Brainscape's Knowledge GenomeTM

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


See full index

Introduction to Metabolism and Pharmacology > Basic Principles 2 > Flashcards

Basic Principles 2 Flashcards

1
Q

Define Apparent volume of distribution (Vd) ?

A

This is the apparent volume into which the drug is distributed, usually expressed in litres (L)

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

Drugs administered orally may undergo ?

A

Extensive first-pass metabolism

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

Metabolism by enzymes in gut wall and in the liver, before systemic circulation results in ?

A

Low bioavailability

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

Such drugs therefore require ?

A

Higher oral dose (e.g. propranolol), or administered via routes that can avoid first pass metabolism: IV, IM, sublingual, nasal, rectal, transdermal, etc

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

Drugs are only effective if ?

A

They reach the target cells, at an appropriate concentration

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

Distribution of drugs depends on ?

A
  • Permeability across membranes
  • Binding within compartments
  • pH partitioning
  • Fat:water partitioning coefficient
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Total body water is about ?

A

60-80% of total body weight, and this is contained in different compartments:

  • Blood plasma
  • Interstitial fluid (between cells)
  • Intracellular fluid (inside cells)
  • Transcellular fluid (e.g. cerebrospinal, intraocular, peritoneal fluid)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Name two beta blockers ?

A

Propranolol and Atenolol

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

Explain Propranolol ?

A

It can cause sleep disturbances (vivid dreams); atenolol less so

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

Propranolol vs Atenolol

A

Propranolol is more lipid soluble and can cross BBB. Whereas Atenolol is more water soluble and does not cross BBB

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

How about Psychoactive drugs ?

A

This is are things such as nicotine, caffeine, LSD and MDMA. They are highly lipid soluble and
therefore able to pass through the blood brain barrier

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

Drugs are often ?

A

Bound to proteins, but only free, unbound drugs are biologically active and can move between compartments

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

In some cases, up to ?

A

99% of total drug can be bound to proteins (e.g. warfarin)

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

What is Albumin and explain the binding ?

A

is the main drug-binding protein. Others include α1-acid glycoprotein and β-globulin. Binding is rapidly reversible and non-specific.

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

Plasma proteins do not reflect ?

A

The target tissue, binding produces no physiological effect.

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

What does binding form ? and which drugs exerts its therapeutic effect ?

A

Forms a reservoir of drugs. Only the free, unbound drug is available to the tissue to exert its therapeutic effect.

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

What is the Apparent volume of distribution ?

A

This is the hypothetical volume into which the drug (Q) would be distributed in order to obtain the measured plasma concentration (Cp) and account for the total amount of drug administered

Q = dose in mg 
Cp = plasma concentration in mg/L
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What does Vd tell us about distribution of a drug in humans ?

A
  • Large molecules that are retained in plasma
    e. g. heparin, an anticoagulant - too large to cross capillary wall
  • Small polar molecules that cannot enter the cells
    e. g. antibiotics such as gentamicin
  • Small drugs that easily cross membranes
    e. g. Ethanol, phenytoin
  • Very hydrophobic, lipid-soluble drugs
    e. g. thiopental
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Plasma concentration decreases ?

A

Over time as drug is excreted and/or metabolised

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

How is drug eliminated ?

A

Metabolism and Excretion

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

Explain how Metabolism does this ?

A
  • Two phases of drug metabolism
  • Cytochrome P450 (CYP) enzymes
  • Enzyme induction and inhibition
  • First-pass metabolism
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Explain how Excretion does this ?

A
  • Excretion via the kidney: glomerular filtration, tubular secretion and tubular reabsorption
  • Excretion via the biliary system
  • Enterohepatic circulation
  • Drug elimination and renal clearance
  • Glomerular filtration rate and kidney function
23
Q

Define Metabolism ?

A

Describes the process by which a drug is altered chemically in the body into its ‘metabolite’, which may be more or less active

24
Q

Where does metabolism occur ?

A

It occurs primarily in the liver, but can take place in the plasma, lungs, stomach, small intestines , kidney, skin and other tissues

25
Q

What are the two phases of drug metabolism ?

A
  • Phase 1 (catabolic)

- Phase 2 (anabolic)

26
Q

Explain Phase 1 reaction ?

A
  1. Oxidation, reduction, hydrolysis
  2. Products are generally more polar
  3. Addition of groups such as 4. OH often makes products more reactive (functionalisation)
    - Allow Phase 2 reactions to occur
    - May make the metabolite more toxic/carcinogenic or more pharmacologically active
  4. Mediated by cytochrome P450 enzymes
27
Q

Explain Phase 2 reaction ?

A
  1. Add a group on to molecule: conjugation
  2. Chemical groups added included glucuronyl, sulfate, methyl, acetyl or glutathione
  3. Often added at the site of functionalisation from Phase 1, e.g. -OH group
  4. Usually products become pharmacologically inactive and more water soluble than the original drug and easier for excretion
28
Q

Example: metabolism of aspirin

A
  1. Phase 1 - Aspirin (Drug)
    - Oxidation, Hydroxylation, Dealkylation, Deamination and Hydrolysis
  2. Salicylic acid (Derivative)
    - due to the OH
  3. Phase 2 - Glucuronide (Conjugate)
    - Conjugation
29
Q

Not all metabolites of drugs are ?

A

Inactive

30
Q

In some cases, both the drugs and the metabolites are ? give example and explain

A

Active

  • E.g. Aspirin (acetyl salicylic acid) is hydrolysed to salicylic acid
  • Both aspirin and salicylic acid have anti-inflammatory activity
  • Only aspirin has antiplatelet activity
31
Q

In other cases, the drug is more active after ?

A

Metabolism

32
Q

What are Prodrugs ? give example and explain

A

These are drugs which are only active after being metabolised in the body

  • e.g. Heroin (diamorphine or diacteylmorphine) is a prodrug of morphine but crosses the BBB more easily and therefore much more potent
  • It is then metabolised to morphine
33
Q

In some drugs, the metabolite is ? give examples and explain

A

Toxic

  • Paracetamol is metabolised to N-acetyl-p-benzoquinone imine (NAPBQI). NABQI causes liver damage in paracetamol overdose
  • Alcohol is oxidised to acetaldehyde by alcohol dehydrogenase. Acetaldehyde causes the ‘hangover’ symptoms
34
Q

What chemicals are poorly excreted by the kidneys into urine ?

A

Hydrophobic (lipid soluble). The process of drug metabolism simply converts lipid soluble drugs to water soluble metabolites

35
Q

Most of the Phase I reactions are caused by ?

A

By the cytochrome P450 microsomal oxidase system

36
Q

There are 18 families of cytochrome P450 genes with?

A

43 subfamilies

37
Q

CYP 1, 2, 3 families are known to ?

A

Metabolize lipophilic

drugs

38
Q

Often have what kind of activity ?

A

Monooxygenase activity: oxidise C-H bond into C-OH bond

39
Q

Give examples of cytochrome P450 (CYP) enzymes inducers

A 
Carbamazepine
Rifampicin
Alcohol (chronic)
Phenytoin 
Griseofulvin 
Phenobarbitone 
Sulphonylureas

CRAPGPS

40
Q

Give examples of cytochrome P450 (CYP) enzymes inhibitor ?

A 
Sodium Valproate 
Isoniazid 
Cimetidine 
Ketoconazole 
Fluconazole 
Alcohol (acute use)
Chloramphenicol 
Erythromycin 
Sulfonamides 
Ciprofloxacin 
Omeprazole 
Metronidazole
41
Q

When does enzyme induction occur ?

A

When a drug administered over a period time increases the activity of microsomal enzymes

42
Q

How is Enzyme induction caused ?

A

It’s caused by increased synthesis and/or reduced breakdown of the enzymes

43
Q

What will happen to drugs metabolised by the same enzymes ?

A

They will be broken down more quickly and circulate in a lower concentration than anticipated

44
Q

When can effects typically be seen ?

A

After the first 2 days, but max. Effects may take 2-3 weeks - the length of time taken to synthesise the enzymes

45
Q

What happens due to enzyme inhibition ?

A

Results in reduced drug metabolism and an increase in concentration

46
Q

Unlike enzyme induction, inhibition usually begins ?

A

With the first dose of the inhibitor, maximal when inhibitor reaches steady state

47
Q

Give an example of a drug that carries out enzyme inhibition ?

A

Many drug (e.g. erythromycin) can have an inhibitory effect on the enzymes that metabolise warfarin

48
Q

When does drug interactions occur ?

A

When 2 or more drugs interact in such a way that the effectiveness or toxicity of one or more of the drugs is altered

49
Q

What can the effect either be ?

A

Harmful or beneficial

50
Q

Enzyme induction or inhibition by one drug can alter?

A

The concentration of another drug

51
Q

Give an example of drug interaction ?

A

E.g. Induction of CYP enzymes by alcohol increases metabolism of paracetamol to its toxic metabolite NABQI. Hence, paracetamol overdose is more serious after drinking alcohol

52
Q

Give example of drug interaction with enzyme inhibitor

A
  • Antibiotics such as clarithromycin and erythomycin inhibit the CYP enzymes that metabolise warfarin (anticoagulant)
  • This can lead to enhanced anticoagulant effect (increased risk of bleeding) - which can be dangerous
53
Q

Give example of drug interaction with enzyme inducer

A
  • St John’s wort is a herbal medicine available to treat mild depressant
  • Induce CYP3A4
  • Increases metabolism of many drugs (e.g. warfarin, digoxin)
  • Should not be taken with oral contraceptive pill as it metabolises and inactivates the drug
  • Can also affect the metabolism of other antidepressants

Introduction to Metabolism and Pharmacology (16 decks)

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