Flashcards in Session 8 Deck (50):
Describe the three categories involved in Virchow's triad.
-Hypercoagulability: alterations in constitution of blood.
-Haemodynamic changes: alterations in normal blood flow
How does warfarin work?
Inhibits production of vitamin K dependent clotting factors (II, VI, IX, X). By preventing reduction of the oxidised vitamin K, hence it cannot be re-used to make more clotting factors.
Give two uses of warfarin.
DVT, PE, AF and for mechanical prosthetic heart valves.
Describe the PKs of warfarin.
Good GI absoption, slow onset of action and heavily protein-bound. Metbaolised via CYP450, and it is also able to cross the placenta.
How do you monitor levels of warfarin?
Via the International Normalised Ratio. This is the time taken for blood to clot compared for specific age and gender. High INR indicates poor clotting.
Between which INRs is warfarin used for DVT, PE or AF?
How can you reverse warfarin?
Administer vitamin K or fresh frozen plasma.
Give two drugs that potentiate warfarin.
Amiodarone, aspirin, cephalosporin antibiotics.
What is heparin?
An anti-coagulant that activates anti-thrombin III to inhibit thrombin and factor XI. Also affects factors IXa, XIa and XIIa.
Describe the role of unfractionated heparin.
Binds to anti-thrombin III and thrombin. Inactivates thrombin and factor Xa.
Describe the role of low-molecular weight heparin.
Binds to anti-thrombin III, inhibiting only factor Xa and has no effect on thrombin. No monitoring is usually required.
How is heparin administered?
Parenteral as poor GI absorption.
How is heparin monitored?
APTT test, which is the activated partial thromboplastin time and measures the efficacy of the coagulation pathways.
Give two indications of heparin.
Prevention of thrombo-embolism peri-operatively.
DVT, PE and AF, prior to warfarin.
Acute coronary syndromes.
Pregnancy, in place of warfarin.
Give two ADRs of heparin.
Bruising, thrombocytopenia, osteoporosis.
How do you reverse heparin therapy?
Protamine sulphate dissociates heparin from anti-thrombin III.
What are the two main thromboxane A2 inhibitors?
-Aspirin prevents thromboxane A2 production, hence platelet aggregation.
-Dipyridamole inhibits its production. Used to prevent strokes.
What is the role of plasmin?
Breaks down fibrin to form fibrin degredation products. Plasminogen is converted to plasmin by tPA or uPA.
What is streptokinase?
Derived from beta-haemolytic streptococci. Binds to plasminogen and induces a conformational change to plasmic, hence there becomes a surplus of plasmin.
Give two examples of recombinant tPAs.
Altepase, reteplase, tenecteplase.
Give the main conditions for which thrombolytics are used.
Acute MI, PE, major venous thrombosis.
What is the window of opportunity fo thrombolytics for coronary occlusion compared to ischaemic stroke.
Coronary occulsion = within 12 hours.
Ischaemic stroke = within 3 hours.
Give three contraindications to thrombolytic therapy.
History of haemorrhagic stroke
Active peptic ulcer
Recent trauma or surgery
Why are r-tPAs used clinically instead of streptokinase?
They can be administered repeatedly and more easily.
Give an example of an IV anaesthetic.
Propofol, Barbiturates, Ketamine.
Give an example of an inhaled anaesthetic.
Halothane, isoflurane, sevoflurane and desflurane.
Give two reversible effects of anaesthesia.
Sedation, amnesia, muscular relaxation, reflex suppression, alalgesia.
Name the four types of anaesthetic.
General, regional, local and dissociative.
What are the differences between general and regional anaesthetic?
General: affects whole body to inhibit sensory, motor and sympathetic nerve transmission in the CNS.
Regional: renders large specific regions of the body insensate. Remains conscious. Transmission block between part of the body and the spinal cord.
What is dissociative anaesthesia?
Uses ketamine to inhibit transmission of nerve impulses between higher and lower centres of the brain.
What is MAC?
Minimum alveolar concentration. This is the end-tidal conc. of inhaled anaesthetic needed to eliminate movement in 50% of patients stimulated by a standardised incision.
Give an example of something that would increase and decrease MAC.
Increase: hyperthermia, chronic alcohol abuse.
Decrease: increased age, hypothermia, pregnancy, sepsis, acute intoxication.
Give two inhibitory ion channels affected by some anaesthetics.
1) GABA-A activated chloride channels. Increases sensitivity to GABA. Causes hyperpolarisation and decreases its excitability.
2) Glycine activated chloride channels. Increases sensitivity to Glycine. Also causes hyperpolarisation and reduced excitability.
Give two excitatory ion channels affected by some anaesthetics.
1) Neural nicotinic ACh receptors: inhibition leads to reduced excitation.
2) NMDA receptors: anaesthetics reduce calcium current involved in modulation of synaptic responses. E.g. Ketamine.
How are inhaled anaesthetics administered?
Titration to vaporise the fluranes. Anaesthetic agent is then mixed with a carrier of oxygen, air and often nitrous oxide. This is then fed to the respiratory system.
What is the blood:gas coefficient?
The volume of gas in litres that can dissolve in one litre of blood.
Describe inhibitory LGIC pharmacodynamics.
These drugs decrease the concentration of the EC50. Hence, a lower level of GABA/glycine is needed to produce the same effect.
Describe excitatory LGIC pharmacodynamics.
EC50 stays unchanged. However, efficacy decreases. Theres reduced inward movement of excitatory currents.
Give three examples of anaesthetic adjuvants.
Benzodiazepines, propofol, nitrous oxide, opioids, neuromuscular blockers.
Describe the role of benzodiazepines.
Facilitate amnesia and anxiolysis, while causing sedation. Have an agnostic effect on GABA receptors.
Describe the role of propofol.
IV sedative/hypnotic used for induction/maintenance of anaesthesia.
Describe the role of neuromuscular blockers.
Abolish normal muscular reflexes that would dangerously interfere with surgery.
Give an ADR of fluranes, nitrous oxide and propofol.
Fluranes: CVS and resp depression, arrythmias and hypotension.
Nitrous oxide: expansion of airway cavities.
Propofol: CVS and resp depression.
What is noted in the pre-surgical review of a patient?
Age, BMI, medical and surgical history, current medication, fasting time and airway assessment.
Name the three stages of anaesthesia.
Induction - propofol and inhalation agent delivered. Adjuvants also IV.
Maintenance - adjuvants kept in balance to maintain adequate anaesthetic depth.
Recovery - agents are withdrawn and physiological function is monitored closely.
What are the four stages of anaesthetic depth?
3) Surgical anaesthesia
4) Medullary paralysis.
What is medullary paralysis?
Severe depression of the respiratory and vasomotor centres. Ventilation and circulation must be supported to prevent death.
What takes place during stage 1?
Loss of pain sensation due to interference of spinothalamic tract.
What takes place during stage 2?
Delirium and possibly combative behaviour. Irregular BP and respiration.