Pharmacology: introduction Flashcards
What are the nomenclature involved in pharmacy?
- Body system: pulmonary, cardiovascular etc
- Site and type of action: bronchodilators (dilates airways)
- Target receptor: beta blockers
- Legal classification: S8 drugs, over the counter (non-prescription)
Drugs can have different names
• Chemical name: the molecular structure (2-acetoxybenzoic acid)
• Generic name: abbreviation of chemical name, describes the active ingredient (acetylsalicylic acid)
* Brand name: the name selected by the pharmaceutical company for the marketing (ASPIRIN)
What is absorption?
When drugs are taken from the site of administration to site of need
Describe the factors that can affect absorption. (6)
Type of administration:
- Intravenous (IV) admin.: no absorption is required
- Orally administered drugs: absorption is done through epithelial lining of gastro-intestinal (GI) tract
Physical and chemical properties:
Dissolution is required for tablets and capsules, liquids are better absorbed. Manufacturing properties and water-solubility affects the dissolution rate: Water-soluble vs fat-soluble, particle size, the inert ingredients, compaction
Delayed/sustained release:
Special formulations can be used that delay drug dissolution to lengthen the absorption time and/or avoid exposure to stomach acid
Method of delivery; passive diffusion
Carrier proteins:
Most drugs follow a concentration gradient across the selectively permeable epithelium and move through passive diffusion. This process is not saturable, and continues until a concentration equilibrium is reached
Substances resembling naturally-occurring molecules can use certain channels/pumps to be carried across membranes. This process depends on the availability of the carrier and is therefore saturable
Bioavailability:
Fraction of a drug that is absorbed from its site of administration and reaches, in an unchanged form, the systemic circulation. It is always calculated in reference to intravenous administration of the drug
First pass effect:
This is when the drug is subject to metabolism by the liver. Some drugs like propranolol or enalapril undergo significant first pass metabolism. In such cases, the bio-availability significantly decreases and thus higher doses need to be administered orally to overthrow the first pass effect
What are patient specific factors affecting absorption? (6)
• Absorption needs blood flow. Patients in shock, or with cardiopulmonary arrest will have to receive IV injection of medications because their blood flow is often impaired
• Most absorption happens in small intestine, since it has a high blood flow; if major parts of small intestine are surgically removed (eg in post-operative cancers), this process is as well impaired
• Changes in contact time with the epithelial lining of the GI tract like fast intestinal movements or diarrhea will negatively impact absorption
• Factors that delay stomach emptying (for example a large meal), can reduce absorption by delaying exchange with the epithelium
• Some medications exhibit drug-food or drug-drug interactions that interfere with absorption
Low levels of stomach acid affects tablet dissolution and hence reduces absorption
How does metabolism in the liver occur?
Metabolism in the liver follows two types of reaction:
1. Enzyme-catalyzed reactions: mainly oxidation (oxygen loss/gain) or hydrolysis (chemical break down due to reaction with water). It uses cytochrome P450 enzyme system and the rate depends on enzyme availability. Examples: Alcohol, Phenytoin
- Conjugation Reactions: the drug is joined with a another substance like glucuronic acid, sulfuric acid, acetic acid or amino acid. The most common is glucuronidation. The result of this reaction is to make substances more water-soluble.
In some cases, the drug is administered as an inactive form (pro-drug) which is only active after being metabolized
What factors affect metabolism? (4)
· Deficiency in some metabolizing enzymes: some deficiencies are genetic. Therefore, some people may exhibit low tolerance and toxicity to such drugs at high doses
· Age: deterioration of tissues and organ malfunction with time
· Competition for metabolising enzymes in the liver
* Effect of the drug or its metabolites on the existing metabolising enzymes
What are the three factors involved in drug distribution?
- Capillary permeability
- Unbound and bound drugs
- Vd and dose calculation
What does distribution refer to?
Refers to how drugs are transported within the body once in the bloodstream.
What are the factors affecting drug distribution? (3)
· For highly protein-bound drugs, levels of serum albumin might be a limiting factor. Low albumin levels ( poor nutrition, chronic illness, etc) will lead to toxicity, since the levels of free drug increases
· In combination therapy, or co-administration of multiple protein-bound drugs, there is competition for bindings sites. The drugs with higher affinity will bind, and that will limit the available binding sites for the second drug, increases the free form and therefore causes potential toxicity and side effects
* Other patient-specific variables that affect distribution are body composition, cardiac failure (decompensation) and age.
What is Vd?
This is a proportionality factor that relates the amount of drug in the body compared to the concentration of drug within biological fluid.
Which enzyme is responsible for metabolism in the liver?
Which enzymes are responsible for conjugation?
Cytochrome P450
Glucuronic acid, acetic acid, amino acid, sulfuric acid
Which drugs are vulnerable to the first pass effect?
Propranolol and Enalapril
