1
Q
Which factors affect drug transfer through the placenta?
A
- Lipid solubility: More lipid soluble, greater transfer
- Ionisation: More ionised, less transfer
- Protein binding: More binding, less transfer
- pH: Affects ionisation and transfer
- Molecular weight: Larger molecules pass less readily.
2
Q
Describe a covalent bond.
A
Two atoms share outer shell electrons. The negatively charged electrons attract both nuclei, overcoming their repulsion, forming a strong bond.
Occurs between non-metals.
3
Q
Describe an ionic bond.
A
An outer electron is transferred from one atom to another, creating a negatively charged ion (anion) and a positively charged ion (cation), resulting in electrostatic attraction.
Occurs between metals and non-metals.
4
Q
What is the rate constant?
A
Rate of change in plasma concentration per unit time.
In first-order kinetics, it relates the rate of change of plasma concentration to the concentration at a given time.
5
Q
What is the time constant?
A
Time taken for plasma concentration to reach zero if it continued at its initial rate.
This is also the time for plasma concentration to reach 1/e (about 37%) of its original value.
6
Q
State the equations that relate half-life to volume of distribution, clearance, rate constant and time constant.
A
t1/2 = 0.693 x Vd/Cl
t1/2 = 0.693/k
t1/2 = 0.693 x time constant
7
Q
List drugs associated with gynaecomastia.
A
- Digoxin
- Spironolactone
- Isoniazid
- Cimetidine
8
Q
State the equation linking volume of distribution, target plasma concentration, and initial dose.
A
Loading dose (mg) = target concentration (mg/ml) × volume of distribution (ml)
9
Q
Which enzyme converts codeine to morphine?
A
CYP2D6
10
Q
Give an example of a drug that is metabolised by red cell esterases.
A
Esmolol
11
Q
How do you determine the steady state concentration of a drug using infusion rate and clearance?
A
- Steady State Conc = Infusion Rate / Clearance
- At steady state, input = output.
- Infusion Rate = Elimination Rate
- Elimination Rate = Clearance (L/min) × Steady State Conc.
12
Q
Which types of reaction are carried out by the CYP450 system?
A
- Oxidation
- Reduction
- Hydrolysis
- Dealkylation
- Deamination
13
Q
What effect does probenecid have on plasma penicillin levels if coadministered?
A
- Probenecid is a renal tubular blocking agent.
- Penicillins are normally excreted via tubular secretion in the nephron. Blocking this secretion increases plasma levels approximately 2-4 times.
14
Q
What is the clearance of hydralazine dependent on?
A
- Genetic polymorphisms
- 50% of Caucasians are slow acetylators
15
Q
List some drugs that can cause interstitial lung disease.
A
- Nitrofurantoin
- Amiodarone
- Azathioprine
- Bleomycin
- Bisulfan
- Chlorambucil
- Cyclophosphamide
- Methotrexate
- Mitomycin
- Sulfasalazine
16
Q
State the equation for elimination of a drug.
A
Elimination (mg/min) = concentration (mg/ml) x clearance (ml/min)
17
Q
List some common CYP450 inducers.
A
- Phenytoin
- Carbamazepine
- Barbiturates
- Rifampicin
- Alcohol (chronic)
- Sulfonylureas
18
Q
List some common CYP450 inhibitors.
A
- Omeprazole
- Disulfiram
- Ethanol (acute)
- Valproate
- Isoniazid
- Cimetidine
- Erythromycin
- Sulfonamides
19
Q
What can happen if thiopentone and suxamethonium are given through the same line without flushing?
A
It can precipitate out of solution.
20
Q
Define:
clearance
A
Volume of plasma from which a drug is completely cleared per unit time (ml/min).
It is equal to the volume of distribution multiplied by the rate constant (the reciprocal of the time constant).
21
Q
What is ion trapping with regards to the placental transfer of bupivacaine?
A
- Foetal circulation has a lower pH than the maternal circulation
- Bupivacaine is a weak base with a pKa of 8.1.
- It is more ionised in the lower pH environment of the foetal circulation leading to accumulation.
22
Q
Why is increasing plasma pH useful in TCA overdose?
A
Protein binding is increased in alkaline blood, and therefore in those with a significant overdose, a plasma pH of 7.5-7.55 is the goal in order to reduce the mass of unbound, active drug.
They cause cardiotoxicity due to their effect on sodium channels
23
Q
What is the relationship between the rate constant and the time constant?
A
Rate Constant = 1/Time Constant
- Rate Constant: Measures how quickly drug concentration changes over time; represents the fraction of drug eliminated (or absorbed) per unit time. Units: inverse time (e.g., min⁻¹).
- Time Constant: Time for drug concentration to change by ~63% toward its final value in a first-order process; inverse of the rate constant: τ = 1/k.
24
Q
Which kinds of drugs use lean body weight for dosing and why?
A
Lipid soluble drugs
(e.g. propofol)
These accumulate in fat but fat is POORLY PERFUSED, so using TBW may overdose the patient when giving a bolus.
25
What is the **difference** between the alpha and beta half-life in a two-compartment model?
**Alpha Half-Life**: initial rapid distribution
**Beta Half-Life**: slower elimination phase (reflect redistribution from peripheral to central compartment, prior to elimination from the body)
26
State the equation for the **steady state concentration** of an infusion.
Css = R/Cl
| Steady State Concentration = Infusion Rate/Clearance
27
Why do drugs with a **small volume of distribution** tend to have longer context-sensitive half-times?
They remain mostly in the **central compartment**.
## Footnote
After stopping an infusion, there is less distribution into peripheral compartments and elimination is mostly dependent on metabolism and clearance (which can be slow).
28
How is the **therapeutic index** of a drug calculated?
Calculated by dividing the **toxic dose 50 (TD50)** by the minimum effective dose 50 (ED50).
29
How does the **Henderson-Hasselbalch** equation differ for **weak acids vs weak bases**?
Acids ionised Above
Bases ionised Below
30
Describe how the extent of **ionisation** affects the duration of action.
With greater ionisation, there is a **greater effective concentration in the plasma** and less redistribution into lipid stores meaning that duration of action could be longer
## Footnote
E.g. propofol is more unionised than fentanyl, meaning that it is REDISTRIBUTED rapidly and the duration of action is shorter
31
What are the two forms of **stereoisomerism**?
* **Geometric**: cis- and trans- around a C=C double bond.
* **Optical**: four different groups attached to a chiral centre forms non-superimposable mirror images. They have the same chemical and physical properties but rotate plane polarised right in opposite direction (D = right, L = left).
32
What are **diastereoisomers**?
When a drug has **more than 1 chiral centre** and hence do not form a mirror image of each other (A with C or D).
## Footnote
Atracurium, tramadol and methohexital are all Diastereoisomers as well as enantiomers.
33
What is the **reciprocal of KD**?
| (dissociation constant)
KA (affinity constant)
## Footnote
Describes the affinity of the drug to its receptor
34
State the **equation** that links observed drug response to **fractional occupancy** and **intrinsic activity**.
E = e x r
## Footnote
e: intrinsic activity
r: fractional occupancy
35
What is the **Michaelis constant**?
Km is the Michaelis constant which is the **concentration of substrate** at which the velocity of the reaction is **½ the Vmax**.
36
What are the three mechanisms by which drugs can **increase enzyme activity**?
* Direct positive allosteric modulation
* Indirect increase via intermediate messengers
* Increase in enzyme concentration (induction)
37
List some examples of drugs that are **reversible** competitive **enzyme inhibitors**.
* Neostigmine (acetylcholinesterase)
* Ramipril (ACE)
* Milrinone (phosphodiesterase 3)
* NSAIDs (COX)
38
Give examples of drugs that are **irreversible enzyme inhibitors**.
* Aspirin (non-selective COX)
* Phenelzine and tranylcypromine (MAO inhibitors)
39
List examples of **enzymes** used as drugs.
* **Fibrinolytics**: streptokinase, urokinase, alteplase
* **Hyaluronidase**: promotes diffusion in the ophthalmic region.
40
Define **adverse drug effect**.
Any noxious or unintended reaction to a drug that has been given at a **standard dose** by an **approved route** for the prevention, treatment or diagnosis of a condition.
41
List some examples of **pharmaceutical incompatibility**.
* Neutralisation (heparin and protamine)
* Precipitation (thiopentone and suxamethonium)
* Chelation (sugammadex and rocuronium)
* Absorption (halothane and rubber)
42
What are the four main types of **pharmacokinetic interactions**?
* **Absorption**: charcoal, prokinetics, antacids
* **Distribution**: beta-blockers reducing cardiac output, drugs affecting protein-binding
* **Metabolism**: liver blood flow, drugs with high hepatic extraction ratio (e.g., lidocaine)
* **Elimination**: doxapram increases minute ventilation, enhancing offset of volatiles.
43
What are the four types of **pharmacodynamic interactions**?
* **Summation**: additive effect (e.g., benzodiazepines and propofol)
* **Synergism**: effect greater than the sum (e.g., propofol and remifentanil)
* **Potentiation**: one drug enhances another's effect (e.g., magnesium and non-depolarising NMBs)
* **Antagonism**: one drug opposes another's effect (e.g., neostigmine and non-depolarising NMBs)
44
Which features of a drug would mean that it is more likely to be **removed by haemofiltration**?
* Low molecular weight
* Lower protein-binding
* Small volume of distribution
* High water solubility
* Low endogenous clearance
## Footnote
Examples: methanol, ethylene glycol, aspirin, lithium, valproate
45
After how many time **constants** and **half-lives** would an intravenously administered drug be at negligible concentrations?
* Time Constants: **3**
* Half-Lives: **5**
46
How do you determine the **elimination rate** of a steady state infusion?
Elimination Rate = Cl x Css
47
How does the **initial loading dose** relate to clearance?
It does **not** change with clearance.
Loading Dose = Target Conc x Vd
## Footnote
Maintenance dose depends on clearance.
48
What are the determinants of the **V1**, **V2**, and **V3** compartments in the **Marsh** and **Schneider** models?
* **Marsh**: Lean body weight affects **all** 3 compartments (V1 is largest).
* **Schneider**: V1 fixed at **4.27 L**; V2 varies with **age**; V3 is **fixed**.
## Footnote
Clearance is determined by age, height, weight, and sex.
49
Which drugs are affected by **N-acetyltransferase**?
* Isoniazid
* Hydralazine
* Procainamide
* Dapsone
* Sulfasalazine
50
List some drugs that can **increase intraocular pressure**.
* Ketamine
* Suxamethonium
* Atropine
* Ephedrine
* Prednisolone
51
Which **vasopressor** is metabolized in the lungs?
**Noradrenaline** is metabolized by pulmonary endothelial cells containing MAO and COMT.
## Footnote
The lungs also heavily metabolize serotonin.
52
What is the **interaction** between omeprazole and clopidogrel?
Omeprazole **inhibits CYP2C19** which is responsible for **converting clopidogrel** into its **active form**.
53
How does aspirin interact with **warfarin**?
* Aspirin and warfarin are **highly protein bound**.
* Aspirin can displace warfarin from protein resulting in a **greater free fraction of warfarin**.
54
Why does diclofenac **increase INR** when coadministered with warfarin more than aspirin?
**Diclofenac** is 99.5% protein bound whereas **aspirin** is 85% protein bound
55
State the equation for **bioavailability**.
Fraction = [AUC (PO) × Dose (IV)] / [AUC (IV) × Dose (PO)]
56
Which properties of a drug would lead to a **high volume of distribution**?
* High lipid solubility
* Highly unionised
* Low plasma protein binding
57
Which drugs can be **inactivated** by sodium bicarbonate?
* Suxamethonium
* Glycopyrrolate
* Adrenaline
* Isoprenaline
* Benzylpenicillin
58
What are **alkanes**?
Carbon chains **without** any functional groups.
## Footnote
E.g. methane, ethane, propane, butane
59
What is an **aromatic compound**?
Contains a benzene ring.
## Footnote
A benzene ring with an alcohol group is called a phenol.
60
# Define:
valency
How many **bonds** an atom of that element can form.
## Footnote
It's essentially the number of electrons an atom needs to gain, lose, or share to achieve a stable electron configuration.
61
What are the **differences** between the metabolism of ester and amide local anaesthetics?
* **Ester**: hydrolysed quickly in the plasma by esterases
* **Amide**: metabolised slowly by the liver
62
How can the structure of **local anaesthetics** be altered to increase lipid solubility and protein binding?
* Increase bulk of the amide side chain
* Add groups to the aromatic portion
63
Describe the acid-base activity of **amines**.
Amines are **bases as the lone pair of electrons** on the nitrogen can bond with a free hydrogen to form a positively charged ammonium group.
64
What is **tautomerisation**?
When a compound rapidly **interconverts** between **two isomeric forms** (keto and enol) typically by the movement of a proton and a shift in bonding.
65
How does **thiopental** demonstrate tautomerism?
* It is prepared in an **alkaline solution (pH 10.5)**.
* At this pH, the **enol** form is favoured which is water soluble.
* At physiological pH, it changes to its **keto** form which is **more lipid soluble** and can cross the BBB.
66
What are some properties of **ionic compounds**?
* High melting and boiling points due to strong forces between ions
* Water soluble
* Conduct electricity which is carried by ions that are free to move when the compound melts or dissolves
67
Which covalent bonds are considered **polar**?
When the **electrons** are pulled more in **one direction** than the other.
68
# Define:
electronegativity
The ability of an atom to **attract shared electrons** in a chemical bond.
69
What are the three main types of **intermolecular interactions** in a gas?
* Van der Waals' forces
* Dipole-Dipole attractions
* Hydrogen bonding
70
What is a **hydrogen bond**?
Strongest type of intermolecular force. It occurs when a **hydrogen is bonded to a strongly electronegative atom** (e.g. oxygen) forming a very polar molecule, this leads to a very strong **dipole-dipole interactions**.
71
What are the two ways in a which a **covalent bond** can be **broken**?
* **Homolytic Fission**: each element takes one electron to form a free radical (required high temp or UV).
* **Heterolytic Fission**: the more electronegative element takes both electrons and oppositely charged ions are formed.
72
# Define:
water solubility
The ability of a compound to **disrupt the normal attraction** between water molecules in their fluid form (requires polarity).
73
What is the **difference** between strong and weak **electrolytes**?
* **Strong**: dissociates completely in water and is VERY water soluble (e.g. NaCl)
* **Weak**: only fraction of molecules exist as ions and can interfere with bonds between water molecules
74
Describe the acid-base activity of **aspirin**.
Weak **acid**
It has a **carboxyl** group
75
Describe the acid-base activity of **morphine**.
Weak **base**
It has an **amine** group
76
# Define:
pKa
The pH at which the proton donor and proton acceptor are **present in equal amounts**.
## Footnote
it is an indicator of how readily a functional group gives up or accepts a proton and becomes ionised in an aqueous environment
77
Briefly describe the **pH** at which weak acids and weak bases **ionise**.
* Weak acids: ionise **above** their pKa
* Weak bases: ionise **below** their pKa
78
What is the pKa of **thiopental**?
7.6
## Footnote
Functional Group: S=O
79
What is the pKa of **propofol**?
11
## Footnote
Functional Group: -OH
80
What is the pKa of **etomidate**?
4.2
## Footnote
Functional Group: -N-
81
What is the pKa of **ketamine**?
7.5
## Footnote
Functional Group: -NH-
82
What is the pKa of **paracetamol**?
9.4
## Footnote
Functional Group: -OH
83
What is the pKa of **ibuprofen**?
4.9
## Footnote
Functional Group: -COOH
84
What is the pKa of **tramadol**?
9.4
## Footnote
Functional Group: -NR3
85
What is the pKa of **fentanyl**?
8.4
## Footnote
Functional Group: -N-
86
State the **Henderson-Hasselbalch** equation.
This can be used to **predict the ratio** of ionised to unionised form of a weak acid or weak base.
## Footnote
For an acid, the ionised form is on top, for a base it is at the bottom.
87
What is a **buffer**?
Consists of a **weak acid** and its **conjugate base**, or a **weak base** and its **conjugate acid**. Most effective at limiting pH changes around its pKa, where both forms are present in **equal amounts**.
88
What is the pKa of the **carbonic acid-bicarbonate buffer** system?
6.1
89
What is the pKa of the **phosphate buffer** system?
6.8
90
What are the three main factors that determine the extent to which a drug crosses the **blood-brain barrier**?
* Lipid Solubility
* Degree of Protein Binding
* pKa
91
What is a **stereoisomer**?
* Same molecular formula
* Same chemical structure
* Different spatial configurations
## Footnote
Two types: geometric and optical
92
What is a **geometric stereoisomer**?
Occurs in compounds with **C=C double bonds** (alkenes). There is **no rotation** around this bond meaning that there are two isomers: **Cis** and **Trans**.
93
What is an example of a commonly used drug in **anaesthesia** that has **geometric stereoisomers**?
Mivacurium
94
What are **optical isomers**?
Occurs when four different groups are attached to a **chiral center**. They form **non-superimposable mirror images**. Pairs of optical isomers are called **enantiomers**.
95
How would two **enantiomers** differ in their properties?
* Identical chemical and physical properties
* Rotate plane polarised light in opposite directions
* Dextrorotatory (+) is to the right
* Levorotatory (-) is to the left
96
What is the difference between **D** and **L** enantiomers?
**D**: Reference group (e.g., –OH in sugars, –NH₂ in amino acids) is on the right in a Fischer projection.
**L**: Reference group is on the left relative to **D- and L-glyceraldehyde**.
97
Describe the effects of the two **enantiomers** of **ketamine**.
* **S(+)**: useful IV agent
* **R(-)**: causes agitation, postoperative pain, emergence reactions.
98
Describe the effects of the two **enantiomers** of **bupivacaine**.
* **S(-)**: prolonged local anaesthesia, less cardiotoxic (levobupivacaine)
* **R(+)**: convulsant and cardiotoxic.
99
Give an example of **charge neutralisation** as a non-specific drug action.
* **Antacids**: neutralise gastric acid.
* **Protamine**: a strong base that neutralises heparin's anticoagulant effect by forming an inactive complex cleared by the reticulo-endothelial system.
100
What is a **coordinate bond**?
Type of covalent bond where **both electrons** in the shared pair come from the **same atom**.
101
Describe the structure of **metal chelating agents** and their role.
These agents contain multiple oxygen, sulfur, or nitrogen atoms that form coordinate bonds with metal ions.
102
What does **encapsulation** mean in pharmacodynamics?
Form of chelation. Cyclodextrins are natural oligosaccharides. **Sugammadex** is a modified gamma-cyclodextrin that encapsulates rocuronium, creating a concentration gradient between NMJ and plasma.
103
List commonly used **anaesthetic drugs** that target **G proteins**.
* Opioids
* Atropine
* Adrenergic drugs
104
What is the **difference** between ionotropic and metabotropic receptors?
* **Ionotropic**: transmitter binding alters activity of ion channel leading to rapid synaptic transmission
* **Metabotropic**: transmitter binding and effector are separate, coupled via G protein that alters ion channel activity, slower response time
105
What are the **five families** of ionotropic receptors?
* Cys-Loop: e.g. nAChR
* Glutamate: e.g. NMDA
* P2X
* Transient receptor potential (TRP)
* Cyclic nucleotide-gated
106
Give examples of **receptor tyrosine kinases**.
* Insulin
* IGF
* VEGF
107
What are the two ways **ligands** can bind to a receptor?
* **Orthosteric**: site for endogenous activators.
* **Allosteric**: distinct modulatory sites.
108
List mechanisms for receptor **desensitization** after prolonged exposure.
* Downregulation of receptor expression
* Receptor internalization
* Receptor phosphorylation
109
Define **affinity** in drug-receptor interactions.
Strength of drug binding to a receptor.
110
What is the **dissociation constant** in drug-receptor interactions?
The dissociation constant (**KD**) is the equilibrium constant for drug–receptor binding, indicating the drug concentration at which 50% of receptors are occupied.
## Footnote
It equals koff/kon.
111
# Define:
potency
**Concentration of drug required** to achieve a desired effect.
## Footnote
**EC50** is a commonly used measure of potency: This is defined as the concentration at which a drug produces 50% of its maximal possible response.
112
Define **efficacy** in the context of pharmacodynamics.
The **maximum effect** that can be expected from a drug once it has bound to the receptor. It is an intrinsic property of the drug.
## Footnote
Ranges from 0 (no effect) to 1 (full effect).
113
State the **law of mass action**.
Rate of a reaction is proportional to the **concentration** of the reacting elements.
114
What is the **affinity constant**?
Reflects the strength of the drug-receptor bond.
## Footnote
KA = kon/koff
115
What is the **difference** between EC50 and ED50?
**EC50**: Concentration of a drug that produces a response halfway between baseline and maximum
**ED50**: Dose that produces a response in 50% of the population to whom it is administered
116
Define **intrinsic activity** of a drug.
Drug’s **maximal efficacy** as a fraction of the maximal efficacy achieved by a **full agonist acting on the same receptor** under the same conditions.
117
Define **functional selectivity** with regards to drug action.
Having **differing efficacies at a single receptor** for a variety of different cellular responses.
## Footnote
A drug, acting at the same receptor, can be an agonist, inverse agonist and antagonist simultaneously depending on the response being measured
118
What are the three mechanisms of **transmembrane signalling**?
1. G-protein coupled receptors
2. Enzyme linked receptors
3. Ion channel receptors
119
What are the three subunits of a **G protein**?
1. Alpha (activates effector molecule)
2. Beta
3. Gamma
120
List classes of drugs that act via **G protein coupled receptors**.
* Adrenergic agents
* Opioids (Gi linked)
* Atropine
* Angiotensin Receptor Blockers
121
Describe the activity of **enzyme-linked receptors**.
Transmembrane receptors that **activate intracellular enzymatic activity** upon ligand binding. Most common are **kinases** that phosphorylate amino acids (serine, threonine, tyrosine) in proteins.
122
Give some examples of **ligand-gated ion** channels.
* Nicotinic acetylcholine receptor
* 5HT-3 receptor
* NMDA
* GABA
123
Give two examples of **intracellular receptors**.
* Steroid
* Thyroid hormone
124
What are the two main **types** of intracellular receptor?
**Type 1**: binds to receptors in cytoplasm or nucleus (e.g. sex hormone, cortisol)
**Type 2**: binds directly to DNA proteins (e.g. thyroid hormone)
125
What are the three **components** of an intracellular receptor?
* Transcription-Activating Domain
* DNA-binding Domain
* Ligand-binding Domain
126
Describe the activity of **steroid hormone receptors**.
* Inactive in the cytoplasm, associated with heat shock proteins (HSPs) that stabilize them.
* Upon hormone binding, HSPs dissociate, revealing the nuclear localization sequence, allowing the ligand-receptor complex to enter the nucleus.
* The active complex interacts with hormone response elements (HRE) via the DNA binding domain, activating gene transcription.
127
State the **Michaelis-Menten equation**.
## Footnote
Where:
v = reaction velocity
Vmax = maximum velocity
[S] = substrate concentration
Km = Michaelis constant
128
Give an example of a **non-competitive enzyme inhibitor**.
Cyanide (cytochrome oxidase in the electron transport chain)
129
Give examples of **phase 1** reactions.
Oxidation, reduction and hydrolysis
130
Give examples of **phase 2** reactions.
Glucuronidation (MOST COMMON), sulfation, acetylation and methylation
131
Which **CYP enzyme** metabolises **lidocaine**?
* CYP1A2
* CYP3A4
132
Which **CYP enzyme** metabolises **propranolol**?
* CYP1A2
* CYP2C19
133
Which **CYP enzyme** metabolises **warfarin**?
CYP2C9
134
Which **CYP enzyme** metabolises **NSAIDs**?
CYP2C9
135
Which **CYP enzyme** metabolises **phenytoin**?
* CYP2C9
* CYP2C19
136
Which **CYP enzyme** metabolises **codeine**?
CYP2D6
137
Which **CYP enzyme** metabolises **sevoflurane** and **isoflurane**?
CYP2E1
138
Which **CYP enzyme** metabolises **midazolam**?
CYP3A4
## Footnote
Also metabolises temazepam and diazepam
139
Which **CYP enzyme** metabolises **fentanyl** and **alfentanil**?
CYP3A4
140
Which commonly used anaesthetic drugs are metabolised by **CYP2D6**?
* Codeine
* Tramadol
* Flecainide
* TCAs
* Metoclopramide
* Ondansetron
* Haloperidol
* Risperidone
141
List some common inhibitors of **CYP1A2**.
* Cimetidine
* Ciprofloxacin
* Erythromycin
* Amiodarone
142
List some common inhibitors of **CYP2C9**.
* Fluconazole
* Amiodarone
* Sertraline
* Metronidazole
143
List some common inhibitors of **CYP2C19**.
* Esomeprazole
* Citalopram
* Voriconazole
144
List some common inhibitors of **CYP2D6**.
* Fluoxetine
* Paroxetine
* Citalopram
* Amiodarone
* Cimetidine
145
List some common inhibitors of **CYP3A4**.
* Amiodarone
* Macrolides
* Azoles
* Diltiazem
* Verapamil
* Grapefruit juice
146
Which commonly used drug induces **CYP1A2**?
Omeprazole
147
Which commonly used drugs induce **CYP2C9**?
* Barbiturates
* Rifampicin
148
Which commonly used drugs induce **CYP2C19**?
* Rifampicin
* Prednisolone
* Carbamazepine
149
Which commonly used drugs induce **CYP2E1**?
* Ethanol
* Isoniazid
150
Which commonly used drugs induce **CYP3A4**?
* Phenytoin
* Carbamazepine
* Barbiturates
* Rifampicin
* Steroids
151
Which common drugs induce **CYP2B6/2C9**?
* Barbiturates
* Rifampicin
152
What is a **pseudoallergic** drug reaction?
Some clinical manifestations that are similar to allergic reactions driven by **histamine release** but they are **not** immunologic.
153
What are **Type A** and **Type B** adverse drug reactions?
* **Type A (Augmented)**: related to drug pharmacological effects, usually dose-related (e.g., hypotension with propofol).
* **Type B (Bizarre)**: unpredictable and NOT dose-related (e.g., malignant hyperthermia).
* **Extended classification**: C (Chronic), D (Delayed), E (End of Use), F (Failure)
154
What are the three components of the **DOTS** classification of unwanted drug effects?
* **Dose-Relatedness**: at normal dose or overdose
* **Time-Relatedness**: during treatment or independent of duration
* **Susceptibility**: e.g., age, sex
155
List factors affecting **absorption of a drug**.
* Drug formulation
* Route of administration
* Physicochemical properties (e.g. solubility, ionisation)
* Local blood flow
156
List some commonly used drugs that undergo high rates of **hepatic first pass metabolism**.
* Morphine
* Midazolam
* Lidocaine
* Aspirin
* GTN
157
How is **bioavailability** calculated?
Calculating the **area under the curve** which describes the blood concentration against time following administration of a drug via a defined route
## Footnote
For drugs taken **orally**:
Bioavailability = AUC(PO)/AUC(IV)
158
# Define:
drug distribution
Reversible **transfer of a drug** from one location to another.
159
# Define:
volume of distribution
The theoretical **volume** that an administered drug would have to occupy, assuming a uniform distribution in the body, to produce the **concentration of drug found in the plasma**.
## Footnote
In other words, based on the dose that we've given and the measured concentration in the plasma, what volume of fluid have we diluted that initial dose in?
160
State the **equation** for the volume of distribution of a drug.
Volume of Distribution = Administered Dose/Plasma Concentration
161
List key **factors** that affect drug distribution.
* Molecular size
* Charge and pKa
* Regional blood flow
* Concentration gradient
* Lipid solubility
* Protein binding
162
What are the **main plasma proteins** that bind to drugs?
Albumin and alpha-1 acid glycoprotein (AAG)
## Footnote
Albumin is alkaline so tends to bind to weakly acidic drugs (e.g. warfarin)
AAG is acidic and tends to bind to weakly alkaline drug (e.g. lidocaine)
163
Which well-known drug is particularly sensitive to **changes in plasma protein binding**?
Phenytoin (albumin concentration)
164
How does **plasma protein binding** affect volume of distribution?
Drugs that bind strongly to plasma proteins **remain in the bloodstream**, leading to higher plasma concentrations and less distribution into tissues. This results in a **lower volume of distribution** (Vd).
165
How does **tissue protein binding** affect volume of distribution?
If a drug binds highly to tissue proteins (e.g., receptors), the Vd is high because most of the drug is outside the vascular space, resulting in lower plasma concentrations.
166
Which enzyme metabolizes volatile agents in the liver?
**CYP2E1**; oxidation produces halogen ions and trifluoroacetic acid (TFCA), which can cause hepatitis.
## Footnote
CYP2E1 is induced by ethanol.
167
What percentage of **halothane** is metabolised in the liver?
20%
168
What percentage of **sevoflurane** is metabolised in the liver?
3-5%
## Footnote
Metabolised to hexafluoro-isopropanol.
169
What percentage of **enflurane** is metabolised in the liver?
2%
170
What percentage of **isoflurane** is metabolised in the liver?
0.20%
171
What percentage of **desflurane** is metabolised in the liver?
0.02%
172
What is the most metabolised **ether anaesthetic agent**?
Sevoflurane
## Footnote
3-5% metabolised to produce inorganic fluoride which can cause nephrotoxicity.
173
# Define:
What is the **hepatic extraction ratio**?
Fraction of **drug removed** during one pass through the liver.
## Footnote
**HER = (Ci - Co)/Ci**
Ci: drug concentration in blood entering the liver
Co: drug concentration in blood leaving the liver
174
What are the **differences** between flow- and capacity-dependent elimination?
* **Flow-Dependent**: for drugs with a high HER > 0.7, dependent on hepatic blood flow (e.g. propofol)
* **Capacity-Dependent**: for drugs with low HER < 0.3, dependent on metabolising capacity of the hepatocytes and on protein binding (e.g. warfarin, phenytoin)
175
What are the three mechanisms of **renal excretion**?
Renal excretion = (Glomerular filtration + Tubular secretion) - Reabsorption.
176
# Define:
partition coefficient
Ratio of substance amounts in **2 phases at equilibrium** with equal volumes.
177
How does drug distribution differ in **elderly patients**?
* Reduced blood volume
* Higher body fat proportion
* Lower plasma protein concentration
## Footnote
Water-soluble drugs have lower Vd; half-life of lipophilic drugs may be prolonged.
178
How are **drug interactions** classified?
* Physicochemical
* Pharmacokinetic
* Pharmacodynamic
179
What is a **physicochemical drug interaction**? Use examples.
Physical incompatibility between agents:
* **Thiopentone** and **suxamethonium** precipitate when mixed.
* **Sodium bicarbonate** and **calcium** form calcium carbonate upon mixing.
180
What are the mechanisms of **pharmacokinetic drug interactions**?
* Absorption (e.g., activated charcoal)
* Distribution (e.g., changes in protein binding)
* Metabolism (CYP450)
* Excretion (e.g., urinary alkalinization)
181
What is **potentiation** with regards to drug interaction?
Form of pharmacodynamic interaction where a drug has **no independent therapeutic effect** on its own, but can increase the therapeutic effect of another drug.
## Footnote
E.g. aminoglycosides and non-depolarising neuromuscular blockers
182
# Define:
ED50
**Graded**: Dose at which 50% of the maximum response is elicited in an individual
**Quantal**: Median effective dose at which 50% of individuals exhibit a specific response.
183
# Define:
What is **bioavailability**?
Proportion of an administered dose that reaches systemic circulation unchanged, compared to intravenous administration.
## Footnote
Determined by comparing the area under the plasma concentration–time curve (AUC).
184
What three factors determine **bioavailability**?
* Fraction absorbed
* Fraction remaining after gut metabolism
* Fraction remaining after hepatic first-pass metabolism
185
What are some examples of **structural isomers**?
* **Positional**: Isoflurane + Enflurane
* **Tautomerism**: Thiopentone
186
What are examples of **stereoisomers**?
* **Geometric**: Cisatracurium + Atracurium
* **Optical**: Levobupivacaine + Dextrobupivacaine
## Footnote
Optical isomers are defined by their rotation of plane-polarized light (right = dextro, left = levo).
187
What are the ways drugs **exert their effects**?
* **Physicochemical**: e.g., antacids
* **Enzymatic interactions**: e.g., ACE inhibitors
* **Voltage-gated ion channels**: e.g., local anaesthetics
* **Receptors**: e.g., steroids
188
What is the rate constant for elimination (**k**)?
Proportionality factor relating elimination rate to plasma concentration.
Can be described as the **fractional volume eliminated per unit time**, represented by the gradient of the log[c] vs time graph.
189
What are important interactions between **antidepressants** and **anaesthetic drugs**?
* **TCAs**: serotonin syndrome with tramadol/pethidine; potentiate ephedrine/metaraminol
* **SSRIs**: serotonin syndrome with tramadol/pethidine
* **MAOIs**: inhibit breakdown of indirectly acting sympathomimetics, causing profound pressor effect
## Footnote
Directly acting sympathomimetics are also metabolised by COMT.
190
Which **anaesthetic drugs** are metabolised by plasma cholinesterase and which by non-specific plasma esterases?
**PLASMA CHOLINESTERASE**
* Suxamethonium
* Mivacurium
* Ester local anaesthetics
**NON-SPECIFIC ESTERASES**
* Remifentanil
* Atracurium
* Etomidate
191
What does an **isobologram** illustrate?
An isobologram illustrates the **interaction between two drugs**, showing their **combined effects** on a specific outcome.
## Footnote
It helps in understanding whether the drugs have additive, synergistic, or antagonistic effects when used together.
192
What are the main mechanisms of **physicochemical drug interaction**? Provide an example for each.
* **Chelation**: sugammadex and rocuronium
* **Precipitation**: thiopentone and suxamethonium
* **Neutralisation**: heparin and protamine
* **Adsorption**: GTN and PVC
193
How does **ageing** affect **pharmacokinetics**?
* **Absorption**: Reduced absorption; bioavailability may increase due to impaired first-pass metabolism.
* **Distribution**: Decreased blood volume, increased body fat, lower plasma protein concentration.
* **Metabolism**: Reduced liver function and renal excretion.
194
What are key **pharmacodynamic** considerations in elderly patients?
* IV induction agents have greater effect due to higher free plasma concentration.
* Slower onset from reduced cardiac output.
* MAC reduced by 30%.
* Duration of volatile anaesthesia may be prolonged due to V/Q mismatch.
* NMB effect may be prolonged due to reduced plasma cholinesterase levels and impaired excretion.
195
How does **Kd** relate to **EC50**?
Relationship depends on spare receptors. Not all receptors need to be occupied for a maximal response (e.g., neuromuscular junction).
If only 10/100 receptors need occupancy for maximum response, **EC50** (concentration for 5/10 receptors) is lower than **Kd** (concentration for 50/100 receptors).
With increased competitive antagonism, **EC50** approaches **Kd** as fewer spare receptors are available.
196
List drugs metabolised by the **lungs**.
* Lidocaine
* Fentanyl
* Noradrenaline
197
What are the forms of **structural isomerism**?
* **Chain**: different carbon skeleton arrangement (e.g., isoflurane, enflurane)
* **Position**: different positions of the same functional group
* **Functional**: different atom positions create different functional groups
198
Give examples of **structural**, **geometric**, and **optical isomers** used in anaesthetics.
* **Structural**: Enflurane, Isoflurane, Dihydrocodeine, Dobutamine
* **Geometric**: Atracurium, Cisatracurium, Mivacurium
* **Optical**: Ketamine (S and R)
199
Give examples of drugs used in anaesthesia that are **racemic mixtures**.
* Ketamine
* Bupivacaine
* Atracurium
200
Give common drugs in **anaesthesia** targeting Gs, Gi, and Gq protein-coupled receptors.
* **Gs**: beta-1, beta-2, D1, V2
* **Gi**: alpha-2, mu opioid, M2
* **Gq**: alpha-1, M3, V1
201
Why are **logarithms** useful in **pharmacokinetics**?
Logs **linearize exponential drug** concentration–time data, simplifying the determination of elimination rates, half-lives, and kinetic parameters.
202
What is **second order kinetics**?
Reaction where the rate depends on the **product of 2 reactant concentrations** or the square of 1 reactant concentration.
203
Why are **log-dose response curves** more useful than dose response curves for partial and full agonists?
Log-dose response curves are **sigmoid**, allowing visualization across a wide dose range and making **Emax** and **EC50** easy to identify and compare.
204
Define suspension, colloid, and emulsion.
* **Suspension**: mixture where heavier particles settle due to gravity.
* **Colloid**: mixture with evenly dispersed particles that do not settle (e.g., human albumin solution).
* **Emulsion**: liquid-in-liquid colloid of immiscible liquids, stabilized by shaking/stirring and sometimes emulsifiers (e.g., propofol).
205
Describe the difference between drugs bound by **albumin** and **alpha-1 acid glycoprotein**.
* **Albumin**: binds acidic drugs (e.g., thiopental, midazolam, diazepam)
* **Alpha-1 Acid Glycoprotein**: binds basic drugs (e.g., opioids, local anesthetics)
206
Describe the mechanism of action of **opioids** on opioid receptors.
Opioids act via **GPCRs (Gi)**. Ligand binding closes **VGCCs** on the presynaptic membrane, reducing **cAMP** levels. This causes potassium efflux, leading to hyperpolarization, decreased neurotransmitter release, and reduced pain transmission.
207
State the equation for **hepatic clearance**.
Hepatic Clearance = Hepatic Blood Flow × Hepatic Extraction Ratio
208
What is the **Ka** in acid-base balance?
Acid dissociation constant. It indicates how much an acid dissociates (high Ka = strong acid).
[H⁺][A⁻]/[HA]
## Footnote
pKa is the negative log of Ka.
209
How do you derive concentration at time 0 in **first-order kinetics**?
Plot a semi-log graph of ln[C₀] vs. time to find the y-intercept. Then, e raised to ln[C₀] gives C₀.
210
Which reactions are **CYP450 enzymes** responsible for?
Primarily **Phase 1** reactions (mostly oxidation).
211
What are the systems for describing **stereoisomers**?
* **R and S**: based on priority
* **+ and -** (aka **d and l**): based on rotation of plane-polarized light
* **D and L**: based on comparison to **glutaraldehyde**
212
How does chronic liver disease affect **pharmacodynamics** and **pharmacokinetics**?
* Reduced drug metabolism
* Decreased plasma protein production (increased free drug fraction)
* Increased total body water (higher volume of distribution)
213
Which common anaesthetic drugs are broken down by **esterases**?
* **Remifentanil** & **etomidate**: non-specific
* **Mivacurium** & **suxamethonium**: pseudocholinesterase
* **Atracurium**: mainly Hofmann elimination + minor non-specific esterases
Primary FRCA
flashcards
Decks in class (17)
# Cards
-
Anatomy for Anaesthesia223
-
Physiology: Respiratory303
-
Physiology: Cardiovascular179
-
Physiology: Renal, Hepatic & GI63
-
Physiology: Neuro, Endo, & Haem237
-
Pharmacokinetics and Pharmacodynamics213
-
Pharmacology: Inhalational & Intravenous Agents232
-
Pharmacology: Analgesics & Muscle Relaxants160
-
Pharmacology: Emergency & Miscellaneous Drugs251
-
Part 1: Physics & Equipment242
-
Part 2: Physics & Equipment227
-
Part 3: Physics & Equipment232
-
Part 4: Physics & Equipment217
-
Statistics & Evidence-Based Practice36
-
Part 1: Applied Clinical Anaesthesia165
-
Part 2: Applied Clinical Anaesthesia169
-
Part 3: Applied Clinical Anaesthesia157
