Pharmacological Flashcards
What type of medication is a thiopentone?
Barbiturate
What are the main issues in the with using thiopentone for RSI? (3)
- Increased laryngospasm
- Low BP (vasodilation and myocardial depression)
- Anaphx
What is the main pro for using thiopentone?
Decreased cerebral metabolic rate and significant anti seizure properties
What is the main benefit of etomidate?
CV stable
What are the cons of using etomidate? (3)
- Adrenal suppression
- Myoclonus
- Pain on injection
What are the main side effects of suxamethonium?
- Raised K+ intravascular by approx 1mmol/L
- Bradycardia - particularly if repeated doses
- Raised ICP and intra-ocular pressure
- Malignant hyperthermia
What are the c/i (5) and relative c/i (2) of suxamethonium?
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.
Why is suxamethonium calculated using TBW?
Due to increased
plasma cholinesterase activity
How are doses for non-depolarising paralytics calculated and why?
Hydrophilic drugs such as neuromuscular blocking drugs are distributed primarily in the central compartment and lean body weight is a suitable dosing scalar.
Broadly speaking which drugs are calculated using TBW and which IBW (or LBW)?
TBW - lipophilic
IBW - hydrophilic
Why does suxamethonium lead to a decreased safe apnoea time?
As a depolarising muscle relaxant will cause significant muscle contraction and therefore increased basal metabolic oxygen consumption and reduce time to hypoxia
What temperature should suxamethonium be stored and once out of the fridge how long can it be used for?
- 4 degrees C
- 4 weeks
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?
- 2-8 degrees C
- 2months
- Protect from light
How long after being removed from the fridge can rocuronium be used?
3 months
Following removal from the fridge, how quickly should the following be used?
1. Suxemathonium
2. Syntometrine
3. Rocuronium
- 1 month
- 2 months
- 3 months
What is the action of glucagon?
Mobilises glycogen and stimulates hepatic gluconeogenesis
What are the licenses uses of glucagon?
- Diabetic hypoglycaemia
- Endogenous hyperinsulinism
Not B-Block OD but still advised by toxbase and used regularly
When is glucagon c/i?
Pheochromocytoma (due to persistent sympathetic hyperstimulation meaning would lead to rebound hypogylcaemia)
Re: glucagon - what is the dose:
1. Hypoglycaemia
2. Beta blocker OD
3. 1unit
- 1 unit
- 10mg
- 1 unit = Img
Can be given IM/IV
What to drugs sometimes used in RSI are chemically incompatible and why?
Thiopentone and rocuronium
Acidic + basic drugs = crystallisation
Thiopentone = basic
Roc = acidic
What is the difference between nitrous oxide and Entonox?
Nitrous oxide is liquid and Entonox is mixed with oxygen 50:50 and is gaseous.
How does nitrous oxide provide analgesic affect? (2)
- Opiate agonist
- NMDA inhibitor
How much more soluble is nitrous oxide than nitrogen in blood?
x 35 more
What is the critical temperature of nitrous oxide
36.5 degrees C
How is are the following stored?
1. Nitrous oxide
2. Entonox
- French blue cylinders as a liquid
- French blue body with white striped shoulders, at a pressure of 137 bar, horizontally and >5 degrees C
Why is Entonox stored hoirzontally?
To avoid the risk of delivering a hypoxic mixture
How long after diving can entonox be used?
> 48 hours
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
What are the c/i to Entonox? (5)
- Diving < 48 hours
- Bowel obstruction
- PTX
- Recent eye surgery (particularly with injected intra-ocular gas)
- Base of skull fractures - risk of pneumocephalus
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
Rank the agonistic affect of the following on alpha-1 receptors - noradrenaline, adrenaline, isoprenaline
- Noradrenaline
- Adrenaline
- Isoprenaline (much less)
Give 4 examples of an alpha-1 agonist?
- Noradrenaline
- Phenylephrine
- Metaraminol
- Midodrine
Give 2 examples of an alpha-1 antagonist?
Doxazosin
Tamsulosin
What is the action of:
1. Beta-1
2. Beta-2
- Chronotropic/ionotropic, dromotropic (increased conduction velocity) and lusitropic affect (increased calcium sequestration)
- Smooth muscle relaxation (bronchi), vasodilation (although usually overwhelmed by alpha affects) and GI tract. Increase uptake of potassium into cells
In what order to the following affect B-receptors - noradrenaline/adrenaline/isoprenaline
- Isoprenaline
- Adrenaline
- Noradrenaline
What are examples of beta-1 agaonists?
- Dobutamine
- Noradrenaline
- Isprenaline
Which beta blocker has both beta-1 and beta-2 agonist affects?
Propanolol
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
What is the mechanism of action of ondansetron?
5-HT3 receptor antagonist
When is ondansetron c/i ? (2)
- Prolonged QTc
- Hepatic impairment - either reduced dose of avoided
What is the mechanism of action of Penthrox?
Poorly understand but thought to be GABA and glycine receptor modulation
How is Penthrox metabolised?
Liver
What is the dose penthrox?
1. 1 dose
2. Max/day
3. Max/week
- 3ml
- 6ml
- 15ml
Can Penthrox be used in pregnancy/breast feeding?
Yes
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.
What endpoint can be used to determine suitable depth of anaesthesia for Thiopentone?
Loss of eyelash reflex
What type of muscle relaxant is rocuronium?
Aminosteroid non-depolarising
What are 2 issues with using atracurium pre-hospital?
3 mins onset of action
significant histamine release which can cause hypotension and bronchospasm
How is rocuronium excreted?
Predominantly unchanged in bile, 10% renal
What is the rate of anaphx with rocuronium?
6 per 100,000
What is the half life of salbutamol and how is it excreted?
3-6 hours and hepatically
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
What type of drug is suggamedex?
Modified gamma cyclodextrin
How is suggamedex excreted?
Renal
How does suggamedex work?
Encapsulates muscle relaxant molecule, forming strong water-soluble complexes.
What is the dose of suggamadex:
1. Routine dose given
2. RSI dose given
- 2-4mg/kg
- 16mg/kg
How long after suggamadex should aminosteroidal paralysing agents be avoided?
24 hours
What are the side effects of suggamadex? (3)
- Theoretical interaction with OCP (give missed pill advice)
- Bronchospams
- Bradycardia
What are 2 specific contraindications to diamorphine?
- Delayed gastric emptying
- Pheochromocytoma - inhibits autonomic nervous system and coudl cause hypertensive crisis
What are the weight restrictions for IN diamporphine?
10kg
What is the mechanism of action of ketamine?
- Non-competitive NMDA receptor antagonist
- Weak affects as an agonist of: MOP, KOP and DOP recepetors
- Weak affect as serotonin, dopamine and noradrenaline reuptake inhibitor
What are the optical isomers of ketamine?
S-ketamine
R - ketamine
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
What is the half life of ketamine?
2.5 hours
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
What affect do benzos have on ketamine?
Help with emergence but increase half life ketamine (unless chronic benzo misuse and will decrease half-life)
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
- Competitive antagonist of GABA
- 100mcg bolus to 1mg max adults/ 0.01mcg/kg paeds
- 1 min
- 15-60mins
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
What is the onset time and duration of action of hypertonic saline?
10 mins onset time and lasts approx 1 hour
What are the advatanges of hypertonic over mannitol?1
Mannitol crysalises at temps <25 degrees and doesn’t cause osmotic diuresis
What are the side effects of hypertonic saline? (4)
- Hypernatreamia (should not be given to someone with Na+ > 155
- Hypokalaemia
- Hyperchloraemic metabolic acidosis
- Rebound IC hypertension
How does suxamethonium increase K+?
Triggers release from extajunctional acetylcholine receptors
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
How does etomidate act?
GABA receport agonist
Which are the advatages (1)
and disadvantages of using etomidate? (2)
- CV very stable
- Causes epileptiform activity on EEG/triggers seizures
- Inhibits steroid production
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.
How are morphine and fentanyl metabolised?
Liver
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.
What is the mechanism of action of benzos?
GABA agonists
How is midazolam metabolised?
Metabolised in liver to active metabolites and excreted renally
What affect does midazolam have on CV system?
Increases HR but reduces SVR - overall maintains CO
What are the affects of midazolam on the respiratory system, when combined with opiates?
Repression and blunts the response to C02
What is the mechanism of action of propofol?
GABA agonist and cannabinoid action +/- antidopaminergic action
Why does propofol have anti-emetic properties?
Thought to be due to antidopaminergic properties
How is propofol metablised
Hepatically to inactive metabolites and excreted renally
Which RSI drugs are c/i (3) in acute intermittent porphyria and which can be used (2)?
- Etomidate
- Ketamine
- Thiopentone
- Midazolam
- Propofol
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
How is TXA metablised/excreted?
Excreted renally largely unchanged with minimum metabolism
What are the contraindications (1) and relative c/i (2) of TXA?
- 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)
What is the mechanism of action of aspirin? (3)
- Irreversible COX-1 and COX-2 inhibitor - more potent against COX-1.
- Reduces prostaglandin production, reducing pain and inflammation and 3. reducing conversion arachidonic acid to thomboxane A2 reducing platelet aggregation
What type of LA is:
1. Lidocaine/bupivicaine
2. Cocaine
- Amides
- Ester
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
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.
What are the side effects of GTN? (3)
- Increase IC pressure due to vasodilation
- Tachyphylaxis in prolonged use
- Hypotension
What is the half life of GTN?
1. IV
2. SL
- 3 mins
- 6 mins
What is the half life of amioderone?
55 days
How is amioderone eliminated?
Primarily hepatically and via bile, 10% renal
How does adrenaline extrt its affect?
Alpha and beta via G-protein coupled receptors
What is the precursor of adrenaline?
Noradrenaline
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
What affects does rocuronium have given at high doses or infusion on CV system?
Vagolytic (mild) - leads to modest increase in HR
If using suxemathonium in paeds, what must be considered?
Need higher intubating doses
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
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
How is a drug/device shown to be new by the MHRA?
Black triangle symbol
What information is required to report a medication/device using the yellow card scheme? (4)
- Side effects
- Age/sex/initials of patient
- Name of meds/device
- Reports full name and address
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
What is the Defective Medicine Report Centre?
Part of MHRA - minimises harm to patient once defective medicine has been distributed
What are the 4 class of recalls and timeframes used by the Defective Medicine Report Centre?
- Immediate Action required - included OOH, National Patient Safety Alert issued
- Action required within 48 hours - pharmacy and wholesale level recall
- Action required within 5 days - pharmacy and wholesale level recall
- Information only - caution in use, defect information distributed to wholesalers and pharmacies.H
