Pharmacology Flashcards
Pharmacology and PT
- Optimal response to therapy
- Interaxns with rehab procedures
- Adverse effects
- Compliance
- Drug alternatives
Pharmacotherapeutics
Use of specific drugs to prevent, treat or diagnose disease
Pharmacokinetics
What BODY does to the drug: Absorbtion Distribution Metabolism Elimination
Pharmacodynamics
What DRUG does to body:
=Mechanism of action
Drug/Ligand + Receptor –> Drug-Receptor Complex
Toxicology
Side effects
Pharmacy
Preparation and dispensing of drugs
Chemical Name
Name of chemical composing drug
Ex: N-Acetyl-p-aminophenol
Generic Name
Common name of drug, describes chemical compound.
*Never capitalized
Ex: acetaminophen
Brand/Trade Name
Name of drug, chosen by marketers or pharmaceutical company
*Always capitalized
Ex: Tylenol
Patent
Company that creates drug has rights to it for 7-10yrs
- ->generic versions
- same therapeutic use
Drug Development
- What constitutes drug
- FDA (Efficacy + Safety)
- Animal studies (Preclinical tests)
- Human studies (Clinical trials - Phases I-III)
- New drug approval
Clinical Trials
Drug testing conducted on humans post animal studies of efficacy + safety:
Phase I: Small # healthy indiv (<1 yr)
*Effect, dosage, pharmacokinetics
Phase II: Limited # with target disease (2 yrs)
*Efficacy of treating specific disease
Phase III: 1000-3000 pts with target disease (3yrs)
*Efficacy + Safety in larger population
Phase IV: General population (Indefinite)
*Monitor problems post approval
OTC Medication
- Availability/convenience
- High safety profile (lower dose = harder to harm)
- Note in patients
- PT implications
- Interaxns with other drugs (doubling up)
Controlled Substances
Drugs with abuse potential, decreases with higher schedule:
Sched I - High Abpot / No med use Sched II - High Abpot / Some med use Sched III - Lower Abpot / Med use Sched IV - Lower Abpot / Med use + barbituates Sched V - Derivatives of high Abpots
Schedule I
Controlled substances with highest abuse potential
*No medical use
Ex: Heroin, LSD, Marijuana (THC), MDMA
Schedule II
Controlled substances with high abuse potential
*Some medical use
Ex: Morphine, Methadone, Methamphetamine,
Oxycontin
Schedule III
Controlled substances with lower abuse potential
*Medical use
Ex: Codeine, Anabolic Steroids, hydrocodone
Schedule IV
Controlled substances with low abuse potential
*Medical use + barbituates
Ex: Meprobromate, phenobarbitol, alprazolam,
diazepam
Barbituates
CNS depressant
- Sedation
- Anesthetic
- Mild analgesic effects
Analgesic
Painkiller
Ex: acetaminophen, NSAIDs, opioids
Schedule V
Controlled substances with lowest abuse potential
*Contain derivatives of high abuse medicines
Ex: Codeine cough syrup, antidiarrheal preps,
phenergan
Dose
Quantity of drug administered at one time
*Concentration of drug at receptor site
Dosage
Administration of drug per unit of time
*How much to give (BID/SID/etc.)
Dose-Response Curve
Relation between dose administration (magnitude of drug) and observed response
–>Shows effect of drug at any given dose
Plotted as Dose (x) vs Effect/Response (y)
- Threshold
- Potency
- Max effect
Drug Response
Extent to which drug reaches intended effect
Potency
Measure of drug dose needed to produce a therapeutic effect
*Potency does not equal efficacy
Higher = less drug needed for target effect
Lower = more drug needed for target effect
Subtherapeutic
Threshold, dose less than amount needed to produce target effect
Max Effect
Point at which increase in dose will not increase effect
Dose-Response Function
-Must specify dose and species
-One drug can have multiple
-Larger dose doesn’t equal greater magnitude of
response (due to max effect)
Max effect = no increase in response with
increase in dose
Quantal Dose-Response Curve
Relation between drug concentration in blood (x) and response percentage of a population (y) to a specified effect chosen for the drug.
-Determines relative safety and efficacy of a particular drug
ED50
Therapeutic Effect
TD50
Toxic Effect
ED50
(Median Effective Dose); Quantal D-R Curve
= Min dose required to produce desired effect in 50% of the
population
Therapeutic Effect
Point at which dose of drug has effect on the body
TD50
(Median Toxic Dose)
= Min dose required to produce toxic effect in 50% of the
population
Toxic Effect
Point at which dose of drug becomes harmful to the body
Therapeutic Index
Ratio of dose that causes toxicity to dose that causes desired effect in a population
TI = (TD50 / ED50)
Absorption
1st step of pharmacokinetics
- Depends on:
- Route of admin
- Drug factors (lipid/water sol, size, ionization)
- Body factors (SA, pH, vascularity)
Bioavailability
Percentage of drug that reaches bloodstream
- Oral ~ 50%
- IV (Direct) ~ 100%
Routes of Administration
- Enteral = GI Tract
- Oral
- Sublingual
- Rectal
- Parenteral = Everything else, *more direct
- Inhalation
- Injection (IV, IM, IT, SC)
- Topical
- Transdermal (Placed on skin –> bloodstream)
- Implanted drug delivery
- Controlled release preparations
- Targeted drug delivery
Enteral Administration
(Route of administration, GI Tract)
1. Oral:
- Safe, easy
- Ltd absorption, 1st pass metab to liver, compliance
2. Sublingual:
- Rapid onset, no 1st pass metab
- Must absorb into mucosa easily
3. Rectal:
- Local effect
- Incomplete absorption, irritation
Parenteral Administration
(Route of administration, Direct)
1. Inhalation
- Rapid onset, respiratory, increased SA
- Irritation, administration, compliance
2. Injection (IV, IM, IT, SC)
- Direct, rapid onset
- Infexn, self-administration
3. Topical
- Local effects
- Can be absorbed into bloodstream
Transdermal Administration
(Route of administration, Placed on skin –> Bloodstream)
- Steady, prolonged delivery - Ltd, drug must penetrate skin unchanged
IA
(Intra-arterial)
= Specific
SC
(Subcutaneous)
= Local response needed
Ex: Novacaine, insulin
IM
(Intramuscular)
Ex: Botox for spasticity
IT
(Intrathecal)
= subarachnoid space of spinal cord
Ex: Analgesics, spasticity
Implanted Drug Delivery
Route of administration
-PCA Pump
Controlled Release Preparations
Route of administration
= Encapsulation to release in intervals, fewer manual
doses
Targeted Drug Delivery
Route of administration
-Monoclonal Ab's (Drug + Ab --> specific problem)
-Viral Transport
-Gene Therapy (Viral cells enter DNA, give new
instructions
-Enzyme Activation (Drugs only activated by specific
enzymes
Absorption Factors
Related to drugs:
Lipid/water sol Molecular/particle size
Ionization Physical form
Dosage form Formulation
Concentration
Related to body:
SA Vascularity
pH Other substances present
GI motility Functional integrity
Disease
Exogenous
Introduced to body from outside
Endogenous
Native to body
Membranes that Affect Absorption and Distribution
Based on lipid solubility:
- GI –> Bloodstream
- ECF –> ICF
- ICF –> ECF
- Kidneys –> Bloodstream
Passive Diffusion
Water soluble: Drug crosses membrane via aqueous
channel
Lipid soluble: Drug dissolved through membrane
Distribution
2nd step of pharmacokinetics
- Affected by:
- Blood flow
- Capillary permeability
- Binding
Depot Binding
Binding of drug to substance besides site of action
- ->Need to increase dose to get desired effect
- ->Adverse/toxic effects
Vd
(Volume of Distribution of drug)
-If evenly dist, = to total body fluid volume
= how much of drug is in bloodstream
Membranes that Affect Distribution
- Cell membranes
- Capillary walls
- Blood brain barrier (Glial cells)
- Placental barrier (not real barrier)
Blood Brain Barrier
Series of unique properties of blood vessels in the nervous system that regulate movement of molecules between blood and neural tissue.
- Glial (Support) Cells
- Astrocyte –> End feet form sheath around BV - Tight junctions of endothelial cells
- Breaks –> detect chemicals
- Area Postrema (Medulla)
- Median Eminence (HT) - Purpose:
- Block toxins
- Maintain homeostasis of brain
Metabolism
3rd step of Pharmacokinetics
= Biotransformation of drug from parent compound into
metabolite
-1st Pass Metabolism
-Lipid-sol –> Water-sol for kidney excretion
*High = drug has less effect
Low = drug has more effect
Biotransformation
Chemical change of drug
*Not really “broken” down
Metabolite
Daughter compound of drug
1st Pass Metabolism
GI Tract –> Portal Circulation –> Liver –> Target Site
*Bypassed by IV drug admin
First-Order Kinetics
Rate of metab & elim proportional to concentration of drug
*Higher dose –> Higher metab of drug
Zero-Order Kinetics
Constant rate of metab regardless of concentration of drug
*Higher does –> Metab stays the same
Enzyme Induction
Tolerance = Increase in concentration of enzymes to be able to biotransform drug
- Drug has less effect due to upreg of enzymes
- ->More drug required for same effect
Cytochrome P450 System
Component of drug metabolism, in liver / GI tract
-Diversified, nonspecific
-Phase I
Oxidation (+O2, -H+)
Reduxn (-O2, +H+)
Hydrolysis
-Phase II (Some drugs enter directly)
Conjugation = coupling to endogenous compound
-->Inactivation --> Water soluble
Elimination
4th step of Pharmacokinetics
Filtration system via kidneys:
- Nephron / Glomerulus / Bowman’s Capsule
- 1L blood/min, 1cm3 urine produced
- Lipid-sol drug –> water-sol drug –> Excretion
*Lipid-sol drugs reabsorbed and return to liver until water-sol
CL Total
(Total Body Clearance)
Rate at which drug is eliminated from the body, sum of hepatic, renal, pulmonary, integumentary clearances
CL = 0.69 x (Vd / (t1/2))
Half-life (t1/2)
Time it takes for 50% of drug to be eliminated from bloodstream
t1/2 = 0.69 x (Vd / CL)
Percentages of original dose:
2 t1/2 = 75%
4 t1/2 = 94%
6 t1/2 = 98%
Ex: 100mg drug
1 t1/2 = 50mg (50% of orig dose)
2 t1/2 = 25mg (75% of orig dose)
3 t1/2 = 12.5mg
4 t1/2 = 6.25mg (94% of orig dose)
Steady State Concentration
Amt administered = Amt Eliminated
- Takes 5-6 t1/2
- Determined by dose, dose interval, t1/2
- ->predictable accumulation
*Repeated fixed dose = continuous oscillations in
plasma concentrations of drug
*Single fixed dose = single peak in plasma
concentration –> decline in drug level
Tolerance
Decreased response to effects of given amt of drug from previous exposure
- Pharmacokinetic: Enzymes (Cross-tolerance) - Pharmacodynamic: Receptors/Neurotransmitters
= More drug for desired effect
Dependence
Drug use necessary for physiological/psychological well-being
Cytochrome P450 System
Component of drug metabolism, in liver / GI tract
-Diversified, nonspecific
-Phase I
Oxidation (+O2, -H+)
Reduxn (-O2, +H+)
Hydrolysis
-Phase II (Some drugs enter directly)
Conjugation = coupling to endogenous compound
-->Inactivation --> Water soluble
Elimination
4th step of Pharmacokinetics
Filtration system via kidneys:
- Nephron / Glomerulus / Bowman’s Capsule
- 1L blood/min, 1cm3 urine produced
- Lipid-sol drug –> water-sol drug –> Excretion
*Lipid-sol drugs reabsorbed and return to liver until water-sol
CL Total
(Total Body Clearance)
Rate at which drug is eliminated from the body, sum of hepatic, renal, pulmonary, integumentary clearances
= 0.69 x (VD/(t1/2))
Half-life (t1/2)
Time it takes for 50% of drug to be eliminated
Percentages of original dose:
2 t1/2 = 75%
4 t1/2 = 94%
6 t1/2 = 98%
Ex: 100mg drug
2 t1/2 = 50mg
4 t1/2 = 25mg
3 t1/2 = 12.5mg
4 t1/2 = 6.25mg (94% of original dose
Steady State Concentration
Amt administered = Amt Eliminated
- Takes 5-6 t1/2
- Determined by dose, dose interval, t1/2
- ->predictable accumulation
*Repeated fixed dose = continuous oscillations in
plasma concentrations of drug
*Single fixed dose = single peak in plasma
concentration –> decline in drug level
Tolerance
Decreased response to effects of given amt of drug from previous exposure
= More drug for desired effect
Dependence
Drug use necessary for physiological/psychological well-being
Drugs
Exogenous substances that mimic endogenous substances
Receptor
Protein with binding site for endogenous substances
Ligand
Substance capable of binding to a receptor
Ex: Drug, hormone
Selectivity
Enzymes: Nonspecific
Receptors: Very specific
Affinity
Drug ability to bind to receptor
-Could block or open
Neurotransmitters
Acetylcholine
Norepinephrine
GABA
Agonist
=Opener
Exogenous ligand that binds receptor & causes biological effect
-Has affinity + efficacy
Antagonist
=Blocker
Exogenous ligand that binds receptor and blocks effect
-Has affinity + efficacy (if intended effect was to block)
