Pharm Flashcards
(146 cards)
1
Q
quantal dose-response
A
all or nothing- you are either protected or you are not
2
Q
ED50
A
where 50% of animals are protected
3
Q
LD50
A
kills 50% of animals
4
Q
chemical vs physical form
A
same drug cannot be in different chemical forms, but can be in different physical forms
5
Q
Therapeutic Index
A
LD50/ED50
ideally 10
6
Q
margin of safety
A
LD1/ED99
comparing extremes of the dose response curves to indicate any over lap
7
Q
Protective Index
A
=ED50 (undesireable)/ED50 (desireable)
8
Q
chronicity index
A
=(1-dose of LD50)/(90-doseLD50)
has to do with clearance
1 is best (total clearance) vs 90 (virtually no clearance)
9
Q
Threshold dose
A
apparent all or none phenomenon at a specific threshold dose
–may not be a REAL threshold but an apparent threshold
10
Q
potency
A
relative dose required to produce a given effect
(should not be equated with therapeutic superiority)
affinity is one component, but not the whole thing
11
Q
intrinsic activity
A
often referred to as efficacy in intact patient; magnitude of maximal response (highest dose)
efficacy is one component, but not whole thing
12
Q
affinity
A
K1/K2
13
Q
efficacy
A
K3
14
Q
Chemical antagonism
A
direct interaction of the agonist and antagonist
15
Q
functional antagonism
A
two agonists act independently but lead to opposite biological effects, so kinda cancel each other out (or one takes over)
16
Q
competitive antagonism
A
the antagonist binds to the receptor, but elicits no response (affinity, but no efficacy)- however, competes with agonist for binding sites
–eq and non-eq
17
Q
Eq antagonism
A
competitive
reversible
can be overcome if dose of against is increase enough
18
Q
non-eq antagonsim
A
competitive
irreversible-perm block of agonist binding and receptor function
cannot be overcome by increasing dose ofagonist
19
Q
non-comp antagonist
A
antagonist acts at a site other than the site of agonist binding but affects the same process
could also bind to another site on same receptor and alter the ability of the receptor to interact with agonist–“allosteric effect”
20
Q
inverse antagonist
A
shifts eq towards inactive
21
Q
synergy
A
need more than one to make–>additive
22
Q
potentiation
A
the effect of one drug makes another work better
23
Q
rate of absorption
A
movement of drug from site of administration to the blood
24
Q
rate of distribution
A
delivery of drug from blood to tissues and target sites
25
bioavailability
amount of drug that actually reaches the target site in a pharmacologically active and bioavailable form
26
only bioavailable drug
drugs that are not bound to albumin
27
passive diffusion
down a concentration gradient in non-ionized form; dependent on partition coefficient
28
filtration
down a pressure gradient
29
bulk flow
across a cap wall (small molecules)
30
mechanisms of drug transport across membranes
1) active transport
2) facilitated transport
3) ion pair transport-
4) endocytosis
31
oral is good for drugs with
high partition coefficient and favorable pKa
32
stomach only absorps
weak acts
33
small intestine uses
passive diffusion
34
5 factors affecting GI absoprtion
```
gastric emptying time
intestinal motility
food and food consumption
formulations of drugs
metabolism & digestion
```
35
high partition coefficient means it is
lipophilic
36
what crosses very readily in lung?
high partition coefficient anesthetics
37
albumin has
positive and negative charged binding sites
38
lung receives
100% CO
39
kidney receives
25%CO
40
what can cross the BBB
high partition, non-ionized, free drugs can cross
| inflammation can increase permeability
41
half-life
t=0.693/Kel
42
Volume of distribution
Vd=D/Co (L/Kg)
43
Clearance
Clp=KelxVd (L/hr/kg)
44
oral fraction
Foral=AUCoral/AUCiv
45
Loading Dose
D*=Css x Vd (mg)
46
Maintenance Dose
MD=Css x Vd x Kel (mg/hr or mg/min)
| =Css x Clp (x time interval)
47
rate of eliminaton
x=xe^(-kt)
48
if route of elimination is saturated,
drug follows0 order onnects
49
Vd: 3-5 L
no penetration from plasma
50
Vd: 12-15 L
no penetration into cells from interstitium
51
Vd: 30-40L
distributed throughout body water
52
>50 L
accumulated in body tissues (e.g. lipophilic)
53
ares of concern in dosing
time to peak concentration (tmax) in blood
Maximum attained concentration (cmax)
area under curve (AUC)
54
steady state
independent of dose and depends only on rate of elimination (Kel), so to avoid delay use a loading dose
55
pro-drug
more active than parent compound
| mitomycin C, cyclophosphamide, codeine
56
Pro-toxin
when metabolized drug turns toxic
| aflatoxin B1, benzoapyrene
57
goal of phase 1 metabolism
make lipophilic drugs more hydrophilic
| CYP liver enzymes add groups, oxidate, reduce
58
phase 2 metabolism
conjugation
take phase 1 metabolite and bind to large, polar glucoronic acid so can be readily excreted from body
occurs predominantly from UDP-GT
59
neonatal hyperbilirubinemia
inability of newborn babies to metabolize bill to bill fluuronide conjugate-->leads to CNS damage
60
chloramphenicol (antibiotic)
deficinecy in UDP-GT leads to excessive free drug in blood and tissue and drug-associateed toxicities
gray baby syndrome
61
crigler-naijar syndrome
almost total genetic deficiency in hepatic UDP-GT
| babies highly jaundiced-->death occurs in early childhood
62
B-glucuronidsae
releases drug
present in mucosa of small intestine
entero-hepatic circulation for drug (re-abs by GI)
63
n-acyetyl conjugation
catalyzed by n-acetyltransferases in population
fast and slow acetylators in population
important for isonizaid, sulfamethazine, paninosaliyclic acid, hydralazine
64
overdosing on acetaminophen
generates reactive metabolites that attack tissues and lead to liver toxicity and failure
65
acute alocohol
inhibits drug metabolism, prolonging and intensifying effects of drugs (esp CNS depressant), though competitive inhibition of metabolism
66
chronic alcohol
increases drug metabolism and clearance through induction of P450 and other enzymes
67
induce drug metabolism because induce P450
green things, brussel sprouts cabbage, cauliflower
68
grape fruit juice
contains furanocoumarins that inhibit CYP3A4 metabolism
also inhibit Pgp- mediated durg efflus in intestine and liver
-->both mechanisms increase bioavailability and toxicity of a large group of CYP3A4 substrate drugs
69
charcoal broiled beef diet
xenobioti metabolizing enzymes induced higher in beef eaters so they have lower phenacetin plasma levels
70
ABC transport proteins
Pglycoprotein: transport large and functionally unrelated molecules
MRP: phase II conjugates of drugs and metabolites
large and diverse group of molecules out of cells
71
Sympathetic Neruons
T1-L3 short-->ACH to ganglia -long-->target organs (NE)
72
Parasympathetic Neruons
cervical and sacral areas-long--->ACH at ganglia near target organ-short--->target organ (ach)
73
pressor center is in
medulla
74
how to cholinergic neurons make Ach
acetyl coa + choline--< acetylcoline-->put in vesicles-->exocytosed
75
M1 Ach R
nerve endings
Gqcoupled-->increase IP3 & DAG
myenteric plexus
76
M2 Ach R
heart, some nerve endings
Gi-->decrease cAMP, activate K+ channels
slow SA node
77
M3 Ach R
smooth muscle glands
Gq coupled-->inc IP3, DAG
contract detruser muscle, increase salivation
78
Nn ACh Receptor
ANS ganglia
Na-K ion channel-->Na
depolarizes postgang fiber-->evokes AP
79
Nm Ach Receptor
neuromuscular end plate
Na-K ion channel-->Na+
depolarizes muscle cell, evokes AP and contraction
80
how to make NE
tyrosine-->DOPA-->Dopamine-->into vesicle-->adds B-hydroxyl-->NE
81
5 Ach Receptors
M1, M2, M3, Nn, Nm
82
6 NE receptors
A1, A3, B2, B3, B4, DA1
83
A1 NE receptor
smooth muscle, glands,
Gq
increase Ca2+-->contraction (vascular SM- vasoconstriction), secretion
also inhivits SA node
*STIMULATE BP**
84
A2 NE receptor
nerve endings (some smooth muscle)
Gi
decrease transmitter release (nerve)- contract, SM
85
Beta 1
Cardiac muscle, JGA
Gs-->increase camp
increase HR and contractility, renin release
also stimualtes SA node
86
Beta 2
smooth muscle, liver, heart
Gs-->inc camp
relax bronchiolar SM, increase glycogenolysis, increase HR and contractility
87
Beta 3
adipose tissue
Gs
increase lipolysis
88
Da1
smoth muscle
Gs
relax vascular SM in renal arterioles
89
sarin nerve gas
increases amount of Ach in body (inhibits AchE)
90
5 ways SNS helps BP go up
```
arterioles (SVR)
SA node (HR)
LV (contractility)
veins (tone)
kidneys (renin)
adrenal medulla (releases E and NE)
```
91
PANS CNS origin
rostral ventrolateral medulla
92
PANS origin
Nucleus ambiguus
93
direct acting sympoatomimetic drugs
act on post-syn receptors
| NE, EPI
94
indirect acting drugs
keep NE in synapse longer
- enhance release of NE at synapse
- block reputake of NE after release at synapse
- blocks degradation of NE
95
enhances release of NE at synapse
amphetamine, meth MDMA
96
blocks reuptake NE
cocaine, amitriptyline
97
blocks degradation of NE
MAO-inhibitors
98
2 alpha agonists
Phenyleprine (a1)
| Clonidine (a2)
99
mixed alpha, beta agonists (3)
Epinephrine
NE
Dopamine
100
4 Beta agonists
Isoproterenol
Dobutamine
Albuterol
Mirabegron
101
alpha antagonists
prazosin/minipress
tamsulosin/flomax
phentolamine/regitine
102
beta antagonists
atenolol
| propanolol
103
Mixed a,b
labetolol
104
nonspecific Ach agonists (2)
Ach
| Carbachol
105
3 Muscarinic Agonists
Methacholine
Bethanechol
Pilocarpine
106
2 Nicotinic Agonists
Nicotine
| Varenicline (Chantix)
107
Short Acting cholinesterase inhibitors
edrophonium
108
Int acting cholinesterate inhibitors
neostigmine
| physostigmine
109
long acting cholinesterase inhibitors
```
echothiphate
parathion
malathion
sarin
soman
```
110
presynaptic indirect cholinomimetics
metoclopramide
111
3 places M receptors are located at
effector tissues innervated by PS fibers
very select postganglionic sympathetic targets (sweat glands)
endothelium (non-innervated tissue)
112
Cholinomimetic overdose-cholinergic syndrome
muscarine poisioning
| DUMBBELSS
113
SLUDGE syndrome
```
major muscarinic/nicotinic effects
salivation
lacrimation
urination
defetation
GI upset
Emesis
```
114
Why do muscarinic receptors cause hypotension?
active eNOS-->makes NO-->stimulates guanlyl cyclase to turn GTP-->cGMP-->binds myosin lightt chain to vasodilate
115
Why does muscarinic activation cause bradycardia?
activation of M receptors on SA node (vagus)
116
other M clinical signs
```
DUMBBELSS
Diarrhea
urination
Miosis
Bronchorrhea/brnchoconstriction
Bradycardia
Emesis
Lacrimation
Salvation
Sweating
```
117
therapeutically useful Ach agents
must be resistant to AchE
118
modified forms of Ach
methacholine
bethanechol
pilocarpine (glaucoma)
119
Nicotine Toxicity
Depolarizing-Desensitization Blockade
initial activation-->deactivation due to phosphotylation--> paradoxical flaccid paralysis due to blockade, have to wait until agonist is cleared
*Nm receptors
120
Major signs of Nicotine Toxicity
Symp and PS stim- tachycardia, hypertension, cold sweat, nausea, vomitting, diarrhea, salivation, urinary incontinence
Nn and Nm blockade- syncopy, collapse, unconsciousness, flaccid paralysis
121
All ChE inhibitors block
true Ache, plasma Che, and RBC Ache
plasma ChE is inhibited first
122
what is the major concern of using cholinesterase inhibitors?
respiratory inundation
--paralysis of intercostal muscles and diaphragm via nicotinic desensitization blockade
--increased bronchial secretions and bronchoconstriction (mud)
central resp arrest
123
AchE mechanism
anionic site binds quat ammoium cation
| esteric site-catalytic hydrolyzes Ach ester bond
124
short acting are
competitive inhibitors and do not form ester bond to AChE
125
what is used to diagnose MG?
Edrophonium
rapid increase in muscle strength because inhibits ChE transiently and makes Ach more available
126
2 Muscarinic Antagonists
atropine
| scopolamine
127
Depolarizing Nm cholinolytuc agonists
succinylcholine
128
Nondepolarizing Nm antagonists
Benzylisoquinolines: d-tubocurarin, Cisatracurium
Aminosterioid: pancuronium, vercuronium, Rocuronium
129
Nn specific
trimethaphan
130
Muscarinic Atagonists act
block PS transmission to end organs
| inverse agonists
131
atropine toxicity
```
mad as a hatter
Blind as a bat
dry as a bone
hot as a hare
red as a beet
performing the pee pee dance
```
132
atropine basically does
unopposed symp acts (no ps)
133
what is most dangerous effect of atropine in adults vs kid
delirum- self destructive acts
| kids- temperature- doesn't respond to antipyretics; need ice bat
134
Scopolamine
motion sickness
| anesthetic adjuvant
135
Dicyclomine
irritable bowel and minor diarrhea
| M3 selective antag
136
Tropicamide
mydriatic eye drops for retinal exam
137
Benzotripine
CNS Parkinsons DIsease
138
Ipratropium**
Inhibits bronchoconstriction
139
succinylcholine
Nm blocker
post-surgical procures and intubations
adverse effects- muscle fasciculations, hyperemia, histamine release, hyperthermia
140
no succinylcholine if
family Hx of malignant hyperthermia
hyperkalemia
burns, trauma, tissue injury
heart failure
141
d-tubocurarine
paralysis in fully conscious patient; only for anesthetized pt
142
nondepol paralysis reversal
neostygmine
143
depolarizing nicotinic blockers
TIME- neostygmine will cause muscurinic syndrome
144
Trimethaphan
nondepol ganglionic Nn blocker
potent effects on BP
only use in hypertensive crises, dissecting aortic aneurysm
145
Botox
indirect anticholinergic
| light chain escapes from vesicles and cleaves SNARES so no docking
146
botox applications
coesmetic
prevent arm pit sweating
strabismus
uncontrolled eye twitching
