ILAs Flashcards
What is atherogenesis?
The formation of fatty deposits in the arteries
What are the four steps of atherogenesis?
- Endothelial cell injury
- Lipoprotein deposition
- Inflammatiory reaction
- Smooth muscle cell cap formation
List some factors that can result in endothelial cell injury
Tobacco, uncontrolled diabetes, hyperlipidaemia, hypertension
How does lipoprotein deposition cause a fatty streak?
The endothelium is injured or disrupted, causing lipoprotein molecules to gain entry, where they are then modified by oxidation of glycation. The LDL is inflammatory and able to be ingested by macrophages, creating foam cells and causing a fatty streak in the arterial wall
How does the fibrous cap of a plaque form?
Smooth muscle cells migrate to the surface of the plaque, forming the fibrous cap.
Are thin or thick capped plaques more likely to cause thrombosis?
Thin capped plaques are thought to be more prone to rupture or erosion, causing thrombosis
List some modifiable risk factors for atherosclerosis
High LDL cholesterol, and low HDL cholesterol, High blood pressure, obestiy, smoking, diabetes
List some non-modifiable risk factors for atherosclerosis
Family history, high blood pressure, being a post-menopausal woman, being over 45 for a man, diabetes
How does high LDL cholesterol promote plaque formation?
LDLs enter the artery walls and then can be phagocytosed by macrophages to form foam cells that promote inflammation.
How does low HDL cholesterol promote plaque formation?
HDLs remove cholesterol from foam cells, inhibit oxidation of LDLs, and limit the inflammatory response underlying atherosclerosis.
How does hypertension promote plaque formation?
In hypertension, there is increased dilation and contraction of arteries, damaging the endothelium. This endothelium is then scarred and thus thicker causing a narrower lumen and increased liklihood of atherosclerosis.
How does obesity promote plaque formation?
There is generally an increase in blood pressure as a result of higher demands in obesity
How does smoking promote plaque formation?
Toxins in tobacco smoke lower HDLs and raise LDLs. The nicotine and carbon monoxide also damage the endothelium. Nicotine is also a vasoconstrictor
How does uncontrolled diabetes promote plaque formation?
Diabetes drives inflammation and slows blood flow, dramatically accelerating atherosclerosis. Diabetes is also liked to obesity
How does increasing age promote plaque formation?
Arteries stiffen with age
How does being post-menopausal promote plaque formation?
A decline in oestrogen may be a risk factor in heart disease. Oestrogen is believed to have a positive effect on the inner layer of the artery wall, keeping vessels flexible
List some preventative measures that could be done to reduce risk of atherosclerosis
Reduce BMI, Reduce cholesterol intake, Lower blood pressure through medications, statins, Smoking cessation
What medications can be used to reduce the risk of atherosclerosis
Aspirin, statins, beta blockers
What is a co-benefit?
Additional benefits that arise from cutting greenhouse gas emissions, specifically health related events
What is anaphylaxis?
Anaphylaxis is a type 1 hypersensitibity reaction that causes a severe and potentially life-threatening reaction to a trigger such as an allergy
What are common triggers for anaphylaxis
Medication Food Insect stings General anaesthetic Contrast Agents Latex
What are some symptoms of anaphylaxis?
Feeling lightheaded or faint Breathing difficulties and wheezing Low blood pressure due to vasodilation A fast heartbeat= to combat low bp High temp= massive vasodilation Skin changes= Inflammatory process Low oxygen saturation= Bronchoconstriction Nausea and vomitting
What is the main chemical released in anaphylaxis?
Histamine
How is anaphylaxis treated?
Airways, circulation, breathing Stop trigger IM adrenaline IV fluids Chlorphenamine Hydrocortisone Oxygen
What does adrenaline do in anaphylaxis?
It targets blood vessels (alpha-1), the heart (beta 1) and bronchus (beta 2), causing vasoconstriction, positive inotropic effects and bronchodilation
Why are IV fluids administered in anaphylaxis?
To raise fluid levels to raise blood pressures
Why is chlorphenamine administered in anaphylaxis?
It is a histamine receptor blocker, meaning the effects of histamine will be less severe. H1 receptor antagonist
Why is hydrocortisone administered in anaphylaxis?
It is an agonist of the glucocorticoid and mineralocorticoid receptors meaning that there will be less inflammation= suppresses prostaglandins and causes vasoconstriction.
Why may adrenaline have to be administered twice after anaphylaxis?
It has a short half life
What test can be done to confirm anaphylaxis?
Mast cell tryptase
(Tryptase protein is released by basophils)
Also do FBC to rule out anaemia and rule out underlying infection
What factors are linked to an increased risk of anaphylaxis?
Certain medications Alcohol Exposure to new allergens Change in season Predisposition to asthma and eczema
What characteristics should a drug have in terms of protein binding and lipid solubility to work quickly?
- Low protein binding as binding lowers the free conc of a drug
- High lipid solubility so it can readily cross BBB
During anaesthesia, why must a drug be given throughout the procedure?
If not, the initial drug will diffuse into muscle, so plasma conc will lower and the patient will wake up
What is an agonist?
A drug that binds to and activates a receptor in the same way that the normal binding chemical would
What are the three types of agonists?
Full agonist
Partial agonist
Inverse agonist
Give an example of a full agonist drug
Opioids activate opioid receptors in the brain, resulting in the full opioid effect
What is an antagonist?
A ligand that prevents an agonist from binding to a receptor and thus prevents its effects
Give an example of an antagonist drug
Propranolol is a beta-adrenoceptor antagonist
This therefore prevents tachycardia
What is a competitive antagonist?
Binds to the same site as the agonist but does not activate it, thus blocking the agonist’s action.
It is reversible and surmountable
What is a non-competitive antagonist?
Binds to an allosteric (non-agonist) site on the receptor to prevent activation of the receptor.
It is irreversible and insurmountable
Give an example of a competitive antagonist drug
Naloxone (Antagonist of opioid receptor= used for opioid overdose)
What are the 4 types of drug targets?
Receptors
Enzymes
Transporters/ carrier proteins
Ion channels
Give an example of a drug that targets a receptor
ARB= Angiotensin II receptor blockers
Prevent RAAS system so reduces blood pressure
Give an example of a drug that targets an enzyme
ACE Inhibitors
Prevents RAAS system, causing vasodilation and reducing blood pressure
Give an example of a drug that targets a transporter
Proton pump inhibitor (Lansoprazole)
Prevents production of stomach acid by inhibiting proton pump mechanism in parietal cells
Give an example of a drug that targets an ion channel
Calcium channel blockers (Nifedipine)
Targets calcium channel which leads to arterial vasodilation improving coronary artery blood flow relieving angina
What is bioavailability?
The amount of drug that reaches the circulation unaltered (IV drugs therefore have 100% bioavailability)
What is first pass metabolism?
Rapid uptake and metabolism of an agent into inactive compounds by the liver
What would the oral dose of morphine be compared to IV?
Oral dose is twice the IM/ IV dose
E.G. IV is 5mg, oral is 10mg
A patient has just had an invasive surgery. She is 80, and has history of hypertension and renal failure. Her doctor prescribes a lower than normal dose of Morphine, and it is given at longer intervals. Why is this?
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.
What are the ideal physical properties for an IV drug?
Stable in solution
Long shelf life
No pain on injection
Cheap
What are arterial thrombosis normally formed of?
Platelets= white thrombus
What are venous thrombosis normally formed of?
Coagulation factors and RBC= Red thrombus
What are some possible complications of arterial thrombus?
MI/STROKE
What are some possible complications of venous thrombus?
DVT/ PE
How are arterial thrombosis treated?
Anti-platelets e.g. aspirin, clopidogerel
How are venous thrombosis treated?
Anti-coagulants e.g. warfarin, heparin, NOACs (Rivaroxaban)
What are the clinical features of arterial thrombus?
- Diminished or absent pulse
- Claudication
- Complications as presentation; MI, Stroke, TIA, critical limb ischaemia
What are the clinical features of venous thrombus?
- Usually in the leg
- Pulse is present
- Dull aching pain
- Skin pigmentation
- Reddish/blue
- Stiffness and swelling
What are the components of Virchow’s triad?
Stasis of blood flow
Hypercoagulability
Endothelial injury
What are some common risk factors for arterial thrombus?
- Hypertension
- Diabetes
- Hypercholesterol
- Obesity
- Older age
- Smoking
- Family history of MI
- Thrombophilia
- Exogenous hormones
What are some common risk factors for venous thrombus?
- Immobility
- Major trauma
- Surgery
- Active cancer
- Pregnancy
- Long distance travel
- Older age
- Obesity
- Family history of MI
- Smoking
What is plasma D dimer and what does it show?
It is a type of fibrinogen degradation product that is released when a clot begins to dissolve. It is not diagnostic, but a normal result can exclude DVT.
What is the action of heparin?
Activates antithrombin III (a serine protease inhibitor). It Inhibits factor Xa in the common pathway of the clotting cascade. Factor Xa is needed to convert prothrombin to thrombin, therefore LMWHs inhibit coagulation
What is the action of Warfarin?
It competitively inhibits vitamin K epoxide reductase. It prevents post-translational gamma-carboxylation clotting factors II, VII, IX and X. This results in depletion of active clotting factors II, VII, IX and X; this produces a potent anticoagulant effect.
What is the diagnostic criteria of AKI?
- A rise in serum creatinine of 26 mmol/L within 48 hr
- A 50% rise in serum creatinine in last 7 days
- A fall in urine output to less than 0.5 mL/Kg/Hour for more than 6 hrs
What are the units of urine output?
mL/Kg/Hour
What are the three major classes of AKI?
- Pre-renal
- Renal
- Post-renal
What can cause pre-renal AKI?
Impaired perfusion of the kidneys= Diarrhoea, vomitting, hypotension, cardiac failure, sepsis
What can cause renal AKI?
Damage to kidney apparatus= Glomerular disease such as nephritis, NSAIDs, glomerulonephritis
What can cause post-renal AKI?
Urinary outflow obstruction= A blockage from something such as an enlarged prostate or kidney stones
What is the minimum ml/ kg/hr of urine flow in a patient?
0.5
What is normal urine output (mL/kg/hr)?
1-2
How do NSAIDs cause kidney injury?
Inhibit prostaglandin synthesis (renal vasodilators)= reduced renal flow
In AKI, what electrolyte may be raised?
Potassium (Hyperkalaemia)
What ECG changes are seen in hyperkalaemia?
- Prolonged QRS interval
- Tall tented T waves
- Absent P waves
In a patient with AKI and resulting hyperkalaemia, how should they be treated?
- Insulin and dextrose
How does insulin correct hyperkalaemia?
Insulin shifts potassium into cells with glucose
Why should dextrose be given at the same time as insulin in hyperkalaemia?
Insulin shifts potassium into cells with glucose
This corrects the hyperkalaemia but may cause hypoglycaemia. Dextrose prevents this
What is a TIA?
A rapid onset of neurological dysfunction due to temporal focal cerebral ischaemia without infarct (Less than 24 hrs)
How do you check the risk of stroke after TIA?
ABCD2
What is amaurosis fugax?
Transient visual disturbance during TIA or stroke
What causes amaurosis fugax?
Insufficient blood flow to one or both the eyes due to a clot
What cardiac rhythm is atrial fibrillation?
Irregularly irregular
What is cushing’s reflex?
When there is a raised ICP, there is systemic hypertension to reperfuse the brain
What are the symptoms of a posterior circulation stroke?
Loss of consciousness
Cerebellar or brainstem syndrome
Isolated homonymous hemianopia
What are the symptoms of an anterior circulation stroke?
Unilateral weakness and/or sensory deficit of the face and/or arms and/or legs
Homonymous hemianopia
What is the most important criteria to consider when initiating a DNACPR?
Autonomy
