Pharmacology Flashcards
Define Additive, Synergistic, Potentiation and Antagonism
2+2=4
2+2=9
2+0=5
2-2=0
Pharmacokinetics
Pharmacodynamics
Body effect on Drug, ADME
Drug effect on Body
Therapeutic Index
Efficacy
Potency
Drug scheduling
The ratio between minimum effective concentration (MEC) and minimum toxic concentrations (MTC) = ED50/T50
The highest level of bodily response, Emax & ED50 (50% of max)
The amount of drug required to produce a specific pharmacological effect, Log of the drug dose
lower dose = more potent, ED50 (50% of max on X-axis)
(1) Highest Abuse Potential (illegal) =>(2) No refill => (3)/(4) Minimum prescription and refills ~5 => (5) Lowest Abuse Potential (no Rx needed)
Therapeutic Equivalence
Pharmaceutical Alternative
Bioequivalence
Pharmaceutically equivalent with same effect & safety (A)
Same drug different form, route, strength (B), and not necessarily therapeutic equivalent
Similar rate and absorption 80-125% comparison
Terms qd qod ac qhs os ad
Drug Dosing Calculation
once daily every other day before a meal (consumption) every night before bed left eye right ear
Doctors Order (D)/Supply (H) X Quantity (Q)
Vd Equation & define Vd
Plasma Volume Equation
Rate of Elimination
Loading Dose & define
Kel
Clearance (2)
Cpss
Vd = Drug Absorbed/Cp = S x F x Dose / Cp
-degree of distribution out of the plasma compared to the total drug in the body
Plasma Volume = 1/4 x 1/3 (55-60% weight)
ROE=Vmax x Cp / Km + Cp
Loading dose=Cpss x Vd / S x F
-the dose needed to rapidly achieve therapeutic drug concentration
Kel x t1/2 = 0.693
Cl = Ke x Vd = S x F x Dose (t) / Cp
Cpss = 1.44 x S x F x Dose (t1/2) / t x Vd
Drug Distribution Factors
Define pH partitioning &pKa
Protein vs Non-protein
P-glycoprotein, BBB
Finite binding sites, drugs only active if unbound
Polarity
weak acids and bases get trapped in there opposite as there ionized form, can only move if unionized
pKa 50% ionized 50% unionized
Drug Metabolism
Phase I?
Phase II?
Goal
Phase I: Oxidation, Reduction, Hydrolysis
Cyp-450 in smooth ER can be induced (lower drug) or inhibited (high/toxic drug)
Phase II:
Conjugation: Glucuronidation (ER), Sulfation (cytoplasm)
Acetylation & Methylation: makes less water-soluble but inactivates
Goal
Inactivate or activate (prodrug), make more polar and larger for excretion
Drug Elimination
Define Clearance
Routes
Factors
Clearance is the plasma volume from which all of the solutes is removed in a given time, based upon the flow rate and is not impacted by a change in plasma concentration
Routes:
Renal (GF, Passive Reabsorption, Active Secretion)
Bile, Sweat, breath, breast milk
Factors:
pH ionization, active secretion competition, GFR decreasing with age
Drug Food Interactions Ca2+ Grapefruit Juice/ St. John's Wort Tyramine (wine, cheese) Na+ Food
Define Idiosyncrasy
Define Teratogenic Effect factors
Most Common Adverse Effects
Drug-Food
Ca2+ Alters tetracycline absorption
Grape Induces CYP3A4
Cant be metabolized in MAO inhibitors => Hyperadrenergic crisis
Na+ lowers lithium effectiveness
Food can prevent upset stomach or slow absorption
Idiosyncrasy is an unusual response to a drug due to inherited alteration, potentially leading to disease or anemia
Rash/Dermatitis, Constipation/Diarrhea, Dizziness/Drowsiness, Dry mouth, HA, insomnia
Age on PK
Pregnancy on PK
Baby: more distribution but poor metabolism and excretion
Kid: Sames as Adult but faster metabolism
Elderly: Low everything ADME, higher toxicity risk
Pregnancy: increased ADME, can cross placenta
Zero Order
First Order
How Variation impacts the efficacy Dosage Absorption Elimination Metabolism/Distribution (inactive)
Constant elimination, saturated, independent to [drug]
Fraction elimination, not saturated, dependent on [drug]
Dosage: same peak time, different heights
Absorption: fast = shorter to peak & higher peak, slow = longer to peak & shorter peak
E/M/D: slow = higher peak & longer time, faster = shorter and shorter
Affinity & Kd
Selectivity
How readily and tightly a drug binds to its receptor.
- Higher affinity = often less drug needed = Low Kd
- Kd: 50% of the sites are occupied
A drug property determined by its affinities at various binding sites
-More selective = Higher Kd ratio (Kd off-target/ Kd target) = Fewer adverse effects
Full Agonist
Partial Agonist
Inverse Agonist
Antagonist
- Pharm
- Chem
- Physio
Competitive Antagonist
Non-Competitive Antagonist
Produces the maximal effect, same Emax
Produces a submaximal effect, lower Emax
Produces an opposite effect, inhibits the function
Does not change function, only prevents activation
- Blocks same receptor
- Removes drug availability
- Blocks another receptor in the pathway
Competes (lower potency, higher ED50), can be displaced (no Emax change), if irreversible (decrease Emax)
Different site (same potency, ED50), will decrease Emax
G-protein pathways
Cycle
Gs & Gi
Gq
G12/13
Cycle
(1) Bind, (2) Release GDP & gain GTP (3) Dissociate GTPa
Activate/Inhibit Adenylyl Cyclase
(1) AC does ATM => cAMP (2) cAMP (+) PKA
Gs = Beta & D1, Gi = a2 d2
Phospholipase C (1) PLC does PIP2 => DAG & IP3 => release Ca2+ & calmodulin Gq = a1
Rho GTPases => Cytoskeleton rearrangments
