GI 07

Question 1

How much drug adhearance required with a patient ?

Answer 1

at least 80 %

Question 2

We measure dose for a patient based on ?

Answer 2

His Clearance

Question 3

If the dose is an overdose also called ?

Answer 3

Supra therapeutic concentration

Question 4

If the dose is an undrdose also called ?

Answer 4

Sub therapeutic concentrations.

Question 5

What are the different ways we dose our drug ?

Answer 5

Average dose determine by drug company so how they determine in three different method

 1. The population method: (Same dose given to everyone) they may under or over dosed for its clinical significance but it is negligible for ex: paracetamol adult and new born are not same dose.
2. Covariate based dosing: (Same dose for similar group) Adults 18 and 65 they might get same dose if they do not have any other complications.
3. Dose individualisation. (Response based dosing) Start with average dose which been determines by the drug company then response measures and monitor that patient and we need dose adjustment.

Question 6

PK is

Answer 6

time Vs Con (Exposure)

Question 7

PD is

Answer 7

Con (Exposure) Vs Effect

Question 8

Why we need to know about PKPD?

Answer 8

That we know about how long it will take to start working and how long it will work and how much effect we can get.so we can say PKPD is time vs Effect

Question 9

Dosing Variability: Types of variability

Answer 9

i) Between subject (means between people).
Age weight height sex organ function pregnancy diet etc

ii) Within subject (within the person): disease progression, diet change (Some people) change diet seasonally
adherence patterns.

iii) Random variability : It happens because of dosing error sampling error assay error etc.

Question 10

Why dosing variability matter between people ?

Answer 10

Because Narrow therapeutic range is problematic. An average dose or same dose may be appropriate for one patient toxic for second patient and sub therapeutic for third patient.

Question 11

What Is called a therapeutic range of a dose ?

Answer 11

Plasma concentration that should lead to effectiveness without toxicity for most patients.

Or we can say drug concentration rang is above MEC and below MTC.

Question 12

What is Lag period ?

Answer 12

After administering a dose into human body it takes time to reach the drug to cross the MEC and reach to Therapeutic window so the time before reaching the TW called lag period for that drug.

Question 13

What is bioavailabiliity ?

Answer 13

A measure of the drug rate and extent
Extent we can determine by Cmax & AUC
Rate can be determined by Tmax and Ka

Question 14

Extent we can determine by

Answer 14

Cmax & AUC

Question 15

Rate can be determined by

Answer 15

Tmax and Ka

Question 16

Bioavailability is determined by

Answer 16

• disintegration & dissolution of the formulation,
• absorption and pre-systemic metabolism and
• elimination of the drug.

Question 17

What is Drug absorption

Answer 17

It is the process by which unchanged drug moves from a site of administration to the systemic circulation.

Question 18

How may sites Drugs can be absorped.

Answer 18

Gut
Lung Muscle eye skin
Buccal cavity rectum etc

Question 19

What are the determinants (affecting) factors can be for drug absorption from the gut ?

Answer 19

1. Disintegration and dissolution of the drug
2. Physiology of GI tract
3. Food and drug interaction in the GI lumen
4. Passage through the gut wall

Question 20

What are the determinants (affecting) factors can be for drug absorption from the gut ?

Answer 20

1. Disintegration and dissolution of the drug: i.e. it depends of the release characteristics of the drug like excipients coating etc & physiochemical properties i.e. partition coefficient size, crystal form etc.
   2. Physiology of GI tract: i) Gastric emptying: highly variable because during fasting or drug in solution or after meal.
      - Small intestine transit time- less variable though. Often 3 hours.
      - Gastric emptying time.
      - Insoluble drugs may have enhanced absorption if transit time is slow.
   3. Food and drug interaction in the GI lumen
      -Passage through the gut wall. Like diffused or transported into the gut wall.
      Food affects stomach ph. as a result some acid labile drugs altered its solubility. PPIs & dabigatran reduce 30% absorption.
   • Complexation can be happen with dairy product. Alendronate quinolone antibiotics.etc
     4. Passage through the gut wall
     - Passive diffusion- active transport

Question 21

What are the rate limiting step for absorption a drug at GI ?

Answer 21

1. Absorption rate limited input: dissolution is quicker than absorption (which is not common)so here the permeability is the rate limiting factor.
2. Dissolution rate limited input: dissolution is slower than absorption.

Question 22

How Altered motility affect drug absorption ?

Answer 22

AUC remains the same. Altered motility will therefore usually impact the rate only. The extent will remain the same of the drug absorption.

Question 23

Duodenum ph is

Answer 23

6-7

Question 24

Ph of stomach is

Answer 24

1.5 to 4 but often 2.5

Question 25

Unionized drug more readily crosses

Answer 25

biological membranes.

Acids are unionised in acid media

Bases are unionised in basic media

Question 26

Grapefruit felodipine interaction :

Answer 26

Grapefruit contains flavonoids that inhibit CYP 3A4 enzyme. Whereas felodipine metabolised by CYP3A4. As a result lead to greatly increased concentrations of felodipine due to low metabolism as a result drug bioavailability increase whereas drug absorption and clearance are unchanged.

Felodipine used for cardiac medication and high concentration can increase multi fold hypotension or tachycardia.

Question 27

Passive diffusion:

Answer 27

The primary absorption process for the most drug. The driving force is a concentration gradient across the membrane. Goes from high concentration to low concentration. Gut to plasma con.

Question 28

Active transport:

Answer 28

is mediated by some proteins which grab the drug across and expel inside the plasma. So it is against concentration gradient And energy required. Transporters are saturable and can be inhibited. Its include efflux transporters that limit drug absorption.