Introduction to Pharmacology Flashcards
Define pharmacokinetics
What the body does to the drug
Define pharmacodynamics
What the drug does to the body
Define drug
a chemical substance of known structure, which when administered to a living organism produces a biological effect
Define medicine
Usually, but not necessarily contains one or more drug, which is administered with the intention of producing a therapeutic effect
Define therapeutics
Use of drugs to diagnoses, prevent, and treat illness
Define formulations
how the drug is packaged
Define excipients
substances formulate alongside the drug
Define medicinal product
any substance or combination of substances presented as having properties of preventing or treating disease in humans
What are a drugs 3 names?
Chemical = chemical structure Generic = class of drug Proprietary = trade name
What is a lignad?
a molecule that binds to the receptor
What is a receptor?
a molecular target for a drug
What is an agonist?
a molecule that activates a receptor
What is an antagonist?
something that blocks or reduces agonist mediated responses
What is an analgesic?
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
Explain what a ligand is and what it does?
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.
What is a target?
A molecule, usually a protein, that is accessed by a drug to produce a therapeutic effect
What would an ideal drug look like?
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.
Explain how drugs produce effects and key aspects of drug binding.
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.
What is affinity?
How well the ligand binds to the receptor
What are the common protein targets?
Receptors, ion channels, carrier molecules and enzymes (RICE)
What is the receptors role?
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.
What is the role of carrier proteins/transporters?
These are the facilitators for transport for example across membranes. Activate transporters which require ATP and facilitate diffusion.
What is the role of enzymes?
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
Explain drug specificity
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.
What are the 4 main processes in pharmacokinetics?
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
What is absorptions role?
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.
What are the different routes of administration?
oral administration, injections, rectal or vaginal, nasal, ocular, otic, parenteral, epidural, topical, and transdermal patch.
What is enteral administration?
Via the gut - oral
What is parenteral administaration?
not via the gut - injection
What are enteral pro’s?
Oral ingestion, gut absorption, low infection risk, and simple self-administration
What are enteral con’s?
Harsh environment in the stomach and duodenum, and first pass metabolism
Explain first pass metabolism
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.
What are the pro’s of topical administration?
local effects, low systemic affects, limited first pass metabolism suited to sloe continuous long period administration, low infection rate risk of systemic absorption.
What are the con’s for topic administration?
Process of lipid permeation, small molecular size, use a carrier molecule, usually limitans to absorption
What are the different injection routes?
intravascular - into bloodstream intramuscular - into skeletal muscle subcutaneous - drug absorbed from subcutaneous tissue dermal - into dermal vascular layer depot - slow releasing
What are injections pro’s and con’s?
Pro's = avoids first pass metabolism, rapid bioavailability for IV/IA, and targeting risks Con's = infection risk
Explain what bioavailability is
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.
What are the factors affecting distribution?
Protein binding, blood flow, membrane permeation/tissue solubility
Explain protein binding.
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
Explain blood flow in distribution
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
Explain membrane permeability in distribution
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
What is the lipophilicity of a drug?
Whether it likes to dissolve in lipids or not
What is metabolisms role?
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
What is pro-drug activation?
little or no activity until they undergo metabolic activation
What are the 2 phases of metabolism?
Phase 1 produces toxic metabolites and phase 2 converts toxins to soluble metabolites for excretion. Some drugs do phase 2 before phase 1
Explain the main excretion route
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.
What are the other routes of excretion?
Biliary, saliva, breast milk, sweat, and tears
Explain biliary excretion
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
What is enterohepatic circulation?
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
What is drug elimination half-life?
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%
