Lecture notes first 2 lectures

Question 1

Examples of drugs absorbed cutaneously

Answer 1

Nitroglycerine
Estrogen
Organophosphates

Question 2

Examples of drugs administered nasally

Answer 2

ADH

Question 3

Examples of drugs administered by eye drops

Answer 3

pilocarpine
carbachol
thimolol

Question 4

Drugs given by inhalation

Answer 4

Salbutamol
Ipratropium
Glucocorticoids
Anesthetics

Question 5

Drugs given intrathecally

Answer 5

Opioids
Baclophen
Penicillin can be

Question 6

Examples of special systems for drug absorption/packaging

Answer 6

Pro-drugs: levodopa. azathioprine, cyclophosphamide, zidovudine

Antibody-drug conjugates: drugs coupled to antibodies for specific tumor antigens

Liposomal packaging of a drug

Implantable devices coated with the drug: Intrauterine devises, coated coronary stents.

Question 7

Digoxin and Aspirin Vd’s. One is very high one is low.

Answer 7

Digoxin, 500L

Aspirin 11L

Question 8

Central compartments (for drug distribution)

Answer 8

Plasma and organs with a good blood supply
Kidney
Heart
Liver
Lung
Brain

Question 9

Peripheral compartments (for drug distribution)

Answer 9

Organs with poor blood supply

Fat
Skin
Muscle

Question 10

Deep compartments (for drug distribution)

Answer 10

Organs with very low blood supply

Bone
Cartilage
Joints

Question 11

Total body water : how many L per kg?

Answer 11

about 60% of body weight 0.6L/Kg
Highest in males and newborns.
Lower in females
Lower in obese people.

42L in 70kg male.

Question 12

Intracellular fluid volume

Answer 12

2/3 of total body water

40% of body weight.

28L in 70 kg male

Question 13

Extracellular fluid volume

Interstitial fluid volume

Plasma volume

Answer 13

1/3 of total body water 14 L
20% of body weight

Interstitial is 75% of extracellular fluid 10.5L
Plasma is 25% of extracellular fluid 3.5L

Question 14

Estimate blood and plasma volume from weight

Answer 14

Blood: 0.08 L/Kg

Plasma 0.04 L/Kg

Question 15

Estimate fat and bone volume by weight

Answer 15

Fat: 0.2-0.35 L/Kg

Bone 0.07 L/Kg

Question 16

Usual fraction of drug reaching systemic circulation, when administered by each route:

IV:
IM:
Oral:
Rectal:
Transdermal:

Answer 16

IV: 100%

IM: 75-100%

Oral: 5 - 99%

Rectal: 30 - 99%

Transdermal: 80 - 100%

Question 17

What are the 4 isozymes of cytochrom P450 enzymes that catalyze most biotransformation reactions

Answer 17

(in order)

CYP 3A4/5

CYP 2D6

CYP 2C8/9

CYP 1A2

Question 18

What CYP isozymes show the most genetic polymorphisms?

Answer 18

CYP2D6 has a great deal of genetic polymorphisms.
1-2% of all Asians are poor CYP2D6 metabolizers
5-10% of Caucasians

CYP2C19 has polymorphisms that affect antidepressant, antipsychotic (haloperidol), antiarrythmic (propafenon), and antiplatelet (clopidogrel)
15-20% of Asians are poor CYP2C19 metabolizers
2-6% of Caucasians are PMs

CYP3A4 also shows great variability in action on some drugs, but no specific polymorphisms are identified

Question 19

What are some drugs metabolized by N-acetylation in the liver?

What populations are slow acetylators?

Answer 19

Isoniazide
Procainamide
Nitrazepam

Egyptians are 90% slow acetylators

Asians 10-20%

Caucasians 40-70%

Can cause severe hepatotoxicity

Question 20

What are the active metabolites of these drugs?

Diazepam

Codeine

Phenacetin

Answer 20

Diazepam - Oxazepam

Codeine - Morphine

Phenacetin - Acetominophin

Question 21

What are some drug metabolites that are active even after phase 2 conjugation reactions?

Answer 21

Morphine-6-OH-glucuronide

Minoxidil Sulphate

N-acetyl-izonicid