Foundations of Pharm Principles Flashcards
Pharmacokinetics
What the body does to the drug
How the drug concentration/dosage in the plasma changes over time
AMDE: Absorption, distribution, metabolism, elimination
Pharmacodynamics
What the drug does to the body
Relationship between drug concentration and effect
Drug names
Chemical name: describes the drug’s chemical composition
Generic name: name recognized by Health Canada under FDA
Trade name: registered trademark and restricted by the drug’s patent owner
Pharmacotherapeutics
The use of drugs and the clinical indications for drugs to prevent and treat diseases
Pharmaceutics
Study of how various drug forms influence pharmacokinetic and pharmacodynamic activities
Routes and drug administration
Routes can affect how quickly and how much drug enters the systemic circulation
- Important to determine peak plasma concentration
Drugs are administered as a formulation due to route, time course, and active drug concentration
Excipients
Non-medicinal ingredients (fillers, colorants, coatings, flavourings and sweeteners)
Enteral administration
Entry via gastrointestinal tract. Most happens in the stomach/small intestine.
Absorption usually <100% depending on drug comp and GI functioning
Benefits: easiest, safest, cheapest. No need for sterility.
Drawbacks: acid-sensitive and protein drugs are unstable, must be conscious and cooperative, upper GI irritation, bioavailability
Parenteral administration
Not by the GI tract (eg. inhalers)
Topical administration
Absorbed through the skin
First pass effect
Pre-systemic elimination
Blood supply from the small intestine enter the hepatic system first to go into the liver, then exits the liver into systemic circulation. The liver metabolizes the drug before it can reach systemic circulation
Enteral Administration - Rectal
Absorbed through the rectal mucosa
Benefits: rapid absorption, cheap and easy, useful with swallowing, less first pass effect
Drawbacks: absorption is often incomplete, many drugs cause irritation of mucosal lining
Formulations for Enteral Admin
Tablets
Capsules (powder in a gelatin coating) - faster absorption
Caplets (capsule shape tablets) - more easily swallowed
Liquids (even faster absorption) - aqueous, suspensions or emulsions
Sublingual EA
Under the tongue
Advantages: relatively rapid absorption, no first-=ass effect, suitable for acid-sensitive drugs, fast easy and cheap
Disadvantages: taste
Parenteral Administrations - Transdermal
Through the skin
Usually for local effects
Benefits: cheap and wasy, simple local admin, no first pass effect
Drawbacks: not suitable for many drugs (fat insoluble), affected by skin hydration
Formulations: creams, gels, ointments, controlled release patches, topical aerosol spray
Parenteral Admin - Inhalation
Inhaled into airways
Advantages: local action, no first pass effect, useful for gasses
Disadvantages: limited absorption for large proteins, possible irritation of lung lining
Formulations: gasses or gas mixtures, inhalers (particulate, powders, nebulized (mist)
Parenteral Admin - Subcutaneous Injection (SC)
Injected under skin
Advantages: rapid effect, useful for local drug delivery (local anesthetics), drug absorption into circulation is controlled
Disadvantages: requries sterile drug, patient preference, absorption affected by blood flow
PA - Intramuscular Injection (IM)
Drug injected into skeletal muscle
Advantages: into a large muscle mass, easy self admin, absorption into systemic circulation
Disadvantages: can be painful
PA - Intravenous (IV)
Drug injected into vein
Advantages: rapid distribution, can come close to 100% bioavailability, large drug volumes
Disadvantages: requires skilled administration and close monitoring, drug must be sterile, greater cost
Topical Routes
Skin, eyes, ears, nose, vagina
Choosing a route
Enteral
- Convenient but first pass effect
Parenteral
- Bypasses the liver
- More drug reaches the circulation
Drug Absorption
Entry to drug into circulatory system
Can be active or passive
Passive: movement of drug with the concentration gradient. Most drugs are absorbed this way.
Chemical factors affecting drug absorption
Drug size: smaller = more absorption
Lipid solubility: does it prefer fatty or liquid environment
Drug charge: prefers to be in watery environment
Physical factors affecting drug absorption
- Blood flow to the site of absorption - intestine favoured
In shock, extremities have less blood so subcutaneous admin is less effective - Total surface area for absorption - high surface area in intestine
- Contact time - greatly affected by diarrhea or constipating drugs
- Drug formulation - particle size
Bioavailability
The proportion of drug that passes into systemic circulation after admin
Often much less than 100%
Affected by first pass effect
Bioequivalence
Two related drugs that show comparable bioavailability, pharmacokinetics and biological effects
Distribution
Determined by 3 factors
- Blood flow to tissues
- Exiting the vascular system
- Entering cells
Affected by
- Fat solubility of the drug - drug accumulation
- Plasma protein binding
Plasma Protein Binding
% of drug bound to protein can be quite high (90% or more)
Albumin - major carrier or drugs
When a person has lower albumin, lower the drug dose because it will have a great affect
Only free drugs can have effects
Drug Metabolism
Occurs in the liver, gut, kidney, lungs, plasma and placenta
Drugs more water soluble - renal elimination
Variation between individuals
Grapefruit juice can inhibit P450s
Enzyme induction - cells stimulated to make more enzymes
Drug Excretion
Occurs mostly through the kidney - GI tract, sweat, breast milk
Drug excretion depends on
- plasma protein binding and drug fat solubility/charge
Most drugs have to be metabolized before excretion - less fat soluble
Which drugs can be excreted in an unaltered form?
Some antibiotics
Steady state
When there is a consistent level of a drug in the body that corresponds to maximum therapeutic benefits
The time taken to reach a steady state is dependent on the drug’s half life
- usually 4-5 T 1/2
Half life T1/2
The time required for the amount of drug in the body to decrease by 50%
How does liver disease effect dosages?
You could lower dosage or extend the period of time between doses
Depends on situation
Drug Target
Drugs usually bind to specific targets (mostly protein receptors or cell membranes)
Protein targets are “receptors”
Drugs should interact only with their target molecule, cell or tissue
Affinity
Binding of drug depends on the “stickiness” of a drug fro tis target
Agonist
Drug A + Receptor = Drug A–Receptor = Response
Antagonist
Drug B + Receptor = Drug B–Receptor = No response
Prevents other drugs/chemcials from reacting (antihistamine or beta blockers)
MEC
Minimum effective concentrtion is the plasma drug level that must be reached for therapeutic effect
What is the difference between a low and a high therapeutic index?
The lower the therapeutic index, the small the amount of the drug it takes to lead to a toxic response
Higher the therapeutic index, the safer the drug
Contraindication
A characteristic of the patient, especially a disease state, that makes the medication dangerous to the patient
Tolerance
A decrease response to repetitive drug doses
Dependence
A physiological/psychological need for a drug
Idiosyncratic reactions
Unusual reaction to a drug
Teratogenic
Drug that crosses the placenta and can affect embryo/fetus l
Mutagenic
Can cause permanent genetic changes
Carcinogenic
Causes cancer
