kinetics

Question 1

Importance of pharmacokinetics

Answer 1

Design optimal drug regimens
✔Route
✔Dose
✔Frequency
✔ Duration of treatment

Question 2

choosing of certain route depend on

Answer 2

▪Properties of the drug (water or lipid solubility, ionization)
▪Therapeutic objectives
✔rapid onset vs long-term ttt
✔ systemic vs local site.

Question 3

Absorption Mechanisms

Answer 3

Passive diffusion
Facilitated diffusion
Active transport
Endocytosis& exocytosis

Question 4

Factors affecting absorption “6”

Answer 4

1.Effect of pH
2.Blood flow to the absorption site
3.Total surface area available for absorption
4.Contact time at the absorption surface
5.Expression of P-glycoprotein (reduces drug absorption and may induce multidrugresistance)
6. Drug properties “ Molecular weight”

Question 5

How to enhance elimination? Aspirin Toxicity

Answer 5

Urine alkalinization bicarbonate, → alkalinizes the urine → drug ionized →↓ its reabsorption.

Question 6

How to enhance elimination? Amphetamine Toxicity

Answer 6

urine acidification with NH4Cl or ascorbic acid→ ionization of the drug →↑ renal excretion

Question 7

Bioavailability

Answer 7

the fraction of administered drug that reaches the systemic circulation.

Question 8

Factors influencing bioavailability “6”

Answer 8

1st-pass hepatic metabolism
Solubility of the drug
Chemical instability (Penicillin G (unstable in gastric acidity) – Insulin (deactivated by GI enzymes).
Nature of the formulation
Drug interaction at site of Absorption

Question 9

First-pass metabolism of Epinephrine

Answer 9

gut MAO.

Question 10

First-pass metabolism of Nitroglycerin

Answer 10

liver

Question 11

Routes By passing the First-pass Effect

Answer 11

Sublingual
Parenteral
Rectal (to some extent)

Question 12

Why is it not recommended to take tetracycline with food or drugs containing calcium (Ca++), magnesium (Mg), aluminum (Al), or iron (Fe), and what will happen if they are taken together?

Answer 12

Tetracycline can form chelates with calcium, magnesium, aluminum, and iron, creating insoluble complexes that are poorly absorbed in the gastrointestinal tract. If taken together, the absorption of tetracycline is significantly reduced, leading to decreased bioavailability and reduced therapeutic effectiveness. This is why it is recommended to take tetracycline at least 2 hours apart from food or medications containing these ions to ensure optimal absorption.

Question 13

DISTRIBUTION

Answer 13

is the process by which the drug reversibly leaves the blood stream and enters the body compartments

Question 14

Factors Affecting Distribution

Answer 14

❑Blood flow
❑ capillary permeability
❑Volume of distribution tissue volume,
❑Plasma protein
❑Lipophilicity of the drug.

Question 15

Metabolized
and Excreted are free parts or bound with protein

Answer 15

free parts

Question 16

Discuss the pharmacokinetic properties of thiopental and propofol that contribute to their rapid onset and short duration of action. How does redistribution play a role in terminating their effects, and how might changes in lipid solubility or tissue perfusion influence their clinical use?

Answer 16

Thiopental and propofol are highly lipid-soluble, allowing them to rapidly cross the blood-brain barrier and produce a quick onset of anesthesia. Their effects are short-lived due to redistribution from the brain to less perfused tissues like muscle and fat. Increased lipid solubility would enhance brain penetration but could also accelerate redistribution, further shortening their duration. Altered tissue perfusion, as seen in conditions like shock, could delay onset or prolong recovery from anesthesia.

Question 17

Significance of PPB

Answer 17

1. Distribution -
2. Metabolism -
3. Excretion -
4. Duration (t½ ) +

Question 18

What clinical implications arise from warfarin and aspirin interaction, and how can healthcare providers manage the risks associated with this drug interaction?

Answer 18

Aspirin has a higher affinity for plasma proteins than warfarin. When administered together, aspirin can displace warfarin from its protein-binding sites, increasing the concentration of free (unbound) warfarin in the bloodstream. This elevation in free warfarin can enhance its anticoagulant effects, increasing the risk of bleeding and hemorrhagic complications.
adjust dose timing and the dose of warfarin

Question 19

Volume of distribution

Answer 19

the fluid that is required to contain the entire drug in the body at the same concentration measured in the plasma = drug in the body “dose”/ plasma concentration.

Question 20

Vd ↑ the drug is more hypophilic or hydrophobic

Answer 20

Drug is more hydrophobic

Question 21

Vd ↓ its afcfinity to plasma protein

Answer 21

Drug has ↑ affinity to plasma proteins

Question 22

Vd ↑ its half life

Answer 22

Drug has ↑ half life

Question 23

Factors Affecting Distribution of Drugs

Answer 23

1.Blood Flow (perfusion) ↑ Blood Flow → ↑ Distribution
2. Capillary Structure
3. Chemical Nature
of the Drug
Capillary Permeability
(& Drug diffusion)
↑ Lipophilicity→ ↑ Distribution

Question 24

Rationalize: Hemodialysis is useful in toxicity of Salicylate But not in Digoxin

Answer 24

most of drug is in the circulation / extensive tissue drug distribution

Question 25

Suggest the Clinical Significance of Plasma protein Binding, illustrate your answer by an example?

Answer 25

Drugs Interaction
Drugs higher affinity to PP (Aspirin) can displace drugs with lower affinity (Warfarin) → ↑ Free part → Bleeding

Question 26

Drug metabolism

Answer 26

changes that occur to the drug after absorption until excretion

Question 27

Neonates particularly vulnerable to drugs

Answer 27

because they are deficient in conjugating system,

Question 28

Phase I reactions are catalyzed by

Answer 28

cytochrome P450

Question 29

Four isozymes are responsible for the majority of P450-catalyzed reactions:

Answer 29

CYP3A4/5, CYP2D6, CYP2C8/9, CYP1A2

Question 30

CYP3A4 are found in

Answer 30

intestinal mucosa, accounting for the first-pass metabolism of drugs.

Question 31

CYP2D6 activates which drug

Answer 31

codeine → morphine

Question 32

Rifampicin (antibiotic) is enzyme inducer or inhibitor

Answer 32

inducer

Question 33

Erythromycin (antibiotic) is enzyme inducer or inhibitor

Answer 33

inhibitor

Question 34

what happen in phase 1

Answer 34

oxidation/reduction/and/or hydrolysis. activation/ unchanging / inactivation.

Question 35

what happen in phase 2

Answer 35

conjugation and inactivation

Question 36

Drug Clearance

Answer 36

Hepatic Metabolism
Lipophilic Drugs
Renal
Excretion
Hydrophilic Drugs

Question 37

Distal tubular reabsorption for :

Answer 37

Non-ionized (lipophilic) drugs

Question 38

what is ION TRAPPING in kidneys

Answer 38

Changing the pH of the urine to ↑ ionized form of the drug →↓ amount of back-diffusion →↑ clearance of an undesirable drug.

Question 39

Elimination Half-Life (t½)

Answer 39

It is the time required to reduce the plasma conc. of drug to half the initial concentration.

Question 40

Importance of t½

Answer 40

to determine dosage interval of drug
Drugs are usually given at intervals equal to their t1/2
- Drugs with very short half life → given by continuous infusion (Na-nitroprosside).
- Drugs with long half life > 3 day are given as initial loading dose followed by maintenance dose (Digoxin).

Question 41

Factors that ↑ t½

Answer 41

↓renal/hepatic blood flow
(Shock, hemorrhage, heart failure)

↓renal drug extraction
(renal disease)

↓metabolism
(drug-induced, liver disease)

Question 42

Factors that ↓ t½

Answer 42

↑ Hepatic blood flow
↑ metabolism
↓ Protein binding