Week 9 Bioscience Flashcards
Sources of drugs: Plants
Plants and plant parts have been used as medicine for centuries and remain an important source of chemicals used for developing into drugs today.
* Morphine - derived from the poppy plant Papaver somniferum →used for pain management
* Digoxin – derived from Digitalis purpurea plant (purple foxglove) →used to slow heart rate and treat congestive heart failure
* Caffeine – derived from the Caffea arabica plant
Sources of drugs: Animals
Animal products have been used to replace human chemicals affected by disease or genetic problems.
* Adrenaline - originally obtained from the adrenal glands of monkeys, sheep and cows, now synthesised artificially →used to treat anaphylaxis, cardiac arrest
* Insulin - originally isolated from pigs and cows, now synthesised artificially by genetically modified bacteria →used to treat diabetes
Drug names (Drug nomenclature)
Drugs have several names
* The chemical name is a description of the chemical composition of the drug and identifies the drugs atomic and molecular structure, e.g. para-acetyl-amino-phenol C8H9NO2
* The generic (non-proprietary) is the abbreviated and approved name given to a drug by the manufacturer to first develop it, e.g. Paracetamol.
A generic name set by the Therapeutic Goods Administration (TGA) for use in Australia is An Australian Approved Name (AAN)
* The trade (proprietary) or brand name is selected by the drug company selling the drug. Protected by a trademark. So the same drug can have several trade names when produced by a number of different manufacturers, e.g. Panadol, Panamax, Dymadon and Tylenol.
The enteral (oral) route
Medications absorbed via the gastrointestinal (GIT or enteral) system. The oral route suggests that, in most instances, the person will swallow the drug before it reaches the gastrointestinal tract but also includes drug administration:
* through a nasogastric tube
* via PEG, gastronomy or other enteral feeding device
Medications administered by the enteral/oral route are subject to first pass metabolism (more on this later)
Most commonly used route of administration
- Drugs administered via the enteral route can take many forms:
* Tablets
* Capsules
* Lozenges
* Liquid preparations
Advantages
* Easily administered
* Pain free
* Non invasive
* Economical
* Normally good absorption along whole length of GI tract
* Gradual increase in plasma concentration of drug
Disadvantages
* Requires patient compliance, i.e. to take the right dose at the right time
* Patient must be conscious and co-operative in order to be given the dose (except where administration is through an enteral tube)
* The medication may cause gastrointestinal irritation
* Medication effectiveness may be altered by food, gastric secretions, emotional stress or physical activity
* The drug may be denatured in the digestive tract, e.g. proteins such as insulin cannot be administered orally
* It takes longer for the drug to take effect
* The drug will be subject to first-pass metabolism (discussed later)
Sublingual and Buccal
- Sublingual administration-drug placed under tongue to dissolve(disperse)
- Buccal administration-drug placed between cheek and gum
- Both routes facilitate rapid absorption of medication via the capillaries of the mucous membrane rather than being processed by the gastrointestinal system
- Both avoid first pass metabolism
The parenteral route
Any method of drug administration that avoids the gastrointestinal tract
* Often refers to where an invasive procedure is used; primarily injecting directly into the body
* Most common parenteral routes include intravenous (IV), intramuscular (IM) and subcutaneous (SC)
* Includes intra-arterial and epidural (drug injected into spinal canal outside duramater)
* Also includes drug injected directly into other body cavities
Advantages
* Provides an alternative when drugs given orally are poorly absorbed, inactive or ineffective.
* The IV and intra-arterial routes provide immediate onset of action.
* The IM and SC routes can be used to achieve a slower or delayed onset of action.
* Problems with patient co-operation, compliance and conscious state can be avoided.
* Avoids first pass metabolism. (more on first pass metabolism soon)
Disadvantages
* Skill required to inject correct site using the required technique
* Aseptic technique required to avoid the risk of infection
* The onset of drug action can be rapid
* Requires accurate dosage
* It can be painful
* It is often more expensive
* May require additional equipment (e.g. I.V. cannula and tubing, plus programmable infusion pump)
Other routes of administration (Parenteral)
Inhalation (pulmonary route) - Drugs administered by gas or fine mist.
* The lungs provide a large surface area for absorption.
* Respiratory membrane and its rich capillary network allows drugs to readily enter the circulation.
* Examples include anaesthetic agents and bronchodilators administered by nebulisers or “puffers”.
Topical route – applying drug to the skin or mucous membranes.
* Used to produce local or systemic effects.
* Includes administration via skin, eyes, ears, nose, vagina and rectum.
* Medication may take the form of an ointment, transdermal patch, drops, pessaries or suppositories.
* Must be applied to intact skin.
Pharmacokinetics
· Once a drug has been administered into the body, the drug must reach its molecular target
· The amount of drug that interacts with its target is influenced by how the drug is:
* Absorbed into the body
* Distributed around the body
* Metabolised by the body
* Excreted from the body
Absorption
- Movement of drug from the site of administration to the systemic circulation.
- Before a drug gains access to internal compartments of the body absorption must take place.
- Most drugs are subject to absorption.
- Exceptions include some of the parenteral injections
- Intravascular administration means a drug will directly enter the systemic circulation, bypassing the many complications of absorption from other routes.
- Intravascular administration includes the intravenous and intra-arterial routes.
- These parenteral routes of administration effectively bypass absorption. Drugs administered in this way immediately commence being distributed around the body.
Movement of drug from the site of administration to the systemic circulation.
· Many drugs are introduced into the body from outside the blood stream, e.g. topical, oral, subcutaneous, and must first be absorbed before having any effect.
In the case of medication(tablet) taken orally
→ disintegrated (broken down)
→ goes into solution (dissolution)
→ is absorbed from the small intestine
→ into the hepatic portal system (blood supplygliver)
→ then into systemic circulation
Factors affecting drug absorption
· The formulation of a drug, i.e. oral route - a liquid medication is more rapidly absorbed than a tablet
· The route of administration
· Tissue surface area and thickness
* absorption through the small intestine (large surface area and single layer of epithelial cells) is quicker than through the local topical administration on skin (small surface area, multiple cell layers to cross)
· The blood supply at the site of administration
* Highly vascularised area (e.g. the sublingual route) →more rapid absorption vs. poorly vascularised area (e.g. subcutaneous injection) → slower absorption
* Patients with cardiovascular disease may have reduced blood circulation → slows absorption rate
The solubility of a drug
- For absorption to occur, a drug must be in solution, able to cross the plasma membrane (e.g. of intestinal epithelial cells, epithelial cells of skin) and enter blood capillaries
- lipid-soluble drugs → easily cross the plasma membrane via simple diffusion → rapid absorption
- water-soluble drugs → cross the plasma membrane via facilitated diffusion or active transport → slower absorption
Distribution
Distribution is the process of reversible transfer of a drug between one location and another in the body
Once the drug has reached the systemic circulation it can be distributed to various body compartments including
* fluid compartments gin particular blood
* intracellular compartments gtarget tissue plus other tissue e.g bone & fat
Depending on the type of drug, the drug may:
* be distributed to organs that are well perfused (i.e. good blood supply)
* be distributed more slowly to areas that are poorly perfused (e.g. adipose tissue)
* remain in the blood
The movement of a drug to body tissues. Depends on:
* Drug solubility (water or lipid soluble) § Cardiovascular functioning (especially cardiac output)
* Perfusion of the area
* Degree of blood flow (vascularisation)
* The permeability of the capillaries, i.e. brain vs. liver
* pH of the area
* Binding of drug to plasma proteins. Upon entering the systemic circulation:
* a proportion of drug molecules bind reversibly to plasma proteins
* a proportion of drug molecules remain “free” or unbound
* pharmacological action is exerted by unbound drug, so a high degree of plasma protein binding will affect drug efficacy.
Once “free” drug is removed from circulation (e.g. via metabolism, excretion) more protein bound drug will be released.
Factors affecting drug distribution
The movement of a drug to body tissues. Depends on:
* Tissue binding. Adipose tissue.
* Lipid soluble drugs have a high affinity for adipose tissue. Low blood flow to this tissue means some drugs may be stored here.
Bone tissue.
* Some drugs have a special affinity for bone and can accumulate here.
This decreases immediate distribution. Drugs having accumulated here may be released slowly over time.
Barriers to drug distribution
Blood-brain barrier.
* Made up of endothelial cells with tight intercellular junctions to protect CNS from potentially damaging microorganisms and other substances.
Placental barrier.
* Membranes and enzymes providing incomplete protection to fetal circulation.
Metabolism
- Metabolism, or biotransformation, is the process where drugs are broken down into substances more easily excreted. These chemicals are termed metabolites.
- The liver is the most important site of drug metabolism. Is facilitated by enzymes located here.
- Rate of metabolism varies markedly between individuals. § Factors affecting metabolism include:
- Genetics
- Environmental factors
- Other medications, diet, alcohol, activity.
- Age and gender
- Infants have immature liver function
- The elderly show delayed metabolism of drugs
- Pregnancy can alter drug metabolism
- Disease states
- The presence of hepatic, renal or cardiovascular disease will slow metabolism
Bioavailability
Refers to the amount of drug that is available to exert a pharmacological effect.
* Is the proportion (%) of the administered drug that reaches the systemic circulation.
* Bioavailability varies with route of administration
* Drugs administered orally undergo first-pass metabolism → bioavailability much lower than originally administered drug dose.
* Drugs administered intravascularly do not undergo first- pass metabolism → bioavailability is 100% of originally administered dose of medication.
Hepatic first-pass metabolism means, therefore, that the oral dose of a medication is often higher than would be given intravascularly
