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Primary FRCA MCQ > Pharmacology > Flashcards

Pharmacology Flashcards

1
Q

What is the chemical name of propofol

A

2,6-di-isopropyl phenol

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2
Q

What are the 2 types of volatile anaesthetic agents?

A

Halogenated hydrocarbons
Ethers

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3
Q

List 4 examples of volatile agents that are ethers

A

Enflurane
Isoflurane
Sevoflurane
Desflurane

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4
Q

List 3 examples of volatile agents that are halogenated hydrocarbons

A

Halothane
Trichloroethylene
Chloroform

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5
Q

What effect does adding a CL or BR group to halogenated hydrocarbons have

A

Increases potency

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6
Q

What effect does adding a F (flouride) group to halogenated hydrocarbons have

A

Increases stability

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7
Q

What are the 2 types of local anaesthetic

A

Amino Esters
Amino Amides

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8
Q

List 2 examples of Amino ester local anaesthetics

A

Procaine
Tetracaine

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9
Q

List 2 examples of amino amide local anaesthetics

A

Lidocaine
Bupivicaine

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10
Q

How are amino esther local anaesthetics metabolised

A

Broken down rapidly in plasma by esterase

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11
Q

How are amino amide local anaesthetics metabolised

A

Broken down slowly in liver

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12
Q

Define an acid

A

Proton donor

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13
Q

Define a base

A

Proton aceptor

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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

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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)

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16
Q

What effect does having a longer carbon chain have on a drugs solubility?

A

Reduced

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17
Q

What effect does having more functional groups have on a drugs solubility?

A

Increases solubility

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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

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19
Q

What happens to weak acids at pH above their pKa

A

They become ionised

Acid Ionised ABOVE pKa

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20
Q

What happens to weak bases at pH below their pKa

A

They become ionised

Base ionised BELOW pKa

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21
Q

What is the pKa of Thiopental

A

7.6

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22
Q

What is the pKa of Propofol

A

11

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23
Q

What is the pKa of Etomidate

A

4.2

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24
Q

What is the pKa of Ketamine

A

7.5

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25
Q

Is propofol ionised or unionised at body pH? How does this affect solubility?

A

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.

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26
Q

Which functional group makes propofol a weak acid?

A

Phenol

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27
Q

Is propofol a weak acid or a weak base?

A

Weak acid

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28
Q

Is thiopental a weak acid or a weak base?

A

Weak acid

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29
Q

Is Etomidate a weak acid or a weak base?

A

Weak base

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30
Q

Is Ketamine a weak acid or a weak base?

A

Weak base

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31
Q

What is the Henderson-Hasselbach equation?

A

pH = pKa + Log( Base/ Acid)

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32
Q

Which 3 factors affect a drugs ability to cross the BBB

A

Lipid solubility - increases ability to cross BBB
pKA - un-ionised form crosses BBB
Protein binding- Protein binding reduces ability to cross BBB

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33
Q

What are the 3 functional groups in a local anaesthetic

A

Aromatic group
Intermediate chain (Ester or Amide)
Amine group

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34
Q

Define isomer

A

Compounds with the same chemical formula but different arrangement of atoms in space

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35
Q

Define tautomerisation

A

When 2 structural isomers exist in dynamic equilibrium

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36
Q

Which phenomenon occurs to Midazolam when exposed to body pH 7.4

A

pH dependent ring closure occurs to form benzodiazepine ring making it lipid soluble and un-ionised

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37
Q

Why do you need carbon-carbon double bonds to have geometric stereoisomers

A

Carbon-Carbon double bonds do not allow rotation

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38
Q

Define stereoisomers

A

Compounds with same chemical and molecular formula but different arrangement of atoms in space

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39
Q

What are the 2 forms of stereoisomers

A

Geometric
Optical

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40
Q

Describe optical isomers

A

A compound with 4 different functional groups attached to a chiral centre. This allows isomers to be mirror images but non-superimposable

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41
Q

Define Enantiomers

A

A pair of optical isomers that each rotate plane polarised light in opposite directions

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42
Q

What is plane polarised light

A

Light where the vibrations travel in one plane

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43
Q

Define dextrorotatory enantiomer (d)

A

The optical isomer that rotates plane polarised light to the right

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44
Q

Define levorotatory enantiomer (l)

A

The optical isomer that rotates plane polarised light to the left

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45
Q

Define racemic mixture (dl)

A

A mixture of levorotatory and dextrorotatory optical isomers

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46
Q

Explain the R S naming system of optical isomers

A

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

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47
Q

Define Diastereoisomers

A

Stereoisomers where the compound has more than 1 chiral centre

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48
Q

Define Potency

A

The amount of drug required to cause a defined effect

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49
Q

Define Affinity

A

The strength with which a drug binds to receptors

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50
Q

Define Intrinsic activity

A

E max of drug / E max of a full agonist

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51
Q

What is the Emax of an inverse agonist

A

-1

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52
Q

What is the Emax of a partial agonist

A

0 - 1

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53
Q

What is the Emax of an full agonist

A

1

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54
Q

Define constitutive activity

A

Receptors can signal in the absence of an agonist

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55
Q

How do inverse agonists work?

A

Inverse agonists are ligand that bind receptors and stop the constitutive activity.

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56
Q

Describe structure of G protein coupled receptors (GPCRs)

A

7 transmembrane helices, extracellular binding site, allosteric binding sites between helices, intracellular binding site for G protein.

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57
Q

What 3 subunits make up a G protein

A

Ga - Alpha
β- Beta
γ- Gamma

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58
Q

What are the 3 domains that make up the structure of an Enzyme linked receptor

A

1- Extracellular ligand-binding domain
2- Transmembrane domain
3- Intracellular active enzyme domain

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59
Q

Describe the structure of intracellular receptors

A

1- Transcription activating domain
2- DNA binding domain
3- Ligand binding domain
4- Inhibitory protein

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60
Q

Describe how steroid hormone receptors work

A

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.

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61
Q

What are the 2 types of intracellular receptors

A

1- Cytosolic
2- intranuclear

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62
Q

What kind of intracellular receptors are thyroid hormone receptor?

A

Type 2 intracellular receptors (intra-nuclear receptors)

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63
Q

Which short acting anti cholinesterase is used to diagnose Myastenia graves

A

Edrophonium
- Strength of muscle contractions increases after

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64
Q

How does Neostigmine work

A

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

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65
Q

List 3 parasympathetic effects of neostigmine

A

Bradycardia
Hypotension
Bronchoconstriction

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66
Q

Define drug idiosyncrasy

A

Genetically determined abnormal reaction to a drug related to enzyme deficiency

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67
Q

Explain what causes suxamethonium apnoea

A

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.

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68
Q

Describe a type A drug reaction

A
  • Most common type of drug reaction
  • Exaggerated or secondary effect to drug
  • Dose related
    e.g tinnitus with aspirin
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69
Q

Describe type B drug reaction

A
  • Bizarre unpredicted drug reaction
  • Not dose related
    e.g Sux apnoea, malignant hyperthermia, porphyria
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70
Q

Which 3 characteristics does DoTS classification of drug reactions use?

A

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

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71
Q

Define Coomb’s type I reaction and examples

A

Allergic
IgE mediated

Atopy
anaphylaxis
asthma

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72
Q

Define Coomb’s type II reaction and examples

A

cytotoxic
IgM and IgG bind to allergen- complement mediated

Thrombocytopenia
Autoimune Haemolytic anaemia

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73
Q

Define Coomb’s type III reaction and examples

A

Immune complex deposition
IgG-allergen complexes

SLE
Rheumatoid arthritis

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74
Q

Define Coomb’s type IV reaction and examples

A

Cell mediated
T-lymphocytes/ macrophages

Chronic transplant rejection
Delayed hypersensitivity reaction
Contact dermatitis

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75
Q

Describe pseudo allergic reactions

A

Reactions with the same clinical manifestations as allergic reaction due to histamine release but not caused by immunological reactions

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76
Q

Describe tachyphylaxis

A

Hyper-acute form of tolerance where rapidly increasing doses required for clinical effect.

E.g Ephedrine and Hydralazine

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77
Q

Describe 3 mechanisms of nitrate tolerance

A

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

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78
Q

What happens if thiopentone is given with suxamethonium

A

Thiopentone precipitates

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79
Q

How does sodium bicarbonate affect aspirin and barbiturate excretion

A

Sodium bicarbonate causes urine to become more alkaline.
This increases water solubility and excretion of weak acids.

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80
Q

How does magnesium affect non-polarising neuromuscular blocking drugs

A

Potentiates effect

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81
Q

Which electrolyte is increased by suxamethonium

A

Potassium

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82
Q

What effect does St John’s Wort have on CYP450

A

Enzyme inducer

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83
Q

What are anaesthetic considerations in patient taking Echinacea?

A

Taken to improve immune system
Causes hepatic failure
avoid hepatotoxic drugs such as amiodarone, methotrexate and halothane

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84
Q

What are anaesthetic considerations in patient taking Ephedra?

A

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

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85
Q

What are anaesthetic considerations in patient taking Garlic?

A

Taken to treat hypertension and hyperlipidaemia
potentiates anti-platelet effect
Bleeding risk with aspirin and NSAIDs

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86
Q

What are anaesthetic considerations in patient taking Ginger?

A

Taken for anti-inflammatory and anti-emetic properties
Bleeding risk with warfarin and NSAIDs

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87
Q

What are anaesthetic considerations in patient taking Gingko biloba?

A

Taken as thought to be neuroprotective
Bleeding risk with aspirin, NSAIDs and warfarin

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88
Q

What are anaesthetic considerations in patient taking Ginseng?

A

Taken as mood enhancer
Bleeding risk with warfarin and NSAIDs

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89
Q

What are anaesthetic considerations in patient taking Valerian?

A

Taken as anxiolytic and hypnotic
Potentiates anaesthetic prolonging emergence

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90
Q

List the CYP450 inhibitors

A

SICKFACES.COM

Sodium valproate
Isoniazid
Cimetidine
Ketoconazole
Fluconazole
Alcohol (acute), amiodarone
Ciprofloxacin, chloramphenicol
Erythromycin
Sulphonamides
.
Cranberry juice, grapefruit juice
Omeprazole
Metronidazole

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91
Q

List CYP450 inducers

A

BS CRAP GPS. - these INDUCE anger

Barbiturates
St John’s wort

Carbemazepine
Rifampicin
Alcohol (chronic)
Phenytoin

Grisofluzin
Phenobarbital
Sulphonylureas

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91
Q

Where are CYP450 enzymes found

A

Endoplasmic reticulum of hepatocytes

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92
Q

Do acids ionise at a pH above or below their pKA

A

Acids ionise at pH above their pKa

HA -> A- + H+

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93
Q

Do bases ionise at a pH above or below their pKa

A

Bases ionise below their pKa

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94
Q

How much stronger is I.V morphine compared to oramorph

A

3X

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95
Q

How much stronger is IV/ SC Diamorphine compared to Oramorph

A

3X

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96
Q

How much stronger is PO oxycodone compared to oramorph

A

2X

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97
Q

How much stronger is I.V fentanyl compared to Oramorph

A

100X

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98
Q

How much stronger is Trans Dermal fentanyl compared to Oramorph

A

100X

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99
Q

How much stronger is Tramadol compared to Oramorph

A

10X

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100
Q

What is the equivalent dose of Oramorph to 60mg Codeine

A

6mg Oramorph

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101
Q

What determines V1, V2, V3 in Schnider model for TIVA

A

V1- Fixed
V2- Age
V3- Fixed

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102
Q

What determines V1, V2, V3 in Marsh model for TIVA

A

V1- Lean body mass
V2- Lean body mass
V3- Lean body mass

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103
Q

When do you give I.V acetylcysteine for paracetamol overdose

A

-Patient presenting 8-24 hours after overdose
- Dose of paracetamol exceeds 150mg/kg

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104
Q

When do you give activated charcoal for paracetamol overdose

A
  • Patient presents <4 hours after overdose
  • Dose of paracetamol exceeds 150mg/kg
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105
Q

Describe mechanism of action of Gentamycin

A
  • Aminoglycoside
  • Binds protein ribosome 30S sub unit- 16S ribosomal ribonucleic acid inhibiting protein synthesis
  • Bactericidal
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106
Q

Which volatile gas causes the largest drop in BP

A

Enflurane

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107
Q

Which volatile gas can cause coronary steal syndrome

A

Isoflurane
- Causes coronary artery dilation- diseased vessels that can’t dilate get less blood

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108
Q

Which NSAID has most specificity for COX-2

A

Lumiracoxib

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109
Q

List 3 side effects of Etomidate?

A
  • Pain on injection
  • Respiratory depression
  • nausea and vomiting
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110
Q

What is the time to peak in Marsh and Schnider models?

A

1.7 minutes

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111
Q

Which TCI model can be used for propofol TIVA in children >3 years old

A

Kataria

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112
Q

Which TCI model can be used for propofol TIVA in children >1 years old

A

Paedfusor

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113
Q

What dose of hydrocortisone is equivalent to 40mg of prednisolone

A

160mg

X4

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114
Q

Which muscle relaxant is a diastereoisomer

A

Atracurium

Has more than 1 chiral centre

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115
Q

Which inhalation agent exerts the highest partial pressure in blood

A

Desflurane

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116
Q

Explain blood: gas partition co-efficient

A

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

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117
Q

What makes Lispro a fast acting insulin

A

Lispro has end molecule translocations in the Insulin. Stops insulin joining with multiple insulin molecules. Makes it more absorbable

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118
Q

What makes Glargine a slow acting insulin

A

Glycine-substituted insulin makes it slower to be absorbed

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119
Q

What is the mechanism of action of Dexmedetomidine

A

Central Alpha 2 agonist
Sedative, amnesic and analgesic effects

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120
Q

What is a Dibucaine number

A

The percentage of pseudocholinesterase enzyme activity inhibited by local anaesthetic Dibucaine

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121
Q

Which inhaled anaesthetic is safest in neurosurgery with increased ICP

A

Isoflurane

  • Reduces brain oxygen requirement
  • Minimal increase in cerebral blood flow
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122
Q

What is the mechanism of action of a tetracycline antibiotic

A

Binds to 30s subunit of bacterial ribosomes preventing protein synthesis

Bacteriostatic

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123
Q

Describe mechanism of Vaughan-williams class I anti-arrhythmics

A
  • Blocks fast sodium channels.
  • Widens QRS
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124
Q

Give example of Class I anti-arrhythmic

A

Procainamide (1a)
Lidocaine (1b)
Fleicanide (1c)

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125
Q

Describe mechanism of Vaughan-williams class II anti-arrhythmics

A

-Beta blockade
- prolongs PR

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126
Q

Give example of Class II anti-arrhythmic

A

Atenalol, Bisoprolol, carvediolol, esmolol, propanolol

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127
Q

Describe mechanism of Vaughan-williams class III anti-arrhythmics

A

Potassium channel blocker
Prolongs QT interval + slows sinus rate

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128
Q

Give example of Class III anti-arrhythmic

A

Amiodarone

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129
Q

Describe mechanism of Vaughan-williams class IV anti-arrhythmics

A

Calcium channel blockers
Prolongs PR interval + slows sinus rate

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130
Q

Give example of Class IV anti-arrhythmic

A

Diltiazem
Verapamil

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131
Q

Describe mechanism of Vaughan-williams class V anti-arrhythmics

A

Work by other mechanisms not in Class I-IV

e.g Magnesium sulphate, Adenosine, digoxin

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132
Q

What is Edrophonium used for and what is its mechanism of action?

A

Edrophonium is an anti cholinesterase drug that works by competitive inhibition.

Used in tensilon test to diagnose myasthenia gravis

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133
Q

Which metabolite of pancuronium is active

A

3-hydroxypancuronium

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134
Q

For which opioid receptors are fentanyl and remifentanyl agonists

A

MOP and KOP

No affinity for DOP receptors

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135
Q

What is the anaphylaxis rate per 100,000 for Suxamethonium

A

11.1 cases per 100,000

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136
Q

Which blood product is most useful for replacing fibrinogen

A

Cryoprecipitate

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137
Q

Why should suxamethonium be avoided in burns patients

A

Burns patients get up regulation of acetylcholine receptors which leads to life threatening hyperkalaemia with Suxamethonium

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138
Q

Which patients should avoid propofol if they have an egg allergy

A

Children with anaphylaxis to eggs only

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139
Q

Which CYP450 enzyme affects rate of metabolism of Morphine

A

CYP2D6

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140
Q

What is a normal Dibucaine number

A

80

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141
Q

Which neuromuscular blocking drug can lower seizure threshold

A

Atracurium and cysatracurium
Metabolite Laudanosine

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142
Q

Which neuromuscular blocking drug should be avoided in burns patients and why

A

Suxamethonium
Burns patients have up regulation of extrajunctional acetylcholine receptors. Causes life threatening hyperkalaemia

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143
Q

Which receptor abnormality predisposes to Malignant hyperthermia

A

Ryanodine receptor in sarcoplasmic reticulum
(RyR1 gene)

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144
Q

How are I.V fluid requirements calculated for children

A

100ml/kg/day for first 10kg
50ml/kg/day for next 10kg
20ml/kg/day for every kg after

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145
Q

When should irreversible MAOis be stopped prior to surgery

A

2 weeks prior
e.g phenelzine

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146
Q

When should reversible MAOis be stopped prior to surgery

A

Day of surgery
e.g moclobemide

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147
Q

Define the law of mass action

A

The rate of a chemical interaction is proportional to molecular concentration of its reacting components

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148
Q

Define dissociation constant (KD)

A

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

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149
Q

Give an example of a drug that is an inverse agonist

A

Naloxone

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150
Q

How does rapid peritoneal distension cause reflex bradycardia

A

Vagal efferents via M2 acetylcholine receptors on the heart

151
Q

How can neuraxial blockade cause reflex bradycardia

A

Cardioacceleratory fibres from T1-T4 spinal segments

152
Q

What is the chemoreceptor trigger zone also known as

A

Area postrema

153
Q

What is the mechanism of action of botulinum toxin

A

Prevents pre-synaptic release of Ach causing placid paralysis

154
Q

Which chromosome encodes acetylcholinesterase

A

Chromosome 3

155
Q

Which anti-arrhythmic drug can be used in wolf-parkinson white

A

Amiodarone

156
Q

Which drug can be given to overcome the effects of increased ADH released as a result of surgical stimulus

A

Furosemide 1mg/kg

157
Q

What is the safe dose of ropivicaine

158
Q

what is the safe dose of levobupivacaine

159
Q

What is the safe dose of lidocaine + adrenaline

160
Q

What is the safe dose of prilocaine

161
Q

Why does pancuronium cause an increase in heart rate

A

Blockade of cardiac muscarinic receptors

162
Q

Which antibiotics is first line for legionella infection

A

Clarithromycin

163
Q

How does adrenaline cause hypokalaemia

A

Beta 2 agonist
Activates sodium-potassium-ATP pump causing cellular influx of potassium

164
Q

What temperatures are packed red cells, platelets and FFP stored at

A

PRCs: 1-4 degrees
FFP: -15 degrees
Platelets: 20-24 degrees - under constant agitation

165
Q

Which drug is given to treat organophosphate poisoning

A

Atropine

also Pralidoxime

166
Q

What are the symptoms seen in organophosphate poisoning

A

Salivation, sweating, nausea, diarrhoea, tremor, confusion

167
Q

Describe the mechanism of action of class 1A antiarrhythmic drugs?

A

Sodium channel blocker
MODERATELY reduce phase 0 of cardiac action potential
reduce action potential duration
decrease effective refractory period

E.G Procainamide

168
Q

Describe the mechanism of action of class 1B antiarrhythmic drugs?

A

Sodium channel blocker
Small reduction in phase 0 of cardiac action potential
reduce action potential duration
decrease effective refractory period

E.G Lidocaine

169
Q

Describe the mechanism of action of class 1C antiarrhythmic drugs?

A

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
Q

What effect does high dose magnesium have on neuromuscular blocking drugs

A

Potentiates muscle relaxation.

171
Q

Describe mechanism of action of phenylephrine

What type of GPCR does it act on

A

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
Q

Which chelating drug is used to treat lead poisoning

A

Dimercaprol

173
Q

Give an example of drugs with a high extraction ratio > 0.7

A

Lidocaine, propanolol, morphine

(High extraction ratio means blood flow through an organ has large effect on its metabolism- less enzyme dependent)

174
Q

Give an example of a drug with an intermediate extraction ratio 0.3 - 0.7

A

Midazolam

(Intermediate extraction ratio means the drugs metabolism is affected partially by blood flow through an organ but also enzyme activity)

175
Q

Give an example of a drug with low extraction ratio < 0.3

A

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
Q

Where is prilocaine metabolised

177
Q

Define Graham’s law of diffusion

A

Rate of passive diffusion is inversely proportional to the square root of molecular size

178
Q

Define Fick’s law

A

rate of transfer across a membrane is proportional to the concentration gradient across the membrane

179
Q

Name 2 drugs that are highly bound to albumin

A

Warfarin
Diazepam

180
Q

What effect does acidifying urine have on weak acid and weak base drug re-absorption

A

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
Q

Give an example where alkalisation of urine is used in management of drug overdose

A

Aspirin (acetylsalicylic acid) overdose- a weak acid which becomes more ionised in alkaline urine and therefore less re-absorbed

182
Q

Define extraction ratio (ER)

A

The fraction of a drug removed from the blood on each pass through the organ

183
Q

What is the formula for ER

A

ER = Ci-Co/ Ci

(Extraction ratio = Concentration in - Concentration out/ Concentration in)

184
Q

Define bioavailability

A

The fraction of administered dose of a drug that reaches the systemic circulation compared to the same dose given I.V

185
Q

What is the formula for bioavailability

A

Bioavailability = (AUC oral/ AUC I.V) X100

186
Q

What is the formula for volume of distribution

A

Vd = Drug dose/ Conc of drug in plasma

187
Q

Define clearance

A

The volume of plasma cleared of a drug per unit time

188
Q

List 3 types of phase 1 metabolism reactions

A

Oxidation
Reduction
Hydrolisis

189
Q

List 3 types of conjugation reactions in phase 2 metabolism

A

Glucoronidation
Sulphation
Acetylation

190
Q

Define elimination

A

The amount of drug removed from the body per unit time

191
Q

Define Euler’s number

A

Base of natural log
2.176
Base rate of change of an exponential process

192
Q

How is rate constant related to time constant

A

They are reciprocals of each other

193
Q

Define time constant (tau)

A

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
Q

How many time constants (tau) does it take for a negative exponential process to be complete

A

3

(94.9% complete)

195
Q

How many half lives does it take for a negative exponential process to be complete

A

5

(97% complete)

196
Q

What is the formula for half life

A

Half life = 0.693 X VD/ Cl

0.693 (decay constant = Ln(2)

197
Q

Explain how morphine undergoes enters-hepatic recycling

A

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
Q

Why do phase 2 metabolic reactions often improve drug clearance

A

Phase 2 reactions
- Make drug polarised and more water soluble
- Increase molecular weight- less reabsorbed
- Increase albumin binding- less active drug

199
Q

Describe paracetamol metabolism

A

40% Glucoronidation
40% Sulphation

small amount undergoes oxidation to toxic metabolite NAPQI.

NAPQI metabolised by Glutathionine

200
Q

Where are CYP450 enzymes predominantly found

A

Bound to lipid bilayer of endoplasmic reticulum of hepatocytes

201
Q

how can polymorphisms of CYP2D6 affect the analgesic effect of codeine

A

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
Q

Which CYP450 enzyme is responsible for warfarin metabolism

203
Q

Which CYP450 enzyme is responsible for Diazepam metabolism

A

CYP2C19

(Absent in 20-30% of asian population)

204
Q

What phase of metabolism are CYP450 enzymes involved in

A

Phase 1

Oxidation reactions

205
Q

How does acetazolamyde reduce intra-ocular pressure

A

Carbonic anhydrase inhibitor. Carbonic anhydrase normally involved with aqueous humour production

206
Q

What is the main active constituent of surfactant

A

80% a phospholipid called Dipalmitoylphospatidylcholine (DPPC)

20% Surfactant proteins (SP-A, SP-B, SP-C, SP-D)

207
Q

What is a treatment of methaemoglobinemia

A

Methylene blue

208
Q

In which rare but serious side effect of EMLA cream do you see chocolate coloured blood and reduced saturation

A

methaemoglobinemia

209
Q

Which local anaesthetic is most commonly associated with methaemoglobinemia

A

Benzocaine

210
Q

Which treatment may be used for methaemoglobinemia in pregnancy or patient with G6PD

A

I.V Vitamin C (Ascorbic acid)

Methylyne blue contra-indicated as teratogenic and triggers haemolysis in G6PD

211
Q

What is the adrenaline dose for children aged 6 to 12

A

0.3ml of 1:1000 adrenaline I.M

212
Q

What is the adrenaline dose for children under the age of 6

A

0.15ml of 1:1000 adrenaline I.M

213
Q

List drugs prominently excreted unchanged in the urine

A

ACED LMNOP

Aminoglycosides
Cephalosporins
Ephedrine
Digoxin

Lithium
Milrinone
Neostigmine
Oxytetracycline
Penicillins

214
Q

List properties of an ideal IV anaesthetic agent

A

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
Q

Outline Thiopental

A

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

217
Q

What is the MAC of xenon

218
Q

How can you tell from the name if a LA is an amide or Esther type

A

Amide LA contain an “I” before Suffix “caine”

e.g Bupivacaine, ropivacaine, Lidocaine, Prilocaine

Esther: Cocaine, procaine

219
Q

Where in the heart does Adenosine act

220
Q

Why are increased doses of Suxamethonum required in neonates

A

Larger extracellular volume so water soluble drugs have higher volume of distribution.

221
Q

Name another depolarising neuromuscular blocking drug other than suxamethonium

A

Decamethonium

222
Q

What percentage protein bound is paracetamol

223
Q

What effect does morphine have on the biliary tree

A

Causes contraction of sphincter of Oddi causing increased pressure in biliary tree

224
Q

What is the formula that relates time constant, volume of distribution and clearance

A

t = Vd/ Cl

225
Q

Describe what zero- order kinetics is

A

Elimination of a drug is constant and independent of drug concentration

226
Q

List 5 drugs that undergo zero order kinetics

A

PESTT

Phenytoin
Ethanol
Salicylates
Thiopental
Theophyline

227
Q

Describe what First - order kinetics is

A

The rate of elimination of a drug is proportional to the concentration of the drug

228
Q

What are the 2 main proteins that are involved in protein binding with drugs

A

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
Q

What is the mechanism of action of barbiturates

A

Bind to GABA dependent chloride channels

Hyper polarisation due to CL- influx

Inhibits action potential in neurone

230
Q

What effect does Ketamine have on myocardial oxygen demand

A

Increases myocardial oxygen demand

231
Q

Why is ketamine useful in patients with brittle asthma

A

Acts as bronchodilator

232
Q

What effect does binding to μ1 opiate receptors have

A

Analgesic effect

233
Q

What effect does binding to μ2 opiate receptors have

A

Respiratory depression
reduce gut motility
miosis
euphoria
bradycardia

234
Q

What effect does binding to κ opiate receptors have

A

Analgesia
sedation
miosis

235
Q

What effect does binding to δ opiate receptors have

A

Analgesia
Respiratory depression

236
Q

For which opiod receptor does Naloxone have the highest affinity

237
Q

Describe mechanism of Vaughan-williams class Ia anti-arrhythmics

A
  • “Intermediate dissociation kinetics”
  • Blocks fast sodium channels. (slows phase 0 of cardiac AP)
  • Widens QRS
  • Prolongs AP
238
Q

Describe mechanism of Vaughan-williams class Ib anti-arrhythmics

A

-“Rapid dissociation kinetics”
- Blocks fast sodium channels
- shorten AP
- No effect on phase 0 of AP
- Prolong QT

239
Q

Describe mechanism of Vaughan-williams class Ic anti-arrhythmics

A

-“Slow dissociation kinetics”
- Blocks fast sodium channels
- Prolong phase 0 of AP
- No overall effect on AP duration
- Prolong QRS

240
Q

Which anti-arrhythmics should be avoided in wolf Parkinson white and why?

A

Beta blockers

Adenosine,
amil, diltiazem also

Slows AV conduction promoting conduction via accessory pathway

241
Q

What is an Inodilator drug

Give 3 examples

A

A drug that increases heart contractility and also causes vasodilation

Milrinone, Enoximone, Dopeximine

242
Q

Which of the following has the largest impact on potency of local anaesthetic

Protein-binding
Lipid solubility
pKa

A

Lipid solubility

243
Q

Which of the following has the largest impact on duration of action of local anaesthetic

Protein-binding
Lipid solubility
pKa

A

Protein binding

244
Q

Which of the following has the largest impact on speed of onset of local anaesthetic

Protein-binding
Lipid solubility
pKa

245
Q

What makes EMLA a eutectic mixture

A

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
Q

Which 2 local anaesthetics are mixed in EMLA cream

A

2.5% Prilocaine
2.5% Lidocaine

247
Q

Which arrhythmia can be caused by suxamethonium

A

Bradycardia (muscarinic activity at SAN)

248
Q

Which drug is an acetylcholine re-activator used in treatment of organophosphate poisoning

A

Pralidoxime

249
Q

name a drug that is a first generation cephalosporins

250
Q

name a drug that is a 2nd generation cephalosporins

A

Cefuroxime

251
Q

name a drug that is a 3rd generation cephalosporins

A

Ceftriaxone
Cefotaxime
Ceftazidime

252
Q

Name a drug that is a carbapenems

A

Meropenam
Imipenam

253
Q

Name a drug that is a tetracycline

A

Doxycycline
Tetracycline

254
Q

Name a drug that is an aminoglycoside

A

Gentamycin
Neomycin

255
Q

Name a drug that is a macrolide

A

Erythromycin
Clarithromycin

256
Q

Name a drug that is a Quinolone

A

Ciprofloxacin

257
Q

At what pH does Midazolam undergo ring closure and becomes unionised

258
Q

What is the mechanism of action of tricyclic anti depressants (TCAs)

A

Inhibit re-uptake of serotonin by blocking uptake 1

259
Q

How do loop diuretics work

A

Inhibit Na+/K+/Cl- co-transporter in ascending loop of Henle

260
Q

How does Spironolactone work

A

Inhibits aldosterone binding in DCT

K+ Sparing diuretic

261
Q

How does acetazolamide work

A

Carbonic anhydrase inhibitor at PCT

262
Q

How do Thiazide diuretics work

A

Inhibits NA+/CL- symporter in DCT. Reducing Na+ and CL- reabsorption

263
Q

Outline the Armitage regimen used in caudal blocks for paediatric patients

A

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
Q

When is recombinant Factor VIIa indicated

A

Used for patients with Haemophilia but can also be given in massive haemorrhage

265
Q

In a 3 compartment model which compartment is the well perfused compartment

A

Compartment 2

266
Q

In a 3 compartment model which compartment is the poorly perfused compartment

A

Compartment 3

267
Q

In a 3 compartment model which compartment is the central compartment

A

Compartment 1

268
Q

Which neuromuscular blocking drug undergoes Hoffman degradation

A

Atracurium

269
Q

What type of isomerisation does Thiopental have

A

Tautomerisation

(Structural)

270
Q

How does blood: gas partition co-efficient affect speed of onset and offset

A

Lower blood:gas co-efficient = faster onset and offset

271
Q

What effect does a high oil:gas partition co-efficient have for inhaled anaesthetic gases

A

Higher oil:gas co-efficient higher potency

272
Q

Which anaesthetic gas causes most respiratory depression

273
Q

Which inhaled anaesthetic gas causes an increased sensitivity to catecholamines

274
Q

Which anaesthetic gas causes most increase in cerebral blood flow and ICP

275
Q

Which inhaled anaesthetic gas causes a lowered seizure threshold

276
Q

List 5 drugs that cause prolonged action of neuromuscular blocking drugs

A

Local anaesthetics
Aminoglycosides- Gentamycin
Lithium
Oral contraceptive pill
CCBs

277
Q

What effect does hypothermia have on neuromuscular blocking drugs

A

Prolongs blockade

278
Q

Which drugs is given pre-operatively for management of pheochromocytoma

A

Phenoxybenzamine (predominantly alpha1 blocker)

279
Q

When would Diltiazem or Verapamil be used in preference to adenosine for SVT

A

During bronchospasm

Asthmatics/ COPD

280
Q

What is the mechanism of action of Digoxin

A

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
Q

Why is Esmolol the shortest acting Beta blocker

A

Rapidly metabolised by plasma esterases

282
Q

Which drug can be used to treat beta blocker overdose

283
Q

Which 2 inhalation anaesthetic gases can precipitate an acute porphyric crisis

A

Halothane
Enflurance

284
Q

Which I.V anaesthetic agents can precipitate an acute porphyric crisis

A

Etomidate
Sodium Thiopental
Ketamine

285
Q

Can Propofol cause excitatory effect during induction

A

Yes

10% may experience dystonic movements

286
Q

What is the active metabolite of midazolam

287
Q

Which benzodiazepam does not have any active metabolites

288
Q

What volume/kg is total body water in an adult

289
Q

How does protein binding affect Volume of distribution (Vd)

A

More plasma bound the lower the volume of distribution

290
Q

How is cocaine mainly metabolised

A

Liver ester hydrolysis

291
Q

To which subunit of ACH receptors do non-depolarising neuromuscular blocking drugs bind

A

α-subunit

292
Q

Which non-depolarising neuromuscular blocking drug has prolonged recovery with patients with plasma cholinesterase deficiency

A

Mivacurium

293
Q

How is Mivacurium metabolised

A

Plasma cholinesterases

294
Q

Do non-depolarising neuromuscular blocking drugs cross the placenta

A

No

They are large polarised molecules

295
Q

How does Glycopyrolate cause increased dead space

A

anti-Muscarinic effect on M3 receptors causing bronchodilation which causes increased dead space

296
Q

What is the mechanism of action of penicillins

A

Inhibits bacterial cell wall synthesis

Bactericidal

297
Q

What is the mechanism of action of Aminoglycosides

A

Inhibit 30s ribosomal sub-unit. Inhibits protein synthesis

Bactericidal

298
Q

What is the mechanism of action of Ciprofloxacin (Quinolones)

A

Inhibits alpha subunit of DNA gyrase so inhibits supercoiling of DNA

Bactericidal

299
Q

What is the mechanism of action of Glycopeptides (Vancomycin/ Teicoplanin)

A

Inhibit bacterial cell wall synthesis

Bactericidal

300
Q

What is the mechanism of action of Metronidazole

A

Damages bacterial DNA

Bactericidal

301
Q

What is the mechanism of action of Rifampicin

A

Inhibits DNA dependant RNA polymerase

Bactericidal

302
Q

What is the mechanism of action of Macrolide (Erythromycin, clarithromycin, Azythromycin)

A

Binds to 50s ribosomal sub unit. inhibits protein synthesis

Bacteriostatic

303
Q

What is the mechanism of action of tetracyclines (Doxycycline, tetracycline)

A

Prevents tRNA from binding to ribosome

Bacteriostatic

304
Q

What is the mechanism of action of Clindamycin

A

Inhibits ribosomal translocation

Bacteriostatic

305
Q

What is the mechanism of action of Chloramphenicol

A

Binds to 50s ribosomal sub unit. inhibits protein synthesis

Bacteriostatic

306
Q

What is the mechanism of action of Trimethroprim

A

Inhibits Dihydrofolate reductase (DHFR). Prevents DNA synthesis

bacteriostatic

307
Q

What is the mechanism of action of Sulphonamides

A

Inhibits Dihydropteroate synthase (DHPS). Inhibits DNA synthesis

Bacteriostatic

308
Q

Define Osmolality

A

The amount of osmotically active particles present per kilogram of solvent

mOsmol/kg

309
Q

Define Osmolarity

A

The number of osmotically active particles per litre of solution

mOsm/L

310
Q

Why is use of Nitrous Oxide during intracranial surgery potentially dangerous

A

Raises ICP

Raises cerebral metabolic rate for oxygen consumption

Impairs auto regulation of cerebral blood pressure

Increased cerebral blood flow

311
Q

What plasma level of Salicilate overdose indicates Sodium Bicarbonate

312
Q

What plasma level of Salicilate overdose indicates renal replacement therapy

313
Q

Which CYP450 enzyme is responsible for metabolsim of most volatile anaesthetic agents

314
Q

Which wave on EEG has frequency 8-10Hz and is associated with eyes being closed

A

Alpha wave

315
Q

Which wave on EEG has frequency 12-30Hz and is associated with being alert

316
Q

Which wave on EEG has frequency 4Hz and is associated with sleep

A

Delta wave

(can be seen normally in children)

317
Q

Which wave on EEG has frequency 4-8Hz and is associated with drowsiness

A

Theta wave

(can be seen normally in children)

318
Q

What effect does ADH have on pulmonary vascular resistance

A

Reduces PVR by causing pulmonary vasodilation

319
Q

What is the MAC of Isoflurane

320
Q

What is the MAC of Enflurane

321
Q

What is the MAC of Halothane

322
Q

What is the MAC of Desflurane

323
Q

What is the MAC of Nitrous Oxide

324
Q

What is the MAC of Sevoflurane

325
Q

What type of isomers are Isoflurane and Enflurane

A

Structural

326
Q

What is the Blood:gas of Isoflurane

327
Q

What is the Oil:gas of Isoflurane

328
Q

What is the Blood:gas of Sevoflurane

329
Q

What is the molecular weight of Sevoflurane

330
Q

Does dry or wet pottasium hydroxide increase production of compound A when using Sevoflurane

331
Q

Which volatile gas sensitises the heart to catecholamines

332
Q

What percentage of Propofol is protein bound

333
Q

What is the recommended paediatric induction dose of Propofol

334
Q

What is the recommended Adult induction dose of Propofol

A

1.5-2mg/Kg

335
Q

What is the Vd of Propofol

336
Q

Why does giving Midazolam and Alfentanil increase the duration of action of both

A

Both drugs metabolised by CYP3A4

337
Q

Which Isomer of Ketamine is more potent and has less emergence phenomena

A

S-Ketamine

338
Q

What is the I.V induction dose of Etomidate

A

0.2- 0.3mg/Kg

339
Q

Which I.V induction agent is associated with adrenal insufficiency

340
Q

Why does Thiopentone cause reduced urine output

A

Thiopentone stimulates ADH release

341
Q

Following a burn when should Suxamethonium be avoided and why

A

Starting from 24 hours after the burn to 18 months after the burn

Upregulation of ACH receptors leading to hyperkalaemia

342
Q

What effect does pregnancy have on duration of action of Suxamethonium

A

Increases duration of action slightly

343
Q

How id Malignant hyperthermia diagnosed

A

Muscle biopsy taken and sample exposed to 2% Halothane and Caffeine

344
Q

Which drugs should be avoided in patients with malignant hyperthermia

A

All volatile anaesthetic gases

Suxamethonium

345
Q

What effect does Lithium have on non-depolarising neuromuscular blocking drugs

A

Prolongs action

346
Q

How many chiral centres does Atracurium have

How many stereoisomers

347
Q

What percentage of Atracurium undergoes Hoffman degradation

What about cys-Atracurium

348
Q

Why should tramadol be avoided in patients taking MAOi drugs

A

Tramadols main action is by inhibiting Serotonin and noradrenaline re-uptake

Risk of serotonergic crisis

349
Q

Which group of antibiotics causes discolouration of teeth in children

A

Tetracyclines

350
Q

Which antibiotic causes red man syndrome

A

Vancomycin

351
Q

Which I.V Anaesthetic agents are Porphyrogenic

A

Thiopentone
Ketamine

352
Q

Which Inhalation anaesthetic gas is porphyrogenic

A

Sevoflurane

353
Q

Which 2 analgesics are porphyrogenic

A

Oxycodone
Diclofenac

354
Q

Which 2 antibiotics are porphyrogenic

A

Rifampicin
Erythromycin

355
Q

Which vasopressor drug is porphyrogenic

356
Q

What is the risk of using Ephedrine in a patient taking an MAOi

A

Hypertensive crisis

357
Q

Give an example of a non- selective MAOi

A

Phenelzine

358
Q

Give an example of a MAO-B inhibitor

A

Selegiline

359
Q

What are the ECG signs of Digoxin toxicity

A

Short QT
ST depression
T wave inversion (reverse tick)

360
Q

Describe the Bowman principle for speed of onset of neuromuscular blocking drugs

A

The less potent the drug the higher the concentration required which causes a larger concentration gradient and increases onset of action

361
Q

What is the pKa of Alfentanil

362
Q

What effect does propranolol have on thyroid hormone

A

Inhibits conversion of T4 to T3

363
Q

What are the signs of cyanide poisoning on ABG

A

High Anion gap metabolic acidosis
raised mixed venous blood PO2 (Narrow oxygen saturation gap)

364
Q

What effect does pregnancy have on dose requirements for spinal local anaesthetics

A

Reduced dose required because:
Reduced CSF volume
Progesterone mediated increased neural sensitivity

365
Q

List factors that increase the MAC of volatiles

A

Infancy
Hyperthyroidism
Hyperthermia
Hypernatraemia
Chronic opiod or Alcohol use
Catecholamines

366
Q

List factors that reduce the MAC of volatiles

A

Elderly
Hypothyroidism
Hypothermia
Pregnancy
Hypotension
acute opiod or alcohol use
Alpha 2 agonists
Lithium

367
Q

Which COX enzyme is predominantly involved in production of prostaglandins which alter renal blood flow

368
Q

Which COX enzyme is predominantly involved in production of prostaglandins which form the protective mucosal barrier in the stomach

369
Q

Inhibition of which COX enzyme has greatest anti-pyretic, anti-inflammatory and analgesic effect

370
Q

How is Rocuronium excreted

A

95% Unchanged into the bile

371
Q

What metabolic disturbance can thiazide diuretics cause

A

hypokalaemic hypochloraemic metabolic alkalosis

372
Q

What is the pKa of lignocaine

373
Q

What is the pKa of bupivacaine

374
Q

What is the pKa of Alfentanyl

375
Q

What is the pKa of Fentanyl

Primary FRCA MCQ (6 decks)

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