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Flashcards in Pharm Deck (146):
1

quantal dose-response

all or nothing- you are either protected or you are not

2

ED50

where 50% of animals are protected

3

LD50

kills 50% of animals

4

chemical vs physical form

same drug cannot be in different chemical forms, but can be in different physical forms

5

Therapeutic Index

LD50/ED50
ideally 10

6

margin of safety

LD1/ED99
comparing extremes of the dose response curves to indicate any over lap

7

Protective Index

=ED50 (undesireable)/ED50 (desireable)

8

chronicity index

=(1-dose of LD50)/(90-doseLD50)
has to do with clearance
1 is best (total clearance) vs 90 (virtually no clearance)

9

Threshold dose

apparent all or none phenomenon at a specific threshold dose
--may not be a REAL threshold but an apparent threshold

10

potency

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

intrinsic activity

often referred to as efficacy in intact patient; magnitude of maximal response (highest dose)
efficacy is one component, but not whole thing

12

affinity

K1/K2

13

efficacy

K3

14

Chemical antagonism

direct interaction of the agonist and antagonist

15

functional antagonism

two agonists act independently but lead to opposite biological effects, so kinda cancel each other out (or one takes over)

16

competitive antagonism

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

Eq antagonism

competitive
reversible
can be overcome if dose of against is increase enough

18

non-eq antagonsim

competitive
irreversible-perm block of agonist binding and receptor function
cannot be overcome by increasing dose ofagonist

19

non-comp antagonist

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

inverse antagonist

shifts eq towards inactive

21

synergy

need more than one to make-->additive

22

potentiation

the effect of one drug makes another work better

23

rate of absorption

movement of drug from site of administration to the blood

24

rate of distribution

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