Flashcards in Session 8 Deck (33):
What colour are arterial/venous clots and with which anti-clotting agents are they treated?
Arterial - white (CVA/MI). Antiplatelets and thrombolysis.
Venous - red (DVT/PE). Anticoagulation
How do platelet reactions and blood coagulation interact to form a thrombus?
Exposure of acidic phospholipids on platlets activates various clotting factors
Thrombin and fibrinogen trigger further aggregation of platelets
Describe the mechanism of action of warfarin
Inhibits production of vitamin K dependent clotting factors. E.g. prothrombin, VII + IX (extrinsic) and X (common pathway)
Onset is days due to slow turnover of clotting factors - consider heparin cover
Describe some basic pharmacokinetic principles of warfarin
Good GI absorption
Slow offset - stop 3 days prior to surgery. Hepatic metabolism (cytochrome p450)
Heavily protein bound
Crosses placenta - avoid in 1st and 3rd trimester
NSAIDs - displacement from albumin
What drugs can potentiate warfarin?
Inhibit hepatic metabolism - amiodarone, quniolone, metronidazole, cimetidine, alcohol
Inhibit platelet function - aspirin
Reduce vitamin K from gut bacteria - cephalosporin antibiotics
Avoid cranberry juice
What drugs can inhibit the action of warfarin?
Inducing hepatic enzymes - Antiepileptics, Rifampicin, St Johns Wort
What is the international normalized ratio (INR)?
A calculation made to standardize prothrombin time. It is based on the ratio of prothrombin time and the normal mean prothrombin time
Describe the indications or warfarin and the target INR in each case
DVT (3-6 months), PE (6 months), AF - INR 2.0-3.0
Mechanical prothetic valves, thrombophilia, recurrent thrombosis - INR 2.5-4.5
What are the side effects of warfarin?
Intracranial bleeds, epistaxis, GI bleed, teratogenic
How can warfarin be reversed?
Parenteral vitamin K (slow) or fresh frozen plasma (fast)
Describe the mechanism of action of heparins
Activate antithrombin III which deactivates factors Xa, prothrombin (IIa) (both common pathway - main action), IXa (intrinsic)
What are unfractionated and low molecular weight heparin and how are they administered?
Unfractionated - mix of long heparin chains. Binds to antithrombin III, increasing its activity. IV. Loading dose then infusion.
LMWH (e.g.dalteparin) - just inactivates factor Xa (same as DOACs). Less likely to cause thrombocytopenia. Long half life. subcutaneous
Describe some basic pharmacokinetic principles of heparin
Poor GI absorption - given parenterally. Rapid onset and offest of action.
Describe the indications of heparin
Prophylaxis of thromboembolism - perioperative (LMWH), immobility
Treatment of DVT/PE/ACS - prior to warfarin, reduces recurrence/extension of coronary artery thrombosis
What are the side effects of heparin?
Haemorrhage, thrombocytopenia, osteoporosis
How are heparins reversed?
Protamine sulphate - irreversibly binds heparin
List some common antiplatelet drugs and briefly describe their mechanism of action
Aspirin - COX1 inhibitor
Clopidogrel - ADP antagonist (stops aggegation)
Dipyridamole - phosphodiesterase inhibitor (stops aggregation)
What is the normal clearance mechanism for thrombi and how is it activated?
Plasmin cleaves fibrin
Plasminogen is activated by tissue plasminogen activator (tPA-e.g. alteplase) amongst others (exogenous-streptokinase)
Why can't streptokinase be used more than once after 4 days?
It is a bacterial protein and therefore antigenic. It can cause allergic reactions and it invariably generates
blocking antibodies which persist for many years
Outline the steps in anaesthesia
Premedication for anxiolysis and amnesia (hypnotic-benzodiazepine)
Induction - IV or inhalational
Intraoperative analgesia - usually opioid (fentanyl) and nitrous oxide
Muscle paralysis (fluranes/tubocurarine/succinylcholine)
Reversal of muscle paralysis and recovery including post operative analgesia
Provision for PONV
What can be used to measure depth of general anaesthesia?
Stage 1 - analgesia and consciousness
Stage 2 - unconscious, breathing erratic but delirium caould occur leading to an excitment phase
Stage 3 - surgical anaesthesia with 4 levels of increasing depth until breathing weak
Stage 4 - Respiratory paralysis and death
How is volatile anaesthetic potency described and what affects this value?
By minimum alveolar concentration (MAC) - conc at which 50% of subjects fail to move to surgical stimulus
At equilibrium alveolar concentration=spinal cord concentration
Factors increasing the value: hyperthermia, pregnancy, alcoholism
Factors decreasing the value: advancing age, other anaesthetics (e.g. nitrous oxide reduces MAC of fluranes) and sedatives
How do the majority of anaesthetic agents work?
Potentiate GABAa (inhibitory) medicated CL- conductance to depress CNS activity
NMDA glutamate (excitation) receptors probable other site for Xe, N20 and ketamine. These resuce the calcium currents through NMDA.
What are the main IV anaesthetics?
Propofol and barbituates - rapid
Ketamine - slower
When can local/regional anaesthesia be used?
Dentistry, obstetrics, regional surgery, Post op for pain, chronic pain management
What are the commonest local anaesthetics and their properties?
Lidocaine, procaine, bupivacaine. Sodium channel blockers.
Lipid solubility, low pKa for faster onset,
What are the main general anaesthetic side effects?
PONV, hypotension, cognitive dysfunction, chest infection, malignant hyperthermia, respiratory depression
What property of anaesthetic agents predicts potency?
Lipid solubility (ability to dissolve and enter cell membranes)
What is the blood:gas coefficient?
The volume of gas in litres that can dissolve in one litre of blood. It describes the degree of absorption across the alveoli
What does a specific tissue:blood (e.g. brain, fat) partition coefficient determine?
The relative uptake from blood to a specific tissue type
E.g. if brain:blood is 1.6, for equivalent volumes of brain and blood the brain will take up 1.6 times more blood
What is the duration of recovery related to?
The length of the procedure
The degree of loading of the muscle and fat compartments with anaesthetic agents (moves back into venous supply gradually)
What are the benefits of IV anaesthetics against inhilation agents?
Reaches sufficient anaesthetic depth much faster and bypasses the confusion of stage 2 excitment/aggression