1
Q
What feature of fentanyl makes it unsuitable as a total intravenous anaesthetic?
A
Highly lipid soluble (600 times more than morphine), leading to accumulation in tissues.
This results in a high context-sensitive half-time, making timely wake-up impractical.
2
Q
What are the benefits of cisatracurium over atracurium?
A
- More potent
- Less histamine release
- Similar duration of action
ONLY degraded by Hofmann degradation.
3
Q
State the pKa, relative lipid solubility, relative potency, and volume of distribution of pethidine.
A
- pKa: 8.7
- Relative lipid solubility: 30x morphine
- Relative potency: 0.1x morphine
- Volume of distribution: 4 L/kg
- Protein binding: 60%
4
Q
Which muscle relaxants can be reversed by sugammadex?
A
Aminosteroids: rocuronium, vecuronium
5
Q
How does the train-of-four output relate to receptor occupancy by muscle relaxants?
A
- All twitches present: < 70% occupancy
- 1 twitch lost: 70%
- 2 twitches lost: 80%
- 3 twitches lost: 90%
- All twitches lost: 95-100%
6
Q
Describe the inheritance pattern of suxamethonium apnoea.
A
Autosomal recessive mutation on chromosome 3.
7
Q
What mechanism causes opioid tolerance?
A
Uncoupling of opioid receptors from G-proteins leads to decreased receptor sensitivity.
8
Q
What is the intramuscular dose of suxamethonium for laryngospasm?
A
4 mg/kg
9
Q
Which opioids are associated with reducing seizure threshold?
A
- Pethidine
- Tramadol
10
Q
How is atracurium metabolised?
A
- 60% ester hydrolysis by non-specific esterases
- 40% Hofmann degradation (slows in acidosis and cold)
11
Q
What is the dose of atracurium?
A
0.5 mg/kg
12
Q
What dose of sugammadex should be used based on the depth of blockade?
A
- Immediate reversal after RSI: 16 mg/kg
- Deep block (1-2 twitches on post-tetanic count): 4 mg/kg
- Moderate block (2 twitches on ToF): 2 mg/kg
No dose alteration in renal impairment.
13
Q
What is the pKa of alfentanil?
A
6.5
14
Q
What is the potency of alfentanil relative to morphine?
A
10
15
Q
What is the lipid solubility of alfentanil relative to morphine?
A
90
16
Q
What is the context-sensitive half-time of alfentanil?
A
< 1 hour after a long infusion
17
Q
What is the pKa of fentanyl?
A
8.4
18
Q
What is the potency of fentanyl relative to morphine?
A
100
19
Q
What is the lipid solubility of fentanyl relative to morphine?
A
600
20
Q
Describe the acid-base status of opiates.
A
Weak bases
21
Q
What is the dose of vecuronium used for intubation?
A
0.1 mg/kg
This is the most potent neuromuscular blocker.
22
Q
Outline the classification of NSAIDs by chemical structure.
A
- Propionic acids: ibuprofen
- Acetic acid derivatives: diclofenac, ketorolac
- Arylacetic acids: indomethacin
- Enolic acids: piroxicam
- Acetylsalicylic acid: aspirin.
23
Q
What is the volume of distribution of fentanyl?
A
4 L/kg
24
Q
What is the protein-binding of fentanyl?
A
0.8
25
What **dose of paracetamol** is associated with **hepatotoxicity**?
150 mg/kg within 24 hours
26
What is the **RSI dose** of **suxamethonium**?
1-2 mg/kg of **total body weight**.
## Footnote
Total body weight is used due to increased extracellular fluid and plasma cholinesterase.
27
Which common **analgesic** should be avoided in patients who are **breastfeeding**?
Codeine
28
Which muscle relaxants **release histamine** in a dose-related manner?
Atracurium and Mivacurium
29
What is the ED95 and intubating dose of **rocuronium**?
**ED95**: 0.3 mg/kg
**Intubating**: 0.6-1.2 mg/kg
30
What is the time to 95% depression of the first twitch on ToF for **rocuronium**?
75 seconds.
## Footnote
Time to 25% recovery of the first twitch is 33 min.
31
What is the **pKa** of morphine?
8
32
By what mechanism do **NSAIDs** cause renal impairment?
NSAIDs reduce synthesis of **PGE₂** and **PGI₂**, leading to decreased renal perfusion.
33
Describe the metabolism of **diamorphine**.
**Diamorphine** → 6-monoacetylmorphine (by plasma esterases)
→ **Morphine**
→ **Morphine-3-Glucuronide** + **Morphine-6-Glucuronide**
## Footnote
**Diamorphine** is diacetylmorphine, highly lipid-soluble, allowing rapid penetration of the BBB before conversion to **morphine** and active metabolites, explaining its potency.
34
What is the **Bowman principle**?
Describes the relationship between **potency** of a NMB and its **speed of onset**. Less potent drugs require higher doses, creating a greater concentration gradient for faster diffusion into the neuromuscular junction, resulting in quicker onset.
35
How is a **post-tetanic count** performed and how are the results interpreted?
PTC involves delivering a 50 Hz tetanic stimulus for 5 sec, waiting 3 sec, then giving single 1 Hz twitches and counting responses.
* 0 twitches = profound block
* 1–2 = very deep block
* 3–5 = deep block
* 6–10+ = moderate block; TOF may soon return
Used when TOF = 0 to assess neuromuscular blockade depth.
36
How long does **neostigmine** take to reverse a non-depolarising neuromuscular blocker?
Approximately 8 minutes.
## Footnote
1-2 mL of 0.5 mg/mL **glycopyrrolate** with 2.5 mg/mL **neostigmine** is typically sufficient.
37
How many **twitches** must be visible on **train-of-four** before administering neostigmine/glycopyrrolate?
2 twitches
## Footnote
It won't work for deep blockade since many receptors remain occupied by the paralysing agent, making increased ACh insufficient to outcompete the muscle relaxant.
38
How is **rocuronium** excreted?
**Not metabolized**; 70% excreted unchanged in bile. Effects may be prolonged in obstructive jaundice.
39
How does **magnesium** affect non-depolarising neuromuscular blockers?
**Magnesium** blocks pre-synaptic voltage-gated calcium channels, reducing acetylcholine exocytosis and enhancing the effects of non-depolarising NMBs.
## Footnote
This can prolong paralysis and delay recovery.
40
Why is **suxamethonium** generally avoided in burn patients?
Burn patients develop extrajunctional acetylcholine receptors after 48 hours post-injury. Stimulation by suxamethonium can cause massive potassium efflux.
## Footnote
This effect lasts for about 6-12 months.
41
List the order of muscle recovery from **neuromuscular blockade**.
* Diaphragm (quickest)
* Laryngeal muscles
* Corrugator supercilii
* Rectus abdominis
* Orbicularis oculi
* Geniohyoid
* Adductor pollicis
* Masseter
42
Which muscle relaxant has the highest rate of **anaphylaxis**?
Suxamethonium (11.1 per 100,000). Note: More **cases** of anaphylaxis occur with **rocuronium** due to its higher usage, but the rate is lower (5.88 per 100,000).
43
List factors that prolong **non-depolarising neuromuscular blockade**.
* Aminoglycosides
* Volatile agents
* Lithium
* Propranolol
* Magnesium
* Nifedipine
44
Which **opioids** have high and low **hepatic extraction ratios**?
* **High**: fentanyl, morphine
* **Low**: methadone
45
List the **time to recovery** from suxamethonium for the different genotypes of **pseudocholinesterase**.
* **Eu-Eu**: 15 mins (96% of people)
* **Eu-Ea**: 30 mins
* **Ef-Ef and Ea-Ea**: hours
46
What are the phases of block with **suxamethonium**?
**Phase 1**: Persistent depolarization of motor endplate causing fasciculations and receptor agonism.
**Phase 2**: Prolonged exposure leads to repolarization and receptor desensitization, resulting in paralysis and competitive antagonism.
47
What proportion of administered **suxamethonium** reaches the neuromuscular junction, and why?
20%
## Footnote
**Pseudocholinesterase** is efficient and widespread, metabolizing most before reaching the NMJ.
48
What occurs at the neuromuscular junction with repeated doses of **suxamethonium**?
Repeated doses block presynaptic receptors, reducing acetylcholine release and deepening the **Phase II block**.
## Footnote
Phase I block: Postsynaptic depolarization → no fade.
Phase II block: Presynaptic blockade → reduced ACh release → fade.
49
Why does a **Phase II block** with **suxamethonium** produce fade on the TOF?
Postsynaptic receptors become desensitized but remain partially responsive, allowing some twitch. Suxamethonium blocks presynaptic receptors, reducing acetylcholine release with repeated stimuli, causing fade.
50
Which part of non-depolarising neuromuscular blockers binds to **acetylcholine receptors**?
The **quaternary nitrogen** binds to the alpha subunit of nicotinic acetylcholine receptors.
51
Which neuromuscular blockers are **aminosteroids**?
* Pancuronium (long-acting)
* Vecuronium
* Rocuronium
52
Which neuromuscular blockers are **benzylisoquinoliniums**?
* Atracurium (INTERMEDIATE-ACTING)
* Mivacurium (SHORT-ACTING)
* Tubocurarine
53
What structural factor affects the potency of **non-depolarising neuromuscular blockers**?
Number of quaternary ammonium groups affects binding to nicotinic acetylcholine receptors.
## Footnote
Other factors also influence potency (e.g., lipid solubility).
54
Which NMBs are **monoquaternary** and **bisquaternary** amines?
* **Monoquaternary**: rocuronium, vecuronium
* **Bisquaternary**: atracurium, mivacurium, pancuronium, tubocurarine
55
What is the **structural difference** between aminosteroids and benzylisoquinoliniums?
* **Aminosteroids**: steroid nucleus with amine substitutions.
* **Benzylisoquinoliniums**: isoquinoline ring structures with quaternary ammoniums.
56
How do changes in **pH** affect the potency of non-depolarising muscle relaxants?
**Monoquaternary amines** (rocuronium, vecuronium) can become more potent as non-quaternary amines get protonated, enhancing receptor binding.
57
Which **pharmacological** and **physiological** factors can prolong the action of **neuromuscular blockers**?
* **Pharmacological**: volatiles, aminoglycosides, LAs, lithium, diuretics, CCBs
* **Physiological**: hypothermia, acidosis, hypokalaemia, hypermagnesaemia
58
Describe the relative affinity of **sugammadex** for different **aminosteroid muscle relaxants**.
**Aminosteroids** affinity:
Rocuronium > Vecuronium
## Footnote
Does not reverse **pancuronium** effectively.
59
Why is it acceptable to give a second dose of **rocuronium** after **sugammadex** has reversed paralysis?
Less **sugammadex** is administered than **rocuronium**; only free **sugammadex** can chelate **rocuronium** to achieve around 70% receptor occupancy for full reversal.
60
How long after a 4 mg/kg dose of **sugammadex** can **rocuronium** or **vecuronium** be given if needed?
* **Rocuronium** (1.2 mg/kg): 5 mins
* **Rocuronium** (0.6 mg/kg): 4 hours
* **Vecuronium** (0.1 mg/kg): 4 hours
61
What is the **active metabolite** of tramadol?
O-desmethyltramadol (excreted by the kidneys)
62
List some conditions that **reduce pseudocholinesterase levels** or activity.
* Newborn
* Pregnancy
* Liver disease
* Malignancy
* Malnutrition
* Severe heart failure
* Renal failure
* Burns
* Hypothyroidism
63
How much **codeine** is equivalent to 10 mg of oral morphine?
1:10
## Footnote
I.e. 100 mg of codeine
This is the same for dihydrocodeine
64
How much **oral tramadol** is equivalent to **10 mg** of oral morphine?
1:10
## Footnote
i.e. 100 mg PO tramadol
65
How to convert daily **morphine** to a **fentanyl patch**?
Fentanyl patch in micrograms/hour = total daily morphine dose ÷ 2.4 to 2.5.
66
Which **acetylcholinesterase inhibitor** crosses the blood-brain barrier to counteract **anticholinergic syndrome**?
Physostigmine
## Footnote
Neostigmine, pyridostigmine, and edrophonium have a quaternary ammonium structure.
67
What is the context-sensitive half-life of **fentanyl**?
Approximately 5 hours.
68
Describe the receptor affinity of **diclofenac**.
COX-2 affinity is 50 times greater than COX-1.
69
Describe the mechanism of action of **opioids** on opioid receptors.
Opioids act via **GPCRs** (Gi). Ligand binding closes **VGCCs** on the presynaptic membrane, reducing **cAMP** levels. This causes potassium efflux, leading to hyperpolarization and decreased neurotransmitter release, which reduces pain transmission.
70
Why does **alfentanil** act faster than **fentanyl**?
Opioids are bases and ionize below their pKa. At physiological pH (7.35 – 7.45), **alfentanil** is less ionized than **fentanyl**, allowing it to act more quickly despite lower lipid solubility.
71
What are the main indications for **neuromuscular blockade**?
* Tracheal intubation
* Aid mechanical ventilation
* Surgical access
72
What are the pKa, lipid solubility, potency, volume of distribution, and protein binding of **alfentanil**?
* **pKa**: 6.5
* **Lipid Solubility**: 90 x Morphine
* **Potency**: 10 x Morphine
* **Volume of Distribution**: 0.6 L/kg
* **Protein Binding**: 90%
73
What are the main **differences** between cisatracurium and atracurium?
**Cisatracurium** is more potent and leads to less histamine release than ‘**atracurium**’, which is actually a mixture of 10 isomers.
74
What effect does **neostigmine** have on the duration of action of **mivacurium** and **suxamethonium**?
Neostigmine inhibits **pseudocholinesterase**, increasing the duration of action for mivacurium and suxamethonium.
75
Which receptors does **methadone** act on?
Mu opioid agonist
NMDA receptor antagonist (non-competitive)
76
What is **pentazocine**?
* Partial agonist at mu receptors
* Full agonist at kappa receptors
* Used in pain management
77
Which **muscle relaxant** is most extensively excreted by the kidneys?
Pancuronium (80%)
## Footnote
Rocuronium and vecuronium are mostly metabolised by the liver.
78
What is the **active metabolite** of pancuronium?
3-hydroxypancuronium
## Footnote
Pancuronium is metabolised by hepatic deacetylation.
79
What is the **structure** of neostigmine?
Quaternary ammonium compound
80
What is the **longest** acting non-depolarising neuromuscular blocker?
Pancuronium (60-90 mins)
81
What is the **shortest**-acting non-depolarising neuromuscular blocker?
Mivacurium (10 mins)
82
How does **neostigmine** prolong the block from **suxamethonium**?
It inhibits plasma cholinesterase, slowing suxamethonium breakdown and prolonging the depolarizing block.
83
What converts **diamorphine** to **6-monoacetylmorphine**?
Plasma esterases (rapid conversion)
## Footnote
**Morphine-6-glucuronide** is 13 times more potent than morphine.
84
Why does **alfentanil** have a quicker onset of action than **morphine**?
Both are weak bases: **morphine** pKa is 7.9, **alfentanil** is 6.4. Morphine is 40% protein bound; alfentanil is 90% bound. **Alfentanil** has a faster onset due to a smaller proportion of free drug, but the difference in unionized drug in the bloodstream is greater (alfentanil is 100 times less ionized than morphine).
85
How does **cisatracurium** compare to **atracurium**?
**Atracurium** is a mixture of 10 isomers.
**Cisatracurium** is 3x more potent, has minimal autonomic effects, causes less histamine release, and has reduced laudanosine levels (which can provoke seizures).
86
Describe the mechanism of action of **neostigmine**.
Carbamylates the active site of **acetylcholinesterase**; hydrolyzed like ACh but slower (acts as a competitive inhibitor). Increases synaptic ACh concentration, outcompeting non-depolarizing NMBs.
Added to **glycopyrronium** to counteract parasympathetic effects (bradycardia, hypotension, bronchoconstriction).
Lasts 1-2 hours.
87
Which neuromuscular blockers does **neostigmine** prolong the duration of action for?
Suxamethonium and Mivacurium.
## Footnote
Due to inhibition of plasma cholinesterases.
88
A reduction in which **prostaglandins** mediates the anti-inflammatory and anti-pyretic effects of **NSAIDs**?
Decrease **PGE₂** and **PGF₂-α**.
89
What genotypes cause **suxamethonium apnoea**?
Normal plasma cholinesterase is **E1u**; atypical is **E1a**. Heterozygote E1u, E1a effects last 30 mins. Homozygous atypical lasts over 2 hours. Rare variants include E1f (fluoride) and E1s (silent), with the silent variant having minimal capacity to hydrolyze suxamethonium, causing **paralysis** for several hours.
## Footnote
Drug is eventually cleared by non-specific esterases.
90
What is the **pKa** of ibuprofen?
4.9
91
What is the **pKa** of tramadol?
9.4
## Footnote
Functional Group: -NR3
92
What is the **pKa** of paracetamol?
9.4
## Footnote
Functional Group: -OH
93
What is the context sensitive **half-life of alfentanil**?
< 1 hour after a prolonged infusion
94
What is the **terminal** elimination half-life of fentanyl?
3-5 hours
95
What is the elimination **half-life of morphine**?
3 hours
96
What is the **volume of distribution** of morphine?
3.5 L/kg
97
What is the **volume of distribution** of alfentanil?
0.6 L/kg
98
State the **protein binding** of Fentanyl, Remifentanil, Morphine, Pethidine and Alfentanil.
* Alfentanil: 90%
* Fentanyl: 83%
* Remifentanil: 70%
* Pethidine: 60%
* Morphine: 35%
99
What dose of alfentanil can be used as a temporising measure in **hypertension**?
0.5-1 mg (10 µg/kg)
100
What dose of **mivacurium** is used for induction?
0.2 mg/kg
101
What is the intubation dose of **cisatracurium**?
0.15 mg/kg
102
What is the intubation dose of **pancuronium**?
0.1 mg/kg
103
What is the **pKa** of codeine?
8.2
104
What is the **terminal** half-life of **codeine**?
3 hours
105
What is the **pKa** of buprenorphine?
8.3
NOTE: it is a mu partial agonist and a kappa antagonist
106
What is the **terminal** half-life of **buprenorphine**?
20-75 hours
107
What is the **terminal** half-life of **alfentanil**?
1.6 hours
108
What is the **terminal** half-life of **remifentanil**?
4 mins
109
What is the elimination half-life of **sugammadex**?
2 hours
110
Tell me about **remifentanil**.
**C**: opioids (phenylpiperidine derivative)
**U**: induction, TIVA, sedation, antitussive
**P**: white powder in 1, 2 and 5 mg vials
**A**: mu opioid receptor agonist
**D**: 20-40 µg bolus, TCI pumps
**O**: 1 --> 5 mins (context insensitive)
**S**: bradycardia, hyperalgesia, chest wall rigidity
**A**: IV
**D**: pKa 7.1
**M**: non-specific plasma and tissue esterases
**E**: renal
111
Tell me about **atracurium**.
**C**: benzylisoquinolinium, non-depolarising
**U**: intubation
**P**: 2.5, 5 and 25 mL vials of 10 mg/mL, stored at 4 degrees
**A**: competitive nAChR inhibition
**D**: 0.5 mg/kg
**O**: 2 mins --> 45-60 mins
**S**: histamine release, laudanosine (seizure)
**A**: IV
**D**: small Vd
**M**: Hofmann (60%), ester hydrolysis (40%)
**E**: renal
112
Tell me about **cisatracurium**.
**C**: benzylisoquinolinium
**U**: intubation
**P**: 2 mg/mL in 5 or 10 mL stored at 4 degrees
**A**: competitive nAChR inhibition
**D**: 0.15 mg/kg
**O**: 2 mins --> 60 mins
**S**: minimal histamine release
**A**: IV
**D**: small Vd
**M**: entirely Hofmann degradation
**E**: renal
113
Tell me about **mivacurium**.
**C**: benzylisoquinolinium
**U**: intubation
**P**: 2 mg/mL in 5 or 10 mL
**A**: competitive nAChR inhibition
**D**: 0.2 mg/kg
**O**: 2 mins --> 20 mins
**S**: histamine release
**A**: IV
**D**: small Vd
**M**: plasma cholinesterase
**E**: renal
114
Tell me about **rocuronium**.
**C**: aminosteroid, monoquaternary
**U**: intubation
**P**: 10 mg/mL, 10 mL vials stored at 4 degrees
**A**: competitive nAChR inhibition
**D**: 0.6 to 1.2 mg/kg
**O**: 0.6 mg/kg: 100-120 sec; 1.2 mg/kg: 60-90 sec, 60 mins duration
**S**: mild hypotension, minimal histamine release, pain on injection, anaphylaxis
**A**: IV
**D**: low Vd (0.3 L/kg)
**M**: unchanged
**E**: biliary (mainly) and renal
115
Tell me about **vecuronium**.
**C**: aminosteroid, monoquaternary
**U**: intubation
**P**: 10 mg freeze-dried powder
**A**: competitive nAChR inhibition
**D**: 0.1 mg/kg
**O**: 2 mins --> 60 mins
**S**: minimal cardiovascular effects, minimal histamine release
**A**: IV
**D**: low Vd (0.3 L/kg)
**M**: hepatic, 3-desacetyl vecuronium (active)
**E**: biliary and renal
116
Tell me about **pancuronium**.
**C**: aminosteroid, bisquaternary
**U**: intubation
**P**: 4 mg in 2 mL stored at 4 degrees
**A**: competitive nAChR inhibition
**D**: 0.1 mg/kg
**O**: 2 mins --> 60-90 mins
**S**: tachycardia, minimal histamine release
**A**: IV
**D**: low Vd (0.3 L/kg)
**M**: hepatic, 3-desacetyl pancuronium (active)
**E**: renal
117
Tell me about **sugammadex**.
**C**: cyclodextrin
**U**: reversal of non-depolarising muscle relaxants
**P**: 2 mL and 5 mL vials of 100 mg/mL
**A**: encapsulation of rocuronium (and vecuronium)
**D**: 2, 4 or 16 mg/kg
**O**: 1 min --> 2 hours
**S**: bradycardia, anaphylaxis
**A**: IV
**D**: low Vd (0.15 L/kg)
**M**: unchanged
**E**: renal
118
Tell me about **suxamethonium**.
**C**: depolarising muscle relaxant
**U**: intubation
**P**: 2 mL ampoules of 50 mg/mL stored at 4 degrees
**A**: persistent depolarisation of motor end plate
**D**: 1-2 mg/kg
**O**: 1 min --> 10 mins
**S**: myalgia, bradycardia, hyperkalaemia, raised IOP, MH, suxamethonium apnoea, anaphylaxis
**A**: IV/IM
**D**: low Vd
**M**: rapidly hydrolysed by plasma cholinesterase to choline and succinic acid
**E**: renal
119
What are some **clinical measures** of neuromuscular blockade?
* Sustained head lift for 5 seconds
* Tidal volume of 10 mL/kg
* Protrude tongue
* Sustained hand grip
* Vital capacity
* Maximum inspiratory pressure
NOTE: these are not very reliable
120
Describe the **classification** of neuromuscular monitoring.
**QUALITATIVE**: Visual assessment of peripheral nerve stimulation (ulnar nerve, common peroneal, or facial).
**QUANTITATIVE**: Records evoked response using:
* Electromyography (muscle action potential)
* Mechanomyography (thumb movement)
* Acceleromyography (muscle acceleration with piezoelectric sensor)
* Kinemyography (signal from bending piezoelectric sensor between thumb and index finger)
121
How is **train of four** stimulation administered and interpreted?
Administer 4 identical stimuli at 2 Hz for 1.5 seconds.
Non-depolarising blockers cause fade:
* 1 twitch lost: 70% occupation
* 2 twitches lost: 80% occupation
* 3 twitches lost: 90% occupation
* 4 twitches lost: 95% occupation
122
How is **neostigmine** dosed based on **QUALITATIVE** monitoring of neuromuscular blockade?
* 4 twitches, no fade: 0.02 mg/kg (1-1.75 mg for 70 kg), TOF > 0.9, no reversal needed
* 4 twitches, with fade: 0.04 mg/kg (2.8 mg)
* 1-3 twitches: 0.05 mg/kg (3.5 mg)
NO TWITCHES: wait until at least 2 twitches.
123
How is **double burst stimulation** administered?
Two 50 Hz tetanic stimuli with a 750 msec interval (3 twitches each).
More accurate qualitative assessment than TOF.
124
How is **post-tetanic stimulation** administered?
Administer a 5-second tetanic stimulus (50 Hz), followed by a 3-second pause, then 20 stimuli at 1 Hz.
## Footnote
Pre-synaptic receptors are activated, leading to synthesis and mobilization of additional acetylcholine.
125
What are the issues with **postoperative residual paralysis**?
* Airway obstruction
* Impaired ventilation leading to respiratory failure
* Increased risk of aspiration pneumonia
* Longer recovery stay
126
Describe the **onset**, **peak effect**, and **duration** of action for **neostigmine**.
**Onset**: 1 min
**Peak Effect**: 8 mins
**Duration**: 20-30 mins.
Should only be given after two twitches have returned.
127
How do **magnesium** and **aminoglycosides** affect the neuromuscular junction?
They block pre-synaptic voltage-gated calcium channels, reducing calcium influx and neurotransmitter release.
128
How can **NSAIDs** be classified?
* **Non-Specific COX Inhibitors**:
- Salicylates: aspirin
- Acetic acid derivatives: ketorolac, diclofenac, indomethacin
- Propionic acids: ibuprofen
* **COX-2 Preferential**:
- Oxicams: meloxicam
* **COX-2 Specific**:
- Pyrazoles: parecoxib, celecoxib
129
Why does **aspirin** reduce thromboembolism risk while **COX-2 inhibitors** increase it?
Low-dose aspirin selectively inhibits thromboxane production in platelets, preserving endothelial prostacyclin production.
COX-2 inhibitors disrupt the balance between thromboxane and prostacyclin, promoting platelet aggregation and vasoconstriction.
130
What are the endogenous ligands for the different types of **opioid receptors**?
* **MOP**: beta endorphins
* **KOP**: dynorphin A
* **DOP**: leu-enkephalin, met-enkephalin
* **NOP**: nociceptin
131
By what mechanism do **opioids** cause respiratory depression?
They reduce sensitivity of central and peripheral chemoreceptors to hypercapnia and hypoxia.
132
Describe the effects of **opioids** on the cardiovascular system.
* Decreased sympathetic activity
* Causes bradycardia and peripheral vasodilation
## Footnote
NOTE: Morphine can also cause histamine release.
133
What is the recommended dose of **paracetamol**?
15 mg/kg every 4-6 hours
134
What is the **protein binding** of paracetamol?
10%
135
Describe the **metabolism** of aspirin.
Rapidly hydrolysed by intestinal and hepatic esterases to salicylate
Metabolised further by liver to salicyluric acid and glucuronide derivatives
136
Describe the effect of **hemicholinum**.
Blocks uptake of choline in the nerve axon, preventing acetylcholine synthesis
137
What advice should patients on **hormonal contraceptives** receive after sugammadex?
Use additional non-hormonal contraception for 7 days.
## Footnote
This has the same effect as missing one dose of an oral contraceptive.
138
What are some contraindications for using **suxamethonium**?
* Malignant hyperthermia
* Suxamethonium apnoea
* Hyperkalaemia
* Severe muscle trauma
* > 10% burns (48 hours to 18 months)
* Spinal cord trauma (24 hours to 18 months)
139
What are the four alleles associated with **suxamethonium apnoea**?
* Usual (normal)
* Silent
* Dibucaine-resistant
* Fluoride-resistant
## Footnote
Autosomal recessive mutation on chromosome 3.
140
List some causes of **acquired cholinesterase deficiency**.
* Pregnancy
* Liver disease
* Renal disease
* Heart failure
* Thyrotoxicosis
* Malnutrition
141
What are the three types of **abnormal plasma cholinesterase** genes?
* **ATYPICAL** (Ea): 0.03% of homozygotes, Dibucaine 15-25%
* **SILENT** (Es): 0.001% of homozygotes, no activity
* **FLUORIDE-RESISTANT** (Ef): 0.0001%, Dibucaine 65-75%
142
How does **paracetamol** cause liver damage?
Most paracetamol is metabolized into non-toxic metabolites by UDP glucuronyltransferases and sulfotransferases, excreted in urine.
Some is converted by CYP450 to **NAPQI**, which binds to hepatocellular proteins and generates ROS, causing oxidative stress and cell death.
143
What is the onset and peak effect time of **paracetamol**?
**ORAL**
Onset: 30 mins
Peak: 60 mins
**IV**
Onset: 5-10 mins
Peak: 15 mins
144
Describe the metabolism and excretion of **fentanyl**.
Metabolised in the liver by CYP3A4 into inactive norfentanyl and excreted mainly in the urine
145
What are the effects of **opioids** on the respiratory system?
* Respiratory centre depression
* Antitussive
* Histamine release (bronchospasm)
* Chest wall rigidity
146
Which muscle relaxants have **active metabolites**?
**Vecuronium**: 3-desacetylvecuronium (80% potency)
**Pancuronium**: 3-desacetylpancuronium (50% potency)
NOTE: both have prolonged effects in renal impairment
147
How would you interpret the **post-tetanic count**?
< 5 profound block
> 15 equal to two twitches on TOF
148
What are rheobase and chronaxie?
**Rheobase**: minimal current required to create a nerve impulse
**Chronaxie**: duration of stimulus at TWICE the rheobase required to create a nerve impulse
149
How are patients tested for **suxamethonium apnoea**?
**Dibucaine number**: Patient's plasma is mixed with benzylcholine. Breakdown emits light. Adding dibucaine (inhibits normal plasma cholinesterase) reduces light emission if cholinesterase is normal. Normal reduction is 80%.
150
What is the mechanism of action of **gabapentin** and **pregabalin**?
* They do NOT act on GABA receptors.
* They bind to the α2δ subunit of voltage-gated calcium channels, reducing calcium influx into presynaptic neurons.
* This inhibits the release of excitatory neurotransmitters like glutamate, norepinephrine, and substance P, decreasing neuronal excitability.
151
By what mechanism do NSAIDs cause **nephrotoxicity**?
* By inhibiting **COX**, NSAIDs inhibit the production of **PGI2** (prostacyclin) and **PGE2**, which are potent dilators of the afferent renal arteriole.
* This **reduces glomerular blood flow**, which in turn can reduce glomerular filtration rate.
152
List some contraindications for using **suxamethonium**.
* Hypersensitivity
* Malignant hyperthermia
* Hyperkalaemia
* Burns (> 24 hours)
* Spinal cord injury (> 24 hours)
153
What are some drugs that are **analgesic adjuncts**?
* Ketamine
* Clonidine
* Magnesium
* Lidocaine Infusion
154
List **acetylcholinesterase** inhibitors in terms of duration of action.
* **RAPID**: edrophonium bromide
* **INTERMEDIATE**: neostigmine, physostigmine, pyridostigmine (carbamylates)
* **LONG**: echothiopate, sarin (phosphorylates)
155
By what mechanism does **magnesium** provide analgesia?
Mg blocks the NMDA receptor-associated calcium channel, reducing calcium influx.
This decreases neuronal excitability and central sensitization.
156
What are the components of a **morphine PCA** prescription?
* Concentration: 50 mg in 50 mL
* Bolus Dose: 1-2 mg
* Background Dose: 0.5-1 mg/hr (generally avoided)
* Max Limit (over 4 hours): 30-40 mg
* Lock Out Interval: 5 mins
## Footnote
Requires regular monitoring of GCS, RR, and SpO₂ (background infusion needs a monitored bed).
157
What are the contraindications for **PCA**?
* Patient refusal
* Lack of understanding
* Physically unable to press button
* Sensitivity/allergy to opiates
* Unsafe nursing environment for monitoring
158
What are the key characteristics of a **phase I block**?
* Reduced twitch height
* Sustained response to tetanic stimulation
* No post-tetanic facilitation
* TOF ratio > 70%
159
What are the key characteristics of a **phase II block**?
* Fade on tetanic stimulation
* Post-tetanic facilitation
* TOF ratio < 0.3 (fourth to first twitch height)
* Antagonized by anticholinesterases
* Tachyphylaxis seen with increased **suxamethonium** infusion rate or bolus dose.
160
Outline the metabolism of **paracetamol**.
90% conjugated in the liver to glucuronide and sulfate (non-toxic).
5–10% oxidized by CYP450 (mainly CYP2E1) to NAPQI (detoxified by conjugation with glucuronide).
Primary FRCA
flashcards
Decks in class (17)
# Cards
-
Anatomy for Anaesthesia223
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Physiology: Respiratory303
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Physiology: Cardiovascular179
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Physiology: Renal, Hepatic & GI63
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Physiology: Neuro, Endo, & Haem237
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Pharmacokinetics and Pharmacodynamics213
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Pharmacology: Inhalational & Intravenous Agents232
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Pharmacology: Analgesics & Muscle Relaxants160
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Pharmacology: Emergency & Miscellaneous Drugs251
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Part 1: Physics & Equipment242
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Part 2: Physics & Equipment227
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Part 3: Physics & Equipment232
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Part 4: Physics & Equipment217
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Statistics & Evidence-Based Practice36
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Part 1: Applied Clinical Anaesthesia165
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Part 2: Applied Clinical Anaesthesia169
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Part 3: Applied Clinical Anaesthesia157
