2.2 Pharmacology - Basic Concepts/Processes Flashcards
Overview of Medication
Medication/drugs alter chemistry in the body.
Most of these changes occur at a cellular level.
When cells receive drugs, they ensure that these drugs are delivered to the appropriate part of the body.
Drug Transport
Drugs used for systemic effects travel and interact through cell membranes.
Gated Channels - Drugs can move through gated channels that regulate movement of ions inside and out of a cell. They open and close in response to neurotransmitters, change in pressure, etc.
Carrier Proteins - Proteins found in a cell membrane attach to drug molecules and move them into the cell
Lipid Bilayer - Contains double layer of polarized phospholipids and phosphate ends. Phosphate end only allows water soluble (hydrophilic) substances. Lipid end only allows Lipid Soluble substances (hydrophobic). Polarity determines if drug can enter lipid bilayer. Most water soluble drugs cannot enter lipid bilayer.
Pharmacokinetics
- What the body does to the drug
- Defined as entry, movement through body to sites of action, metabolism, and absorption of a drug.
- Used to determine the most effective route of administration, dosage, and administration schedule of a drug.
4 Processes of Pharmacokinetics
Absorption - Movement of drug from site of administration to blood stream
Distribution - Drug movement from blood to interstitial spaces then into cells.
Metabolism - Biotransformation: Alteration of drug structure through enzymatic activity.
Excretion - Movement of drugs and metabolites out of body.
Absorption
- A drug must cross the cell membrane to reach systemic circulation
- Bioavailability is the percentage of drug that reaches systemic circulation in an unchanged form.
Rate of Absorption
Rate of dissolution - more rapid dissolution yields a faster rate of absorption.
Fastest to slowest absorption for Oral Drugs
(Liquids, Suspension Solutions, Powders, Capsules, Tablets, Enteric-Coated Tablets)
Intramuscular (IM) is more rapid than Subcutaneous (SQ) but both are absorbed relatively quicky.
Intravenous (IV) are not absorbed, they are put directly into the bloodstream.
What affects rate of absorption
Surface Area - Larger surface area, faster absorption
Blood Flow - Faster the blood flow to area, Faster the absorption.
Lipid Solubility - Highly lipid soluble drugs are absorbed more rapidly because they cross cell membranes quickly. (Channeling through cell channels is rare for drugs, aid of transport system, and direct penetration (most common)).
pH Differential - If PH difference between site of administration and blood stream favors ionization, than absorption is enhanced.
Physiological Condition - Circulation, Condition of GI Tract, pH, Body Fluids, can impact absorption
Distribution (Rate of Absorption)
Rate of Absorption - Drugs can bind with proteins (most important albumin) which due to large size, remain in blood stream. These drugs do not reach site of action. Free (unbound) drugs are active. Bound drugs are inactive
Protein binding can affect drug interactions. If 2 drugs are competing for protein binding, one drug may bind with protein while the other is released into system at greater quantities than it would have been. This can lead to increased distribution and toxicity.
Distribution (Blood Brain Barrier)
Unique anatomy of capillaries in the CNS.
Cell junctions are so tight they prevent drug passage.
Only lipid soluble or drugs with transport systems can cross through the capillary wall.
Brain also has a active transport (P-glycoprotein) that pumps variety of drugs out of the cells back into blood.
Brain is protected from toxins but difficult to get drugs there to treat disorders.
Other factors of distribution
Pregnancy - Lipid-soluble and nonionized compounds pass readily across the placenta. Ionized and protein bound drugs do not.
Lactation - Drugs can cross into breast milk via concentration gradient that allows passive diffusion of nonionized non-protein bound drugs.
Metabolism
Process where intracellular enzymes breakdown drugs into inactive compounds or convert prodrugs to active drugs.
Metabolites - product of metabolism, usually inactive. Active metabolites can exert independent effects on the body either therapeutic or adverse.
Majority of metabolizing happens in the liver.
First Pass
Metabolism of a drug before it reaches the systemic circulation.
Drugs are metabolized at different rates with each pass through the liver.
Drugs that are highly metabolized during their first pass often need higher doses to achieve therapeutic effects.
Only drugs that go through portal vein go through First Pass Metabolism (Rectal/Oral).
Drugs that don’t go through first pass and directly into systemic circulation (Sublingual, Intramuscular, IV)
Therapeutic Consequences of Metabolism
Accelerated Renal Excretion - Kidneys cannot excrete highly lipid-soluble drugs. Metabolism converts drugs to less lipid-soluble.
Drug Inactivation - Metabolism inactivates drugs
Increased Therapeutic Action - Metabolism can increase effectiveness of drugs (Codeine -> Morphine)
Activation of prodrugs - Prodrugs are inactive and become active after metabolism.
Increased Toxicity - Metabolism can sometimes covert safe compounds to toxic forms. (Acetaminophen)
Decreased Toxicity - Metabolism converts toxic substances into inactive forms.
Hepatic Microsomal Enzyme System (P-450)
- P450 System is metabolism through liver specific Enzymes
- 12 Enzyme Families (CYP1, CYP2, CYP3 - Metabolize Drugs, Others Metabolize Endogenous Compounds)
- Some drugs inhibit/induce elements of P-450 which in turn also alter metabolism of other drugs.
- Drugs affecting this system are the reason for drug interactions.
Enzyme Induction/Inhibition
Enzyme Induction - CYP inducers increase activity of isoenzyme, rapid reduction of drug levels.
Enzyme Inhibition - CYP inhibitors decrease isoenzyme resulting in decreased metabolism of drug and increase blood level of drug and increase action level.
