* Pharmacology - 2 (4) Flashcards

1
Q

What most drugs leave the body in?

Where else are drugs excreted via? (3)

A

Urine (excretion via the bile is occasionally significant + minor contributions via exertion via the sweat or milk)

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

What kind of molecule must drugs be to be excreted by the body?
Why?

A

Polar

So that they can be regularly reabsorbed by the kidney facilitating excretion

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

What is a xenobiotic?

A

A foreign chemical substance that is found within an organism that is not naturally produced by or expected to be present within that organism

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

What does metabolism usually do in terms of rendering the activity of the drug?
What are 3 other things that metabolism less rarely does to drug activity?

A

Usually make the drug less pharmacologically active
Converts them from inactive to active compounds or gain activity
Have unchanged activity
Possess a different type, or spectrum of action

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

What is an example of a drug that gains activity during metabolism?

A

Codeine to morphine

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

What is an example of a drug that has unchanged activity after metabolism?

A

Diazepam to nordiazepam

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

What is an example of a drug that possess a different type, or spectrum, of action after metabolism?

A

Aspirin (anti-inflammatory and andti-platelet) to salicylic acid (anti-inflammatory with no anti-playlet activity)

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

What is the main organ of drug metabolism?

What other places have metabolism activity? (3)

A

Liver
GI tracy
Lungs
Plasma

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

How many steps does drug metabolism usually have?

A

2 sequential steps

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

What is the purpose of phase 1 drug metabolism?

A

To make the drug more polar and also to add a chemical “handle” permitting conjugation during phase 2

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

What are the 3 things involved in phase 1 drug metabolism?

A

Oxidation
Reduction
Hydrolysis

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

What is the purpose of phase 2 drug metabolism?

A

To add an endogenous compound increasing polarity for excretion

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

What is the 1 thing involved in phase 2 drug metabolism?

A

Conjugation

some drugs skip straight to phase 2 whilst some drugs are excreted unchanged

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

What are examples of the chemicals that are drugs are conjugated with during phase 2 drug metabolism?

A

Glucuronyl
Sulphate
Methyl
Acetyl

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

What are the 2 phases of drug metabolism of aspirin (acetylsalicylic acid)?

A

Aspirin is converted to salicylic acid (OH added) before being converted to the conjugate (glucuronide) during phase 2

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

What are the cytochrome P450 (CYP) family of monooxygenases?

A

Haem porteins located in the endoplasmic reticulum of liver hepatocytes (and elsewhere) mediating oxidation reaction (phase 1) of many lipid soluble drugs

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

How many gene families is the Cytochrome P450 family of monooxygenases made up of?

A

74 gene families - it is a superfamily

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

what are the main 3 gene families in the liver?

A

CYP1
CYP2
CYP3

19
Q

What are 3 examples of common cytochrome P450s?

A

CYP3A4 - accounts for 50% of metabolism of all presciription drugs
CYP2D6
CYP2C

20
Q

What are the basics of what happens in the monooxygenase P450 cycle?

A

Drug enter the cycle as a drug substrate, RH
Molecular oxygen (O2) provides 2 atoms of oxygen
One atom of oxygen is added to the drug to yield the hydroxyl product (ROH) which leaves the cycle
The second oxygen combines with protons to form H2O
this is mediated by monooxygenases

21
Q

In phase 2 reactions, what type of groups on the drugs are the endogenous molecules commonly added to?

A

Chemical reactive groups e.g. hydroxyl (OH), thiol (SH) or amino (NH2)

22
Q

What is a common reaction in phase 2 that tends to detoxify most drugs?

A

Glucuronidation

23
Q

What does glucuronidation commonly involve?

A

The transfer of glucuronic acid to electron-rich atoms on the drug (such as N, O or S ) forming amide, ester or thiol bonds

24
Q

what enzyme mediates glucuronidation?

A

UDP-glucuonyl transferase

25
Q

what are 2 endogenous substances that are subject to glucuronidaiton?

A

Bilirubin

Adrenal corticosteroids

26
Q

Give an example of a drug that is excreted by the kidneys very fast and drugs that are excreted by the kidneys very slowly?

A
Penicillin = extremely fast
Diazepam = extremely slow
27
Q

What are the 3 basic processes by which the kidney filters?

A

Glomerular filtration
Active tubular secretion
Passive reabsorption by diffusion across the tubular epithelium

28
Q

What drugs are freely filtered during glomerular filtration?

A

Drugs with a MW less than 20000 (most) provided they are not bound to large plasma proteins (which are not filtered)
*drug charge is unimportant

29
Q

How do many drugs exist in the blood?

A

In an equilibrium between unbound and protein-bund forms e.g. albumin (only unbound drugs can enter the filtrate via glomerular filtration)

30
Q

What is the equation for clearance by filtration?

A

CL(fil) = GFR x fraction of drug unbound in plasma (fup)

31
Q

What is GFR?

A

The glomerularfiltration rate (normally 120ml min-1)

32
Q

What are the names of the 2 independent transporter systems that are present in the epithelial cells of the proximal tubule that actively secrete drugs into the lumen of the nephron?

A

Organ anion transport (OAT)

Organic cation transporter (OCT)

33
Q

What does the organic anion transporter handle? (3)

A
Acidic drugs (e.g. penicillins)
Endogenous acids (e.g. uric acid)
The marker for renal plasma flow (i.e. para-aminohippuric acid)
34
Q

What does the organic cation transporter handle?

A

Basic drugs e.g. morphine

35
Q

What of the 3 mechanisms for drug elimination by the kidney is the most effective?

A

Excretion by tubular secretion e.g. benxylpenicillin and PAH

36
Q

How is the rate at which a drug is secreted from the body related to the concentration of the drug?

A

They are linearly related (as plasma concentration of drug increases, the rate of excretion also increases)

37
Q

Are the transporters across the epithelial cells of the proximal tubule able to become saturated?

A

Yes - each carrier has a transport maximum (Tm) for a particular drug

38
Q

How can drugs that are highly protein-bound be secreted?

A

By tubular secretion

39
Q

How can frusemide and thiazides lead to gout?

A

They are both excreted by the same tubular transporter system as uric acid meaning they can compete with the transport system leading to a build up of uric acid

40
Q

Why are drugs passively reabssrobed across the distal tubule by diffusion?

A

Concentration of the urine favours this

41
Q

What are the factors that influence drug reabsorption? (4)

A

Lipid solubility (drugs with high lipid solubility will be extensively reabsorbed and excreted slowly)
Polarity (highly polar drugs will be excreted without reabsorption)
Urine flow rate (diuresis decreases reabsorption)
Urinary pH

42
Q

How does alkaline and acidic pH affect the excretion of acidic and alkaline drugs?

A

Alkaline pH = increases excretion of acids

Acidic pH = increases excretion of bases

43
Q

What can be used to accelerate the excretion of aspirin (weak acid) in the case of an overdose?

A

Can be used to accelerate the excretion of aspirin (weak acid)