Pharmacokinetics

Question 1

Pharmacokinetics

Answer 1

The effect of the drug on the body

Question 2

Define drug

Answer 2

• single chemical entity
• which is one of the constituents of a medicine

Question 3

Define medicine

Answer 3

• Contains one or more active contituents together
• With additives to facilitate administration

Question 4

Individual variation of Drugs

Answer 4

• Age
• Genetic factors
• Physiological status
• Altered pathology
• Drug interactions

Question 5

Administration routes: Enteral (via gut)

Answer 5

• Oral
• Rectal

Question 6

Parenteral (avoid gut)

Answer 6

• Buccal
• Sublingual
• Topical
• Transdermal
• Intranasal
• Intradermal
• Subcutaneous
• Intraocular
• Epidermal
• Intarvenous

Question 7

Enteral routes

Answer 7

• Slow and unpredictable absorption
• Safe
• Non-invasive

Question 8

Parenteral routes

Answer 8

• Used for drugs that are destroyed by gut or first pass metabolism
• Allows access to otherwise protected or hard to access areas
• Enables lower dose of drug to be used

Question 9

Difference between lipid soluble and water soluble drug

Answer 9

Lipid-soluble compounds can dissolve through a membrane, while water soluble compounds can not.

Question 10

Gastrointestinal Factors which influence absoption

Answer 10

Oesophageal passage
The pH of the gastrointestinal tract
Gastric motility
Presence of food and drink

Question 11

Drug Efflux

Answer 11

These proteins use energy to push drugs back into the intestine, limiting the absorption of fat soluble drug via the intestinal wall

Question 12

Absorption in paediatrics

(be cautious of this one ddont make sense)

Answer 12

• Smaller size
• Infants have a proportionally larger body fluid content than adults
• Thus larger dose per body weight

Question 13

How does respiratory affect absorption

Answer 13

Less mucous in the respiratory tract
Less well developed immune response

Question 14

How does the brain and the BBB affect absoption

Answer 14

The BBB(blood brain barrier) is not fully developed until the brain matures.
Normally takes a year
SO care to be taken with compounds that may cause cerebral irritation.

Question 15

How Does skin affect absorption

Answer 15

• Neonates Larger Surface
• Skin is thinner and more permeable than adults
• Steroidal creams should be avoided

Question 16

How does stomach affect the absorption of drugs

Answer 16

• Less stomach acid
• Some drugs more permeable than normal in stomach

Question 17

Distribution

Answer 17

The amount of drug in body tissues fluids or spaces

Question 18

Other factors that affect drug distribution

Answer 18

• Blood flow in the tissue
• Binding to plasma proteins
• Cellular binding
• Adipose store in the tissue

Question 19

Plasma Binding

(also referred to as Protein binding)

Answer 19

• Drug binding varies widely. For example the presence of plasma albumin in cells cause drugs to bind to it.
• Therefore only the drug that is unbound or free is able to distribute to target tissues.

Question 20

Effects of plasma binding

Answer 20

• Highly bound drugs require larger loading doses
• Highly bound drugs have limited tissue distribution
• Changes in available plasma protein, may have a profound effect on free drug availability

Question 21

What is volume of distribution

Answer 21

Hypothetical proportion of how much drug the body can absorb

Calculation:
V/D

V=volume
D=Distribution

Question 22

Example Question for Volume Distribution :
What’s the volume distribution of a drug confined to blood stream of a 70kg Person with 3 litres of blood?

Hint: formula V/D

Answer 22

3/70=

0.042 Lt/kg

Question 23

Drug Metabolism

Answer 23

• Primarily takes place in the liver
• Phase 1 Metabolism
• Phase 2 Metabolism

Drugs may go through
* Phase 1 Metabolism alone
* Phase 2 metabolism alone
* Phase 1 metabolism then phase 2 metabolism

Question 24

Phase 1 Metabolism

Answer 24

causes breaking down of the molecule to more water soluble components

Question 25

Phase II Metabolism

Answer 25

Adds on water soluble conjugate molecules to make the whole complex more water soluble

Question 26

got to slide 34 on pharmacokinetics for paracetamol metabolism

Question 27

Whats cytochrome P450

Answer 27

* Phase 1 metabolic enzyme * Responsible for metabolising >60% of all therapeutic drugs * Cytochrome P450 inhibited by a number of substances found in grapefruit juice

Question 28

Drugs that are metabolised by CYP 3A4 (cytochrome) | More on PPT

Answer 28

* fentanyl * Ketoconazole * Oxycodone * Diazepam * Midazolam * Metoprolol * Amlodipine

Question 29

Inhibitors of CYP 3A4 | More on PPT

Answer 29

* Protease inhibitors * Grapefruit * Black pepper * Conazoles

Question 30

Inducers of CYP 3A4

Answer 30

* Phenytoin * Dexamethasone * Rifampicin

Question 31

Metabolism of drugs in liver of infants

Answer 31

* Infant Livers have fewer metabolic enzyme systems * Slower elimination * Longer half lives * Less frequent dosing for some medication * Protein levels lower in paediatric patient especially in premature babies * Higher concentration of un-protein bound drug in the blood

Question 32

Drug elimination

Answer 32

The final phase of drug cycle is elmination. Drugs are eliminated in three ways: * Redistribution * Liver metabolism * Renal Excretion

Question 33

Drug Excretion

Answer 33

In bile from the liver In urine from the kidney Drugs can also be excreted via lungs, faeces, saliva, sweat, breast milk, hair

Question 34

Role of kidneys in drug elimination

Answer 34

1. Glomerulus * Filtration occurs 2.Proximal Tubule * Drug re-absorption * Drug efflux 3.Collecting Duct * Drug re-absorption * Drug efflux | Water soluble drugs are largely voided in the urine without being reabso

Question 35

GI/liver clearance

Answer 35

1. Liver eliminates drug into the kidney. 2. While in the kidney some drugs get reabsorbed into the liver 3. liver metabolises frug into the gall bladder. 4. Bile 5. Small intestine then digests so this drug is then cleared out from the faeces. 6. Sometimes the intestinal flora de-conjugates metabolised drug to liberate the parent drug back to the liver.