Pharmacology 1

Question 1

What is Pharmacokinetics? What is ADME?

Answer 1

Pharmacokinetics describes what the body does to a drug. It refers to the movement of the drug through the body.

ADME abbreviates: Absorption, Distribution, Metabolism and Excretion

Question 2

What are the different routes of drug administration?

Answer 2

• Oral (cannot be used in drugs that are broken down by first pass metabolism)
• Intramuscular (e.g. vaccine)
• Intravenous (can use lower doses as full dose is absorbed. Poses a risk of toxicity and side effects)
• Transdermal (e.g. nicotine patch. Surpasses FPM. Effective only in small doses an lipid soluble drugs)
• Topical (creams, foams, ointment)
• Buccal (under the tongue, surpasses FPM. Drugs must be water and lipid soluble)
• Epidural (Into epidural sac therefore comes with risk of failure and infection.)
• Inhalation (produces localised effect so reliant on patient technique. Particles must be small enough o be absorbed)
• Intrathecal (straight into CSF e.g. chemo and pain management. Produces rapid ocarina’s effects. May introduce infection and relies on expert technique)
• Subcutaneous (under the fat layer of the dermis. Must be fat soluble. Cannot be used to deliver large doses so in fluids they are given over long periods of time. Can irritate subcutaneous tissue)

Question 3

What are modified dose forms?

Answer 3

Modified-release dosage and its variants are mechanisms used in tablets
and capsules to dissolve a drug over time in order to be released slower and steadier into the bloodstream while having the advantage of being taken at less frequent intervals than immediate-release formulations of the same drug.

Question 4

What is first pass metabolism?

Answer 4

The concentration of a drug is greatly reduced before it reaches the systemic circulation. This greatly affects drugs that are ingested. First pass metabolism can occur in the liver or in the gut.

Question 5

What is first pass metabolism? Where can it occur?

Answer 5

The concentration of a drug is greatly reduced before it reaches the systemic circulation. This greatly affects drugs that are ingested.

It can occur in:

• Liver
• Lungs - cells in the liver may have a higher affinity for the drug than for hormones in that area
• Intestinal wall - rich in enzymes that break down the drug
• Intestinal lumen - there are enzymes secreted by the mucosa and pancreas that can break down the drug

Question 6

What is clearance?

Answer 6

The volume of blood/plasma cleared of the drug per unit of time. It does not indicate the drug amount of drug removed. This includes metabolic clearance as well as renal and biliary.

Question 7

What is bioavailability?

Answer 7

The proportion of the drug that reaches the systemic circulation. This applies to oral medication.

Question 8

What is volume of distribution?

Answer 8

The volume of plasma that accounts for the total concentration of the drug.

Question 9

What is volume of distribution?

Answer 9

The volume of plasma that accounts for the total concentration of the drug. Used to determine drug dosage and estimate blood concentration in an overdose.

Question 10

What is bulk distribution?

Answer 10

Circulation into the blood where it can travel long distances

Question 11

What is diffusion transfer distribution?

Answer 11

The drug travels short distances. Mainly occurs by passive diffusion of un-ionises form across plasma membranes.

Question 12

What is eGFR?

Answer 12

Estimated glomerular filtration rate. This should not be used to estimate creatine clearance as it does not take into account the weight of the individual - better to use Cockcroft-Gault Equation. GFR is a key factor is measuring renal function.

Question 13

Define pharmacodynamics?

Answer 13

Pharmacodynamics describes what the drug does the body. It is more specific than pharmacokinetics. Harder to change.

Question 14

How to drugs move across membranes?

Answer 14

1. Passive diffusion - must be unionised and lipid soluble.
2. Facilitated diffusion
3. Pinocytosis
4. Phagocytosis

Question 15

How does pH influence drug diffusion?

Answer 15

In order to cross the membrane, drugs should be uncharged and lipid soluble. Most drugs are designed to be lipid soluble. With increasing pH, the stomach becomes more acidic. The more acidic, the more ionised the stomach becomes and the less ionised the small intestine becomes. Drugs that are bases are more absorbent and so are usually lipophilic.

Question 16

What Factors influence distribution of drugs from plasma?

Answer 16

• Plasma proteins
• specific drug receptor sites in tissues as for a drug to have an effect it must bind to a receptor
• Regional blood flow - If an area is well perfused, more of the drug will reach the area
• Lipid solubility
• Disease - liver disease can mean not enough albumin is produced

Question 17

What factors affect absorption?

Answer 17

• GI tract motility - a higher motility means the drug does not stay in the GI tract for long and so not well absorbed.
• Physiochemical factors (solubility and charge)
• Particle size and formulation
• GI tract enzymes and acid which can break down the drug
• Food - some drugs have strict instructions on what you can eat with them do to interactions with food.

Question 18

How do you determine the concentration of drugs at the site of action?

Answer 18

Half life calculation. Different drugs have different half lives.

Estimation of creatine clearances also can be used to estimate the clearance of drugs filtered at the glomerulus.

Question 19

What factors affect metabolism?

Answer 19

• Age
• Alcohol
• Hepatic blood flow
• First pass effect
• Genetic factors - may be genetically unable to break down a drug e.g. 33% of caucasians cannot break down codeine
• Other drugs
• Liver disease

Question 20

What is and enzyme inducer? What is its affect on the concentration of the product in the blood?

Answer 20

Enzyme inducers increase the activity of an enzyme which break down drugs, this therefore increases the concentration of the product in the blood. This occurs when there is a combination of drugs given to a patient.

Question 21

What is and enzyme inhibitor? What is its affect on the concentration of the product in the blood?

Answer 21

Inhibit the action of an enzyme that breaks down drugs. This therefore decreases the concentration of a product in the blood. This occurs when there is a combination of drugs given to a patient.

Question 22

What percentage of an orally administered drug is absorbed?

Answer 22

Approximately 75% of a drug given orally will be absorbed in 1-3 hours.

Question 23

What are cytochrome p450s?

Answer 23

A family of enzymes produced in the liver and each individual enzyme is known as an isoenzyme. They function as mono-oxygenases. In mammals they oxidise steroids, fatty acids and xenobiotics.

Question 24

What is bioequivalence?

Answer 24

Two or more chemically or pharmaceutically equivalent products. You can then switch between the drugs without having any clinical implications.

Question 25

How is paracetamol broken down?

Answer 25

Paracetamol undergoes the first phase of oxidation and hydrolysis to produce a NAPQ1. This is toxic to the liver so is produced in small amounts and is immediately detoxified by the liver. This combines with glutamate to produce cysteine derivatives. Paractetamol can also undergo conjugation to produce paracetamol sulphate and paracetamol glucuronide. This can then have an effect.

Question 26

What happens in a paracetamol overdose?

Answer 26

The receptors are saturated and so paracetamol cannot go down the conjugation route. Instead they go back to be oxidised for produce more of the NAPQI derivative which is toxic.

Question 27

What is the treatment for a paracetamol overdose?

Answer 27

Acetylcysteine which pushes the paracetamol back down the conjugation route.