Pharmacology Flashcards
1
Q
What is the chemical name of propofol
A
2,6-di-isopropyl phenol
2
Q
What are the 2 types of volatile anaesthetic agents?
A
Halogenated hydrocarbons
Ethers
3
Q
List 4 examples of volatile agents that are ethers
A
Enflurane
Isoflurane
Sevoflurane
Desflurane
4
Q
List 3 examples of volatile agents that are halogenated hydrocarbons
A
Halothane
Trichloroethylene
Chloroform
5
Q
What effect does adding a CL or BR group to halogenated hydrocarbons have
A
Increases potency
6
Q
What effect does adding a F (flouride) group to halogenated hydrocarbons have
A
Increases stability
7
Q
What are the 2 types of local anaesthetic
A
Amino Esters
Amino Amides
8
Q
List 2 examples of Amino ester local anaesthetics
A
Procaine
Tetracaine
9
Q
List 2 examples of amino amide local anaesthetics
A
Lidocaine
Bupivicaine
10
Q
How are amino esther local anaesthetics metabolised
A
Broken down rapidly in plasma by esterase
11
Q
How are amino amide local anaesthetics metabolised
A
Broken down slowly in liver
12
Q
Define an acid
A
Proton donor
13
Q
Define a base
A
Proton aceptor
14
Q
Why is Midazolam buffered to a pH of 4 in its preperation
A
Midazolam has amine group which accepts proton in acidic conditions making it ionised and therefore water soluble
15
Q
What happens to Midazolam at body pH 7.4
A
The amine group becomes incorporated into ring making it unionised and therefore lipid soluble (can cross BBB)
16
Q
What effect does having a longer carbon chain have on a drugs solubility?
A
Reduced
17
Q
What effect does having more functional groups have on a drugs solubility?
A
Increases solubility
18
Q
Define pKa
A
The pH at which the proton donor (acid) and proton acceptor (base) forms of a drug are at equal concentrations
19
Q
What happens to weak acids at pH above their pKa
A
They become ionised
Acid Ionised ABOVE pKa
20
Q
What happens to weak bases at pH below their pKa
A
They become ionised
Base ionised BELOW pKa
21
Q
What is the pKa of Thiopental
A
7.6
22
Q
What is the pKa of Propofol
A
11
23
Q
What is the pKa of Etomidate
A
4.2
24
Q
What is the pKa of Ketamine
A
7.5
25
Is propofol ionised or unionised at body pH? How does this affect solubility?
Propofol a weak acid which at body pH 7.4 is largely unionised because it is below its pKa of 11. This makes it more lipophilic.
26
Which functional group makes propofol a weak acid?
Phenol
27
Is propofol a weak acid or a weak base?
Weak acid
28
Is thiopental a weak acid or a weak base?
Weak acid
29
Is Etomidate a weak acid or a weak base?
Weak base
30
Is Ketamine a weak acid or a weak base?
Weak base
31
What is the Henderson-Hasselbach equation?
pH = pKa + Log( Base/ Acid)
32
Which 3 factors affect a drugs ability to cross the BBB
Lipid solubility - increases ability to cross BBB
pKA - un-ionised form crosses BBB
Protein binding- Protein binding reduces ability to cross BBB
33
What are the 3 functional groups in a local anaesthetic
Aromatic group
Intermediate chain (Ester or Amide)
Amine group
34
Define isomer
Compounds with the same chemical formula but different arrangement of atoms in space
35
Define tautomerisation
When 2 structural isomers exist in dynamic equilibrium
36
Which phenomenon occurs to Midazolam when exposed to body pH 7.4
pH dependent ring closure occurs to form benzodiazepine ring making it lipid soluble and un-ionised
37
Why do you need carbon-carbon double bonds to have geometric stereoisomers
Carbon-Carbon double bonds do not allow rotation
38
Define stereoisomers
Compounds with same chemical and molecular formula but different arrangement of atoms in space
39
What are the 2 forms of stereoisomers
Geometric
Optical
40
Describe optical isomers
A compound with 4 different functional groups attached to a chiral centre. This allows isomers to be mirror images but non-superimposable
41
Define Enantiomers
A pair of optical isomers that each rotate plane polarised light in opposite directions
42
What is plane polarised light
Light where the vibrations travel in one plane
43
Define dextrorotatory enantiomer (d)
The optical isomer that rotates plane polarised light to the right
44
Define levorotatory enantiomer (l)
The optical isomer that rotates plane polarised light to the left
45
Define racemic mixture (dl)
A mixture of levorotatory and dextrorotatory optical isomers
46
Explain the R S naming system of optical isomers
Each functional group around a chiral centre is given a priority with the highest atomic number getting highest priority (1) and lowest (4) (e.g hydrogen). If the priorities are from high to low (1-4) clockwise around the chiral atom this is R if it is anti-clockwise this is S
47
Define Diastereoisomers
Stereoisomers where the compound has more than 1 chiral centre
48
Define Potency
The amount of drug required to cause a defined effect
49
Define Affinity
The strength with which a drug binds to receptors
50
Define Intrinsic activity
E max of drug / E max of a full agonist
51
What is the Emax of an inverse agonist
-1
52
What is the Emax of a partial agonist
0 - 1
53
What is the Emax of an full agonist
1
54
Define constitutive activity
Receptors can signal in the absence of an agonist
55
How do inverse agonists work?
Inverse agonists are ligand that bind receptors and stop the constitutive activity.
56
Describe structure of G protein coupled receptors (GPCRs)
7 transmembrane helices, extracellular binding site, allosteric binding sites between helices, intracellular binding site for G protein.
57
What 3 subunits make up a G protein
Ga - Alpha
β- Beta
γ- Gamma
58
What are the 3 domains that make up the structure of an Enzyme linked receptor
1- Extracellular ligand-binding domain
2- Transmembrane domain
3- Intracellular active enzyme domain
59
Describe the structure of intracellular receptors
1- Transcription activating domain
2- DNA binding domain
3- Ligand binding domain
4- Inhibitory protein
60
Describe how steroid hormone receptors work
Intracellular receptor bound to chaperone protein - heat shock protein (HSP). When ligand binds- conformational change HSP dissociated. NLS (nuclear location sequence) revealed, can travel to nucleus. Binds to hormone response element (HRE) causing gene transcription.
61
What are the 2 types of intracellular receptors
1- Cytosolic
2- intranuclear
62
What kind of intracellular receptors are thyroid hormone receptor?
Type 2 intracellular receptors (intra-nuclear receptors)
63
Which short acting anti cholinesterase is used to diagnose Myastenia graves
Edrophonium
- Strength of muscle contractions increases after
64
How does Neostigmine work
Anticholinesterase drug binds to acetylcholinesterase to reversibly inhibit Ach binding
Also hydrolysed but over much longer period of time making the acetylcholinesterase inactive
also inhibits pseudocholinesterases
65
List 3 parasympathetic effects of neostigmine
Bradycardia
Hypotension
Bronchoconstriction
66
Define drug idiosyncrasy
Genetically determined abnormal reaction to a drug related to enzyme deficiency
67
Explain what causes suxamethonium apnoea
Genetic variant of plasma cholinesterase gene E1a instead of normal E1u reduces the enzymes ability to hydrolyse acetylcholine. In homozygous E1a patients can take more than 2 hours to clear suxamethonium.
68
Describe a type A drug reaction
- Most common type of drug reaction
- Exaggerated or secondary effect to drug
- Dose related
e.g tinnitus with aspirin
69
Describe type B drug reaction
- Bizarre unpredicted drug reaction
- Not dose related
e.g Sux apnoea, malignant hyperthermia, porphyria
70
Which 3 characteristics does DoTS classification of drug reactions use?
1 Dose relatedness of drug reaction (standard or supra therapeutic dose)
2 Time relatedness ( late reaction, reaction on second dose, speed of admin of drug)
3 Susceptibility (person specific like genetics, gender and age
71
Define Coomb's type I reaction and examples
Allergic
IgE mediated
Atopy
anaphylaxis
asthma
72
Define Coomb's type II reaction and examples
cytotoxic
IgM and IgG bind to allergen- complement mediated
Thrombocytopenia
Autoimune Haemolytic anaemia
73
Define Coomb's type III reaction and examples
Immune complex deposition
IgG-allergen complexes
SLE
Rheumatoid arthritis
74
Define Coomb's type IV reaction and examples
Cell mediated
T-lymphocytes/ macrophages
Chronic transplant rejection
Delayed hypersensitivity reaction
Contact dermatitis
75
Describe pseudo allergic reactions
Reactions with the same clinical manifestations as allergic reaction due to histamine release but not caused by immunological reactions
76
Describe tachyphylaxis
Hyper-acute form of tolerance where rapidly increasing doses required for clinical effect.
E.g Ephedrine and Hydralazine
77
Describe 3 mechanisms of nitrate tolerance
1 NADPH oxidase production - Increase peroxynitrite- inhibition of guanylate cyclase and prostacyclin
2 Uncoupled endothelial nitric oxide synthase production- Increase peroxynitrite- inhibition of guanylate cyclase and prostacyclin
3 Inhibition of mitochondrial aldehyde dehydrogenase
78
What happens if thiopentone is given with suxamethonium
Thiopentone precipitates
79
How does sodium bicarbonate affect aspirin and barbiturate excretion
Sodium bicarbonate causes urine to become more alkaline.
This increases water solubility and excretion of weak acids.
80
How does magnesium affect non-polarising neuromuscular blocking drugs
Potentiates effect
81
Which electrolyte is increased by suxamethonium
Potassium
82
What effect does St John's Wort have on CYP450
Enzyme inducer
83
What are anaesthetic considerations in patient taking Echinacea?
Taken to improve immune system
Causes hepatic failure
avoid hepatotoxic drugs such as amiodarone, methotrexate and halothane
84
What are anaesthetic considerations in patient taking Ephedra?
Taken for weight loss and treatment of asthma
Sympatomimetic drug which depletes catecholamines.
Can lead to cardiovascular instability and tachyphylaxis of other sympathomimetic drugs e.g ephedrine
85
What are anaesthetic considerations in patient taking Garlic?
Taken to treat hypertension and hyperlipidaemia
potentiates anti-platelet effect
Bleeding risk with aspirin and NSAIDs
86
What are anaesthetic considerations in patient taking Ginger?
Taken for anti-inflammatory and anti-emetic properties
Bleeding risk with warfarin and NSAIDs
87
What are anaesthetic considerations in patient taking Gingko biloba?
Taken as thought to be neuroprotective
Bleeding risk with aspirin, NSAIDs and warfarin
88
What are anaesthetic considerations in patient taking Ginseng?
Taken as mood enhancer
Bleeding risk with warfarin and NSAIDs
89
What are anaesthetic considerations in patient taking Valerian?
Taken as anxiolytic and hypnotic
Potentiates anaesthetic prolonging emergence
90
List the CYP450 inhibitors
SICKFACES.COM
Sodium valproate
Isoniazid
Cimetidine
Ketoconazole
Fluconazole
Alcohol (acute), amiodarone
Ciprofloxacin, chloramphenicol
Erythromycin
Sulphonamides
.
Cranberry juice, grapefruit juice
Omeprazole
Metronidazole
91
List CYP450 inducers
BS CRAP GPS. - these INDUCE anger
Barbiturates
St John's wort
Carbemazepine
Rifampicin
Alcohol (chronic)
Phenytoin
Grisofluzin
Phenobarbital
Sulphonylureas
91
Where are CYP450 enzymes found
Endoplasmic reticulum of hepatocytes
92
Do acids ionise at a pH above or below their pKA
Acids ionise at pH above their pKa
HA -> A- + H+
93
Do bases ionise at a pH above or below their pKa
Bases ionise below their pKa
94
How much stronger is I.V morphine compared to oramorph
3X
95
How much stronger is IV/ SC Diamorphine compared to Oramorph
3X
96
How much stronger is PO oxycodone compared to oramorph
2X
97
How much stronger is I.V fentanyl compared to Oramorph
100X
98
How much stronger is Trans Dermal fentanyl compared to Oramorph
100X
99
How much stronger is Tramadol compared to Oramorph
10X
100
What is the equivalent dose of Oramorph to 60mg Codeine
6mg Oramorph
101
What determines V1, V2, V3 in Schnider model for TIVA
V1- Fixed
V2- Age
V3- Fixed
102
What determines V1, V2, V3 in Marsh model for TIVA
V1- Lean body mass
V2- Lean body mass
V3- Lean body mass
103
When do you give I.V acetylcysteine for paracetamol overdose
-Patient presenting 8-24 hours after overdose
- Dose of paracetamol exceeds 150mg/kg
104
When do you give activated charcoal for paracetamol overdose
- Patient presents <4 hours after overdose
- Dose of paracetamol exceeds 150mg/kg
105
Describe mechanism of action of Gentamycin
- Aminoglycoside
- Binds protein ribosome 30S sub unit- 16S ribosomal ribonucleic acid inhibiting protein synthesis
- Bactericidal
106
Which volatile gas causes the largest drop in BP
Enflurane
107
Which volatile gas can cause coronary steal syndrome
Isoflurane
- Causes coronary artery dilation- diseased vessels that can't dilate get less blood
108
Which NSAID has most specificity for COX-2
Lumiracoxib
109
List 3 side effects of Etomidate?
- Pain on injection
- Respiratory depression
- nausea and vomiting
110
What is the time to peak in Marsh and Schnider models?
1.7 minutes
111
Which TCI model can be used for propofol TIVA in children >3 years old
Kataria
112
Which TCI model can be used for propofol TIVA in children >1 years old
Paedfusor
113
What dose of hydrocortisone is equivalent to 40mg of prednisolone
160mg
X4
114
Which muscle relaxant is a diastereoisomer
Atracurium
Has more than 1 chiral centre
115
Which inhalation agent exerts the highest partial pressure in blood
Desflurane
116
Explain blood: gas partition co-efficient
The ratio of the amount of anaesthetic agent in the blood compared to the alveolar gas.
Reflects solubility.
Agents with a low blood:gas partition coefficient are less soluble
117
What makes Lispro a fast acting insulin
Lispro has end molecule translocations in the Insulin. Stops insulin joining with multiple insulin molecules. Makes it more absorbable
118
What makes Glargine a slow acting insulin
Glycine-substituted insulin makes it slower to be absorbed
119
What is the mechanism of action of Dexmedetomidine
Central Alpha 2 agonist
Sedative, amnesic and analgesic effects
120
What is a Dibucaine number
The percentage of pseudocholinesterase enzyme activity inhibited by local anaesthetic Dibucaine
121
Which inhaled anaesthetic is safest in neurosurgery with increased ICP
Isoflurane
- Reduces brain oxygen requirement
- Minimal increase in cerebral blood flow
122
What is the mechanism of action of a tetracycline antibiotic
Binds to 30s subunit of bacterial ribosomes preventing protein synthesis
Bacteriostatic
123
Describe mechanism of Vaughan-williams class I anti-arrhythmics
- Blocks fast sodium channels.
- Widens QRS
124
Give example of Class I anti-arrhythmic
Procainamide (1a)
Lidocaine (1b)
Fleicanide (1c)
125
Describe mechanism of Vaughan-williams class II anti-arrhythmics
-Beta blockade
- prolongs PR
126
Give example of Class II anti-arrhythmic
Atenalol, Bisoprolol, carvediolol, esmolol, propanolol
127
Describe mechanism of Vaughan-williams class III anti-arrhythmics
Potassium channel blocker
Prolongs QT interval + slows sinus rate
128
Give example of Class III anti-arrhythmic
Amiodarone
129
Describe mechanism of Vaughan-williams class IV anti-arrhythmics
Calcium channel blockers
Prolongs PR interval + slows sinus rate
130
Give example of Class IV anti-arrhythmic
Diltiazem
Verapamil
131
Describe mechanism of Vaughan-williams class V anti-arrhythmics
Work by other mechanisms not in Class I-IV
e.g Magnesium sulphate, Adenosine, digoxin
132
What is Edrophonium used for and what is its mechanism of action?
Edrophonium is an anti cholinesterase drug that works by competitive inhibition.
Used in tensilon test to diagnose myasthenia gravis
133
Which metabolite of pancuronium is active
3-hydroxypancuronium
134
For which opioid receptors are fentanyl and remifentanyl agonists
MOP and KOP
No affinity for DOP receptors
135
What is the anaphylaxis rate per 100,000 for Suxamethonium
11.1 cases per 100,000
136
Which blood product is most useful for replacing fibrinogen
Cryoprecipitate
137
Why should suxamethonium be avoided in burns patients
Burns patients get up regulation of acetylcholine receptors which leads to life threatening hyperkalaemia with Suxamethonium
138
Which patients should avoid propofol if they have an egg allergy
Children with anaphylaxis to eggs only
139
Which CYP450 enzyme affects rate of metabolism of Morphine
CYP2D6
140
What is a normal Dibucaine number
80
141
Which neuromuscular blocking drug can lower seizure threshold
Atracurium and cysatracurium
Metabolite Laudanosine
142
Which neuromuscular blocking drug should be avoided in burns patients and why
Suxamethonium
Burns patients have up regulation of extrajunctional acetylcholine receptors. Causes life threatening hyperkalaemia
143
Which receptor abnormality predisposes to Malignant hyperthermia
Ryanodine receptor in sarcoplasmic reticulum
(RyR1 gene)
144
How are I.V fluid requirements calculated for children
100ml/kg/day for first 10kg
50ml/kg/day for next 10kg
20ml/kg/day for every kg after
145
When should irreversible MAOis be stopped prior to surgery
2 weeks prior
e.g phenelzine
146
When should reversible MAOis be stopped prior to surgery
Day of surgery
e.g moclobemide
147
Define the law of mass action
The rate of a chemical interaction is proportional to molecular concentration of its reacting components
148
Define dissociation constant (KD)
Measure of the propensity of a complex to dissociate into its constituent parts in equilibrium
Inverse of drug affinity
The drug dose at which 50% of drug receptors are bound and 50% are unbound
149
Give an example of a drug that is an inverse agonist
Naloxone
150
How does rapid peritoneal distension cause reflex bradycardia
Vagal efferents via M2 acetylcholine receptors on the heart
151
How can neuraxial blockade cause reflex bradycardia
Cardioacceleratory fibres from T1-T4 spinal segments
152
What is the chemoreceptor trigger zone also known as
Area postrema
153
What is the mechanism of action of botulinum toxin
Prevents pre-synaptic release of Ach causing placid paralysis
154
Which chromosome encodes acetylcholinesterase
Chromosome 3
155
Which anti-arrhythmic drug can be used in wolf-parkinson white
Amiodarone
156
Which drug can be given to overcome the effects of increased ADH released as a result of surgical stimulus
Furosemide 1mg/kg
157
What is the safe dose of ropivicaine
3mg/kg
158
what is the safe dose of levobupivacaine
2mg/kg
159
What is the safe dose of lidocaine + adrenaline
7mg/kg
160
What is the safe dose of prilocaine
6mg/kg
161
Why does pancuronium cause an increase in heart rate
Blockade of cardiac muscarinic receptors
162
Which antibiotics is first line for legionella infection
Clarithromycin
163
How does adrenaline cause hypokalaemia
Beta 2 agonist
Activates sodium-potassium-ATP pump causing cellular influx of potassium
164
What temperatures are packed red cells, platelets and FFP stored at
PRCs: 1-4 degrees
FFP: -15 degrees
Platelets: 20-24 degrees - under constant agitation
165
Which drug is given to treat organophosphate poisoning
Atropine
also Pralidoxime
166
What are the symptoms seen in organophosphate poisoning
Salivation, sweating, nausea, diarrhoea, tremor, confusion
167
Describe the mechanism of action of class 1A antiarrhythmic drugs?
Sodium channel blocker
MODERATELY reduce phase 0 of cardiac action potential
reduce action potential duration
decrease effective refractory period
E.G Procainamide
168
Describe the mechanism of action of class 1B antiarrhythmic drugs?
Sodium channel blocker
Small reduction in phase 0 of cardiac action potential
reduce action potential duration
decrease effective refractory period
E.G Lidocaine
169
Describe the mechanism of action of class 1C antiarrhythmic drugs?
Sodium channel blocker
Strong reduction in phase 0 of cardiac action potential
No effect on action potential duration or effective refratory period
E.G Flecainide
170
What effect does high dose magnesium have on neuromuscular blocking drugs
Potentiates muscle relaxation.
171
Describe mechanism of action of phenylephrine
What type of GPCR does it act on
Alpha 1 agonist
Gq receptor
Activates phospholipase C (PLC) which causes formation of inositol triphosphate (IP3) and diacylglycerol (DAG)
Leads to influx of calcium ions
172
Which chelating drug is used to treat lead poisoning
Dimercaprol
173
Give an example of drugs with a high extraction ratio > 0.7
Lidocaine, propanolol, morphine
(High extraction ratio means blood flow through an organ has large effect on its metabolism- less enzyme dependent)
174
Give an example of a drug with an intermediate extraction ratio 0.3 - 0.7
Midazolam
(Intermediate extraction ratio means the drugs metabolism is affected partially by blood flow through an organ but also enzyme activity)
175
Give an example of a drug with low extraction ratio < 0.3
Thiopentone
(low extraction ratio drugs are less affected by blood flow through an organ but more on enzyme activity and protein binding for metabolism)
176
Where is prilocaine metabolised
The lungs
177
Define Graham's law of diffusion
Rate of passive diffusion is inversely proportional to the square root of molecular size
178
Define Fick's law
rate of transfer across a membrane is proportional to the concentration gradient across the membrane
179
Name 2 drugs that are highly bound to albumin
Warfarin
Diazepam
180
What effect does acidifying urine have on weak acid and weak base drug re-absorption
Increases re-absorption of weak acids because more of the drug is unionised
Decreases re-absorption of weak bases because more of the drug is ionised
181
Give an example where alkalisation of urine is used in management of drug overdose
Aspirin (acetylsalicylic acid) overdose- a weak acid which becomes more ionised in alkaline urine and therefore less re-absorbed
182
Define extraction ratio (ER)
The fraction of a drug removed from the blood on each pass through the organ
183
What is the formula for ER
ER = Ci-Co/ Ci
(Extraction ratio = Concentration in - Concentration out/ Concentration in)
184
Define bioavailability
The fraction of administered dose of a drug that reaches the systemic circulation compared to the same dose given I.V
185
What is the formula for bioavailability
Bioavailability = (AUC oral/ AUC I.V) X100
186
What is the formula for volume of distribution
Vd = Drug dose/ Conc of drug in plasma
187
Define clearance
The volume of plasma cleared of a drug per unit time
188
List 3 types of phase 1 metabolism reactions
Oxidation
Reduction
Hydrolisis
189
List 3 types of conjugation reactions in phase 2 metabolism
Glucoronidation
Sulphation
Acetylation
190
Define elimination
The amount of drug removed from the body per unit time
191
Define Euler's number
Base of natural log
2.176
Base rate of change of an exponential process
192
How is rate constant related to time constant
They are reciprocals of each other
193
Define time constant (tau)
Time taken for negative exponential process to fall to 36.7% of the starting value
Time taken for negative exponential process to be complete if initial rate of decline maintained
194
How many time constants (tau) does it take for a negative exponential process to be complete
3
(94.9% complete)
195
How many half lives does it take for a negative exponential process to be complete
5
(97% complete)
196
What is the formula for half life
Half life = 0.693 X VD/ Cl
0.693 (decay constant = Ln(2)
197
Explain how morphine undergoes enters-hepatic recycling
Morphine undergoes glucoronidation in the liver to form metabolite morphine-6-glucoronide.
Gut flora bacteria metabolise M6G back to morphine which can be re-absorbed in the enterohepatic circulation.
198
Why do phase 2 metabolic reactions often improve drug clearance
Phase 2 reactions
- Make drug polarised and more water soluble
- Increase molecular weight- less reabsorbed
- Increase albumin binding- less active drug
199
Describe paracetamol metabolism
40% Glucoronidation
40% Sulphation
small amount undergoes oxidation to toxic metabolite NAPQI.
NAPQI metabolised by Glutathionine
200
Where are CYP450 enzymes predominantly found
Bound to lipid bilayer of endoplasmic reticulum of hepatocytes
201
how can polymorphisms of CYP2D6 affect the analgesic effect of codeine
Codeine is a pro drug metabolised to active form by CYP2D6.
If ultra fast metaboliser you get rapid onset of drug effect and unwanted effects. Duration of analgesia shorter
Slow metabolisers get less or not adequate analgesic effect
202
Which CYP450 enzyme is responsible for warfarin metabolism
CYP2C9
203
Which CYP450 enzyme is responsible for Diazepam metabolism
CYP2C19
(Absent in 20-30% of asian population)
204
What phase of metabolism are CYP450 enzymes involved in
Phase 1
Oxidation reactions
205
How does acetazolamyde reduce intra-ocular pressure
Carbonic anhydrase inhibitor. Carbonic anhydrase normally involved with aqueous humour production
206
What is the main active constituent of surfactant
80% a phospholipid called Dipalmitoylphospatidylcholine (DPPC)
20% Surfactant proteins (SP-A, SP-B, SP-C, SP-D)
207
What is a treatment of methaemoglobinemia
Methylene blue
208
In which rare but serious side effect of EMLA cream do you see chocolate coloured blood and reduced saturation
methaemoglobinemia
209
Which local anaesthetic is most commonly associated with methaemoglobinemia
Benzocaine
210
Which treatment may be used for methaemoglobinemia in pregnancy or patient with G6PD
I.V Vitamin C (Ascorbic acid)
Methylyne blue contra-indicated as teratogenic and triggers haemolysis in G6PD
211
What is the adrenaline dose for children aged 6 to 12
0.3ml of 1:1000 adrenaline I.M
212
What is the adrenaline dose for children under the age of 6
0.15ml of 1:1000 adrenaline I.M
213
List drugs prominently excreted unchanged in the urine
ACED LMNOP
Aminoglycosides
Cephalosporins
Ephedrine
Digoxin
Lithium
Milrinone
Neostigmine
Oxytetracycline
Penicillins
214
List properties of an ideal IV anaesthetic agent
Highly lipid soluble
Water soluble formation
Short half life
Analgesic at low doses
pre-prepared solution
rapid recovery after stopping infusion
anti-emetic properties
no histamine release
long shelf life
no drug interactions
painless on I.V injection
215
Outline Thiopental
Sulphur analogue of pentobarbital
Presented as yellow power in glass vial stored in nitrogen.
made up with water to form alkaline solution
pKa 7.6
Highly lipid soluble
80% protein bound
Undergoes hepatic metabolism
Severe damage if intra-arterial injection
216
217
What is the MAC of xenon
71%
218
How can you tell from the name if a LA is an amide or Esther type
Amide LA contain an "I" before Suffix "caine"
e.g Bupivacaine, ropivacaine, Lidocaine, Prilocaine
Esther: Cocaine, procaine
219
Where in the heart does Adenosine act
SAN
220
Why are increased doses of Suxamethonum required in neonates
Larger extracellular volume so water soluble drugs have higher volume of distribution.
221
Name another depolarising neuromuscular blocking drug other than suxamethonium
Decamethonium
222
What percentage protein bound is paracetamol
10%
223
What effect does morphine have on the biliary tree
Causes contraction of sphincter of Oddi causing increased pressure in biliary tree
224
What is the formula that relates time constant, volume of distribution and clearance
t = Vd/ Cl
225
Describe what zero- order kinetics is
Elimination of a drug is constant and independent of drug concentration
226
List 5 drugs that undergo zero order kinetics
PESTT
Phenytoin
Ethanol
Salicylates
Thiopental
Theophyline
227
Describe what First - order kinetics is
The rate of elimination of a drug is proportional to the concentration of the drug
228
What are the 2 main proteins that are involved in protein binding with drugs
Albumin- basic protein so binds acidic drugs e.g NSAIDs, warfarin, diazepam, propofol, thiopental
α1 glycoprotein- acidic protein so binds basic drugs e.g lidocaine, fentanyl, morphine, quinine
229
What is the mechanism of action of barbiturates
Bind to GABA dependent chloride channels
Hyper polarisation due to CL- influx
Inhibits action potential in neurone
230
What effect does Ketamine have on myocardial oxygen demand
Increases myocardial oxygen demand
231
Why is ketamine useful in patients with brittle asthma
Acts as bronchodilator
232
What effect does binding to μ1 opiate receptors have
Analgesic effect
233
What effect does binding to μ2 opiate receptors have
Respiratory depression
reduce gut motility
miosis
euphoria
bradycardia
234
What effect does binding to κ opiate receptors have
Analgesia
sedation
miosis
235
What effect does binding to δ opiate receptors have
Analgesia
Respiratory depression
236
For which opiod receptor does Naloxone have the highest affinity
μ
237
Describe mechanism of Vaughan-williams class Ia anti-arrhythmics
- "Intermediate dissociation kinetics"
- Blocks fast sodium channels. (slows phase 0 of cardiac AP)
- Widens QRS
- Prolongs AP
238
Describe mechanism of Vaughan-williams class Ib anti-arrhythmics
-"Rapid dissociation kinetics"
- Blocks fast sodium channels
- shorten AP
- No effect on phase 0 of AP
- Prolong QT
239
Describe mechanism of Vaughan-williams class Ic anti-arrhythmics
-"Slow dissociation kinetics"
- Blocks fast sodium channels
- Prolong phase 0 of AP
- No overall effect on AP duration
- Prolong QRS
240
Which anti-arrhythmics should be avoided in wolf Parkinson white and why?
Beta blockers
Adenosine,
amil, diltiazem also
Slows AV conduction promoting conduction via accessory pathway
241
What is an Inodilator drug
Give 3 examples
A drug that increases heart contractility and also causes vasodilation
Milrinone, Enoximone, Dopeximine
242
Which of the following has the largest impact on potency of local anaesthetic
Protein-binding
Lipid solubility
pKa
Lipid solubility
243
Which of the following has the largest impact on duration of action of local anaesthetic
Protein-binding
Lipid solubility
pKa
Protein binding
244
Which of the following has the largest impact on speed of onset of local anaesthetic
Protein-binding
Lipid solubility
pKa
pKa
245
What makes EMLA a eutectic mixture
Eutectic mixture is when the combination of two substances create unique physical properties.
EMLA has a lower boiling point than both of its constituents.
246
Which 2 local anaesthetics are mixed in EMLA cream
2.5% Prilocaine
2.5% Lidocaine
247
Which arrhythmia can be caused by suxamethonium
Bradycardia (muscarinic activity at SAN)
248
Which drug is an acetylcholine re-activator used in treatment of organophosphate poisoning
Pralidoxime
249
name a drug that is a first generation cephalosporins
Cefalexin
250
name a drug that is a 2nd generation cephalosporins
Cefuroxime
251
name a drug that is a 3rd generation cephalosporins
Ceftriaxone
Cefotaxime
Ceftazidime
252
Name a drug that is a carbapenems
Meropenam
Imipenam
253
Name a drug that is a tetracycline
Doxycycline
Tetracycline
254
Name a drug that is an aminoglycoside
Gentamycin
Neomycin
255
Name a drug that is a macrolide
Erythromycin
Clarithromycin
256
Name a drug that is a Quinolone
Ciprofloxacin
257
At what pH does Midazolam undergo ring closure and becomes unionised
pH >4
258
What is the mechanism of action of tricyclic anti depressants (TCAs)
Inhibit re-uptake of serotonin by blocking uptake 1
259
How do loop diuretics work
Inhibit Na+/K+/Cl- co-transporter in ascending loop of Henle
260
How does Spironolactone work
Inhibits aldosterone binding in DCT
K+ Sparing diuretic
261
How does acetazolamide work
Carbonic anhydrase inhibitor at PCT
262
How do Thiazide diuretics work
Inhibits NA+/CL- symporter in DCT. Reducing Na+ and CL- reabsorption
263
Outline the Armitage regimen used in caudal blocks for paediatric patients
0.25% Bupivacaine at volume 0.5ml/Kg for Lumbrosacral block to L1
0.25% Bupivacaine at volume 1ml/Kg for thoracolumbar block to T10
0.25% Bupivacaine at volume 1.2ml/kg for block to T6
264
When is recombinant Factor VIIa indicated
Used for patients with Haemophilia but can also be given in massive haemorrhage
265
In a 3 compartment model which compartment is the well perfused compartment
Compartment 2
266
In a 3 compartment model which compartment is the poorly perfused compartment
Compartment 3
267
In a 3 compartment model which compartment is the central compartment
Compartment 1
268
Which neuromuscular blocking drug undergoes Hoffman degradation
Atracurium
269
What type of isomerisation does Thiopental have
Tautomerisation
(Structural)
270
How does blood: gas partition co-efficient affect speed of onset and offset
Lower blood:gas co-efficient = faster onset and offset
271
What effect does a high oil:gas partition co-efficient have for inhaled anaesthetic gases
Higher oil:gas co-efficient higher potency
272
Which anaesthetic gas causes most respiratory depression
Enflurane
273
Which inhaled anaesthetic gas causes an increased sensitivity to catecholamines
Halothane
274
Which anaesthetic gas causes most increase in cerebral blood flow and ICP
Halothane
275
Which inhaled anaesthetic gas causes a lowered seizure threshold
Enflurane
276
List 5 drugs that cause prolonged action of neuromuscular blocking drugs
Local anaesthetics
Aminoglycosides- Gentamycin
Lithium
Oral contraceptive pill
CCBs
277
What effect does hypothermia have on neuromuscular blocking drugs
Prolongs blockade
278
Which drugs is given pre-operatively for management of pheochromocytoma
Phenoxybenzamine (predominantly alpha1 blocker)
279
When would Diltiazem or Verapamil be used in preference to adenosine for SVT
During bronchospasm
Asthmatics/ COPD
280
What is the mechanism of action of Digoxin
Inhibits Na+/K+/ATPase pump. Causes increased Na+ which leads to increased Ca2+ due to sodium-calcium exchange mechanism. This causes increased contractility
Increases vagal outflow to SAN and AVN which decreases HR
281
Why is Esmolol the shortest acting Beta blocker
Rapidly metabolised by plasma esterases
282
Which drug can be used to treat beta blocker overdose
Glucagon
283
Which 2 inhalation anaesthetic gases can precipitate an acute porphyric crisis
Halothane
Enflurance
284
Which I.V anaesthetic agents can precipitate an acute porphyric crisis
Etomidate
Sodium Thiopental
Ketamine
285
Can Propofol cause excitatory effect during induction
Yes
10% may experience dystonic movements
286
What is the active metabolite of midazolam
Oxazepam
287
Which benzodiazepam does not have any active metabolites
Lorazepam
288
What volume/kg is total body water in an adult
0.6L/kg
289
How does protein binding affect Volume of distribution (Vd)
More plasma bound the lower the volume of distribution
290
How is cocaine mainly metabolised
Liver ester hydrolysis
291
To which subunit of ACH receptors do non-depolarising neuromuscular blocking drugs bind
α-subunit
292
Which non-depolarising neuromuscular blocking drug has prolonged recovery with patients with plasma cholinesterase deficiency
Mivacurium
293
How is Mivacurium metabolised
Plasma cholinesterases
294
Do non-depolarising neuromuscular blocking drugs cross the placenta
No
They are large polarised molecules
295
How does Glycopyrolate cause increased dead space
anti-Muscarinic effect on M3 receptors causing bronchodilation which causes increased dead space
296
What is the mechanism of action of penicillins
Inhibits bacterial cell wall synthesis
Bactericidal
297
What is the mechanism of action of Aminoglycosides
Inhibit 30s ribosomal sub-unit. Inhibits protein synthesis
Bactericidal
298
What is the mechanism of action of Ciprofloxacin (Quinolones)
Inhibits alpha subunit of DNA gyrase so inhibits supercoiling of DNA
Bactericidal
299
What is the mechanism of action of Glycopeptides (Vancomycin/ Teicoplanin)
Inhibit bacterial cell wall synthesis
Bactericidal
300
What is the mechanism of action of Metronidazole
Damages bacterial DNA
Bactericidal
301
What is the mechanism of action of Rifampicin
Inhibits DNA dependant RNA polymerase
Bactericidal
302
What is the mechanism of action of Macrolide (Erythromycin, clarithromycin, Azythromycin)
Binds to 50s ribosomal sub unit. inhibits protein synthesis
Bacteriostatic
303
What is the mechanism of action of tetracyclines (Doxycycline, tetracycline)
Prevents tRNA from binding to ribosome
Bacteriostatic
304
What is the mechanism of action of Clindamycin
Inhibits ribosomal translocation
Bacteriostatic
305
What is the mechanism of action of Chloramphenicol
Binds to 50s ribosomal sub unit. inhibits protein synthesis
Bacteriostatic
306
What is the mechanism of action of Trimethroprim
Inhibits Dihydrofolate reductase (DHFR). Prevents DNA synthesis
bacteriostatic
307
What is the mechanism of action of Sulphonamides
Inhibits Dihydropteroate synthase (DHPS). Inhibits DNA synthesis
Bacteriostatic
308
Define Osmolality
The amount of osmotically active particles present per kilogram of solvent
mOsmol/kg
309
Define Osmolarity
The number of osmotically active particles per litre of solution
mOsm/L
310
Why is use of Nitrous Oxide during intracranial surgery potentially dangerous
Raises ICP
Raises cerebral metabolic rate for oxygen consumption
Impairs auto regulation of cerebral blood pressure
Increased cerebral blood flow
311
What plasma level of Salicilate overdose indicates Sodium Bicarbonate
>300mg/L
312
What plasma level of Salicilate overdose indicates renal replacement therapy
>700mg/L
313
Which CYP450 enzyme is responsible for metabolsim of most volatile anaesthetic agents
CYP2E1
314
Which wave on EEG has frequency 8-10Hz and is associated with eyes being closed
Alpha wave
315
Which wave on EEG has frequency 12-30Hz and is associated with being alert
Beta wave
316
Which wave on EEG has frequency 4Hz and is associated with sleep
Delta wave
(can be seen normally in children)
317
Which wave on EEG has frequency 4-8Hz and is associated with drowsiness
Theta wave
(can be seen normally in children)
318
What effect does ADH have on pulmonary vascular resistance
Reduces PVR by causing pulmonary vasodilation
319
What is the MAC of Isoflurane
1.17
320
What is the MAC of Enflurane
1.63
321
What is the MAC of Halothane
0.75
322
What is the MAC of Desflurane
6.6
323
What is the MAC of Nitrous Oxide
104
324
What is the MAC of Sevoflurane
1.8
325
What type of isomers are Isoflurane and Enflurane
Structural
326
What is the Blood:gas of Isoflurane
1.4
327
What is the Oil:gas of Isoflurane
91
328
What is the Blood:gas of Sevoflurane
0.7
329
What is the molecular weight of Sevoflurane
200
330
Does dry or wet pottasium hydroxide increase production of compound A when using Sevoflurane
Dry
331
Which volatile gas sensitises the heart to catecholamines
Halothane
332
What percentage of Propofol is protein bound
97%
333
What is the recommended paediatric induction dose of Propofol
4mg/Kg
334
What is the recommended Adult induction dose of Propofol
1.5-2mg/Kg
335
What is the Vd of Propofol
4L/kg
336
Why does giving Midazolam and Alfentanil increase the duration of action of both
Both drugs metabolised by CYP3A4
337
Which Isomer of Ketamine is more potent and has less emergence phenomena
S-Ketamine
338
What is the I.V induction dose of Etomidate
0.2- 0.3mg/Kg
339
Which I.V induction agent is associated with adrenal insufficiency
Etomidate
340
Why does Thiopentone cause reduced urine output
Thiopentone stimulates ADH release
341
Following a burn when should Suxamethonium be avoided and why
Starting from 24 hours after the burn to 18 months after the burn
Upregulation of ACH receptors leading to hyperkalaemia
342
What effect does pregnancy have on duration of action of Suxamethonium
Increases duration of action slightly
343
How id Malignant hyperthermia diagnosed
Muscle biopsy taken and sample exposed to 2% Halothane and Caffeine
344
Which drugs should be avoided in patients with malignant hyperthermia
All volatile anaesthetic gases
Suxamethonium
345
What effect does Lithium have on non-depolarising neuromuscular blocking drugs
Prolongs action
346
How many chiral centres does Atracurium have
How many stereoisomers
4
10
347
What percentage of Atracurium undergoes Hoffman degradation
What about cys-Atracurium
40%
80%
348
Why should tramadol be avoided in patients taking MAOi drugs
Tramadols main action is by inhibiting Serotonin and noradrenaline re-uptake
Risk of serotonergic crisis
349
Which group of antibiotics causes discolouration of teeth in children
Tetracyclines
350
Which antibiotic causes red man syndrome
Vancomycin
351
Which I.V Anaesthetic agents are Porphyrogenic
Thiopentone
Ketamine
352
Which Inhalation anaesthetic gas is porphyrogenic
Sevoflurane
353
Which 2 analgesics are porphyrogenic
Oxycodone
Diclofenac
354
Which 2 antibiotics are porphyrogenic
Rifampicin
Erythromycin
355
Which vasopressor drug is porphyrogenic
Ephedrine
356
What is the risk of using Ephedrine in a patient taking an MAOi
Hypertensive crisis
357
Give an example of a non- selective MAOi
Phenelzine
358
Give an example of a MAO-B inhibitor
Selegiline
359
What are the ECG signs of Digoxin toxicity
Short QT
ST depression
T wave inversion (reverse tick)
360
Describe the Bowman principle for speed of onset of neuromuscular blocking drugs
The less potent the drug the higher the concentration required which causes a larger concentration gradient and increases onset of action
361
What is the pKa of Alfentanil
6.5
362
What effect does propranolol have on thyroid hormone
Inhibits conversion of T4 to T3
363
What are the signs of cyanide poisoning on ABG
High Anion gap metabolic acidosis
raised mixed venous blood PO2 (Narrow oxygen saturation gap)
364
What effect does pregnancy have on dose requirements for spinal local anaesthetics
Reduced dose required because:
Reduced CSF volume
Progesterone mediated increased neural sensitivity
365
List factors that increase the MAC of volatiles
Infancy
Hyperthyroidism
Hyperthermia
Hypernatraemia
Chronic opiod or Alcohol use
Catecholamines
366
List factors that reduce the MAC of volatiles
Elderly
Hypothyroidism
Hypothermia
Pregnancy
Hypotension
acute opiod or alcohol use
Alpha 2 agonists
Lithium
367
Which COX enzyme is predominantly involved in production of prostaglandins which alter renal blood flow
COX-1
368
Which COX enzyme is predominantly involved in production of prostaglandins which form the protective mucosal barrier in the stomach
COX-1
369
Inhibition of which COX enzyme has greatest anti-pyretic, anti-inflammatory and analgesic effect
COX-2
370
How is Rocuronium excreted
95% Unchanged into the bile
371
What metabolic disturbance can thiazide diuretics cause
hypokalaemic hypochloraemic metabolic alkalosis
372
What is the pKa of lignocaine
7.8
373
What is the pKa of bupivacaine
8.1
374
What is the pKa of Alfentanyl
6.5
375
What is the pKa of Fentanyl
8.4
376
