Pharmacology 1 Flashcards
What is Pharmacokinetics? What is ADME?
Pharmacokinetics describes what the body does to a drug. It refers to the movement of the drug through the body.
ADME abbreviates: Absorption, Distribution, Metabolism and Excretion
What are the different routes of drug administration?
- Oral (cannot be used in drugs that are broken down by first pass metabolism)
- Intramuscular (e.g. vaccine)
- Intravenous (can use lower doses as full dose is absorbed. Poses a risk of toxicity and side effects)
- Transdermal (e.g. nicotine patch. Surpasses FPM. Effective only in small doses an lipid soluble drugs)
- Topical (creams, foams, ointment)
- Buccal (under the tongue, surpasses FPM. Drugs must be water and lipid soluble)
- Epidural (Into epidural sac therefore comes with risk of failure and infection.)
- Inhalation (produces localised effect so reliant on patient technique. Particles must be small enough o be absorbed)
- Intrathecal (straight into CSF e.g. chemo and pain management. Produces rapid ocarina’s effects. May introduce infection and relies on expert technique)
- Subcutaneous (under the fat layer of the dermis. Must be fat soluble. Cannot be used to deliver large doses so in fluids they are given over long periods of time. Can irritate subcutaneous tissue)
What are modified dose forms?
Modified-release dosage and its variants are mechanisms used in tablets
and capsules to dissolve a drug over time in order to be released slower and steadier into the bloodstream while having the advantage of being taken at less frequent intervals than immediate-release formulations of the same drug.
What is first pass metabolism?
The concentration of a drug is greatly reduced before it reaches the systemic circulation. This greatly affects drugs that are ingested. First pass metabolism can occur in the liver or in the gut.
What is first pass metabolism? Where can it occur?
The concentration of a drug is greatly reduced before it reaches the systemic circulation. This greatly affects drugs that are ingested.
It can occur in:
- Liver
- Lungs - cells in the liver may have a higher affinity for the drug than for hormones in that area
- Intestinal wall - rich in enzymes that break down the drug
- Intestinal lumen - there are enzymes secreted by the mucosa and pancreas that can break down the drug
What is clearance?
The volume of blood/plasma cleared of the drug per unit of time. It does not indicate the drug amount of drug removed. This includes metabolic clearance as well as renal and biliary.
What is bioavailability?
The proportion of the drug that reaches the systemic circulation. This applies to oral medication.
What is volume of distribution?
The volume of plasma that accounts for the total concentration of the drug.
What is volume of distribution?
The volume of plasma that accounts for the total concentration of the drug. Used to determine drug dosage and estimate blood concentration in an overdose.
What is bulk distribution?
Circulation into the blood where it can travel long distances
What is diffusion transfer distribution?
The drug travels short distances. Mainly occurs by passive diffusion of un-ionises form across plasma membranes.
What is eGFR?
Estimated glomerular filtration rate. This should not be used to estimate creatine clearance as it does not take into account the weight of the individual - better to use Cockcroft-Gault Equation. GFR is a key factor is measuring renal function.
Define pharmacodynamics?
Pharmacodynamics describes what the drug does the body. It is more specific than pharmacokinetics. Harder to change.
How to drugs move across membranes?
- Passive diffusion - must be unionised and lipid soluble.
- Facilitated diffusion
- Pinocytosis
- Phagocytosis
How does pH influence drug diffusion?
In order to cross the membrane, drugs should be uncharged and lipid soluble. Most drugs are designed to be lipid soluble. With increasing pH, the stomach becomes more acidic. The more acidic, the more ionised the stomach becomes and the less ionised the small intestine becomes. Drugs that are bases are more absorbent and so are usually lipophilic.
What Factors influence distribution of drugs from plasma?
- Plasma proteins
- specific drug receptor sites in tissues as for a drug to have an effect it must bind to a receptor
- Regional blood flow - If an area is well perfused, more of the drug will reach the area
- Lipid solubility
- Disease - liver disease can mean not enough albumin is produced
What factors affect absorption?
- GI tract motility - a higher motility means the drug does not stay in the GI tract for long and so not well absorbed.
- Physiochemical factors (solubility and charge)
- Particle size and formulation
- GI tract enzymes and acid which can break down the drug
- Food - some drugs have strict instructions on what you can eat with them do to interactions with food.
How do you determine the concentration of drugs at the site of action?
Half life calculation. Different drugs have different half lives.
Estimation of creatine clearances also can be used to estimate the clearance of drugs filtered at the glomerulus.
What factors affect metabolism?
- Age
- Alcohol
- Hepatic blood flow
- First pass effect
- Genetic factors - may be genetically unable to break down a drug e.g. 33% of caucasians cannot break down codeine
- Other drugs
- Liver disease
What is and enzyme inducer? What is its affect on the concentration of the product in the blood?
Enzyme inducers increase the activity of an enzyme which break down drugs, this therefore increases the concentration of the product in the blood. This occurs when there is a combination of drugs given to a patient.
What is and enzyme inhibitor? What is its affect on the concentration of the product in the blood?
Inhibit the action of an enzyme that breaks down drugs. This therefore decreases the concentration of a product in the blood. This occurs when there is a combination of drugs given to a patient.
What percentage of an orally administered drug is absorbed?
Approximately 75% of a drug given orally will be absorbed in 1-3 hours.
What are cytochrome p450s?
A family of enzymes produced in the liver and each individual enzyme is known as an isoenzyme. They function as mono-oxygenases. In mammals they oxidise steroids, fatty acids and xenobiotics.
What is bioequivalence?
Two or more chemically or pharmaceutically equivalent products. You can then switch between the drugs without having any clinical implications.
