Introduction to Pharmacology

Question 1

Define pharmacokinetics

Answer 1

What the body does to the drug

Question 2

Define pharmacodynamics

Answer 2

What the drug does to the body

Question 3

Define drug

Answer 3

a chemical substance of known structure, which when administered to a living organism produces a biological effect

Question 4

Define medicine

Answer 4

Usually, but not necessarily contains one or more drug, which is administered with the intention of producing a therapeutic effect

Question 5

Define therapeutics

Answer 5

Use of drugs to diagnoses, prevent, and treat illness

Question 6

Define formulations

Answer 6

how the drug is packaged

Question 7

Define excipients

Answer 7

substances formulate alongside the drug

Question 8

Define medicinal product

Answer 8

any substance or combination of substances presented as having properties of preventing or treating disease in humans

Question 9

What are a drugs 3 names?

Answer 9

Chemical = chemical structure
Generic = class of drug
Proprietary = trade name

Question 10

What is a lignad?

Answer 10

a molecule that binds to the receptor

Question 11

What is a receptor?

Answer 11

a molecular target for a drug

Question 12

What is an agonist?

Answer 12

a molecule that activates a receptor

Question 13

What is an antagonist?

Answer 13

something that blocks or reduces agonist mediated responses

Question 14

What is an analgesic?

Answer 14

an objective treatment in all types of pain, irrespective of its origin, to achieve symptom control and improve quality of life - relieves or reduced pain

Question 15

Explain what a ligand is and what it does?

Answer 15

Ligands are a molecule that binds to the receptor. They can be exogenous (outside human body), or endogenous (inside human body). A ligand might be a drug, a neurotransmitter, or a hormone. Ligands can act on different receptors, and they can be synthetic or natural drugs.

Question 16

What is a target?

Answer 16

A molecule, usually a protein, that is accessed by a drug to produce a therapeutic effect

Question 17

What would an ideal drug look like?

Answer 17

A drug with a desirable pharmacological action, with acceptable or no side effects, reaches its target in the right concentration at the right time, remains at the site of action for sufficient time, and be rapidly and completely removed from the body when no longer needed.

Question 18

Explain how drugs produce effects and key aspects of drug binding.

Answer 18

Drugs usually interact in a structurally specific way with its target. Drugs bind like a lock and key. The shape of the drug binds specifically with their receptor, the physical shape of the drug is compatible with the receptors shape. Local electrostatic charges on the receptor and ligand are also important in binding. Opposite charges attract, and drug and receptor have different charges to be able to attract and attach. Therefore, the physico-chemical properties and steric properties affect drug receptor binding.

Question 19

What is affinity?

Answer 19

How well the ligand binds to the receptor

Question 20

What are the common protein targets?

Answer 20

Receptors, ion channels, carrier molecules and enzymes (RICE)

Question 21

What is the receptors role?

Answer 21

It is the biologically relevant molecular site with which a drug binds to produce a response. The endogenous ligand and exogenous ligand activates the receptor. The ligand binds to the receptor and alters the receptor conformation. This activates the intracellular second messenger cascade, which creates diverse intracellular effects such as cellular excitability. The modulation of other ion channels are created, and the down-regulation of G-protein linked receptors.

Question 22

What is the role of carrier proteins/transporters?

Answer 22

These are the facilitators for transport for example across membranes. Activate transporters which require ATP and facilitate diffusion.

Question 23

What is the role of enzymes?

Answer 23

Enzymes inhibitors bind to the enzyme and act as a substrate analogue, where they inhibit or block the enzymes normal activity by the drug. False substrate are drugs that bind to the enzyme and produce an abnormal metabolite. Pro-drug are drugs that bind to the enzymes and produce an active drug, can be activated by enzymes in the body

Question 24

Explain drug specificity

Answer 24

The binding site specificity is a key feature but no drugs act with complete specificity. Non specific interactions are very possible and highly likely, only some drugs will target one specific place in the body. A drug may preferentially bind to a promiscuous and bind to other targets. More likelihood of non-specific interactions becoming significant with larger doses.

Question 25

What are the 4 main processes in pharmacokinetics?

Answer 25

Absorption, distribution, metabolism and excretion. They determine the time of onset and duration of drug action in the body. They also describe the disposition of the drug

Question 26

What is absorptions role?

Answer 26

It is defined as the process by which drug reaches the systemic circulation. It is affected by the route of administration and permeation. Regardless of administration, drugs must be in solution to be absorbed.

Question 27

What are the different routes of administration?

Answer 27

oral administration, injections, rectal or vaginal, nasal, ocular, otic, parenteral, epidural, topical, and transdermal patch.

Question 28

What is enteral administration?

Answer 28

Via the gut - oral

Question 29

What is parenteral administaration?

Answer 29

not via the gut - injection

Question 30

What are enteral pro's?

Answer 30

Oral ingestion, gut absorption, low infection risk, and simple self-administration

Question 31

What are enteral con's?

Answer 31

Harsh environment in the stomach and duodenum, and first pass metabolism

Question 32

Explain first pass metabolism

Answer 32

The drug dissolved in the gut, however some will be lost straight away through excretion. The bulk of the drug will be absorbed by the lining of the gut, and then blood from the gut goes via the portal vein and straight into the liver. The metabolism of the drug in the gut wall and liver will also loose some of the drug. Only once the blood/drug leaves the liver will it have reduced bioavailability. This means it is able to go to its target receptors and do its job. However, not the whole portion of the drug can do its job as it has been lost throughout the process. This also happens when inhaling a drug, as the lung metabolises a lot of the drug. The only way to avoid first pass metabolism is to enter in a region of the gut that doesn't drain into the hepatic portal vein.

Question 33

What are the pro's of topical administration?

Answer 33

local effects, low systemic affects, limited first pass metabolism suited to sloe continuous long period administration, low infection rate risk of systemic absorption.

Question 34

What are the con's for topic administration?

Answer 34

Process of lipid permeation, small molecular size, use a carrier molecule, usually limitans to absorption

Question 35

What are the different injection routes?

Answer 35

``` intravascular - into bloodstream intramuscular - into skeletal muscle subcutaneous - drug absorbed from subcutaneous tissue dermal - into dermal vascular layer depot - slow releasing ```

Question 36

What are injections pro's and con's?

Answer 36

``` Pro's = avoids first pass metabolism, rapid bioavailability for IV/IA, and targeting risks Con's = infection risk ```

Question 37

Explain what bioavailability is

Answer 37

The proportion of active drug that reaches the systemic circulation and is free to bind to its target. Its a measure of how much it gets into the systemic circulation system. The bioavailability is affected by route administration and the formulation. Intravenous injections have a high rate, however oral is slower and slow releasing is even lower.

Question 38

What are the factors affecting distribution?

Answer 38

Protein binding, blood flow, membrane permeation/tissue solubility

Question 39

Explain protein binding.

Answer 39

There is a dynamic equilibrium for most drugs, and they are partly bound to plasma protein and partly bound to plasma water. The binding is reversible however only the unbound fraction can cross membranes or bind to receptors. Protein binding can reduce the availability of the drug and its half-life. Only unbound drugs can diffuse through capillary walls and produce a pharmacologic effect

Question 40

Explain blood flow in distribution

Answer 40

The blood flows primarily through the circulatory system and tissue perfusion rate per tissue is important. The perfusion rate of ml min per 100g is lung = 1000, brain = 56, gut = 300 and bone/cartilage/fat = 3

Question 41

Explain membrane permeability in distribution

Answer 41

Fick's law is important showing that the area of the surface is important to diffuse or dissolve. Charge molecules, ions and ionised molecules diffuse less efficiently. Uncharged, non-ionised drugs have better access to membrane bound compartments

Question 42

What is the lipophilicity of a drug?

Answer 42

Whether it likes to dissolve in lipids or not

Question 43

What is metabolisms role?

Answer 43

It typically inactivates drugs. The key organ involved is the liver, but the kidney, intestine, lungs, plasma, skin and placenta are also involved. The metabolic rate can determine the duration of drug action

Question 44

What is pro-drug activation?

Answer 44

little or no activity until they undergo metabolic activation

Question 45

What are the 2 phases of metabolism?

Answer 45

Phase 1 produces toxic metabolites and phase 2 converts toxins to soluble metabolites for excretion. Some drugs do phase 2 before phase 1

Question 46

Explain the main excretion route

Answer 46

The kidney/renal route. It filtrates the drug, however only the unbound drug metabolites can be processed via glomerular filtration. The proximal convoluted tubule cells actively secrete into nephron and the reabsorption of lipophilic drugs unionised at urine ph.

Question 47

What are the other routes of excretion?

Answer 47

Biliary, saliva, breast milk, sweat, and tears

Question 48

Explain biliary excretion

Answer 48

The principal excretory route is where the hepatocyte uptake metabolites and drugs, direct them to the biliary system and then via the bile ducts they are injected into the duodenum as bile, and then excreted into faeces

Question 49

What is enterohepatic circulation?

Answer 49

Where gut bacteria can convert drug back to its original form, the drug can be reabsorbed across the intestinal wall and re circulate in blood, to be metabolised in the liver again and re secreted into bile

Question 50

What is drug elimination half-life?

Answer 50

The time taken to decrease plasma concentration to 50%. It is different for each individual drug, ibuprofen estimated is about 2 hours, aspirin is about 4-6 hours, After 2 half lives there's 25%, 3 half life's 12.5%, 4 half lives is 6.25% and 5 half life's is pretty much 0%