Principles of Pharmacology Flashcards
Pharmacodynamics
What the drug does to the body
-the connection between drug concentration and effect
Pharmakinetics
What the drug does to the body
-How the drug concentration in plasma changes over time
What does pharmakinetics provide information to
- extent and duration
- preferred dose and dosing interval
- Preferred route of administration
- how to optimize therapies
- how to avoid toxicities
- how to avoid drug interactions
4 Stages of pharmakinetics
Administration
Distribution
Metabolism
Excretion
(ADME)
Administration
(3)
- can affect how quick + how much drug enters systemic circulation
- Not all routes of administration are suitable for all drugs
- drug must be administered to reach site of administration
Formulations for administration depend on:
- Route of admission
- Time course of action
- Active drug concentration
How quick and how much drug enter systemic circulation are important factors for
- Determining peak plasma concentrations + duration of drug
Chosen route of drug depends on
desired outcome
Enteral administration
Entry through the GI tract
Where is enteral administration absorbed
- between the mouth and anus
- Usually stomach or small intestine
How much drug is absorbed through enteral absorption
Less then 100% due to first pass metabolism
Enteral absorption depends on
- disintegration/solubility
- acidity of GI tract
- GI blood flow
- drug stability
- gastric emptying and motility
Enteral administration benefits
- Easy, safe, cheap
- No need for sterility/purity
Enteral administration Drawbacks
- Acid sensitive + protein drugs are unstable
- Ph must be conscious and cooperative
- variable absorption + bioavailability
- possible upper GI irritation
First pass metabolism is also called
pre-systemic elimination
First pass metabolism
drugs passing through liver before entering systemic circulation
what does the liver do during first pass metabolism
- Site of drug metabolism
- drug concentration can dramatically decrease
- extent of drug metabolism varies for different drugs
What does liver damage do to first pass metabolism
- decreased liver metabolism
- creates unpredictable drug metabolism and concentrations
What does metabolism do to drugs
changes molecules
eg. Codeine becomes morphine
When does first pass metabolism occur
with enteral administration
-especially PO
Rectal (PR) Administration
Absorption through rectal mucosa
Rectal (PR) Benefits
- Rapid absorption
- cheap, easy
- Useful if pt. can’t or won’t swallow
- Less first pass effect
Rectal (PR) drawbacks
- often incomplete absorption
- irritation on mucosal lining
Sublingual (SL) Administration
Drug is placed under tongue to dissolve and absorbe
Sublingual (SL) Benefits
- Rapid
- no first pass effect
What does no first pass effect mean
drug enters systemic blood immediately
Sublingual (SL) drawbacks
- many drugs taste bad
Buccal Administration
drug placed between gums and lip to be absorbed
Types of enteral Administration
- PO
- PR
- SL
- Buccal
Enteral administration formulations
- Tablets
- Capsules
- Liquids
- Buccal film
Parenteral Administration
Not absorbed through GI tract
Subcutaneous Injection (SC)
Drug is injected under skin
Subcutaneous injection benefits
- Rapid effect due to general circulation
- useful for local injection/delivery
- easy self administration
- easy to control
Subcutaneous injection drawbacks
- requires sterile drug
- some pts don’t like injections
- absorption affected by blood flow and injection volume
Intramuscular Injection (IM)
Drugs injected into skeletal muscle
Intramuscular injection benefits
- cane be into a large muscle mass
- self administered
- absorption into systemic circulation can be controlled
- oil based formulation allow for slower absorption (depot bolus)
Intramuscular injection drawbacks
- can be painful
- must be sterile
Intravenous (IV)
Drugs injected directly into vein as a rapid bolus (Push) or continuous infusion (Drip)
Intravenous benefits
- all drug enters the bloodstream
- rapid distribution + onset of drug
- large drug volumes
- very predictable
Intravenous drawbacks
- requires skilled administration + close monitoring
- Drug must be sterile
- greater cost
Inhalation
drug inhaled into airways
Inhalation benefits
- useful for local action (bronchodilators) but also into pulmonary circulation
- no first pass effect
3.useful for gasses
Inhalation drawbacks
- limited absorption of large proteins
- possible irritation of lung lining
Inhalation formulations
- gasses or gas mixtures
- inhalers for pulmonary use
- pressurized aerosol and other containers allow unused product to remain uncontaminated for later use
Types on inhalers
- particulate powders
- nebulized (mists)
Other parenteral routes
- intraarticular injection (joints)
- intracardiac injection (cardiac)
3.epidural injection - spinal injection (spinal fluid)
Topical Administration
applied on surfaces
Topical administration locations
- skin
- eyes
- ears
- nose
- vagina
Transdermal Administration
- Absorbed through the skin
- Local and systemic effects
Transdermal benefits
- cheap and easy
- simple local administration
- no first pass effect
Transdermal drawbacks
- not suitable for many drugs (fat insoluble)
- absorption affected by skin hydration
Transdermal formulations
- creams, gels, ointments
- absorption can be enhanced by suspension in an oily vehicle
- controlled by release patched (nicotine)
- topical aerosol spray
Absorption
Entry of drug into circulating system
Example of absorption
- Drug must pass through the epithelial cells of the GI tract
- Then into blood flowing through the capillaries of the gut wall
Chemical factors affecting drug absorption
- Drug size
- Lipid solubility
- Drug charge
- Bioavailability
Bioavailability
The proportion of drug that passes into systemic circulation post administration, taking into account both absorption and metabolic degradation
Bioavailability for enteral routes
Less then 100%
Bioavailability for parenteral routes
High
What affects bioavailability
- first pass effect
- drug absorption
What factors of drug absorption affect bioavailability
- Solubility of drug
- Stability of drug
- Formulation of drug
Distribution
- follows absorption
- mixed into blood quick
3 Determining factors of distribution
- Blood flow to tissues
- Exiting the vascular system
- Entering cells
Initial distribution
rapid in the first few minutes, depends entirely of rate of blood flow to given tissues
Tissues with high bloodflow
exposed to drug more quickly then those with less
Rapid distribution goes to
heart, liver, kidneys
slow distribution goes to
muscles, skin, fat
Second distribution
- slower
- depends on where drugs like to be
What affects distribution
- lean mass (watery environment)
- fat solubility of drug accumulation
- Plasma protein binding
Plasma protein binding
- most drug molecules don’t float freely in blood
- often bound to plasma proteins (up to 90%)
- Albumin
- only free drugs create effects
Albumin
- most common plasma protein
- major carrier drug
liver disease affect on distribution
decreases blood albumin- more free drug molecules to create effects
Metabolism
- modification/change of drug molecule by enzymes
- mostly occur in liver, gut, kidney, lungs, plasma, placenta
- metabolized by cytochrome enzymes
4.varies between people - inhibiting cyps can be dangerous
- cyp enzyme induction
What inhibits CYPs
-grape fruit juice
-other drugs
CYP enzyme induction
cells stimulated to make more enzymes
Therapeutic consequences of drug metabolism
- accelerated renal drug excretion
- drug inactivation
- increased therapeutic action
- activation of prodrugs
- increased or decreased drug toxicity
Accelerated renal drug excretion
- most common effect
- acids water solubility
Drug excretion
- removal from body
- mostly through kidney
- some may be excreted in an altered form
- most drugs must be metabolized before they work
- Drug enters tubular fluid
Excretion depends on
- Plasma protein binding
- Drug fat solubility
Excretion is through
- Kidney
- GI tract
- Sweat
- Breast milk
Drug enters tubular fluid
- filtration through glomular capillaries
- active transport through specialized carriers
What can be excreted in unaltered formes
some antibiotics
Why do most drugs need to be metabolized first
- renders the drug active
- makes the drug more water soluble/less fat soluble
Dosage Regimes
Effective treatment requires effective dosage regimes
-dose size
-dose frequency
Time course of drugs
duration of effects is determined by the combination of metabolism + excretion
Drug steady state
When there is a consistent level of drug in the body
What does drug steady state depend on
Half life of the drug
Half life
- time required for the amount of drug in the body to decrease 50%
What does half life measure
the rate drugs are removed from the body
A long half life takes
a long time to reach steady state with multiple doses
A short half life takes
a short amount of time to reach steady state with multiple doses
How many half lives does it take to reach steady state
4-5
Most drugs get metabolized/excreted according to
principles of percentage loss of drug over time
Very few drugs leave the body at a consistent rate: what are 2 examples
- Ethanol (alcohol)
- Phenytoin
Pharmacodynamics is the
relationship between drug concentration at the site of action and its biological effect
Drug receptors
- to elicit an effect on the body drugs must interact directly with cells
- usually binding to specific targets
drug receptors are
protein targets
drugs exhibit selectively for their receptors: meaning
- they interact with their target molecules, cell, or tissues
- high concentrations they lose this selectively
2 common possibilities of drug action
- response
- no response
What does drug binding depend on
the affinity or stickiness of the drug for its target
Agonist
elicits a response
Antagonist
Prevents a response to an endogenous or neurotransmitter agent
Dose response relationship
- relationship between size of administered dose and intensity of response produced
Dose response relationship is determined by
- minimum amount of drug to be used
- maximum response a drug can elicit
- how much to increase the dose to increase the desired effect
Onset
Time it takes for the drug to elicit a therapeutic response
Peak
Time it takes for a drug to reach max therapeutic response
-Troughs and MEC
Trough
lowest blood level of the drug
- too low drug becomes ineffective
MEC
Minimum effective communication
Minimum effective communication (MEC)
plasma drug level that must be reached for therapeutic effect
Duration
time for which a drug concentration is sufficient to elicit a therapeutic response
Therapeutic Index
- Measures drug safety
- Ratio of the drug toxic: effective drug concentration
- Smaller the therapeutic index the less safe the drug
Be extra careful with drugs with a _____ Therapeutic index, ____ dangerous
Narrow, more dangerous
Non-receptor Drugs
simple physical or chemical interactions with other molecules
-Antacid, saline laxatives, chelating agents
