What is the role of GPIIb/IIIa in platelet aggregation?
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GPIIb/IIIa is a receptor for fibrinogen and von Willebrand factor, facilitating platelet aggregation.
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What is the role of GPIIb/IIIa in platelet aggregation?
GPIIb/IIIa is a receptor for fibrinogen and von Willebrand factor, facilitating platelet aggregation.
Which receptors do ADP bind to during platelet activation?
ADP binds to P2Y1 and P2Y12 receptors.
What is the principal benefit of red cell transfusion?
Improvement in oxygen-carrying capacity by increasing hemoglobin levels.
What is the primary mechanism of action of aspirin as an anti-platelet agent?
Aspirin irreversibly acetylates and inhibits the enzyme COX, changing the balance between prostacyclin and thromboxane, thus preventing platelet aggregation.
What is the function of thrombin in platelet activation?
Thrombin binds to protease-activated receptors (PAR-1 and PAR-4), promoting platelet activation.
How does raising the hematocrit benefit trauma and septic patients?
It improves microcirculation.
What is antimicrobial stewardship?
A coordinated program that promotes appropriate prescribing and use of antimicrobials to reduce microbial resistance and improve patient outcomes.
How does aspirin affect thromboxane and prostacyclin synthesis?
Aspirin inhibits the conversion of arachidonic acid to endoperoxide, preventing the synthesis of thromboxane (TXA2) in platelets and prostacyclin (PGI2) in endothelial cells.
How is thromboxane A2 (TXA2) produced?
TXA2 is produced from arachidonic acid through conversion by cyclo-oxygenase-1.
What is a major risk associated with blood transfusions?
Hemolytic transfusion reactions, such as life-threatening ABO incompatibility.
In which patient group should gentamicin be used with caution?
During pregnancy, as it can cross the placenta and cause fetal ototoxicity.
What is the molecular weight range of Unfractionated Heparin?
3000–40,000 Da.
What role do platelets play in clotting?
Platelets are critical in haemostasis and the development of arterial thrombi.
What is the main class of drug used to treat type 1 diabetes mellitus?
Insulin.
What are the main principles of good antibiotic prescribing?
Prescribe only when clinically indicated, collect specimens for culture before therapy, follow local guidelines, choose the correct antibiotic class, use narrow-spectrum agents when possible, de-escalate broad-spectrum therapy, ensure correct treatment duration and dose, switch to oral preparations promptly, source control where applicable, and ensure surgical prophylaxis compliance.
What is the primary action of antibiotics that inhibit bacterial protein synthesis?
They bind to the 30S or 50S subunit of bacterial ribosomes.
What is the effect of ADP receptor blockers like ticlopidine and clopidogrel?
They inhibit the ADP-dependent pathway of platelet activation by preventing binding of ADP to its receptor on the platelet surface.
What receptors are activated by thromboxane A2?
The TXA2 receptor (TP) is activated by TXA2 and prostaglandin endoperoxides PGG2 and PGH2.
What infections can be transmitted through blood transfusions?
HIV, hepatitis A, B, C, malaria, variant CJD, CMV, syphilis, HTLV.
What dietary factors can potentiate the action of warfarin?
Foodstuffs and supplements like St John's wort, ginger, and ginseng.
How are aminoglycosides, including gentamicin, excreted?
They are excreted unchanged by the kidneys, primarily by glomerular filtration.
What is the mechanism of action of Heparin?
Binds to antithrombin III (ATIII) reversibly, increasing the rate at which ATIII binds to thrombin by 1000x.
What initiates the interaction between platelets and the extracellular matrix?
Damaged endothelium.
When did insulin treatment first become available?
Since 1925.
What is the recommended time to discontinue aspirin monotherapy for primary prevention before surgery?
7–10 days before surgery.
What is the primary difference in Xa inhibition between unfractionated heparin (UFH) and low molecular weight heparins (LMWH)?
UFH has + Xa inhibition, while LMWH has +++ Xa inhibition.
What should be done before starting antibiotic therapy?
Collect specimens for culture (e.g., blood, urine).
Which antibiotics are susceptible to β-lactamase?
Benzylpenicillin, Amoxicillin, Ceftriaxone, and others.
What distinguishes ticagrelor from other ADP receptor blockers?
Ticagrelor indirectly inhibits ADP by acting on an independent ligand-binding site on the P2Y12 receptor, resulting in reversible non-competitive binding.
What is the significance of membrane glycoproteins GPia/IIa, GPV, and GPV in platelets?
They function as receptors in platelet adhesion to collagen.
What metabolic complications can arise from blood transfusions?
Hyperkalemia and hypocalcemia.
How does resistance to penicillins develop?
Inappropriate use of antibiotics and poor prescribing play a vital role in propagating antibiotic resistance.
How does thyroid status affect warfarin?
Hypothyroidism reduces the effect of warfarin.
What formula is used to estimate creatinine clearance?
Cockcroft and Gault formula.
What happens when thrombin is complexed with ATIII?
Clot formation is inhibited.
What is the function of von Willebrand factor (vWF) in platelet activation?
vWF binds to GP Ibα and collagen, activating platelets.
What type of insulin has largely replaced animal insulin?
Genetically engineered human insulin analogues.
In what situation should aspirin be continued despite the risk of bleeding?
Secondary prevention with low risk of bleeding.
What is the bioavailability of subcutaneous doses for UFH and LMWH?
UFH has 40% bioavailability, while LMWH has 90%.
What is naturally occurring heparin?
A highly sulphated glycosaminoglycan carbohydrate weighing between 3000 and 50,000 daltons, produced by basophils and mast cells.
What is the minimum inhibitory concentration (MIC)?
The lowest concentration of antibiotic required to completely inhibit the growth of a particular bacterium in vitro.
What type of antibiotics are resistant to β-lactamase?
Carbapenems and monobactams.
What effect does massive transfusion of stored blood have on oxygen delivery?
It adversely affects oxygen delivery to the tissues due to high oxygen affinity.
What is the mechanism of action of dipyridamole?
Dipyridamole inhibits cellular uptake of adenosine, increasing extracellular adenosine levels, which elevates cAMP levels in platelets and inhibits their activation.
What is the role of fibrinogen in platelet aggregation?
Fibrinogen cross-linking leads to platelet aggregation.
What is a potential risk of transfusing cold stored blood?
Hypothermia.
What is one mechanism by which bacteria develop resistance to penicillins?
Drug inactivation through bacterial production of β-lactamase, leading to hydrolysis of the β-lactam ring.
What impact does severe sepsis have on warfarin binding?
Changes in plasma pH alter protein structure, reducing binding sites.
What are the main components of whole blood after centrifugation?
Red cells, plasma, and platelets.
What effect do aminoglycosides have on non-depolarising muscle relaxants?
They can potentiate their action or cause recurrence of the blockade.
What factors are inhibited by Heparin at higher doses?
Factors IXa, XIa, and XIIa.
How do platelets adhere to the endothelium?
Bound vWF activates GP IIb/IIIa glycoproteins, allowing them to bind fibrinogen.
How are insulins categorized?
According to onset of action, peak, and duration of action.
How is UFH administered clinically?
As an infusion to prevent DVT and PE, during cardiopulmonary bypass, ECMO, vascular surgery, and for thrombosis prophylaxis.
What is unfractionated heparin (UFH)?
A synthetic agent weighing between 5000 and 25,000 daltons that binds to and potentiates the action of antithrombin III 1000-fold.
What is the primary metabolism route for Warfarin?
Hepatic metabolism.
What is the minimum bactericidal concentration (MBC)?
The lowest concentration of antibiotic required to kill a particular bacterium in vitro.
When should dual anti-platelet therapy be discontinued before surgery in low-risk situations?
5–7 days before surgery, while continuing aspirin.
What is the mode of action of β-lactams?
They inhibit bacterial cell wall synthesis.
How quickly do 2,3 DPG levels rise after transfusion?
They rise rapidly, usually restoring normal oxygen affinity in a few hours.
What is the role of GP IIb/IIIa inhibitors in platelet aggregation?
They inhibit the final common pathway of platelet aggregation by blocking fibrinogen binding to the GP IIb/IIIa receptor, providing the greatest antiplatelet activity.
What is a serious immune-related complication of blood transfusion?
Graft-versus-host disease.
Why is warfarin contraindicated in pregnancy?
Due to its teratogenic effects and risk of maternal bleeding.
What is another mechanism of penicillin resistance?
Alteration of penicillin binding proteins, preventing antibiotics from binding to the bacterial cell wall.
At what temperature must plasma be stored after separation?
Frozen as soon as possible to under –18 °C.
Why are aminoglycosides contraindicated in patients with myasthenia gravis?
Due to their effect on neurotransmission, interfering with calcium entry and acetylcholine release.
How is Heparin metabolized and excreted?
Metabolized in the liver, kidney, and reticuloendothelial system; excreted in urine.
What substances do activated platelets release?
TXA2 and ADP, which recruit and activate surrounding platelets.
What are the main groups of insulin?
Rapid-, short-, intermediate-, and long-acting.
What is the typical monitoring method for UFH therapy?
Activated partial thromboplastin time (APTT) is measured.
How is Warfarin excreted from the body?
In urine and faeces.
How does activated antithrombin III function?
It inhibits thrombin and other serine proteases that promote blood clotting.
What should be done in high-cardiovascular risk situations regarding elective surgery?
Delay elective surgery.
What is the ideal timing for administering surgical prophylaxis antibiotics?
Ideally 30 minutes prior to skin incision.
Which class of antibiotics is known to be bacteriocidal and inhibits bacterial DNA synthesis?
Fluoroquinolones.
How long does it take for platelet function to return to normal after administration of GP IIb/IIIa inhibitors?
Platelet function returns to normal in 48 hours with abciximab and in 6–8 hours with tirofiban.
What defines a massive transfusion?
Transfusion of 10 units of blood within 6 hours or replacement of the entire circulating volume within 24 hours.
What causes hypocalcaemia during blood transfusion?
Citrate in each unit of blood binds ionised calcium.
What is the main adverse effect of warfarin overdose?
Bleeding.
What is a third mechanism of resistance to penicillins?
Alteration of bacterial cell wall permeability, which prevents antibiotics from penetrating the cell wall.
What is the storage temperature for red blood cells?
1–6 °C.
What is the basic structure of penicillin?
A thiazolidine ring nucleus attached to a β-lactam ring.
What mediates platelet aggregation?
Fibrinogen binds to GP IIb/IIIa receptors and converts to fibrin, stabilizing the thrombus.
Why is Heparin not given orally?
Due to low lipid solubility, it does not cross the blood-brain barrier or placenta.
What are biphasic insulins?
Ready mixed combinations of rapid- or short-acting insulins with intermediate-acting insulins.
What is the typical dosage range for Warfarin?
Usually 2–9 mg/day, patient-specific and titrated to effect.
What is the half-life of UFH compared to LMWH?
UFH has a half-life of 30–150 minutes, while LMWH has a half-life 2–3 times longer for an equivalent dose.
What is a potential requirement during emergency surgery if anti-platelet therapy is not discontinued?
May require platelet transfusion in life-threatening bleeding.
What are low molecular weight heparins (LMWH)?
Newer drugs weighing between 2000 and 8000 daltons that directly inhibit factor Xa.
What should be done if broad-spectrum therapy is commenced?
De-escalate as soon as possible based on microbiology-sensitivity data.
What is the function of glycopeptides in antibiotic action?
They inhibit bacterial cell wall synthesis and are bacteriocidal.
What is a common problem encountered during massive transfusion?
Dilutional thrombocytopenia.
What is the metabolism rate of citrate in a healthy adult liver?
The liver metabolizes 3 g of citrate every 5 minutes.
What is the specific treatment for major bleeding due to warfarin overdose?
Stop warfarin, administer vitamin K, and consider prothrombin complex concentrate or fresh frozen plasma.
What are the major side effects of penicillins?
Hypersensitivity, gastrointestinal disturbances, encephalopathy in renal failure patients, and rash with ampicillin in infectious mononucleosis.
What is a major side effect of heparin therapy?
Haemorrhage, which can be fatal if given in overdose.
How should platelets be stored?
At room temperature (20–24 °C) on shaking platforms.
What is the mechanism of action of penicillin?
It inhibits bacterial cell wall synthesis by binding to cell wall proteins and preventing peptidoglycan cross-links.
What are the primary uses of Heparin?
Prophylaxis of DVT, prevention of clot propagation in DVT/PE/vessel occlusion, and to prevent clot formation on extra-corporeal membranes.
What inhibits platelet activation, adhesion, and aggregation?
Nitric oxide (NO) and prostacyclin (PGI2).
What is the onset time for rapid-acting insulin analogues?
Less than 15 minutes.
What is the protein binding percentage of Warfarin?
99%.
What is the common practice for administering UFH?
A bolus of 5000 IU followed by a continuous infusion based on the patient's weight.
What factors should be considered when ensuring the correct dose of antibiotics?
Weight, renal function, liver function, and if on renal replacement therapy.
How are doses of LMWH and UFH calculated?
In units of activity rather than weight.
What is the relative risk associated with regional anaesthesia in patients on anti-platelet agents?
Carries a relative risk of bleeding.
What type of antibiotics are aminoglycosides?
Bacteriocidal.
What coagulation factors are absent in stored blood?
Factors V and VIII.
What plasma potassium concentration can stored blood reach?
It may exceed 30 mmol/L.
What percentage of patients allergic to penicillin may experience cross-reactivity with other β-lactam antibiotics?
Up to 10%.
What is a restrictive red cell transfusion trigger?
Accepting a lower hemoglobin level that is safe for the individual patient, e.g., 10 g/dL for a patient with ischemic heart disease or as low as 7 g/dL for a fit 20-year-old.
What is Rivaroxaban?
A direct factor Xa inhibitor that can be taken orally once daily.
How is heparin administered to avoid complications?
Subcutaneously, to avoid intramuscular haematoma.
What is leuco-depletion?
The process of removing white blood cells via filtration.
What types of organisms are penicillins active against?
Most gram-positive organisms and some gram-negative cocci.
What hematological effects does Heparin have?
Increases APTT, TT, and ACT; no effect on bleeding time; can cause thrombocytopenia (Type I and Type II).
What are the primary uses of Warfarin?
Prophylaxis of DVT/PE, clot formation on prosthetic heart valves, and prevention of clot propagation.
What is the recommended administration timing for short-acting human insulin?
30 minutes before meals.
How can anti-platelet agents be classified?
They decrease platelet aggregation and inhibit thrombus formation.
How does LMWH differ in administration compared to UFH?
LMWH is given as a twice-daily or once-daily subcutaneous injection.
What is the significance of the size of heparin molecules in thrombin inactivation?
To inactivate thrombin, the heparin molecule must bind both antithrombin III and thrombin, requiring a size greater than 18 saccharide ternary units.
What guidelines are recommended for performing neuraxial and peripheral nerve blocks?
Performed by experienced clinicians and under ultrasound guidance where possible.
Which antibiotics are classified as bacteriostatic?
Tetracyclines, macrolides, and lincosamides.
What is pre-donation in the context of blood conservation?
Patients for planned surgery with significant expected blood loss may be candidates for pre-donation of blood followed by intra-operative transfusion of their own blood.
What is the incidence of anaphylaxis in patients taking penicillins?
Approximately 0.01%.
What is a common issue related to potassium levels during transfusion?
Hypokalaemia is more common as red cells restart potassium uptake.
What is a major drawback of Dabigatran?
There is no way to reverse its effect.
What should be done with heparin dosage in patients with renal failure?
The dose should be reduced due to potential accumulation.
Why is leuco-depleted blood beneficial?
It minimizes alloimmunisation, reduces febrile transfusion reactions, and decreases cytomegalovirus (CMV) transmission.
What is the effect of probenecid on penicillin?
It inhibits the tubular secretion of penicillin, increasing plasma levels significantly.
What is the antidote for Heparin?
Protamine.
What hematological effects does Warfarin have?
Increases PT and INR.
What are the main types of anti-platelet agents in clinical use?
COX inhibitors, ADP receptor inhibitors, dipyridamole, and GPIIb/IIIa inhibitors.
What is the duration of action for long-acting insulin analogues?
12-24 hours.
What does APTT measure in the context of heparin therapy?
APTT measures the activity of the intrinsic clotting cascade and is prolonged by UFH.
What procedures carry the greatest risk of haematoma?
Epidural with a catheter, one-shot epidural, spinal, paravertebral blocks.
What is the role of smaller heparin molecules?
They can only inhibit the activity of other proteases such as factor Xa.
What is the role of antifolates in antibiotic therapy?
They act as bacteriostatic agents.
How do penicillins and aminoglycosides act synergistically?
Penicillins weaken the bacterial cell wall, allowing aminoglycosides to penetrate the cell and inhibit protein synthesis.
What is hypotensive anaesthesia used for?
To reduce blood loss in certain types of surgery such as middle ear surgery or neurosurgery.
How can heparin's action be reversed?
Using protamine sulphate.
What acid load does stored blood contribute to the recipient?
Stored blood can give an acid load of up to 30–40 mmol/L of lactic acid.
How can unfractionated heparin (UFH) be reversed?
With protamine; 1 mg of protamine reverses 100 IU of heparin.
How are penicillins categorized based on their spectrum of action?
Narrow spectrum, β-lactamase resistant, broad spectrum, and anti-pseudomonal.
What type of blood do severely immunosuppressed patients require?
Irradiated blood.
What is a key advantage of low molecular weight heparin?
It inhibits factor Xa via ATIII and only needs once daily dosing without requiring monitoring.
What should be done with Warfarin before elective surgery?
Stop Warfarin 1 week before and replace with heparin if necessary; INR should be < 2 to operate.
What type of insulin regimen is suitable for type 2 diabetes?
Once daily.
What is the effect of anti-platelet agents?
They are most effective in the treatment or prevention of arterial clots composed largely of platelets.
Is monitoring required for LMWH therapy?
Usually no monitoring is required, but anti-factor Xa levels can be measured as needed.
What is the recommended time to stop clopidogrel before performing a block?
7 days.
What is the significance of β-lactamase inhibitors like clavulanic acid?
They protect β-lactam antibiotics from being broken down by β-lactamase.
What are anti-fibrinolytic agents?
Agents like tranexamic acid and aprotinin that inhibit clot breakdown.
What are the methods to reverse warfarin's action?
Intravenous vitamin K, fresh frozen plasma, or prothrombin complex concentrate.
What metabolic disturbance can occur due to citrate metabolism?
Profound metabolic alkalosis may ensue.
What is non-immune thrombocytopenia and when does it occur?
It occurs after approximately 4 days of therapy and platelets recover spontaneously.
What changes occur in stored blood?
Fall in 2,3-DPG levels, left shift of the oxyhemoglobin dissociation curve, fall in pH (to approximately 7.0), rise in potassium concentration.
What are the three important pharmacokinetic parameters when evaluating antibiotic efficacy?
Peak serum level (C max), Trough serum level (C min), Area under the serum concentration–time curve (AUC).
What is the mechanism of action of Warfarin?
Inhibits synthesis of vitamin K dependent clotting factors II, VII, IX, and X.
How can episodes of hypoglycaemia be minimized in insulin treatment?
By using rapid-acting analogues instead of short-acting human insulins.
How long after stopping ticagrelor should a block be performed?
5 days.
What is intra-operative blood salvage?
The use of cell savers in certain types of surgery to recover and reinfuse a patient's own blood.
What is heparin-induced thrombocytopenia (HIT)?
An immune-mediated process that usually develops around 5 days after heparin exposure.
What complications can hypothermia cause during transfusion?
It can lead to reduced citrate and lactate metabolism, hypocalcaemia, and increased cardiac dysrhythmias.
What does the Peak/MIC ratio represent?
It is the C max divided by the MIC.
What is the purpose of acid-citrate-dextrose in blood storage?
Citrate acts as an anticoagulant by binding calcium, while dextrose serves as an energy source for glycolysis.
How long does it take for Warfarin to start working?
It takes 72 hours to work as it only affects the synthesis of new factors.
What is recombinant factor VII used for?
Used in hemophilia and in massive bleeding, provided platelet count is adequate.
What happens in HIT regarding platelets?
IgG antibodies bind to the heparin-PF4 complex, activating platelets and forming thrombi.
What is the recommended ratio for blood product administration in major hemorrhage?
1:1:1 ratio of packed red cells, FFP, and platelets.
What is T > MIC?
The percentage of a dosage interval in which the serum level exceeds the MIC.
How long can red cells survive when stored in citrate-phosphate-dextrose?
28 days.
What can decrease the absorption of fat-soluble vitamins and potentiate the effect of Warfarin?
Cholestyramine.
What are artificial oxygen carriers?
Perfluorocarbons and modified hemoglobins that transport oxygen differently than blood.
What should be done if HIT is suspected?
Discontinue heparin and send blood for a HIT screen; alternative anticoagulation should be used.
How often should calcium levels be checked during massive transfusion?
After every 10 units of blood products.
What is the effect of adding adenine to blood storage solutions?
It increases red cell survival to 35 days.
Which pharmacokinetic index correlates best with the efficacy of concentration-dependent killing antibiotics?
The 24-h AUC/MIC ratio and the Peak/MIC ratio.
How do perfluorocarbon emulsions differ from blood in oxygen transport?
Blood exhibits a sigmoidal oxygen dissociation curve, while perfluorocarbon emulsions have a linear relationship between oxygen partial pressure and oxygen content.
What are some other side effects of heparin?
Hypotension, osteoporosis with long-term use, and alopecia.
What is the composition of the saline-adenine-glucose-mannitol storage solution?
Saline (140 mmol/l), adenine (1.5 mmol/l), glucose (50 mmol/l), mannitol (30 mmol/l).
What may be required to boost coagulation in major hemorrhage cases?
Recombinant factor (rFVII).
What is the best predictor of antibiotic efficacy for time-dependent killing antibiotics?
T > MIC.
Are artificial oxygen carriers widely used in the UK?
No, no artificial oxygen carriers are used extensively within the UK at present.
What are the advantages of low molecular weight heparin (LMWH)?
Requires once or twice daily dosing, does not need monitoring, and is less likely to cause HIT.
How do antibiotics exert their effects?
By inhibiting (bacteriostatic) or killing (bacteriocidal) bacteria.
How does warfarin exert its anticoagulant effect?
By inhibiting the synthesis of vitamin K-dependent clotting factors (II, VII, IX, and X).
What is the mode of action of aminoglycosides like gentamicin?
They bind irreversibly to the 30S subunit of the bacterial ribosome and inhibit bacterial protein synthesis.
What is the purpose of monitoring warfarin therapy?
It is monitored via the international normalized ratio (INR).
What are the potential toxicities associated with high plasma concentrations of aminoglycosides?
Ototoxicity and nephrotoxicity.
Why is heparin often started alongside warfarin?
Because it takes at least 48 hours for warfarin to achieve its clinical effect.
What is the recommended dose of gentamicin?
3–5 mg/kg/day, given in divided doses every eight hours.
Which drugs may potentiate the action of warfarin?
NSAIDs and simvastatin, as they compete for protein binding sites.
What are the target 'peak' and 'trough' plasma gentamicin levels?
'Peak' levels should be 5–10 mg/L and 'trough' levels should be less than 2 mg/L.
What effect do antibiotics that affect gut flora have on warfarin?
They increase the effect of warfarin by affecting vitamin K production.
What is an alternative dosing regimen for gentamicin?
A once-daily regimen where the full dose is given as a single dose, adjusted according to 'trough' levels using a nomogram.
