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Flashcards in Day 1.1 Pharm Deck (142):
1

What is Km?

Substrate conc at 1/2 Vmax

Shows affinity of enz for substrate

2

If Km is decreased, what does this say abt affinity?

Affinity is increased if Km is decreased.

3

What is Vmax directly proportional to?

Enz conc

4

Lineweaver-Burke: What is the y-int?

1 / Vmax

5

Lineweaver-Burke: What is the x-int?

1 / -Km

6

Lineweaver-Burke: As the y-int increases, what happens to the Vmax?

Vmax decreases.

Y-int is 1 / Vmax. A bigger Y-int means a smaller number in the denominator.

7

Lineweaver-Burke: What happens as the x-int moves to the right?

Km increases.

X-int is 1 / -Km. As it moves to the right, it gets less negative. (So Km increases)

8

Lineweaver- Burke: If Vmax decreases, what happens to the y-int?

It increases.

Y-int = 1 / Vmax

9

Lineweaver-Burke: As Km increases, what happens to the X-int?

It increases.

X int = 1 / -Km

10

Lineweaver-Burke: What happens to the slope of the line when an uninhibited rxn gets a competitive inhibitor?

It increases.

Competitive inhibitors Cross Competitively. The Y-int stays the same (bc the Vmax stays the same), but the X-int increases (bc the Km increases)

11

Lineweaver-Burke: What happens to the slope of the line when an uninhibited rxn gets an non-competitive inhibitor?

It increases

The X-int stays the same (bc the Km stays the same) but the Y-int increases (bc the Vmax decreases)

12

What happens to Km with a competitive inhibitor?

It increases. (You need more substrate to get to 1/2 Vmax)

13

What happens to Vmax with a competitive inhibitor

It stays the same. The reaction can still go at the same max rate, you will just need more substrate (a higher Km) to get there.

14

With a competitive inhibitor, how does affinity change?

Affinity decreases. When Km goes up (as with competitive inhibition), affinity goes down.

15

With a competitive inhibitor, how does potency change?

Decreased potency.

16

T/F Competitive inhibitors can be overcome by increased substrate.

True

17

What effect do non-competitive inhibitors have on Vmax?

Vmax is decreased. The rxn can't get to the same max rate, no matter how much substrate there is (bc the non-comp inhibitor doesn't bind to the active site)

18

What effect does a non-comp inhibitor have on Km?

No change in Km. The amount of substrate needed to get to 1/2 Vmax is the same, it's only that the Vmax itself is smaller.

19

How is non-competitive inhibition related to efficacy?

Non-competitive inhibitors decrease efficacy.

20

T/F Km is a measure of affinity

True.

Note: As Km is decreased, there is MORE affinity. (You don't need as much substrate to get to Vmax)

21

What is the slope of the Lineweaver-Burke plot?

Km / Vmax

Slope = y / x
Y = 1 / Vmax
X = 1 / -Km

22

Equation for Vol of Distribution

Vd = amt of drug given IV / plasma conc of drug

23

Equation for Clearance

CL = 0.7 x Vd / t1/2

or CL = K x Vd where elim constant K = 0.7 / t1/2

24

Equation for loading dose

LD = Cp x Vd

Cp, or Css - it's the plasma conc, or the desired conc at steady state

25

Equation for maintenance dose

MD = Cp x CL

26

How does renal dz affect LD and MD?

Renal dz = decreased CL.

LD (Cp x Vd) is unchanged, bc not affected by CL.

MD (Cp x CL) will decrease with decreased clearance.

27

What units are used to measure Vd

Liters (or any unit of volume)

If given L/kg, determine Vd by factoring in the weight of the pt in kg.

28

Half life

The amt of time needed for a drug conc to reach 50% when infused at a constant rate. Conversely, the time needed for 50% of a drug to be eliminated.

29

How long does it take a drug to reach 94% of steady state if constantly infused?

4 half lives

30

concentrations and # of half lives needed to get there

50% one half life
75% two
87.5% three
94% four

It takes between four and five half lives for a drug to reach steady state (or to be eliminated completely)

31

Bioavailability

Amt of drug that actually reaches blood after metabolism (1st pass in liver, etc). If given IV, F = 1 (100%). If given orally, usu not. If given F other than 100%, just divide the equations by F. (e.g. LD = Cp x Vd / F)

32

Zero-order elimination

Rate of elim is CONSTANT, regardless of amount. Conc decreases linearly with time. A constant amount is eliminated.

33

Drugs w/ Zero-order elim

PEA:
Phenytoin (anti-epileptic)
Ethanol
Aspirin

34

First-order elimination

Rate of elim is PROPORTIONAL to the drug conc- a constant fraction is eliminated. Cp decreases exponentially with time.

35

If a constant amount of drug is eliminated, what order elim is this?

Zero-order

36

If a constant fraction of drug is eliminated, what order elim is this?

First-order

37

Urine pH: why do ionized species get trapped in urine?

Bc ions can't easily cross the plasma mbr. (Uncharged molecules do cross)

38

Are weak acids charged or uncharged?

Uncharged. Weak acid = HA

39

For acids, bases:
Is the protonated form charged?

Acids: No. Protonated form = HA
Bases: Yes. Protonated form = BH+

40

For acids, bases:
Is the unprotenated form charged?

Acids: Yes. Unprotonated = H+ and A-
Bases: No. Unprotonated = H+ and B

41

Are weak bases charged or uncharged?

Charged. Weak base = BH+

42

Uncharged molecules can cross the plasma membrane. Which form of acid and which form of base will cross the membrane?

Uncharged acid: Protenated form HA
Uncharged base: Dissociated form H+ and B

43

What is pKa

Acid dissociation constant. The pH at which protenated = unprotenated

44

If the pH is decreased below the pKa, what happens?

Low pH = acidic. So EVERYTHING will be in protenated form. For acids, this means they will be HA (uncharged), and for bases, it means they will be BH+ (charged). So bases will be trapped since they are charged.

45

If the pH is increased above the pKa, what happens?

High pH = basic. So EVERYTHING will be dissociated. For acids, this means they will be H+ and A- (charged), and for bases, it means they will be H+ and B (uncharged). Thus, acids will be trapped since they are charged.

46

Rx for aspirin overdose

Aspirin is a weak acid, so give NaHCO3 to make the urine basic and trap the acidic drug in basic urine.

47

Rx for amphetamine overdose

Amphetamines are basic, so give NHCl4 to make the urine acidic- trap the basic drug in acidic urine.

48

Drug metabolism: by what processes do Phase I rxns usually occur?

Reduction
Oxidation
Hydrolysis
Usually uses a Cytochrome P450 enz.

49

What kind of metabolites are produced in Phase I metabolism?

Slightly polar, water-soluble metabolites; they are often still active.

50

T/F Phase I and Phase II drug metabolism occur in a specific order.

False. They are non-sequential. You can have Phs II before Phs I or Phs I before Phs II.

51

T/F Phase I and II metabolism can both activate or inactivate drugs.

True.

52

Drug metabolism: by what processes do Phase II rxns generally occur?

GAS:
Glucuronidation
Acetylation
Sulfation
Usually occurs using conjugation.

53

What kind of metabolites are produced in Phase II rxns?

Very polar, inactive metabolites. Often, these metabolites are renally excreted.

54

Which phase of drug metabolism do eldery pts usually lose first?

Phase I.
Elderly pts have GAS (GAS = Phase II processes, Glucuronidation, Acetylation, Sulfation) They have GAS, so they don't have Phase I.

55

Where does Phase I and II drug metabolism take place?

Mostly in the liver
Also in the kidney

56

What is efficacy?

The maximum effect a drug can produce.
Vmax

57

What is potency?

The amount of drug needed.
Km

58

What determines efficacy?

The Vmax

59

What determines potency?

The Km
Note: Higher Km = LESS potency

60

What happens to efficacy if the Vmax is lowered?

The efficacy is lowered.
In the case of a non-competitive inhibitor, Vmax would be lowered, so the efficacy would also be lowered.

61

What happens to potency is the Km is increased?

The potency is reduced.
In the case of a competitive inhibitor, Km is increased, which means potency is lowered.

62

What is the difference b/t a competitive and non-competitive inhibitor?

Competitive competes for the same active site. Non-comp binds elsewhere and changes the confirmation of the active site so that the enz can't bind.
Non-comp = Irreversible inhibitor. (same thing)

63

What effect does a competitive inhibitor have on potency?

Competitive inhibitors increase Km. An increase in Km means that potency is lowered.

64

What effect do irreversible inhibitors have on efficacy?

An irreversible inhibitor (aka a non-competitive inhibitor) decreases the Vmax. Decreased Vmax means decreased efficacy.

65

What effect does a partial agonist have on Vmax?

It always lowers Vmax (and thus always lowers efficacy.)

66

What effect does a partial agonist have on Km?

It depends on the agonist. It can either increase Km (so decrease potency), or it can decrease Km (so increase potency). Potency is an independent variable.

67

What is the therapeutic index?

TI = LD50 / ED50
The dose that kills 50% / the dose that is effective (treats) 50%

68

Is it better to have a high or low therapeutic index?

Higher = safer drug

69

How can you get a high TI?

High TI when LD50 is high (so the dose it takes to kill 50% is really big), or when ED50 is low (so the amount needed to treat is small)

70

Which drugs have a low TI (meaning they are unsafe and need to be monitored)?

Phenobarbital (for seizures)
Lithium (bipolar)
Digoxin
Coumedin/Warfarin

71

What drugs inhibit Cytochrome P450?

PICK EGS:
Protease inhibitors
Isoniazid
Cimetidine
Ketoconazole

Erythromycin
Grapefruit juice
Sulfonamides

72

What are the characteristics of a good clinical trial?

Randomized
Controlled
Double-blinded

73

What is a Phase I clinical trial?

"Is it safe?"
Testing healthy volunteers
Test for safety, toxicity, pharmacokinetics

74

What is a Phase II clinical trial?

"Does it work?"
Testing pts with dz
Efficacy, dosage, side effects

75

What is a Phase III clinical trial?

"Does it work better?"
Testing pts w dz
Compare to existing Rx/Standard of Care

76

What is a Phase IV clinical trail?

Post-market surveillance

77

How long does the process of Phase I to III take for clinical trials?

5-10 years

78

What systems are affected by autonomic drugs?

The SNS and PNS systems. The drugs can:
Activate PNS
Inactivate PNS (NOT the same as SNS)
Activate specific receptors of SNS
Inactivate specific receptors of SNS

79

What is a cholinomimetic?

Stimulates the PNS Ach Muscarinic (?M) receptor

80

Cholinomemetics: How do direct cholinergic agonists work?

They bind to the PNS Muscarinic Ach receptor and stimulate it.

81

Cholinomimetics: How do indirect agonists work?

They inhibit the AChE, which means that the ACh is degraded at a slower rate.
Aka anti-acetylchoinesterases

82

What does AChE do?

Breaks down ACh into choline and acetate (thus inactivating it)

83

-chol is what drugs?

Cholinergic agonists (at the PNS muscarinic receptor)
eg Bethanechol, Carbachol

84

Bethanechol

Cholinomimetic - Direct Agonist of M ACh receptor.
Used for post-op ileus, neurogenic ileus, urinary retention
(makes you more leaky)

85

Carbachol

Cholinomimetic - Direct Agonist of M ACh receptor.
Used for glaucoma, pupillary contraction, and rls of interocular prs (so basically, glaucoma)

86

What is glaucoma?

Elevated interocular pressure

87

Pilocarpine

Cholinomimetic - Direct Agonist of M ACh receptor.
Used for glaucomic emergencies. Also stim's sweat, tears, saliva (makes you more leaky)
Contracts ciliary musc of eye for open angle glauc, contracts pupillary spincter for narrow angle glauc.
Resistant to AChE

88

Methacholine

Cholinomimetic - Direct Agonist of M ACh receptor.
Used as a challenge test for asthma- causes bronchoconstriction. (so get asthma symptoms when you take it)

89

Neostigmine

Cholinomimetic - Indirect Agonist of M ACh receptor. (Anti-AChE)
Used for post-op ileus, neurogenic ileus, urinary retention, MysGrav, reversal of NMJ blockade post-op.
NEO = NO CNS penetration

90

-stigmine

AChE inhibitor (Indirect agonist)

91

What is Myasthenia Gravis?

Ab to the ACh receptor. Px with ptosis (droopy eyelid) or diplopia (dbl vision) which worsens throughout day.

92

What are the paralyzing agents (anesthesia)?

Succanylcholine
Rocuronium
Vecuronium
These cause NMJ blockade. Use neostigmine to reverse their effect.

93

Pyridostigmine

Cholinomimetic - Indirect Agonist of M ACh receptor. (Anti-AChE)
Used for MysGrav (long-term)
No CNS penetration.
Gets "rid" of MysGrav

94

Edrophonium aka Tensilon

Cholinomimetic - Indirect Agonist of M ACh receptor. (Anti-AChE)
Dx MysGrav, v short acting- if sympt of MysGrav go away when you give it, pt has MysGrav

95

Myasthenia Gravis is related to problems with which organ?

Thymus
50% of MG pts have thymic hyperplasia
20% have thymic atrophy
15% have thymoma

96

What is a myasthenic crisis?

rapidly progressing weakness, esp in respi muscles (diaphragm)

97

Rx for Myasthenia Gravis?

AChE inhibitors
Corticosteroids
Thymectomy
Plasmapheresis (wash out Ab)

98

Physostigmine

Cholinomimetic - Indirect Agonist of M ACh receptor. (Anti-AChE)
Phys Phyxes (fixes) atropine OD.
Also used for Glaucoma
Crosses BBB

99

Echothiophate

Cholinomimetic - Indirect Agonist of M ACh receptor. (Anti-AChE)
For Glaucoma

100

Cholinesterase inhibitor poisoning (excess PNS)

DUMBBELSS:
Diarrhea
Urination
Miosis
Bronchospasm
Bradycardia
Excitiation of CNS and smth musc
Lacrimation
Sweating
Salivation
Abd cramping

101

What causes cholinesterase inhibitor poisoning (excess PNS)?

Organophoshates = Insecticides = Parathion
Usu in farmers/gardeners

102

What is Parathion?

Insecticide, causes DUMBBELSS symptoms

103

How do you treat excess PNS / cholinesterase inhibitor poisoning /organophosphates / parathion?

Pralidoxime (regenerates AChE) and atropine

104

What are the anti-AChE durgs used in Alzheimer's? (Alz = decreased ACh)

Donepezil
Galantamine
Rivastigmine

105

"trop" drugs

Muscarinic antagonist aka anit-cholinergic

106

What happens if you inhibit PNS activity?

Hot as a hare
Dry as a bone
Red as a beet
Blind as a bat
Mad as a hatter
Bloated as a toad
Incrsd body temp, dry/flushed skin, cycloplegia, delirium/disorientation, constipation & urinary retention

107

What receptors do the anti-cholinergics inhibit?

Muscarinic receptors.
Aka muscarinic antagonists

108

What are the muscarinic antagonists? (list)

Atropine, homatropine, tropicamide
Benztropine
Scopolamine
Ipratroprium
Oxybutynin
Glycopyrrolate
Methscopolamine, propantheline

109

What anti cholinergics (muscarinic antagonists) are used to treat urge-type incontinence?

Oxybutynin
Tolterodine
Darifenacin and solifenacin
Trospium

110

What does atropine do?

Muscarinic antagonist (anti-cholinergic)
Eye: increases pupil dilation, cycloplegia
Airway: decreased secretions
Stomach: decresased acid secretion
Gut: Decreased motility
Bladder: decreased urgency in cystitis

111

Side effects of atropine?

Increased body temp, rapid pulse, dry mouth, dry flushed skin, cycloplegia, constipation, urinary retention, delirium/disorientation.

112

What is cycloplegia?

Paralysis of the ciliary muscles of the eye, causing lack of accomodation and therefore blurry vision

113

Contraindications for atropine

Elderly pts
Glaucoma
BPH or any urinary retention
GI obstruction/ileus
Pts w dementia, delirium
Infants w fever (can cause hypothermia)

114

Atropine, homatropine, tropicamide

Muscarinic antagonists, used to produce mydriasis (dilation) and cycloplegia in eyes

115

Benztropine

Muscarinic antagonist, used in CNS for Parkinson's
Park my Benz

116

Scoploamine

Muscarinic antagonist, used for motion sickness (ear patch) or in end of life care

117

Ipratroprium

Muscarinic antagonist, used for Asthma, COPD
I Pray I can breathe soon!

118

Oxybutinin

Muscarinic antagonist used for Genitourinary sympt - reduces urgency in mild cystitis, reduces bladder spasm

119

Glycopyrrolate

Muscarinic antagonist, genitourinary and also used to decrease airway secretions

120

Methscopolamine, propantheline

Muscarinic antagonist- GI, used for peptic ulcer treatment

121

What happens to the level of ACh in:
Parkinson's?
Alzheimer's?
Huntington's?

Parkinson's = Increased ACh
Alz and Huntington's = Decreased ACh

122

Categorize: Physostigmine

-stigmine = Cholinomimetic: Indirect agonist (Anti-AChE)

123

Categorize: Pilocarpine

Cholinomimetic: Direct muscarinic agonist

124

Categorize: Echothiophate

Cholinomimetic: Indirect agonist (Anti-AChE)

125

Categorize: Oxybutinin

Muscarinic antagonist (urge incontinence)

126

Categorize: Atropine

trop = Muscarinic antagonist

127

Categorize: Donepezil

Cholinomimetic: Indirect agonist (Anti-AChE) for Alzheimer's

128

Categorize: Pralidoxime

AChE regenerator (So inhibits ACh) Use after organophosphate poisoning.

129

Categorize: Bethanechol

-chol = Cholinomimetic: Direct muscarinic agonist

130

Categorize: Neostigmine

-stigmine = Cholinomimetic: Indirect agonist (Anti-AchE) for Alz

131

Categorize: Darifenacin

Muscarinic antagonist (urge incontinence)

132

Categorize: Ipratroprium

trop = Muscarinic antagonist

133

Categorize: Tropicamide

trop = Muscarinic antagonist

134

Categorize: Benztropine

trop = Muscarinic antagonist

135

Categorize: Scopolamine

Muscarinic antagonist

136

Categorize: Edrophonium

Cholinomimetic: Indirect agonist (Anti-AchE). Tensilon test for MG.

137

Categorize: Tolterodine

Muscarinic antagonist (urge incontinence)

138

Categorize: Trospium

Muscarinic antagonist (urge incontinence)

139

Categorize: Rivastigmine

-stigmine = Cholinomimetic: Indirect agonist (Anti-AchE) for Alz

140

Categorize: Homatropine

trop = Muscarinic antagonist

141

Categorize: Pyridogstigmine

-stigmine = Cholinomimetic: Indirect agonist (Anti-AChE)

142

Categorize: Carbachol

-chol = Cholinomimetic: Direct muscarinic agonist