PK

Question 1

F of High ER hepatic drugs are very sensitive to changes in ER

Answer 1

Yes.
F=1-ER
E.g. for ER 0.8, F =0.2
If ER decreased to 0.6, due to liver function impaired, F =0.4 ( which doubles)

Question 2

PHASE I of liver metabolism involve:

Answer 2

Oxidation

Hydrolysis

Question 3

Phase II of liver metabolism involves:

Answer 3

1. Conjugation

2. Acetylation

Question 4

If the metabolites are active, it would have:

Answer 4

Cummulative effects,

May leads to toxicity (such as panadol—>NAPQI)

Question 5

Hepatic clearance for high ER drug:

Answer 5

CL= Q×ER

Depend on Q. hepatic flow rate ( flow limited hepatic clearance)

Question 6

Factors affecting metabolism:

Answer 6

1. Pharmacological factors (enzyme inducer or inhibitor)
2. Pharmarcogenetic factors; e.g hydroxylation (CYP2D6)
3. PHysiological status ( age)
4. Pathological Factors ( liver disease)

Question 7

List some potent inducer

Answer 7

Antiepilectic ( except diazepam)
Rafampicin
Alcohol
Cigarette smoking

Question 8

Renal extraction rate low drug , renal clearance depends on

Answer 8

Renal GFR
(renal function)

Question 9

For weak acid drugs, in acid urine:

Answer 9

More non-ionized, more be reabsorbed to plasma.

Slower the clearance

Question 10

In order to clear weak acid drugs, the urine should be:

Answer 10

Alkaline.

More ionized acid drug, more be excreted in urine

Question 11

To clear weak base drugs, the urine should be

Answer 11

Acid.

Weak base drug in acid environment, more ioned, more to be excreted in urine

Question 12

Factors afftecting renal clearance

Answer 12

1. Urine pH
2. URINE FLOW ( higher flow rate dilute drug comc and reduces reabsorption)
3. Plasma protein bonding ( as only unbond drugs are filtered through GF)
4. Competition for tubular secretion ( such as competing for the acid pump)
5. State of renal function: ClCr

Question 13

Calculate T1/2

Answer 13

T1/2= 0.693x Vd/Cl

Question 14

What are thr barriers or factors to drugs movement, before reaching to site of action?

Answer 14

1. Blood flow
2. Blood permeability
3. Interstitial compartments ( e.g. albumin)
4. Cell membrane and cytoplasm
5. The environment, including aqueous (blood) and lipid ( fatty tissues)
6. Blood brain barrier
7. Properties of the drug

Question 15

Fsctors influencing individual response to drugs (dosage to effect relationship)

Answer 15

1. Patient compliance
2. pk: Absorption ( the ratr and the extent, i.e. F),
3. distributiom ( binding to inactive site; body size anf composition; entry into body compartment)
4. Metabolism/ biotransformation
5. Excretion
   ( PK affted the PDC)
6. Concentration at sites of action( tissue responsiveness, functional states, psychological states, placebo effects)
7. Pharmacological effects - therapeutic(clinical useful)
   - subtherapeutic (too low PDC)
   - Adverse effects (avoidable or unavoidable)
   -toxic (overdose, PDC too high)

PK AND PD is affected by 
# physiological variables 
# pathological factors 
# genetic factors 
# environmental factors ( pomelo as ezyme inducer)
# development of tolerance 
# dosage form 
# route of administration 
# DDI