Principles of Pharmacology Flashcards
Pharmacokinetics
What the body does to the drug
How the drug concentration in the plasma changes over time
Pharmacodynamics
what the drug does to the body
relationship between drug concentration and its biological effect
ADME
Absorption
Distribution
Metabolism
Excretion (Elimination)
Excipients
non-medicinal ingredients such as fillers, antioxidants, disintegrants, colorants and coatings, flavourants and sweeteners
Enteral Administration (PO)
entry of drug through the gastrointestinal (GI) tract (per os - orally, or anally)
cannot administer acid-sensitive or protein drugs PO
Parenteral Administration
not by the GI tract (colloquially injection)
bypasses the liver, avoids first pass effect
Absorption
entry of drug into circulatory system
moves from the external environment to the internal environment
First Pass Metabolism (and consequences)
most drugs given orally first pass through the liver before entering the systemic circulation
Drug concentration can drop dramatically when given PO
Sublingual (SL)
dissolved under the tongue
rapid absorption, can give acid-sensitive drugs this way
NO first pass effect (directly into bloodstream)
Subcutaneous (SC)
beneath the skin
local drug delivery, but requires sterile drug
Intramuscular (IM)
injected into muscle
fast but somewhat painful
Intravenous (IV)
Directly into vein
rapid bolus (IV push) or as a continuous infusion (IV drip)
Inhalation
gasses or gas mixtures, particulate powders, nebulized (mist)
Topical Routes
Skin Eyes (drops – gtt [Latin guttae]) Ears Nose Vagina
Skin administration
no first pass effect
must be lipid-soluble
creams, gels, ointments, patches, sprays
Other routes:
intra-articular injection intra-cardiac injection epidural injection spinal injection buccal
joints heart very close to spinal cord into spinal fluid absorption between gum & cheek
Most drugs are absorbed: actively or passively?
passively
Chemical Factors Affecting Drug Absorption (3)
- Drug size (molecular, how many atoms)
- Lipid solubility (passes through membranes more easily)
- Drug charge (more charged = less lipid soluble)
Physical Factors Affecting Drug Absorption (4)
- Blood flow to the site of absorption (faster blood = more quickly removed from site of administration)
- Total surface area of site (Higher the surface area, the quicker/better the absorption)
- Contact time with site of absorption
- Drug formulation (dissolve speed)
Bioavailability
the proportion of drug that passes into the systemic circulation after administration, taking into account both absorption and local metabolic degradation
Insulin route of administration?
injected (subcutaneous because it’s a protein)
Distribution Factors (3)
Blood flow to tissues
Exiting the vascular system
Entering cells
e.g.
rapid distribution: heart, liver, kidneys, brain
slow distribution: muscle, skin, fat
Plasma Protein Binding
albumin transports fat soluble molecules around the blood
bound molecules cannot leave bloodstream
most drugs are bound to plasma proteins, are not free-floating
liver creates albumin, so there are more free molecules in a person with liver disease
Metabolism (what is it?)
Modification (change) of drug molecule by cell enzymes
mostly occurs in the liver by the cytochrome P450 enzymes
Consequences of Metabolism
Accelerated renal drug excretion
Drug inactivation
Increased therapeutic action
Activation of prodrugs
Increased or decreased toxicity
Grapefruit Juice
affects metabolism by inhibiting CYP enzymes
Excretion
occurs mostly through the kidneys
nephrons are the functional unit of the kidney
most drugs must be metabolized first (made more water-soluble) in order to be excreted
Duration of effects is determined largely by the combination of:
metabolism and excretion
Half-life
the time required for the amount of drug in the body to decrease by 50%
a measure of the rate at which drugs are removed from the body
Steady State
When there is a consistent level of drug in the body
dependent on the drug’s half-life
reached after 4-5 half-lives
e.g. drug half-life is 4 hours: 4x4 = 16, 4x5 = 20 so approx. 18 hours to reach steady state
Agonist
elicits a response in the receptor of the cell
Antagonist
prevents a response to an endogenous agonist
Onset
time it takes for the drug to elicit a therapeutic response
Peak
time it takes for a drug to reach its maximum therapeutic response
consider MEC – Minimum Effective Concentration
Therapeutic index
Ratio of the drug’s toxic to effective blood concentration
The larger/higher the therapeutic index, the safer the drug
The smaller/lower the therapeutic index, the less safe the drug
