cogulation cascade, explain the action of each?

Answer 45

Heparin: binds to antithrombin, increases its activity, indirect thrombin inhibitor, acts on the extrinsic pathway Warfarin: antagonist of vitamin K, preventing synthesis of active factors II, VII, IX, X, acts on the intrinsic pathway

Question 46

What potentially fatal complication of a DVT should a patient be made aware of and what signs and symptoms should he look out for?

Answer 46

Symptoms: breathlessness, pleuritic chest pain, may have S+S of DVT Signs: Tachycardia, tachypnoea, pleural rub, those of precipitating cause

Question 47

Advice for long haul flights to reduce risk of DVT?

Answer 47

move around as often as possible by walking in the aisles when allowed • avoid crossing your legs • avoid wearing tight clothes that can restrict blood flow • stay hydrated, and avoid alcohol before and during travel • stretch legs and feet while sitting • If you are young, non-smoker, not overweight