Basic Principles Flashcards
1
Q
Actions of body on the drug
A
Pharmacokinetics
2
Q
4 components of pharmacokinetics
A
Absorption
Distribution
Metabolism
Excretion
3
Q
What determines the reversibility of drug effects
A
Strength of bond
Covalent > electrostatic > hydrophobic
4
Q
Movement of drug molecules into and within biologic environments
A
Permeation
5
Q
Passive movement of non-protein bound drugs b/w blood and extravascular space through water-filled PORES
A
Aqueous diffusion
6
Q
Transport NOT governed by Fick’s Law of Diffusion
A
Transport by special carriers
7
Q
Movement of drugs through lipid membranes;
most important limiting factor for permeation
A
Lipid diffusion
8
Q
Large drugs bind to receptors, internalized and released after vesicle breakdown
A
Endocytosis
9
Q
Predicts rate of movement of molecules across a barrier
A
Fick’s Law of Diffusion
10
Q
Aqueous solubility is _______ proportional to electrostatic charge (ionization, polarity)
A
DIRECTLY
11
Q
Lipid solubility is _________ proportional to electrostatic charge (ionization, polarity)
A
INVERSELY
12
Q
fraction of drug molecules charged vs uncharged
A
pH
13
Q
pH is determined by what equation
A
Henderson-Hasselbalch
14
Q
Drug route that partially avoids hepatic first-pass effect
A
Rectal route
15
Q
4 major factors in drug distribution
A
Size of organ Blood flow Solubility Protein binding Volume of distribution
16
Q
Drugs displaying zero-order kinetics (WHATPET)
A
Warfarin Heparin Aspirin Tolbutamide Phenytoin Ethanol Theophylline
17
Q
Rate of elimination is proportionate to concentration; uses T1/2
A
First-order elimination
18
Q
Rate of elimination is CONSTANT regardless of concentration
A
Zero-order elimination
19
Q
Actions of drug on the body
A
Pharmacodynamics
20
Q
Has small MW (rarely selective in action); anticoagulant that can cross placenta; inhibits Vit K dependent factors synthesis
A
Warfarin
21
Q
Antidote for Warfarin
A
Vit K, FFP
22
Q
Has large MW (poorly absorbed & distributed); cannot cross the placenta; activates anti-thrombin III
A
Heparin (LMWH)
23
Q
Aspirin intake should be stopped 1 week prior to OR because of what drug-receptor bond?
A
Covalent bond
24
Q
Antidote for Heparin
A
Protamine sulfate
25
Why must pralidoxime be given within 6-8 hours after organophosphate poisoning?
It will become ineffective if covalent bonds has been formed with the organophosphates.
26
Activated charcoal is an example of _______ antagonist.
chemical antagonist
27
Slowest form of diffusion; very important among weak acids and weak bases
Lipid diffusion
28
Fick's law of diffusion:
The greater the difference in conc gradient,
The _______ the rate of diffusion.
(Remember formula)
faster
29
Fick's law of diffusion:
The greater the surface area,
The ________ the rate of diffusion.
faster
| e.g. Small intestine's SA > stomach's
30
Fick's Law of Diffusion:
The higher the permeability coefficient,
the _______ the rate of diffusion.
faster
31
Fick's law of diffusion:
The greater the thickness of the membrane
The _______ the rate of diffusion
slower
32
The more ionized the drug, the _______ is its kidney CLEARANCE.
greater
33
The more unionized the drug is, the _______ is its absorption.
greater
34
pKa
```
dissociation constant
(Henderson-Hasselbach equation)
```
35
The unprotonated (A-, B) is ______ water-soluble thus undergoes better clearance.
more
36
The protonated (HA, BH+) is _____ lipid soluble thus more likely to cross biological membranes.
more
37
Excretion of a weak acid may be accelerated by...
alkalinizing urine with bicarbonate
| unprotonate with HCO3- to make A-
38
Excretion of a weak base may be accelerated by...
acidifying the urine with ammonium chloride/ ascorbic acid
| protonate to make BH+
39
Location safest for IM buttock injection
superolateral
| superomedial: superior gluteal n.; inferomedial: sciatic n.
40
Suppository safe for preggies with thyroid storm
PTU
41
Anatomy correlate: Rectal suppositories have only partial first-pass effect because the superior rectal vein drains to IMV then to the portal vein. What are the other veins that drain eventually to the IVC?
Middle & inferior rectal vein
MRV--> Internal iliac v. --> IVC
IRV --> Internal pudendal v --> IIV --> IVC
42
Only ____ drugs can be absorbed, distributed, metabolized, excreted and exert pharma effect.
free/ unbound
43
Give examples of drugs that are eliminated without metabolism.
Mannitol, lithium
44
Which type of elimination is faster? (1st-order or 0-order?)
Zero-order elimination
45
The smaller the Kd, the ____ the affinity of a drug to bind to its receptor.
greater
| Kd = drug conc required to bind 50% of the receptors
46
TD 50/ ED 50
Therapeutic index
| measure of drug safety based on 50% of population
47
Tamoxifen is an example of a _______ agonist.
Partial agonist
| antagonist to breast, agonist to uterus
48
Maximal effect an agonist can produce if the dose is taken to very high levels; measured only with graded dose-response curves (NOT quantal curves)
Emax
49
Concentration of the drug wherein half of the maximal effect is achieved
EC50
50
fraction of the population that responds at each dose against the log of the dose administered; where ED50, TD50, LD50 is derived
Quantal dose-response curve
51
receptors that do not bind drug when the drug conc is sufficient to produce maximal effect; Kd > EC50
Spare receptors
52
agonists that result in all receptors achieving the activated state
Full agonist
53
Agonist that produces less than full effect even when it has saturated the receptors; can act as an inhibitor in the presence of another agonist
Partial agonist
54
Chemical antagonist for lead poisoning
Dimercaprol
55
Antagonist that causes a DOWNWARD shift to the dose-response curve
Noncompetitive/ irreversible antagonist
56
Antagonist that acts on the allosteric site causing conformational change; overcome by adding more agonist
Competitive/ reversible antagonist
57
Frequent exposure to agonist results in short-term diminution of the receptor response
Tachyphylaxis
58
Drugs that display tachyphylaxis
| MEDical students Love to watch CNN in HD
```
Metoclopramide
Ephedrine
Dobutamine
LSD
Calcitonin
Nitroglycerin
Nicotine
Hydralazine
Desmopressin
```
59
Continuous activation may lead to depletion of substrates
Tolerance
60
Long term reduction in receptor number d/t continuous exposure to agonist
Downregulation
61
Occurs when receptor activation is blocked for prolonged periods
Upregulation
62
Infrequently observed variation in drug response; genetically predertermined
(e.g. cataracts w/ allopurinol, aplastic anemia w/ chloramphenicol, hemolytic anemia w/ methyldopa)
Idiosyncratic drug response
63
Vol at w/c drug would be uniformly distributed to produce an observed blood conc; can be altered by liver or kidney dse (low serum albumin)
Volume of distribution (Vd)
64
Factors affecting absorption
Chemical nature (water/lipid-soluble)
Particle size
Polymorphism (amorphous/crystalline; hydrous/anhydrous)
Form (tablet/enteric-coated)
65
main Vd compartment for High MW & CHON-bound drugs
Plasma
66
Main Vd compartment for low MW and hydrophilic drugs
ECF
67
Main Vd compartment for low MW and hydrophobic drug
Intracellular
68
state where rate of drug administration equals the rate of elimination; reached in 4-5 T1/2 of a drug
Steady state
69
Most impt pharmacokinetic parameter to be considered in defining a rational steady state during dosage regimen
Clearance
70
fraction of drug reaching the systemic circulation; determined by AUC
Bioavailability
71
After oral admin of 500mg of Drug A, only 300mg were absorbed into the systemic circulation. What is the drug's bioavailability?
60% (300/500)
72
Rate of elimination at steady state
| =(clearance x desired plasma conc)/bioavailability
```
Maintenance dose
(Vd not involved in calculating MD)
```
73
given if therapeutic conc must be achieved rapidly and Vd is large
= (Vd x desired plasma conc)/ bioavailability
Loading dose
74
Safe range b/w minimum effective conc (MEC) and minimum toxic conc (MTC)
Therapeutic window
75
=average dose x (Crea clearance/ 100mL/min)
Corrected dose in renal impairment
76
equation used to calculate Crea clearance
Cockroft-Gault equation
| = (140-age) x Wt in kg / 72 x serum crea
77
Practice problem for corrected dose:
A drug is 50% cleared by the kidney and 50% cleared by the liver. Its normal dosage is 200 mg/d. What is the corrected dosage in a patient with crea clearance of 20mL/min?
120 mg/d
78
Phase I reactions
| A HORDe of Phase I reactions
Hydrolysis
Oxidation
Reduction
Deamination
79
Type of drug metabolism involving cytochrome P450 enymes; converts parent drug to water-soluble form by inserting a polar FUNCTIONAL group
Phase I reaction
| functionalism
80
Type of drug metabolism involving conjugation of subgroups to -OH, -NH2, -SH
Phase 2 reactions
| glucuronidation, acetylation, glutathione conjugation, glycine conjugation, sulfation, methylation
81
Drug that can be metabolized by glucorinidation, glutathione conjugation or sulfation; can cause gray baby syndrome
Paracetamol
82
Common drugs that are metabolized by acetylation
| HIPS
```
Hydralazine
INH
Procainamide
Sulfonamides
(HIP: SLE-like sx; Sulfonamide: SJS)
```
83
Cytochrome P450 inducers
| Ethel Booba takes Phen-Phen and Refuses Greasy Carb Shakes
```
Ethanol
Barbiturates
Phenytoin
Rifampicin
Griseofulvin
Carbamazepine
St. John's Wort/ Smoking
```
84
Enzyme inhibitors -> dec metabolism
| HIV-infected Ami drinks grapefruit juice with fungi, causing tummy ache
```
amiodarone
cimetidine
furonacoumarins (grapefruit)
azole antifungals
Ritonavir (HIV protease inhibitor)
```
85
Duration of subacute toxicity
2-4 weeks
86
Chronic toxicity
6-24 mos.
87
FDA drug category (reproductive toxicity):
| preggy human & animal SAFE
A
| Folic acid, thyroid hormones
88
FDA drug category (reproductive toxicity)
| Preggy human: NO STUDY, preggy pet: SAFE
B
| Zidovudine
89
FDA drug category (reproductive toxicity)
| Preggy human SAFE, Preggy pet NOT SAFE
B
90
FDA drug category (reproductive toxicity)
| Preggy human NO STUDY, preggy pet UNSAFE
C
| Aspirin
91
FDA drug category (reproductive toxicity)
| Preggy human & pet NO STUDIES
B
92
FDA drug category (reproductive toxicity)
| Preggy human and pet UNSAFE
D
| ACEI, anticonvulsants
93
FDA drug category (reproductive toxicity)
| Preggy human & pet UNSAFE
X
| Statins, OCPs, clomiphene, misoprostol, high-dose vit A
94
Period of organogenesis
3-8 weeks AOG
95
Teratogenic effect of ACEIs
fetal RENAL damage
96
Teratogenic effect of Anti-epileptic drugs
Neural tube defects
97
Teratogenic effect of OHA
neonatal HYPOglycemia
98
Teratogenic effect of barbiturates and opioid abuse
Neonatal DEPENDENCE
99
Teratogenic effect of DES (morning after-pill)
vaginal clear call adenoCA
100
Teratogenic effect of ethanol
Fetal alcohol syndrome
| flat philtrum
101
Teratogenic effect of lithium
Ebstein's anomaly
102
Teratogenic effect of isotretinoin
| Ganda face mo pero wasak kay baby
cranioFACIAL malformation
103
Teratogenic effect of iodide
| Wag i-spoil si baby, magiging tamad ant pituitary
congenital HYPOTHYroidism
104
Teratogenic effect of Misoprostol
Mobius sequence
| MOve the MISO
105
Teratogenic effect of penicillamine
| Si Peni maganda ang cutis
Cutis laxa
106
Teratogenic effect of thalidomide
| I-thali mo extremities para ma-amputate
Phocomelia
107
Teratogenic effect of smoking
IUGR
108
Teratogenic effect of streptomycin
Ototoxicity
109
Teratogenic effect of Tetracyclines
Tooth discoloration, brittle bones
| Tetra colors & break your bones
110
Teratogenic effect of methimazole
Aplasia cutis congenita
111
Teratogenic effect of sulfonamide
Kernicterus
| Remember paracetamol given in neonates undergo sulfation
112
Teratogenic effect of fluroquinolones
| Floxacin have limp ears
cartilage damage
113
Teratogenic effect of warfarin on the 1st tri
Chondrodysplasia
114
Teratogenic effect of heparin on 2nd tri
CNS malformation
115
Teratogenic effect of warfarin on 3rd tri
Bleeding disorders
