pharmacology 1

Question 1

What is pharmacology?

Answer 1

the branch of medicine concerned with the uses, effects, and modes of action of drugs

• Their design and synthesis
• Measurement of the effects of drugs and their mechanisms
• Absorption
• Metabolism
• Excretion

Question 2

What is pharmacy?

Answer 2

the science or practice of the preparation and dispensing of medicinal drugs

handling drugs

• Preparing
• Preserving
• Compounding
• Dispensing of drugs

Question 3

What are therapeutics?

Answer 3

the branch of medicine concerned with the treatment of disease and the action of remedial agents

Medicinal use of drugs

• how drugs can be used as remedies for diseases
• how drugs can be used to ameliorate symptoms of disease

Question 4

What is toxicology?

Answer 4

The branch of medicine concerned with the nature, effects and detection of poisons

Unwanted drug effects

• toxic effects of drugs
• actions of poisons
• unwanted effects of therapeutic drugs that are hazardous

Question 5

What is a drug? Examples of therapeutic and abused drugs.

Answer 5

A chemically defined agent that can be used to provoke a measurable response in a biological system.

Question 6

What is a drug molecule?

Answer 6

Drugs are exogenous molecules that mimic or block the action of endogenous molecules of systems

Although derived from an exogenous source a given drug may be:

1. chemically identical to an endogenous molecule or
2. chemically distinct from any known endogenous molecule

Question 7

What is exogenous and endogenous?

Answer 7

exogenous= growing or originating from outside an organism

endogenous= growing or originating from within an organism.

Question 8

Concept of receptor

Answer 8

Receptors have specific BINDING SITES for a drug

Question 9

Physiological receptors

Answer 9

These are endogenous proteins that are the receptors for endogenous chemical signaling compounds such as hormones or neurotransmitters. Many drugs bind to such receptors

Question 10

Give examples of other proteins (pharmacological receptors)

Answer 10

Such as enzymes or ion channels; drugs may bind to specific sites on proteins and prevent them from doing their job or, less commonly, they may stimulate them e.g. an ion channel in a membrane may be ‘blocked’ or it maybe opened.

Question 11

Nucleic acids (pharmacological receptors)

Answer 11

Drugs may bind to regulatory sites on nucleic acids to influence gene expression or protein synthesis.

Question 12

What are agonists and antagonists drugs?

Answer 12

Agonists: drugs that occupy receptors and activate them

Antagonists: Drugs that occupy receptors but do not activate them

Question 13

What determines the primary effects of the drug?

Answer 13

The type of binding site

nature of interaction of drug and binding site on receptor

Question 14

What are reversible and irreversible drug interactions?

Answer 14

reversible: interactions between drug and receptor binding site mediated by ionic attractions or hydrophobic interactions
irreversible: interactions between drug and receptor binding site mediated by covalent bonds.

Question 15

What is pharmacodynamics?

Answer 15

What a drug does to an organism- the sum of all actions of a drug

Question 16

what is pharmacokinetics?

Answer 16

what the organism does to a drug- absorption, distribution, metabolism and excretion

Question 17

what does pharmacokinetics determine for a drug?

Answer 17

• Determines how quickly a drug acts in a patient
• Determine whether a drugs effects are local or systemic
• Determines how long the effects of the drug last

Question 18

What is absorption?

Answer 18

• How much drug enters the system?
• How quickly does it enter the system?

Question 19

What is the amount of drug absorbed and the speed of absorption influenced by?

Answer 19

1. The chemical properties of the drug
2. routes of administration
3. the properties of the subjects or patients

Question 20

Chemical properties of drugs

Question 21

what are the different routes of administration?

Answer 21

• inhalational: inhaled (gas, fine powder, spray, vapour, smoke)
• intra-arterial (ia): injected into an artery - very rare in human medicine (liquid)
• intradermal: injected into the skin layer (liquid or suspension)
• intramuscular (im): injected into the muscle mass(liquid or suspension)
• intrathecal (it): injected into the membranes that enclose the spinal cord
• intracerebroventricular (icv): injected into the cerebral ventricles
• intravaginal: ‘plug’ containing drug (pessary)
• intravenous (iv): ‘bolus’ or ‘infusion’ injected into a vein (liquid)
• nasal: applied to nasal membranes (drops, fine powder, spray)
• oral (po): swallowed (tablet, capsule, liquid)
• rectal: (suppositories)
• subcutaneous (sc): injected just beneath skin (liquid or suspension)
• sublingual: held beneath the tongue (usually tablets or capsules)
• topical: applied directly to affected area (creams, patches)
• transcutaneous: fine powder (through the skin under pressure/by diffusion from adherent patch)

Question 22

What are the ‘properties of the subject or patients’?

Answer 22

• Fat or thin?
• Light or heavy?
• Just fed or empty stomach
• Healthy or infirm?

Question 23

What is distribution?

Answer 23

where does the drug go after it has been absorbed?

Question 24

What does a drug need to diffuse through in order to achieve its effects?

Answer 24

In order to achieve its effects a drug may be required to diffuse through tissue or be carried in the blood

• Is the drug soluble in blood?
• Does the drug stick to proteins or cells in the blood?
• Will the drug concentrate in fats or in aqueous compartments?
• Does the patient have an adequate circulation ?

Question 26

What is pharmacokinetics influenced by?

Answer 26

Drug metabolism and drug excretion - How long does the effect last? - When a drug is metabolized (i.e. broken down, usually in the liver) its duration of action is reduced - Similarly if the drug is excreted rapidly (urine, faeces, sweat, breath) it may have a short duration of action * Where is the drug metabolized - does the patient have a healthy liver? * How is the drug excreted - does the patient have good kidneys? * Are the metabolites active? * Are the metabolites toxic?

Question 27

What are the two overlapping categories of pharma companies in the pharmaceutical industry?

Answer 27

1) Those that sell drugs that are not protected by patents. These companies usually sell cheap versions of commonly used drugs but do not have extensive research and development facilities and do not discover or develop new drugs 2) Those that have extensive research facilities and are usually global corporations

Question 28

What are the steps of pre-clinical drug development?

Answer 28

* From an idea originating from basic research a hypothesis will be developed * Assay systems (measurement systems) will be devised to identify chemical tools to test the hypothesis * When a chemical tool has been discovered that works in the assay system: the the hypothesis can be tested in an animal model * If the hypothesis holds up then chemists will change the chemical structure of the active compound * If and when promising compounds are found they are tested extensively for toxic effects and pharmacokinetic properties. A safety pharmacology program will be started to measure unanticipated effects of the drugs that, though not overtly toxic, may nevertheless compromise the use of the chemical as a drug * The best compounds will go forward into the first phase of clinical development as drug candidates. From original idea to drug candidate usually takes 5 to 10 years or even longer

Question 29

How long does it usually take for compounds to go from original idea to drug candidate?

Answer 29

usually takes 5 to 10 years or even longer.

Question 30

What is clinical drug development? How many phases?

Answer 30

divided into 4 phases. At all stages patients are monitored for side effects and info on drug safety is gathered as a priority. phase 0 phase I phase II phase III

Question 31

Clinical drug development- Phase 0

Answer 31

* A transitional phase between the pre-clinical testing stage and full clinical trials * Sub-therapeutic doses are monitored for any unexpected effect * This ‘phase’ is most commonly used in development of chemotherapeutic agents for cancer treatment

Question 32

Clinical drug development- Phase I

Answer 32

* Is relatively small scale, usually involving around 20-80 healthy volunteers (often undergraduate students) and is concerned primarily with dose finding and tolerability * Volunteers are given progressively larger doses of drug until an effect is registered * Information gathered during phase I will allow estimates to be made of the amount of drug the body will tolerate without causing side effects and what side effects might occur * Several rounds of Phase I trials may occur for any given drug, in different countries and patient groups.

Question 33

Clinical drug development- phase II

Answer 33

* Trials are of medium size, involving 100-300 patient volunteers * At this stage the drug is tested for effectiveness against a specific disease which will be the intended ‘indication’ of the drug * Again, several phase II studies may be performed for a given drug

Question 34

Clinical drug development- phase III

Answer 34

* Large scale trials involving 1000-3000 patients where effectiveness is tested again and comparison is made with other treatments that are available * If a drug survives phase III then it may be registered and sold as a therapeutic agent. More than one phase III trial may be performed

Question 35

How long does the transition through phases I, II, and III take?

Answer 35

6-10 years