Pharmacokinetics

Question 1

what is Pharmacokinetics ?

Answer 1

What the body does to the drug, this science denotes the alterations & mv of the drug within the body including : Absorption, Distribution, Metabolism, Execretion.

Question 2

What are 2 steps preceding the Absorption step : …….. & ……….

Answer 2

Disintegration & dissolution

Question 3

What’s meant by Absorption ?

Answer 3

Passage of drug from the site of Administration to the Blood W/O being chemically altered

Question 4

Ex of Drugs w/ rapid absorption : ……….. &………
Ex of Drugs w/ Stable Absorption : ……….

Answer 4

1. Analgesics & Hypnotics
2. Antiarrythmic Drugs

Question 5

What is the mechanism of Absorption ?
What is the form of the drugs that can pass by lipid diffusion ?

Answer 5

1. Simple diffusion (lipid diffusion) from High conc to low conc.
2. The nin ionized form as is lipophilic, but the ionized forms w/ are hydrophilic are water soluble that can only pass through specific proes w/ are too narrow for large molecules.

Question 6

1. Ionization of the drug depends on ………. & ………

Answer 6

Its PKa and The PH of the surrounding medium.

Question 7

1. When PH = PKa => ………..
2. Ionization of weak acids ………… at PH < PKa. EX : ?
3. Ionization of weak bases ………. at PH > PKa. EX : ?

Answer 7

1. 50 % of the drug is ionized & 50% is non ionized.
2. decreases // EX: Aspirin esxists mainly in the non ionized form in gastric PH (1.2 - 2.5)
3. Decreses // EX: Theophylline is nostly in non ionizd form at intestine PH.

Question 8

What is Bioavilibility ?
How is it calculated ?

Answer 8

Rate & Extent of Absorption.
Its the % of the drug released from a formulation that reached the systemic circulation & becomes available for biologic effect.

It’s calculated by dividing the AUC (Area Under the blood time-coc Curve) after any route of administration by AUC of IVI.

Question 8

What is the clinical significance of PKa in GIT & Kidney ?

Answer 8

IN GIT: Apririn exists in the non ionized form in an empty stomach (very low PH) => crosses the cell memb gastric muscosal cells => increase PH of stomach => trapping the Aspirin inside => death of cells => peptic ulceration.

Kidney: in drug poisining, renal drug elimination can be enhanced by changing the urinary PH. This increases the drug ionization & inhibits renal reabsorption.
Alkalization of urine (urine PH > drug PKa) is useful for acidic Drug elimination : Apririn & Phenobarbital.
Acidification of urine (Urine PH < drug PKa) is useful for basic drug elimination : Amphetamine.

Question 9

1. What is Bioavailibility ?
2. How is it calculated ?

Answer 9

1. Percentage of drug from administartion site that reaches the systemic circulation having biological effect.
2. AUC after any route of administartion / AUC after IV.
   AUC is Area Under blood concentration-time Curve.

Question 10

1. When can I say that 2 drugs are bioequivalent ? and are therapeutic equivalent ?

Answer 10

• 2 drugs are bioequivalent when they have same bioavailibility & same time to reach Peak.
• 2 drugs are therapeutically equivalent if they are bioequivalent w/ same efficacy & toxicity.

Question 11

What are factors affecting bioavailibility ?

Answer 11

1. Factors affecting drug absorption by GIT:
=> factors related to dosage forms : synthetic tech & exipient added during preparation can affec the desintegration of drug to particles.
=> factors related to drug: molecular weight & solubility coeff can affect the dissolution of drug particles into molecules.
=> Gut Ph & drug PKa can affect the ionization form in gut.
=> factors related to absorpative system : GIT disease // GIT motility // surface area of absorption (intestine = 200m2 then lung = 70m2)
=> factors affecting drugs stability in gut : gut secretion destroying it // food & coadministrated drug that interact w/ it.

2. First-Pass effects:

Question 11

what is first Pass metabolis ?
types ?

Answer 11

=> metabolism of some drugs in a single passage by liver, GIT or lungs b4 reaching the circulation.
=> types :
1. Hepatic First Pass : drugs absorbed By GIT are carried by protal circu;ation nto the liver to be metabolized as Nitroglycerein & propanolol.
2. Intestinal First Pass : by intestinal mucosal surface (estrogen)
3. Pulmonary First Pass : by inhalation (nicotine)

Question 11

Wgat are factors that decrease Hepatic First Pass ?

Answer 11

1. Reduction of portal blood flow : portal hypertension (propanolol)
2. **Inhibition of hepatic enzymes **: liver failure or enzymatic inhibitors (erythromycin)

Question 12

Routes bypassing first Pass effects : ?

Answer 12

1. Rectal
2. Parentral
3. sublingual

Question 13

What is Vd ?
How can it be calculated ?

Answer 13

The volume of distribution (Vd) is the volume that would accomodate the entire amount of drug in the body if its conc throughout the body is the same as in plasma.

Vd = Amount of drug in body / Plasma conc. (L)

Question 14

What arefactors affecting drug distribution ?

Answer 14

1. Perfusion
2. Diffusion
3. Binding to plasma proteins
4. Binding to tissue constituents
5. Cap. Permeability

Question 15

What’s meant by Perfusion ?

Answer 15

the amount of drug delivered into an organ depends on its blood flow.

Question 16

What’s meant by Diffusion ?

Answer 16

ability of drug to diffuse across cell memb w depends on lipophilicity.

Question 17

Clinical Significane of lipophilicity on ADME ?

Answer 17

lipophilicity can :
increases A / D / M (hepatic elimination)
Decreases renal E (as can induce tubular re-absorption.)

Question 18

The drug in blood exists in 2 forms : ……….. & ……..
explain their ccc ?

Answer 18

1. Bound fraction : inactive // non-diffusible // cannot be metabolized or excreted.
2. Free Fraction : active // diffusible // can be metabolized & excreted

Question 19

Free & Bound fraction exists in ……….. / if free part is metabolized, bound part acts as a ………. w releases more drug particles.

Answer 19

equilibrium // resevoir

Question 20

Significance of Binding to plasma proteins on ADME.

Answer 20

A => Increase in absorption as decrease in free conc in plasma.
D => decrease in distribution as limits tissue penetration & decreases Vd.
M & E => decrease as cannot be eliminated providing a resevoir => prolongation of T 1/2
Increase in duration of action.

Question 21

Drugs binding to plasma proteins can displace each other. Explain ?

Answer 21

Warfarin attached to acidic binding site of Albumin => Aspririn displacing Warfarin => increase Warfarin in plasma => bleeding

Question 22

1. Why do drugs bind to tissues constituents ?
2. EX: ??

Answer 22

1. affinity of drug to some tissue component.
2. EX :
   => Chloroquine : conc in liver
   => Tertracyclins : conc in teeth & bone as chelates (remove) Ca
   => Iodides : conc in thyroid & salivary.

Question 23

Importance of Vd ?

3

Answer 23

1. measure the extent of tissue uptake of drugs :
   => Low Vd (frusemide) indicates poor tissue uptake.
   => High Vd (Digoxin) => extensive drug uptake.
2. in case of drug toxicity :
   => Low Vd (conc in plasma & ECF) => approved dialysis
   => High Vd (conc in tissue) => no dialysis
3. Calculate LD (Loading dose) :
   LD = Vd x Css

Question 24

What is the loading dose ?

Answer 24

it’s an initial higher dose given at the begining of a couyrse of treatment b4 dropping down to a lower mainteanace dose at Css.

Question 25

```

drugs can cross the placental barrier depending on …….. & ……….

Answer 25

lipophilicity // degree of ionization

Question 26

```

1. ………… drugs can pass through BBB as ……… & ……….
2. …….. & …….. amines can pass while …….. cannot.

Answer 26

1. Lipid soluble drugs // General anasthetics // CNS depressants
2. 2ry // 3ry // 4ry NH4+

Question 27

What type of drug given during Parkinson & why ?

Answer 27

Dopamine cannot cross the BBB so the drug given is Levodopa w will be decraboxylated in the brain into Dopamine.

Question 28

1. Penicillins can pass slightly through normal barrier but readly in ……….
2. In tuberculous meningitis, ……… // ……… & …….. are effective as pass readly while ……… cannot

Answer 28

1. Acute meningitis
2. INH (Izoniazid) // rifampin // Pyrazinamide // streptomycin

Question 29

drugs given in ……………. weeks cause teratoginicity

Answer 29

3-10th weeks

Question 30

effects of Morphine // Oral Anti-coagulants // Oral hypoglycemics // Antithyroid drugs // Aminoglycosided

Answer 30

1. Mrophine => asphyxia neonatorum
2. Oral Anti-coagulants => Fatal haemorhhage of newborn
3. Oral hypoglycemics (sulfonulureas) => neonatal prolonged hypoglycemia
4. Antithyroid drugs => goiter // hypothyroidism
5. Aminoglycosided => 8th cranial nerve damage (vestibulucochlear)