Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Primary FRCA > Pharmacology 2 > Flashcards

Pharmacology 2 Flashcards

1
Q

What is the law of mass action?

A

‘The velocity of a chemical reaction is proportional to the molecular concentrations of the reacting components’

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What do k1, k2 and KD denote in the context of mass action?

A

k1: rate of forward (association) reaction
k2: rate of backward (dissociation) reaction
KD: dissociation constant - defines equilibrium point of overall system

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is an example of a mass action equation for a drug/receptor interaction?

A

D + R ⇋ DR

D: drug
R: receptor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What factors represent the forward and backward ‘pressure’ of a reaction?

When is equilibrium reached?

A

forward = k1 x [D][R]

backward = k2 x [DR]

Equilibrium is reached when k1[D][R] = k2[DR]

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Why is KD important/useful?

A

It represents the constant ratio of dissociation:association for a particular interaction at equilibrium.

It permits comparison of equilibrium points for different combinations of molecules

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

How is affinity related to KD?

A

Affinity, or the affinity constant (KA) is the reciprocal of KD (1/KD)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is fractional occupancy?

Why is it relevant?

A

The proportion of receptors occupied by a drug. Denoted by r

When the drug concentration is equal to the dissociation constant, then r = 0.5

Thus the dissociation constant (KD) for a D-R interaction is the concentration at which half of the receptors are occupied

Thus the relationship between KD, r and [D] is as follows:

r = [D] / KD + [D]

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

How is KD made more visible on graphs of drug-receptor interactions?

A

Using a semi-logarithmic plot results in the changes at lower values becoming more apparent and thus comparable

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is the relationship between KD and ED50?

A

For agonists, intrinsic activity will be related to fractional occupancy. In vitro the KD = ED50

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are the features of the semi-logarithmic plot for drug concentration and fractional occupancy/intrinsic activity?

A
  • Sigmoid curve

- Occupancy rises with increasing [D]

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What effect does increasing the KD have on the fractional occupancy curve?

A

Shift to the right

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How are occupancy, efficacy and response related?

How can response be quantified without knowing fractional occupancy?

A

E = e r

E: response

e: efficacy
r: fractional occupancy

substituting into the fractional occupancy equation gives:

E = e[D] / KD + [D]

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is a full agonist?

A

A molecule with an efficacy of 1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is a partial agonist?

A

A molecule with an efficacy of >0 but <1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is an inverse agonist?

A

A molecule with efficacy <0 and ≥-1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is Michaelis-Menten kinetics?

A

Describes the relationship between the concentration of a substrate [S] and the velocity of the enzyme-substrate reaction.
It is a hyperbolic relationship and a graphical representation can be used to determine the Michaelis constant (Km) which is the substrate concentration at which the velocity of the reaction is half-maximal (Vmax/2)

Michaelis-Menten equation: V = Vmax [S] / (Km + [S])

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What factors may alter enzyme activity in constant environmental conditions?

A

By changing:

  • Substrate concentration
  • Km or Vmax
  • Changing the amount of enzyme present
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

How may drugs increase enzyme activity in the body?

A
  • Directly increasing Vmax or Km by positive allosteric modulation
  • Indirectly increasing Vmax or Km through intermediary messengers
  • Increasing quantity of enzyme via enzyme induction
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

How does insulin exhibit a direct allosteric effect?

A

Insulin functions as an allosteric modulator of the tyrosine kinase receptor, increasing its phosphorylating activity and mediating its intracellular actions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is an example of an indirect positive allosteric interaction?

A

G-protein coupled receptor agonists indirectly activate AC through the Gα subunit of the G-protein

eg. beta adrenoceptors, D1 receptors and H2 receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

How may drugs cause induction of enzymes?

A

Drug-induced increase in transcription and enzyme production

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What are the CYP enzyme subtypes and their inducers?

A

CYP1A2: Tobacco, Omeprazole

CYP2B6/C9: Barbiturates, Rifampicin

CYP2C19: Prednisolone, Carbamazepine, Rifampicin

CYP2E1: Ethanol, Isoniazid

CYP3A4: Phenytoin, Carbamazepine, Barbiturates, Rifampicin, Glucocorticoids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are some important drug interactions due to enzyme induction?

A

Vecuronium + Phenytoin / Carbamazepine - Reduced length of blockade

Warfarin + Rifampicin / Carbamazepine - Reduced efficacy of warfarin

Ciclosporin + Rifampicin - Reduced efficacy of ciclosporin

Barbiturates + Corticosteroids - Reduced efficacy of steroids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

How may drugs reduce enzyme activity?

A

By reducing:

  • Vmax/Km or both
  • Activity of second-messengers
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

How does allopurinol work?

A

Inhibition of xanthine oxidase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

How may enzyme inhibition be classified?

A

Reversible / Irreversible

Substrate / non-substrate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What are some examples of competitive enzyme inhibitors?

A
  • Neostigmine (AChE)
  • Ramipril (ACE)
  • Theophylline / Milrinone (PDE)
  • NSAIDs (COX)
28
Q

Describe the mechanism of ACh breakdown by AChE

A

Anionic / Esteratic site

  1. Anionic site attracts NH+ from choline end of molecule and serine residue in esteratic site binds OH of acetyl group.
  2. Hydrolysis breaks ester bond and releases choline.
  3. Rapid reaction of water with the acetylated enzyme forms acetic acid which is released from the esteratic site.
29
Q

Name 3 cholinesterase inhibitors which have different mechanisms of action

A

Neostigmine / pyridostigmine:

  • Act as substrates and bind to both sites
  • Carbamylate AChE (instead of acetylating)
  • Carbamyl group takes much longer to react with water, increasing occupation time at esteratic site
  • Reversible, competitive

Edrophonium:

  • Binds to anionic site only
  • Short-acting competitive inhibitor
  • Used diagnostically to confirm MG

Organophosphates:

  • Binds to both sites, but after cleavage leaves esteratic site phosphorylated.
  • Phosphorylated AChE reacts very slowly with water and the complex ‘ages’ with time, becoming irreversibly bound, resulting in permanent inactivity (and thus non-competitive inhibition)
30
Q

Where do organophosphate molecules exert their effects?

A

AChE and plasma cholinesterases

31
Q

How may organophosphate toxicity be treated?

A

Pralidoxime administered before ‘aging’ occurs (36-48h) displaces phosphate from esteratic site of AChE until sufficient time has allowed the clearance of the toxins.

Anticholinergic treatment (atropine) must be used until either the the above has been acheived or the patient has synthesised new AChE

32
Q

What is an example of an organophosphate?

A

Parathion / malathion

-Metabolised to paraoxon / malaoxon (active compound) in vivo

33
Q

What is the action of the phosphodiesterases (PDEs)?

A

Degrade the phosphodiester bond of cAMP and cGMP

34
Q

What are the important intracellular functions of cAMP and cGMP?

A

cAMP:

  • Activation of protein kinase A (PKA)
  • Results in increased glucose metabolism, lipid metabolism and Ca2+ release

cGMP:

  • Activation of protein kinase G (PKG)
  • Results in SM relaxation and reduced platelet activation
35
Q

How may PDEs be classified?

A

Non-selective / Selective

Non-selective:

  • eg. Methylxanthines (Aminophylline / theophylline)
  • Inhibit PDE in many tissues
  • Used for effect on bronchial smooth muscle
  • Side effects include positive inotropy, vasodilatation, lipolysis and platelet inhibition

Selective:

  • PDE3 inhibitors (Enoximone / milrinone) are cardioselective, acting as positive inotropes
  • PDE5 inhibitors (Dipyridamole / sildenafil) inhibit platelet aggregation and cause vascular SM relaxation
36
Q

What is the mechanism of action of NSAIDs?

A
  • Inhibition of cyclooxygenase (COX) which metabolises arachidonic acid into several products
  • Reduces inflammation through reduced production of prostaglandins
  • Aspirin is an irreversible non-selective COX inhibitor
  • Other NSAIDs are reversible, though have relatively long half-lives
  • Other effects of COX inhibition may be platelet inhibition, gastric ulceration and renal dysfunction
37
Q

How is vitamin K recycling affected by warfarin?

What effect does enzyme inhibition have on this?

A
  • Reduction of used (epoxide) vitamin K by Vit K epoxide reductase (VKOR) is needed for re-use (and thus activation of clotting factors)
  • Warfarin inhibits VKOR and exists in 2 enantiomers, of which S-warfarin is the more potent inhibitor
  • CYP2C9 metabolises S-warfarin
  • CYPs 1A1, 1A2 and 3A4 metabolise R-warfarin

-As well as drugs, pharmacogenomic and genetic variants of VKOR can affect warfarin dose requirements/complications

38
Q

How long does aspirin affect platelet function for?

A
  • Non-selective irreversible COX inhibitor

- Acetylates COX for duration of platelet lifespan (5-10 days)

39
Q

Other than aspirin, what are some more examples of irreversible enzyme inhibiting drugs?

A

Older non-selective MAOIs:

  • Phenelzine
  • Tranylcypromine
40
Q 
What enzymes do the following drugs affect?
Allopurinol
Aminophylline
Aspirin
Enalapril
Methyldopa
Edrophonium
Benzylpenicillin
Selegiline
A 
All inhibit:
Allopurinol - Xanthine oxidase
Aminophylline - PDE
Aspirin - COX
Enalapril - ACE
Methyldopa - DOPA decarboxylase
Edrophonium - AChE
Ben-pen - Bacterial wall peptidase
Selegiline - MAO
41
Q

Name the most important CYP subtypes that are inhibited and their associated important inhibitors

A

CYP1A2: Fluvoxamine

CYP2C9: Fluconazole, Amiodarone

CYP2C19: Lansoprazole, Omeprazole

CYP2D6: Fluoxetine, Paroxetine, Quinidine
-Note not subject to induction

CYP3A4: Clarithromycin, Grapefruit juice, Ketoconazole, Verapamil

42
Q

What are some important drug interactions due to P450 inhibition?

A

Beta-blockers + Verapamil / Diltiazem - Bradycardia, asystole, hypotension

Warfarin + Amiodarone - Increased bleeding risk

Ciclosporin + Grapefruit - Risk of toxicity

NSAIDs + paroxetine - Increased bleeding risk

Terfenidine + Clarithromycin - TdP

Buprenorphine + Ketoconazole - Risk of toxicity

43
Q

How may a drug reduce adenylyl cyclase activity?

Give an example

A

Gi-coupled receptor activation leads to a reduction in AC activity

Eg. mu-Opioid receptor agonists

44
Q

Give an example of a drug that inhibits Gs GPCRs?

A

Beta blockers

45
Q

Give an example of a class of drugs that are therapeutic enzymes

A

Fibrinolytics (plasminogen activators):

  • Streptokinase
  • Urokinase
  • Alteplase
46
Q

What is the mechanism of action of hyaluronidase?

How is it used clinically?

A

Degrades hyaluronic acid, which holds tissues together

Used mixed with LA in ophthalmic regional blocks to increase diffusion.

47
Q

What is an unwanted drug effect?

A

‘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’

48
Q

What type of adverse drug reactions may occur in anyone?

A
  • Overdose
  • Side effects
  • Interactions
49
Q

What types of ADRs may occur only in susceptible individuals?

A
  • Intolerance
  • Idiosyncrasy (genetically determined abnormal reaction)
  • Allergy and pseudoallergy
50
Q

What is the gene affected in suxamethonium apnoea?

How common is it?

A

Plasma pseudocholinesterase E1a gene

4% of caucasians carry an abnormality - more common in Asian/Middle-Eastern people and less common in Africans

51
Q

What are some common P450 genetic abnormalities?

A

CYP2D6:

  • metabolises codeine, tramadol, ondansetron and beta-blockers
  • Genetic variation may increase codeine metabolism (Saudi Arabian / Ethiopian) or decrease metabolism (Chinese). Low metabolism may result in poor analgesia.

CYP2C19:
-Affects metabolism of diazepam and TCAs. Found mostly in Chinese populations

52
Q

What is the significance of G6PD gene abnormality?

A

Causes haemolytic anaemia in susceptible individuals

Most common in Mediterranean, African and Asian populations. Affects use of sulphonamides and nitrofurantoin

53
Q

What is the abnormality responsible for acute intermittent porphyria?

A

Porphobilinogen deaminase deficiency

Most common in Switzerland, Sweden and the Netherlands. Affects barbiturate and nitrofurantoin use.

54
Q

How are ADRs traditionally classified?

What classifications have been added?

A

Type A / B

Type A (Augmented)

  • 85-90% of ADRs
  • Commony dose related and related to the pharmacological effect of the drug
  • May be primary (exaggerated drug response) or secondary (unrelated to desired effect)

Type B (Bizarre)

  • 10-15%
  • Unpredicted, not dose related
  • eg. sux apnoea, MH, porphyria

Added-
Type C (Cumulative)
-Cumulative dose and time related
-Eg. propofol infusion syndrome

Type D (Delayed)

  • Time related (but also to dose)
  • Fluoride nephrotoxicity
  • Trichloroethylene carcinogenesis
Type E (End of use)
-withdrawal

Type F (Failure)

  • Common, dose related
  • Often caused by interactions, eg. OCP failure with inducers
55
Q

What is the DoTS classification for ADRs?

A
  1. Dose-relatedness
    - Supra-/standard/sub-therapeutic doses
  2. Time-relatedness
    - Rapid/ early/ intermediate/ late/ delayed
    - First dose reactions
  3. Susceptibility
    - Sex
    - Genetics
    - Age
    - Physiological variation
    - Disease
    - Exogenous factors
56
Q

How may risk factors for immune drug reactions be classified?

A
  • Patient factors
  • Drug factors
  • Exacerbating factors
57
Q

Summarise the Coombs’ Types of immune reaction

A

Type I:

  • Allergy
  • IgE-mediated

Type II:

  • Cytotoxic, antibody-dependent
  • IgM, IgG, Complement mediated

Type III:

  • Immune complex mediated
  • IgG, Complement mediated

Type IV:

  • Cell-mediated
  • Lymphocyte mediated
58
Q

How does the World Allergy Organisation classify immune drug reactions?

A

Immediate / Delayed

Delayed is >1h from exposure

59
Q

How may allergies be diagnosed?

A
  • Skin prick tests
  • RAST
  • Mast cell tryptase
  • Provocation tests
60
Q

How may drug interactions be classified?

A

Pharmaceutical incompatibility:

  • Physical/chemical incompatibility
  • Neutralisation
  • Precipitation
  • Chelation
  • Absorption

Pharmacokinetic interactions
-ADME

Pharmacodynamic interactions

  • Summation / Potentiation / Synergism / Antagonism
  • Direct / Indirect
61
Q

How may hypokalaemia interact with drugs?

A

Increased myocardial instability -> increased risk of arrhythmia with catecholamines + anticholinergics

May be caused by :

  • Diuretics
  • Corticosteroids
  • Insulin
62
Q

How may hyperkalaemia interact with drugs?

A

Reduced cardiac automaticity

May be caused by:

  • Sux
  • K+ sparing diuretics
63
Q

How may hyponatraemia interact with drugs?

A

Potentiation of LAs

May be caused by:

  • Diuretics
  • Sulphonylurea
64
Q

How may hypernatraemia interact with drugs?

A

May be caused by

  • Mannitol
  • Sodium bicarb
  • Hypertonic saline
65
Q

How may hypomagnesaemia interact with drugs?

A

May cause cardiac arrhythmia

May be caused by:

  • Diuretics
  • Laxatives
66
Q

How may hypermagnesaemia interact with drugs?

A

Bradycardia, AV block
May prolong neuromuscular block
May cause peripheral vasodilation

67
Q

List the commonly used herbal medications relevant to anaesthesia and their effects

A

Echinacea:

  • Said to improve immune system
  • Modulates cytokines & stimulates macrophages and NK cells
  • Avoid co-administration of hepatotoxic drugs

Ephedra:

  • CNS stimulant, weight loss drug, asthma treatment
  • Sympathomimetic (may contribute to tachyphylaxis)
  • Caution with other sympathomimetics
  • Arrhythmia with halothane

Garlic:

  • Treatment of HTN, hyperlipidaemia and atherosclerosis
  • Antiplatelet effects
  • Caution if bleeding risk

Ginger:

  • Anti-inflammatory, antiemetic
  • Inhibit 5-HT, GI stimulant
  • Caution if bleeding risk

Gingko biloba:

  • Neuroprotective, improved blood flow
  • Free radical scavenger
  • Antiplatelet effects
  • Caution if bleeding risk

Ginseng:

  • Mood enhancer, aphrodisiac
  • Sympathomimetic
  • Caution if bleeding risk
  • Hypoglycaemic effect
  • Caution with other sympathomimetics

St John’s Wort:

  • Antidepressant
  • Induces CYP3A4 + 2C9
  • Possible MAOI type effects
  • Increased risk of serotonergic crisis
  • Sedative effect

Valerian:

  • Anxiolytic, hypnotic
  • Potentiates GABAergic system
  • Potential for withdrawal phenomena
  • Reduces anaesthetic requirement

Primary FRCA (34 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions