ILA + EXTRAS Flashcards
In order to induce anaesthesia quickly, what characteristics should the drug have in terms of its protein binding and lipid solubility?
- Low protein binding
==> (if protein bound, its not included in the plasma concentration of the free drug) - High lipid solubility
In anaesthetics, why does an additional volatile drug needs to be given as soon as possible
Giving the second anaesthetic as a volatile gas means close control of the anaesthesia levels can be maintained.
Because plasma levels of initial drug drop
Where does a drug need to be in order to have its effect?
The tissue.
Define and explain the terms agonist and antagonist in relation to drug action and give an example of each.
An agonist is a compound with high affinity and efficacy to a receptor i.e. Salbutamol, opiods
An antagonist is a compound with high affinity but low efficacy - binds to ligand i.e. Gliclazide, Beta Blockers, CCBs
Inverse agonist vs Antagonist - What’s the difference?
Inverse agonists - Will stop baseline function of a receptor (turn tap off)
Antagonists - stop anything binding, so receptor remains in whatever state it was in. (So if tap was dripping, it stays dripping and nothing can change that will the antagonist
Outline what a competitive agonist is and give an example of it
● Competitive= receptor antagonist that binds to a receptor but does not activate it, thus blocking the agonist’s action. Dose response curve = just to right (reversible, surmountable)
o Impact can be overcome by increasing the concentration of the agonist
o E.g., naloxone at opioid receptors
DECREASE POTENCY. AS MORE OF THE FURG IS THEREFORE NEEDED TO ILLICT THE SAME RESPONSE
Outline what non - competitive antagonist is and give an example of it
● Non-competitive= an antagonist that causes a decrease in receptor function either by binding to an allosteric site or irreversibly binding to the receptor (irreversible), dose response curve= to right and down. Binds to an allosteric site on the receptor to prevent activation of the receptor.
o E.g., ketamine at the NMDA-glutamate receptor
DECREASE EFFICACY AND POTENCY
Define Efficacy
Define Potency
Efficacy - how well a ligand activates the receptor
the amount of drug needed to elicit an effect (higher the affinity of the drug, the higher the potency)
Briefly outline morphine metabolism
morphine becomes Morphine 6 Glucuronide (10%) and Morphine 3 Glucuronide (90%)
Morphine 6 Glucuronide is the most potent metabolite
Outline the 3 main layers of a vessel wall
Tunica externa – normally thinner than the media in all except the largest arteries. Contains collagenous and elastic fibres, and blood supply / nerves that supply the vessel (vasa vasorum, nervi vasorum)
Tunica media – normally the thickest layer of the artery. Contains smooth muscle cells and elastic fibres. External elastic lamina may be present in larger vessels.
Tunica intima – endothelium may appear wavy due to contraction of smooth muscle. Internal elastic lamina in larger vessels. (Internal elastic lamina is absent in veins!)
Outline the pathophysiology of arterial thrombus, that can be compared to a venous thrombus
Arterial
occur in high shear conditions
Rich in platelets
Involves disrupted atherosclerotic plaques
White clots
Down to platelet adhesion and aggregation prior to activation of coagulation cascade
Outline the pathophysiology of venous thrombus, that can be compared to an arterial thrombus
Develops under low shear stress
Fewer platelets involved
TF generates thrombin prior to platelet aggregation
Made up mainly of coagulation factors
Red clots
Give some symptoms for arterial thrombosis
The six P’s of the acutely ischaemic limb (from arterial blockage): pulseless, perishingly cold, paraesthesia, paralysis, pulselessness, pain, pallor.
Thrombosis of arteries may build up to these six P’s more slowly, or . Arterial embolus (breaking off a thrombus) may result in these symptoms more quickly.
Both groups are at risk of developing ulcers
Give some symptoms for venous thrombosis
WOES
Warm
Oedema
Engorged veins
Swollen
Both groups are at risk of developing ulcers
What are two coagulation tests you can do in thrombus formation?
aPTT - activated prothrombin time
PT - Prothrombin time
For both coagulation tests, what pathway does aPTT measure, and what factors does it look at?
aPTT - activated prothrombin time
measures intrinsic pathway - (FACTORS 12, 11, 9, 8,), and the common pathway 10, 5, 2 (prothrombin) and 1 (fibrinogen)
Think aPTT - (TT - table tennis = indoors = intrinsic)
For both coagulation tests, what pathway does PT measure, and what factors does it look at?
PT - Prothrombin time EXTRINSIC AND COMMON
measures extrinsic pathway (factors 3 and 7) and then common pathway factors 10, 5, 2 (prothrombin) and 1 (fibrinogen)
(T - tennis - outdoors )
What test would use for DVT?
D Dimer
Outline the differences between
senstiivty n
specificty
Sensitivity - likelihood of detecting a true positive -
High specificity - If the test is positive, you are very likely to have the disease
Specificity - Correctly being able to exclude a negative test
High specifity - if the test is negative, you are very likely TO NOT Have the disease
outline the specificity and sensitivity of D dimer in DVT
Its highly sensitive , due to inflammation, (in other words it will always pick up a DVT)
but not specific as you can’t specifically diagnose DVT from it as as positive result can be due to different things that aren’t DVT
What score can you use for DVT and PE?
Wells Score
Test for DVT and PE - outline some things seen in the Wells Score
- Cancer
- Paralysis,
- Recently bedridden for >3d or major surgery in last 12wks
- Local tenderness along distribution of deep venous system
- Entire leg swollen 1 point
- Calf swelling >3cm 1 point
- Oedema 1 point
- Collateral superficial veins (non-varicose) 1 point
- Previously documented DVT 1 point
- Alternative diagnosis at least as likely as DVT -2 points
Treatments of DVT:
Outline what heparin/DOACs does
Anti coagulants
DOACs - all the apixabans
inhibit factor 10a (remeber bc Xa is in the drug names, inhibtis factor 10a)
Binds to antithrombin and increases its activity (antithrombin inactivates several enzymes of the coagulation system)
Indirect thrombin inhibitor
Treatments of DVT:
How do you monitor the effects of Heparin?
Anti coagulants
DOACs - all the apixabans ac
Monitor with Activated partial thromboplastin time (APTT), aim ration 1.2-2.8
Given by continuous infusion
What are the advantages and disadvantages of warfarin compared to DOACs
Warfarin - good bc can be used in valve replacements when DOACs cant use, can be reversed with vitamin K easily
Disadvantages - need to measure INR all the time with it, so dosing is tricky
What are the advantages and disadvantages of warfarin compared to DOACs
Warfafin - good bc can be bused in valve replacemnts when DOACs cant use, can be reveresed with vitamin K easily
Disadvateabes - need to measeure INR all teh time with it, so dosing is tricky – this isnt the case with DOACs
Warfarin is Contraindicated in pregnancy!!
Outlien how warfarin works.
Prevents synthesis of active factors II, VII, IX, and X
Antagonist of vitamin K
Long half-life (36 hours)
Prolongs the prothrombin time
outline how DOACs work
(namely Rivaroxaban which is a Xa inhibitor)
Directly acting on factor II or X
No blood tests or monitoring
Shorter half-lives so bd or od
Used for extended thromboprophylaxis and treatment of AF and DVT/PE (equivalent to INR 2-3, not higher, so not heart valves)
Not used in pregnancy – as can pass to the baby
routine management option for DVT
What are some risk factors for DVT???
Old
Long haul flight
COMBIINED CONTRACEPTION PILL
What is the diagnostic criteria for an AKI?
Rise in serum creatinine of 26µmol/l or greater within 48 hours
50% or greater rise in serum creatinine (1.5 times more than baseline) known or presumed to have occurred within 7 days
Fall in urine output to less than 0.5ml/kg/hour
How can NSAID use lead to an AKI?
Because they inhibit prostaglandin synthesis, by inhibiting the COX-1 enzyme so renal vasoconstriction cannot be counteracted
NSAIDs can reduce blood flow to the kidneys by causing vasoconstriction, especially in the afferent arteriole
This narrowing can reduce the amount of blood that flows to the kidneys, which can impair their ability to filter toxins from the bloodstream and can lead to an AKI, As GFR is reduced
INTRA RENAL CAUSE OF AKI, NEPHROTOXIC
What changes does Hyperkalaemia cause on an ECG?
Tall Tented T waves
Flattened P waves
Prolonged PR
Wide QRS
name for types of drugs that can have been known to cause/exascerabte an AKI.
DAMN
diuretics
ACE inhibitors
metformin
NSAIDs
Fundamental Biological therapies
Name a Biologic response modifier that specifically suppresses
T cells
B Cells
T Cells - Abatacept
B Cells - Rituximab
T cells end in T
B cells end in B
picture = treatment for Rheumatoid Arthritis
Fundamental Biological therapies
Name a Biologic response modifier that specifically suppresses
TNF alpha
Interleukin 1
TNF alpha - infliximab
Interleukin 1 - Anakinra
picture = treatment for Rheumatoid Arthritis
Outline what happens in the initial, “priming stage” of anaphylaxis
● Type 1 hypersensitivity reactions are IgE mediated.
o The IgE antibodies are formed to an antigen (or allergen), with an individual’s tendency towards making IgE being determined by factors including genetics, T cell responsiveness and antigenic burden.
o The IgE binds to high-affinity IgE receptors on the surfaces of mast cells and basophils, and these cells are now primed to react the next time the cells come into close proximity with the allergen.
Outline what happens in anaphylaxis when a patients primed Mast cells are exposed to the allergen
o The cross-linking of IgE on the cell surfaces causes rapid (mast cell) cellular degranulation and liberation of a number of chemical mediators.
The mediators released by mast cell degranulation include the preformed molecules histamine, protease enzymes, proteoglycans and chemotactic factors.
o Reaction of antigen with IgE on mast cells also stimulates synthesis and release of platelet activating factor (PAF), leukotrienes and prostaglandins.
What is the Treatment for anaphylactic shock?
ABCDE assessment
IM Adrenaline (500mg) - If ineffective then give second IM 500mg Adrenaline Dose
Then
Chlorphenamine - Anti-histamine (H1)
Hydrocortisone - Steroid
What would Hypercalcaemia cause on an ECG?
Short ST segment, and Widened T wave, Shorted QT interval
What would Hypocalcaemia cause on an ECG?
Prolonged ST segment
Prolonged QT interval
What signs would you see in someone with acute appendicits? What examinations would you do?
- Right iliac fossa tenderness: rebound tenderness (pain when pressure is taken off) or percussion tenderness (pain during percussion) suggests localised peritonism
- Guarding
- Rovsing’s sign: pain in the right iliac fossa is worsened by pressing on left iliac fossa
- Psoas sign: pain is worsened by extending the hip
- Obturator sign: pain is worsened by flexing and internally rotating the hip
Tachycardia, hypotension and generalised peritonism: suggests perforation
