Pharmacology + Blood Flashcards
1
Q
What type of medication is a thiopentone?
A
Barbiturate
2
Q
What are the main issues in the with using thiopentone for RSI? (3)
A
- Increased laryngospasm
- Low BP (vasodilation and myocardial depression)
- Anaphx
3
Q
What is the main pro for using thiopentone?
A
Decreased cerebral metabolic rate and significant anti seizure properties
4
Q
What is the main benefit of etomidate?
A
CV stable
5
Q
What are the cons of using etomidate? (3)
A
- Adrenal suppression
- Myoclonus
- Pain on injection
6
Q
What are the main side effects of suxamethonium?
A
- Raised K+ intravascular by approx 1mmol/L
- Bradycardia - particularly if repeated doses
- Raised ICP and intra-ocular pressure
- Malignant hyperthermia
7
Q
What are the c/i (5) and relative c/i (2) of suxamethonium?
A
C/i:
1. Recent burns
2. Spinal cord trauma causing paraplegia (can be given immediately after the injury, but should be avoided
from approximately day 10 to day 100 after the injury),
3. Hyperkalaemia
4. Severe muscle trauma, or 5. Hx of malignant hyperpyrexia
Relative c/i
1. Atypical plasma cholinesterase (metabolised by cholinesterase)
2. Muscle diseases.
There may be prolonged paralysis
or dangerous rises in potassium levels.
8
Q
Why is suxamethonium calculated using TBW?
A
Due to increased
plasma cholinesterase activity
9
Q
How are doses for non-depolarising paralytics calculated and why?
A
Hydrophilic drugs such as neuromuscular blocking drugs are distributed primarily in the central compartment and lean body weight is a suitable dosing scalar.
10
Q
Broadly speaking which drugs are calculated using TBW and which IBW (or LBW)?
A
TBW - lipophilic
IBW - hydrophilic
11
Q
Why does suxamethonium lead to a decreased safe apnoea time?
A
As a depolarising muscle relaxant will cause significant muscle contraction and therefore increased basal metabolic oxygen consumption and reduce time to hypoxia
12
Q
What temperature should suxamethonium be stored and once out of the fridge how long can it be used for?
A
- 4 degrees C
- 4 weeks
13
Q
Re: syntometrine
1. What temp should it be stored at
2. How quickly should it be used after removing it from the fridge?
3. What should also be done with regards to storing it?
A
- 2-8 degrees C
- 2months
- Protect from light
14
Q
How long after being removed from the fridge can rocuronium be used?
A
3 months
15
Q
Following removal from the fridge, how quickly should the following be used?
1. Suxemathonium
2. Syntometrine
3. Rocuronium
A
- 1 month
- 2 months
- 3 months
16
Q
What is the action of glucagon?
A
Mobilises glycogen and stimulates hepatic gluconeogenesis
17
Q
What are the licenses uses of glucagon?
A
- Diabetic hypoglycaemia
- Endogenous hyperinsulinism
Not B-Block OD but still advised by toxbase and used regularly
18
Q
When is glucagon c/i?
A
Pheochromocytoma (due to persistent sympathetic hyperstimulation meaning would lead to rebound hypogylcaemia)
19
Q
Re: glucagon - what is the dose:
1. Hypoglycaemia
2. Beta blocker OD
3. 1unit
A
- 1 unit
- 10mg
- 1 unit = Img
Can be given IM/IV
20
Q
What to drugs sometimes used in RSI are chemically incompatible and why?
A
Thiopentone and rocuronium
Acidic + basic drugs = crystallisation
Thiopentone = basic
Roc = acidic
21
Q
What is the difference between nitrous oxide and Entonox?
A
Nitrous oxide is liquid and Entonox is mixed with oxygen 50:50 and is gaseous.
22
Q
How does nitrous oxide provide analgesic affect? (2)
A
- Opiate agonist
- NMDA inhibitor
23
Q
How much more soluble is nitrous oxide than nitrogen in blood?
A
x 35 more
24
Q
What is the critical temperature of nitrous oxide
A
36.5 degrees C
25
How is are the following stored?
1. Nitrous oxide
2. Entonox
1. French blue cylinders as a liquid
2. French blue body with white striped shoulders, at a pressure of 137 bar, horizontally and >5 degrees C
26
Why is Entonox stored hoirzontally?
To avoid the risk of delivering a hypoxic mixture
27
How long after diving can entonox be used?
> 48 hours
28
What is the pseudocritical temperature of Entonox?
- 7 degrees C
This is the temperature above which the mixture of gases cannot be liquified by pressure alone
29
What are the c/i to Entonox? (5)
1. Diving < 48 hours
2. Bowel obstruction
3. PTX
4. Recent eye surgery (particularly with injected intra-ocular gas)
5. Base of skull fractures - risk of pneumocephalus
30
Generally what do alpha receptors do and more specificically:
- alpha -1
- alpha - 2
Vasoconstriction and decreased flow and gastric smooth muscle
Alpha-1 = vasoconstriction and smooth muscle contraction of urinary system/GI/brain/hair
Alpha -2 = decrease insulin, increase glucagon, decreased SVR
31
Rank the agonistic affect of the following on alpha-1 receptors - noradrenaline, adrenaline, isoprenaline
1. Noradrenaline
2. Adrenaline
3. Isoprenaline (much less)
32
Give 4 examples of an alpha-1 agonist?
1. Noradrenaline
2. Phenylephrine
3. Metaraminol
4. Midodrine
33
Give 2 examples of an alpha-1 antagonist?
Doxazosin
Tamsulosin
34
What is the action of:
1. Beta-1
2. Beta-2
1. Chronotropic/ionotropic, dromotropic (increased conduction velocity) and lusitropic affect (increased calcium sequestration)
2. Smooth muscle relaxation (bronchi), vasodilation (although usually overwhelmed by alpha affects) and GI tract. Increase uptake of potassium into cells
35
In what order to the following affect B-receptors - noradrenaline/adrenaline/isoprenaline
1. Isoprenaline
2. Adrenaline
3. Noradrenaline
36
What are examples of beta-1 agaonists?
1. Dobutamine
2. Noradrenaline
3. Isprenaline
37
Which beta blocker has both beta-1 and beta-2 agonist affects?
Propanolol
38
What is the mechanism of action for labetalol and what is the difference when given orally vs IV?
Non selective beta-blocker but also has selective alpha-1 inhibitory affect
PO - 3 x more action on beta receptors
IV - 7 x more action on beta receptors
39
What is the mechanism of action of ondansetron?
5-HT3 receptor antagonist
40
When is ondansetron c/i ? (2)
1. Prolonged QTc
2. Hepatic impairment - either reduced dose of avoided
41
What is the mechanism of action of Penthrox?
Poorly understand but thought to be GABA and glycine receptor modulation
42
How is Penthrox metabolised?
Liver
43
What is the dose penthrox?
1. 1 dose
2. Max/day
3. Max/week
1. 3ml
2. 6ml
3. 15ml
44
Can Penthrox be used in pregnancy/breast feeding?
Yes
45
What are the c/i for Penthrox?
The ‘CHECK ALLL’ checklist should be used to screen for contraindications
C-ardiovascular instability
H-ypersensitivity to Penthrox or any fluorinated anaesthetic
E-stablished or genetically susceptible to malignant hyperthermia.
C-onsciousness reduced due to any cause including head injury, alcohol or drugs
K-idney impairment* (clinically significant, eGFR<30) or nephrotoxic drugs (tetracycline, gentamicin, colistin, amphotericin, polymyxin B)
-----------------------------------------------------------------
- Age < 18 years
- Lung/respiratory impairment* (anything which causes respiratory compromise or respiratory depression. A managed diagnosis is not a contra-indication)
- Liver impairment* (deranged LFTs or synthetic function) or CYP450 inducers (carbamazepine, isoniazid, phenobarbital, phenytoin, primidone, rifampicin)
- Last administration of Penthrox (maximum dose 6 ml (2 bottles)/24 hrs or 15 ml/7 days). Should not receive doses on consecutive days.
46
What endpoint can be used to determine suitable depth of anaesthesia for Thiopentone?
Loss of eyelash reflex
47
What type of muscle relaxant is rocuronium?
Aminosteroid non-depolarising
48
What are 2 issues with using atracurium pre-hospital?
3 mins onset of action
significant histamine release which can cause hypotension and bronchospasm
49
How is rocuronium excreted?
Predominantly unchanged in bile, 10% renal
50
What is the rate of anaphx with rocuronium?
6 per 100,000
51
What is the half life of salbutamol and how is it excreted?
3-6 hours and hepatically
52
What is the mechanism of action of salbutamol?
Beta-adrenoreceptor agonist with higher affinity for beta-2 than beta-1
- activates adenyl cyclase, leading to a decrease in intracellular calcium and increase in cAMP activity
53
What type of drug is suggamedex?
Modified gamma cyclodextrin
54
How is suggamedex excreted?
Renal
55
How does suggamedex work?
Encapsulates muscle relaxant molecule, forming strong water-soluble complexes.
56
What is the dose of suggamadex:
1. Routine dose given
2. RSI dose given
1. 2-4mg/kg
2. 16mg/kg
57
How long after suggamadex should aminosteroidal paralysing agents (-roniums) be avoided?
24 hours
58
What are the side effects of suggamadex? (3)
1. Theoretical interaction with OCP (give missed pill advice)
2. Bronchospams
3. Bradycardia
59
What are 2 specific contraindications to diamorphine?
1. Delayed gastric emptying
2. Pheochromocytoma - inhibits autonomic nervous system and coudl cause hypertensive crisis
60
What are the weight restrictions for IN diamporphine?
10kg
61
What is the mechanism of action of ketamine?
1. Non-competitive NMDA receptor antagonist
2. Weak affects as an agonist of: MOP, KOP and DOP recepetors
3. Weak affect as serotonin, dopamine and noradrenaline reuptake inhibitor
62
What are the optical isomers of ketamine?
S-ketamine
R - ketamine
63
What is the difference between the following preparations of ketamine
1. Racemic preparation (both)
2. S-ketamine
3. R-ketamine
S-ketamine twice as potent as the racemic preparation
S-ketamine inhibits dopamine x 8 and NMDA x 4 than R-ketamine
S-ketamine has less hallucinogenic and psychogenic affects
64
What is the half life of ketamine?
2.5 hours
65
How is ketamine metabolised?
In liver by cytochrome P450 to norketamine (30% less potent) and then metablised into an inactive substance and excreted into urine
66
What affect do benzos have on ketamine?
Help with emergence but increase half life ketamine (unless chronic benzo misuse and will decrease half-life)
67
Re: flumezanil what is?
1. Mechanism of action
2. Dose (paeds and adults)
3. Onset of action
4. Duration of action
5. Main side effect
1. Competitive antagonist of GABA
2. 100mcg bolus to 1mg max adults/ 0.01mcg/kg paeds
3. 1 min
4. 15-60mins
68
Aside from shifting fluid into intravascular space, what other systemic affect does the increased serum osmolality causes by hypertonic saline have?
Releases endogenous vasopressin, causing vasoconstriction and renal fluid retention
69
What is the onset time and duration of action of hypertonic saline?
10 mins onset time and lasts approx 1 hour
70
What are the advatanges of hypertonic over mannitol?1
Mannitol crysalises at temps <25 degrees and doesn't cause osmotic diuresis
71
What are the side effects of hypertonic saline? (4)
1. Hypernatreamia (should not be given to someone with Na+ > 155
2. Hypokalaemia
3. Hyperchloraemic metabolic acidosis
4. Rebound IC hypertension
72
How does suxamethonium increase K+?
Triggers release from extajunctional acetylcholine receptors
73
In severe burns, when can suxamethonium be used and when should it be avoided?
Can be used in first 24 hours but then should be avoided for up to a year
74
How does etomidate act?
GABA receport agonist
75
Which are the advatages (1)
and disadvantages of using etomidate? (2)
1. CV very stable
2. Causes epileptiform activity on EEG/triggers seizures
3. Inhibits steroid production
76
Explain the reasons fentanyl has a quicker onset time but shorter duration of action compared to morphine
Higher lipid solubility so quicker onset of action but is rapidly redistributed resulting in a shorter duration of action.
77
How are morphine and fentanyl metabolised?
Liver
78
What is the difference in haemodynamics between morphine and fentanyl?
Morphine leads to a histamine release and vasodilation, whereas fentanyl does not
Fentanyl can inhibit sympathetic nervous system and lead to bradycardia, morphine does not.
79
What is the mechanism of action of benzos?
GABA agonists
80
How is midazolam metabolised?
Metabolised in liver to active metabolites and excreted renally
81
What affect does midazolam have on CV system?
Increases HR but reduces SVR - overall maintains CO
82
What are the affects of midazolam on the respiratory system, when combined with opiates?
Repression and blunts the response to C02
83
What is the mechanism of action of propofol?
GABA agonist and cannabinoid action +/- antidopaminergic action
84
Why does propofol have anti-emetic properties?
Thought to be due to antidopaminergic properties
85
How is propofol metablised
Hepatically to inactive metabolites and excreted renally
86
Which RSI drugs are c/i (3) in acute intermittent porphyria and which can be used (2)?
1. Etomidate
2. Ketamine
3. Thiopentone
1. Midazolam
2. Propofol
87
How does TXA act?
Reversibly binds to lysine binding site on plasminogen and competitively inhibits plasminogen activation.
This prevents conversion of plasminogen to plasmin which is responsible for fibrin clot breakdown
88
How is TXA metablised/excreted?
Excreted renally largely unchanged with minimum metabolism
89
What are the contraindications (1) and relative c/i (2) of TXA?
1. Fibrinolytic conditions following DIC
Relative:
1. Current VTE
2. Seizures (increased seizure activity at higher doses so c/i for elective operations but not haemorrhage)
90
What is the mechanism of action of aspirin? (3)
1. Irreversible COX-1 and COX-2 inhibitor - more potent against COX-1.
2. Reduces prostaglandin production, reducing pain and inflammation and 3. reducing conversion arachidonic acid to thomboxane A2 reducing platelet aggregation
91
What type of LA is:
1. Lidocaine/bupivicaine
2. Cocaine
1. Amides
2. Ester
92
What is the mechanism of action of GTN?
Converted to nitric oxide in vascular smooth muscle.
This increases cyclic guanosine-3,5-monophosphate and smooth muscle relaxation by potassium channel activation and hyperpolarisation of the muscle cell membrane
93
What is the affect of GTN on the CV system?
Produces both venous and arterial dilatation reducing both preload and afterload and therefore myocardial work.
Improves coronary artery blood flow dilating the coronary arteries.
94
What are the side effects of GTN? (3)
1. Increase IC pressure due to vasodilation
2. Tachyphylaxis in prolonged use
3. Hypotension
95
What is the half life of GTN?
1. IV
2. SL
1. 3 mins
2. 6 mins
96
What is the half life of amioderone?
55 days
97
How is amioderone eliminated?
Primarily hepatically and via bile, 10% renal
98
How does adrenaline extrt its affect?
Alpha and beta via G-protein coupled receptors
99
What is the precursor of adrenaline?
Noradrenaline
100
What affect do non-depolarising neuromuscular blocking drugs have on infants + children compared to adults?
Higher CO leads to faster circulation times and quicker onset
101
What affects does rocuronium have given at high doses or infusion on CV system?
Vagolytic (mild) - leads to modest increase in HR
102
If using suxemathonium in paeds, what must be considered?
Need higher intubating doses
103
What products are the MHRA responsible for?
Statutory responsibility for safety of:
1. Medicines (inc. herbal)
2. Medical devices (inc second hand)
3. Blood and blood products
104
What does the MHRA do? (4)
Regulation: The MHRA regulates medicines, medical devices, and blood products to ensure they meet required standards of safety, quality, and efficacy before they can be marketed.
Licensing: Reviews and grants licenses for new medicines and medical devices
Surveillance: The MHRA monitors the safety of medicines and medical devices on the market, collecting data on adverse effects and taking action when necessary (can force withdrawal of products)
Research and Development: Gives permission for clinical trials relating to safety of new meds
105
How is a drug/device shown to be new by the MHRA?
Black triangle symbol
106
What information is required to report a medication/device using the yellow card scheme? (4)
1. Side effects
2. Age/sex/initials of patient
3. Name of meds/device
4. Reports full name and address
107
What are SABRE and SHOT and what is the difference between them?
Serious Adverse Blood Reactions Events:
MHRA system for mandatory reporting of adverse blood events
Serious Hazards of Transfusion:
Not mandatory and run by NHS Blood and Transplant Service
108
What is the Defective Medicine Report Centre?
Part of MHRA - minimises harm to patient once defective medicine has been distributed
109
What are the 4 class of recalls and timeframes used by the Defective Medicine Report Centre?
1. Immediate Action required - included OOH, National Patient Safety Alert issued
2. Action required within 48 hours - pharmacy and wholesale level recall
3. Action required within 5 days - pharmacy and wholesale level recall
4. Information only - caution in use, defect information distributed to wholesalers and pharmacies.H
110
What are the differences between hydrophobic/hydrophillic medications in terms of:
1. Solubility
2. Polarity
3. Excretion
4. Absorption/distribution
5. Onset of action
6. Accumulation
1. Hydrophilic water soluble, phobic lipid soluble
-
2. Hydrophilic polar, phobic non-polar
-
3. Philic directly excreted kidney, phobic need biotranformation liver to bile first
-
4. Philic less readily absorbed through membranes as water soluble, phobic readily absorbed inc. BBB. Philic distribution widespread, whereas phobic more concentrated in tissues with high concentration of lipid
5. Philic quicker onset of action
6. Philic more likely to accumulate
111
What is the onset time of suggamedex?
<1 min
112
What is the difference in mechanism of action for reversal rocuronium etc between suggamedex and neostigmine?
Neostigmine: anticholinesterase therefore leads to increased acetylcholine at receptor and increased muscle contraction
Suggamedex: encapsulates molecule and stops any interaction at acetylchloline receptor - leads to more complete reversal
113
What are the benefits/drawbacks of neostigmine vs suggamedex
Neostigmine:
1. Cheaper, well known
2. Slower action, can lead to incomplete reversal
114
What does the British Haematology Society (BHS) state as minimum observation needed for transfusion? (4)
1. Observations (pulse, blood pressure, temperature and respiratory rate) <60 mins pre-transfusion.
2. Obs 15 minutes after the start of each unit.
3. Post-transfusion obs < 60 mins post infusion ending
4. Regular visual monitoring
115
What does BHS define as mild and moderate febrile transfusion reactions?
1. Mild – temperature ≥38°C or 1-2°C above pre-transfusion baseline
2. Moderate – temperature ≥39°C or ≥2°C above pre-transfusion baseline
116
How does BHS recommend managing mild febrile transfusion reactions?
Paracetamol + continue with close observation
117
How should suspected bacterial decontamination of blood products being managed? (4)
1. Stop transfusion
2. Broad spectrum abx
3. Return blood to lab
4. Report to National Blood Transfusion Service to make sure that other components recalled
118
How should non life threatening allergic reactions to blood products be managed?
1. Anti-histamine
2. Slow down infusion
119
What are the signs/symptoms of acute haemolytic reactions?
Occurs during/immediately after transfusion:
1. pyrexia
2. rigors
3. flank or back pain
4. ’impending sense of doom’.
5. Severe = renal failure, hypotension and DIC.
120
When does TRALI occur?
< 6 hours of transfusion
121
What is TRALI?
Transfusion related acute lung injury
Non-cardiogenic pulmonary oedema - inflammatory immune response
122
What is the treatment of TRALI?
Supportive
123
What is TACO and when does is occur?
Tranfusion Associated Circulatory Overload
< 12 hours of transfusion
124
What are the issues with rhesus status and pregnancy?
Issue with rhesus negative women:
- baby rhesus +ve and sensitisation event (mixture blood) then mother may create anti-bodies to babies RBC
- usually child birth the sensitising event (but can be trauma).
- If first pregnancy may not be an issue, but if second baby rhesus -ve antibodies can then cross the placenta and lead to haemolytic disease.
- trauma can be sensitising event and therefore need anti-rhesus D to avoid this in same pregnancy.
125
What which blood types can be used emperically in trauma in men + women?
1. Men O- and O+
2. Women O- (if child bearing age)
+ve = rhesus +ve
therefore could lead to antibodies being formed and crossing placenta
126
What considerations should be made with regards to drug choice in RSI in a patient with cerebral palsy?
1. Propofol is recommend to reduce upper airway reactivity.
2. Rocuronium over suxamethonium
127
What receptors does ergometrine act on?
Ergot alkaloid that is a partial agonist (stimulates) Alpha-1A Adrenergic-R, Dopamine (D2)-Receptors and 5HT-1 (serotonin) receptors
128
What analgesia should be offered to patients with sickle cell disease in crisis in:
1. Moderate pain
2. Severe pain
1. Weak opioid if no analgesia previously, strong opioid if take some analgesia
2. Strong opioid
129
With regards to polypharmacy?
1. What is the definition?
2. What % of admissions related to it?
3. What is the average number of medications elderly patients take?
1. 5 or more medications
2. 25%
3. 4-6
130
What does the BNF say with regards to NSAIDS in the elderly?
Can be given if needed but should try paracetamol/exercise etc. first for pain
131
What is the generic advice in the BNF with regards to prescribing in the eldery?
Start at 50% adult dose and titrate up
132
What is the most important age related factor in response to medications?
Reduced renal clearance
133
What is the consequence of reduced liver clearance in the elderly in terms of pharmacology?
Lipid soluble (hydrophobic) medication is excreted slowly
134
With respects to PRC what:
1. Temp should they be stored at?
2. Time can they be out of the fridge and still administered
3. Is the shelf life?
1. 2-6 degrees C
2. Transfusion completed 4 hours, cannot go back into fridge once out over 30mins
3. 35 days
135
With respects to FFP:
1. what temp should it be stored in?
2. what is the shelf life?
-after thawing, how quickly must it be administered if kept at:
3- 22 degrees
4. 2-6 degrees
1. < -25 degrees
2. 36 months
3. 4 hours
4. Extends time to administer by 24 hour
136
What is TACO defined as?
Transfuion Associated Circulatory Overload
Acute or worsening pulmonary oedema within 6-12 hurs
137
How long after transfusion should a TRALI occur?
2-6 hours
138
What is a TRALI?
Transfusion Related Acute Lung Injury
- antibodies in donor blood reacting to patients pulmonary endothelium
- inflam response and non-cardiogenic pulmonary oedema
139
How much blood is needed to cause and ABO incompatibility reaction?
As little as 30ml
140
What is LyoPlas?
Freeze dried plasma
Donated lyophilised plasma (lyophilisation is process by which water removed)
141
With respects to LyoPlas?
1. What is the shelf life?
2. What temp should it be stored?
3. Once reconsitituted how quickly should it be administered?
1. 15 months
2. 2-25 degrees
3. < 6 hours
142
What is in PCC?
Isolated vit K dependent factors: II, VII, IX and X + protein C and S
143
What is the dose of PCC?
25-50 units/kg
