Pharmacology:adme,targets And Therapeutic Ranges

Question 1

What is ADME

Answer 1

Absorption → Distribution → Excretion
Absorption → Distribution  Metabolism → Excretion

Question 2

What does the rate of drug absorption depend on

Answer 2

~ route of administration & local blood flow
~ solubility & ability to cross membranes
~ most drugs absorbed by passive diffusion

Question 3

What is bioavailability

Answer 3

• Bioavailability refers to the amount of drug that, once ingested (or administered), is absorbed into the bloodstream:

~ the time course of drug action follows the time course of its concentration in blood plasma / bioavailability
~ the fall in drug activity is due to the rate of a drugs elimination via metabolism and / or excretion)

Question 4

Oral administration and gastrointestinal absorption

Answer 4

-Most drugs are swallowed as tablets, powders or liquids
-Absorption of most drugs takes place in the small intestine>75% of a drug dose is absorbed within 1-3h
-it is cheap, easy,convenient and no need for medical supervision

Question 5

Factors affecting absorption

Answer 5

-formulation / particle size, drug solubility & blood flow
-enzymes or acids may inactivate drugs
-ionisation of acidic / basic drugs reduces their absorption

Question 6

What is sublingual administration

Answer 6

-Latin for under the tongue
-it avoids gut absorption variability
>avoids stomach acid and enzymes
>avoids first pass effects
>onset is rapid(nicotine,oxytocin,glycery trinitate)

Question 7

Intramuscular into(Im) or subcutaneous(sc|) injections

Answer 7

~ im and sc often used as they have faster effects than the oral route and are safer than intravenous (iv)
~ sc implants of oestrogen-progesterone pellets for birth control give prolonged hormone release

Question 8

Intravenous(iv) injections

Answer 8

~ drugs can be injected rapidly or infused slowly into a vein
-rapid speed of onset is required(Adrenalin)
-good control of drug levels needed(cytotoxic drugs )

-slow iv infusions give better control over plasma levels
-cytotoxic drugs can damage blood vessels

Question 9

Inhalation and topical/skin absorption

Answer 9

• Volatile drugs / gaseous anaesthetics are absorbed by lungs:
~ large surface area and good blood supply give very rapid
equilibration between plasma and alveolar air
~ rapid systemic effects are achieved
• Drugs intended for direct action may be inhaled by the lungs: ~ bronchodilators for asthma (salbutamol)
• Drugs of abuse:
~ smoking (nicotine, cannabis, cocaine)
• Used for topical effects, but systemic effects may also occur • Percutaneous absorption and transdermal patches:
~ steroid creams / oestrogen for HRT
~ hyoscine patches for travel / nicotine patches for smokers ~ nitroplasters for angina
10
• Nasal sprays ~ anti-diuretic hormone 1. • Eye drops ~ cyclopentolate

Question 10

Enterohepatic re-circulation & Drug Distribution

Answer 10

• Enterohepatic re-circulation and storage of drugs in bile can cause secondary peaks of drug into blood after eating

• Drugs distribute into tissues via extracellular fluid:

•
Drug solubility and ionisation affects a drugs distribution:
~ lipid soluble compounds rapidly enter all tissues
~ ionised compounds tend to stay in the circulation

Question 11

Drug metabolism

Answer 11

(biotransformation) is required to facilitate the inactivation and / or excretion of a drug from the body:
~ metabolism is usually sequential and involves two phases

Question 12

Drugs that inductive drug metabolism

Answer 12

~ increase their own metabolism and that of other drugs reactive / toxic less reactive / toxic
~ may reduce the activity of other drugs & increase toxicity

Question 13

Inhibitors

Answer 13

• Inhibitors slow metabolism and increase the activity of drugs metabolised by an inhibited enzyme (usually a Cyt P450)

Question 14

Phase 1 and phase 2 of aspirin

Answer 14

Phase 1- hydrolysed Into salicylic acid
Phase 2-conjugated into salicylglucuronide

Question 15

What happens to the drug elimination by bile,GI Tract and lungs

Answer 15

• The liver transfers drugs from plasma to bile where they can be stored in the gall bladder for a few hours:
~ these drugs enter the duodenum / GI tract where they and their metabolites may be reabsorbed

• Most drugs in bile are recycled as a result of reabsorption from the small intestine (enterohepatic shunt):
~ there may be secondary peaks of drug activity as a
result of intestinal reabsorption in to blood (eg: morphine)
• Faecal excretion eliminates drugs and their metabolites that are not reabsorbed by the GI tract
• Pulmonary excretion eliminates anaesthetic gases and volatile
drugs such as alcohol

Question 16

Kidney / Glomerular Filtration & Tubular reabsorption

Answer 16

• The kidney is the most important organ for elimination of drugs and their metabolites, but they must be water soluble
• Most small drugs are freely filtered by the glomerulus:
~ molecular weight below 5,000 (ionised or unionised)
• Drugs that bind plasma proteins are poorly filtered (warfarin)
• Tubular reabsorption of most drugs reflects lipid diffusion:
~ lipid soluble drugs tend to be reabsorbed
~ water soluble drugs tend to be excreted
• Some drugs are reabsorbed / excreted via transport proteins
• Drugs stored in the bladder before elimination may damage the bladder and may cause bladder cancer

Question 17

What actions of drugs focussing on receptors and actions:

Answer 17

~ agonists and antagonists
~ affinity and efficacy
~ drug targets and receptor sub-types

Question 18

Pharmacology

Answer 18

• Pharmacologists study interactions that occur between living organism and drugs that affect normal / abnormal function
• Pharmacology involves the study of:
# drug composition and properties
# drug interactions and toxicology
# medical / anti-pathogenic / therapeutic uses of drugs

Question 19

Pharmacodynamics

Answer 19

interactions of chemicals with biological receptors

Question 20

Pharmacokinetics

Answer 20

absorption, distribution, metabolism, and excretion of drugs

Question 21

Pharmacy

Answer 21

preparation, dispensing, dosage, and the safe and effective use of medicines

Question 22

What shape do receptors have

Answer 22

• Receptors have complex 3-dimentional structures that have ligand / drug - binding sites:
~ natural ligands include neurotransmitters and hormones

Question 23

Agonist drugs

Answer 23

bind to and activate natural receptors
causing changes in cell / biological functions

Question 24

Antagonist drugs

Answer 24

bind to but do not activate receptors; such drugs are often referred to as inhibitors or blockers

Question 25

Competitive drugs

Answer 25

usually displace natural ligands from their binding sites causing dose-dependent actions

Question 26

Non competitive drugs

Answer 26

via alternative mechanisms

Question 27

What type of drug is morphine

Answer 27

Agonist drug that inhibits pain

Question 28

What is affinity

Answer 28

tendency of a drug to bind to a receptor:
~ affinity constants (KA) can be calculated
~ represent the concentration of a drug that produces 50% of the maximum response; ie 50% effective dose (ED50)

Question 29

Efficacy

Answer 29

Efficacy is the tendency of a bound drug to activate a receptor by altering the conformation of the receptor:
~ drugs usually have high affinity and efficacy

Question 30

What do drugs act as

Answer 30

Many drugs are analogues of natural ligands that are more
stable and resistant to enzymatic breakdown:
~ salbutamol is a stable analogue of adrenalin

Question 31

ED-50, Therapeutic effect and Toxic effects

Answer 31

• The dose required to cause a therapeutic effect (positive response) in 50% of a population is the ED50
• Most drugs have toxic side-effects as the dose increases

Question 32

Drug targets

Answer 32

-most drug targets are proteins
>enzymes
~ high blood pressure drugs block angiotensin converting enzymes (ACE inhibitors)
~ aspirin-like drugs block cyclooxygense enzymes
>transporter proteins
~ anti-depressants block serotonin re-uptake transporters (SSRI’s) Fluoxetine
>receptors
~ many drugs act via cell membrane hormone receptors or intracellular steroid receptors e.g. salbutamol acts on nor-adrenalin B2 receptors in asthma and steroids such as prednisolone are used for arthritis
>ion channels

~ local anesthetics block Na+ channels in nerves (lidocaine)
~ some blood pressure drugs that lower blood pressure are calcium channel blockers (verapamil)
~ some anti-epileptic drugs act on neurotransmitter receptors in the brain (phenobarbital) ~ GABA Chloride channels

Question 33

Drugs affecting the autonomic nervious system

Answer 33

Watch lecture 7th December

Question 34

G protein coupled receptors

Answer 34

Watch lecture 7th December

Question 35

What are beta-blockers and their affect on intracellular 2nd messengers

Answer 35

Watch lecture