Pharmacology:adme,targets And Therapeutic Ranges Flashcards
What is ADME
Absorption → Distribution → Excretion
Absorption → Distribution Metabolism → Excretion
What does the rate of drug absorption depend on
~ route of administration & local blood flow
~ solubility & ability to cross membranes
~ most drugs absorbed by passive diffusion
What is bioavailability
• 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)
Oral administration and gastrointestinal absorption
-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
Factors affecting absorption
-formulation / particle size, drug solubility & blood flow
-enzymes or acids may inactivate drugs
-ionisation of acidic / basic drugs reduces their absorption
What is sublingual administration
-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)
Intramuscular into(Im) or subcutaneous(sc|) injections
~ 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
Intravenous(iv) injections
~ 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
Inhalation and topical/skin absorption
• 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
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• Nasal sprays ~ anti-diuretic hormone 1. • Eye drops ~ cyclopentolate
Enterohepatic re-circulation & Drug Distribution
• 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
Drug metabolism
(biotransformation) is required to facilitate the inactivation and / or excretion of a drug from the body:
~ metabolism is usually sequential and involves two phases
Drugs that inductive drug metabolism
~ increase their own metabolism and that of other drugs reactive / toxic less reactive / toxic
~ may reduce the activity of other drugs & increase toxicity
Inhibitors
• Inhibitors slow metabolism and increase the activity of drugs metabolised by an inhibited enzyme (usually a Cyt P450)
Phase 1 and phase 2 of aspirin
Phase 1- hydrolysed Into salicylic acid
Phase 2-conjugated into salicylglucuronide
What happens to the drug elimination by bile,GI Tract and lungs
• 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
Kidney / Glomerular Filtration & Tubular reabsorption
• 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
What actions of drugs focussing on receptors and actions:
~ agonists and antagonists
~ affinity and efficacy
~ drug targets and receptor sub-types
Pharmacology
• 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
Pharmacodynamics
interactions of chemicals with biological receptors
Pharmacokinetics
absorption, distribution, metabolism, and excretion of drugs
Pharmacy
preparation, dispensing, dosage, and the safe and effective use of medicines
What shape do receptors have
• Receptors have complex 3-dimentional structures that have ligand / drug - binding sites:
~ natural ligands include neurotransmitters and hormones
Agonist drugs
bind to and activate natural receptors
causing changes in cell / biological functions
Antagonist drugs
bind to but do not activate receptors; such drugs are often referred to as inhibitors or blockers
