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Pharmacology > Katzung Exam 1 Chapters 1-7 > Flashcards

Katzung Exam 1 Chapters 1-7 Flashcards

1
Q

What are the three drugs with zero-order kinetics?

A

APE
Aspirin
Phenytoin
Ethanol

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2
Q

Which form of a drug is more water-soluble?

A

Ionized

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3
Q

Which form of drug is more lipid-soluble?

A

Non-Ionized

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4
Q

A weak base (RNH2) in basic solution renders it?

A

RNH2

  1. Not protonated
  2. Not ionized
  3. Lipid-Soluble
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5
Q

A weak acid (RCOO-) in basic solution renders it?

A

RCOO-

  1. Not protonated
  2. Ionized
  3. Water-soluble
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6
Q

A weak base (RNH2) in acidic solution renders it?

A

RNH3+

  1. Protonated
  2. Ionized
  3. Water-soluble
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7
Q

A weak acid (RCOO-) in acidic solution renders it?

A

RCOOH

  1. Protonated
  2. Not ionized
  3. Lipid soluble
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8
Q

At 1 pH unit more acidic than pKa, the ratio of protonated/unprotonated changes from 50/50 at pH=pKa to…

A

10/1

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9
Q

What is the insulin receptor effector?

The nicotinic Ach receptor effector?

A
  1. Tyrosine Kinase

2. Na+K+ channel

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10
Q

How do membrane-spanning molecules that bind intracellular tyrosine kinase molecules work?

A
  1. Cytokines usually activate
  2. Separate tyrosine kinase molecules dimerize (JAK-Janus Kinases)
  3. Results in phosphorylation of STAT (signal transducers and activators of transcription)
  4. STATS dimerize and travel to nucleus to regulate transcription
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11
Q

What kind of receptors do sympathomimetics have?

How do they work?

A
  1. Linked to effectors via G proteins

2. Activate or inhibit adenylyl cyclase

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12
Q

What does the therapeutic index estimate?
What is the equation?
Where do you find the variables?

A
  1. Safety of drug
  2. TD50 (or LD50)/ED50
  3. Quantal-dose curves
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13
Q

How is dimercaprol a chemical antagonist?

Pralidoxime?

A
  1. Chelator of lead

2. Combines with phosphorus in organophosphate cholinesterase inhibitors

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14
Q

How do chemical antagonists work?

A

Interact directly with drug to remove it or prevent it from reaching target

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15
Q

In asthma, leukotriene’s bronchoconstriction at leukotriene receptors is physiologically antagonized by…?

A

Terbutaline at adrenoreceptors

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16
Q

Histamine bronchoconstriction at histamine receptors are physiologically antagonized by…?

A

Epinephrine bronchodilation at B adrenoreceptors

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17
Q

What can a competitive antagonist be overcome by?

A

More agonist

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18
Q

How does a competitive antagonist work?

A

It binds to receptor in a REVERSIBLE way WITHOUT activating effector system (at binding site)

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19
Q

Concentration or dose that produces 50% of max possible response

A

EC50 in graded dose response

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20
Q

What does the graded dose drug-binding relationship measure?

A

Fraction of receptors bound by a drug

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21
Q

What does the graded dose-response measure?

A

Response vs concentration of drug

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22
Q

How do physiological antagonists work?

A

They bind a different receptor which produces the opposite effect to that produced by the agonist

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23
Q

How can irreversible antagonists be overcome?

A

They can’t.

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24
Q

How do irreversible antagonists work?

A

Change conformation so agonists cannot bind

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25
Q

What are the two pharmacological antagonists?

A

Competitive and irreversible

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26
Q

In the presence of an agonist, a partial agonist acts as a ?

A

Inhibitor

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27
Q

The two most important plasma proteins with binding capacity

A
  1. Albumin

2. Orosomucoid (alpha 1-acid glycoprotein)

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28
Q

How do inert binding sites contribute to the concentration gradient of a drug?
Why?

A
  1. They buffer the concentration gradient

2. Because the bound drug does not contribute to the concentration gradient that drives diffusion

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29
Q

How are spare receptors determined?

A

By comparing the concentration for 50% of max effect (EC50) and concentration for 50% of max binding (Kd)

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30
Q

Dose that causes the specified response in 50% of population

A

EC50 in quantal dose-response

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31
Q

What is potency determined by?

A

Affinity of receptor for drug

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32
Q

Define potency

A

The amount of drug needed to produce an effect

EC50 in graded-response

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33
Q

What does the quantal dose-response relationship measure?

A

Minimum dose required to produce specific response

AKA statistical distribution of sensitivity to a drug

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34
Q

What is Kd?
What does it measure?
The smaller the Kd…

A

The concentration of drug required to bind 50% of receptor sites
Affinity of a drug to a binding site
The higher the affinity

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35
Q

Define efficacy

A

Max effect an agonist can produce if dose taken at very high levels

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36
Q

The smaller the EC50 the greater the…

A

potency

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37
Q

What is the loading dose equation?

A

loading dose= VD x desired P [ ] / bioavailability

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38
Q

What is the adjusted dosage equation?

A

Corrected dose= Avg. dose x patient’s creatinine CL/100ml/min

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39
Q

What is the maintenance dosage equation?

A

Dosing rate= CL x desired P [ ] / bioavailabity

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40
Q

What is half-life completely determined by?

Equation?

A

Vd and CL

t1/2= 0.693 x Vd/ CL

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41
Q

What does clearance measure?

Equation?

A

Relates rate of elimination to plasma [ ]

CL= rate of elimination / plasma drug [ ]

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42
Q

What does the volume of distribution measure?

Equation?

A

Amount of drug in body compared to plasma [ ]

Vd= Amount of drug in body/ Plasma drug [ ]

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43
Q 
A drug reaches \_\_% of steady state [ ] at
1?
2?
3?
4?
half lives
A 
1= 50%
2= 75%
3= 87.5%
4= 93.75%
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44
Q

Clearance of a particular drug by individual organ depends on what 2 factors?

A
  1. Extraction capability of that organ for that drug

2. Rate of delivery of drug to the organ (blood flow)

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45
Q

How is bioavailability lowered in the intestine?

A

Expulsion by P-glycoprotein transporter

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46
Q

How can liver disease alter the Vd of drugs that are normally bound to plasma proteins?
Kidney disease?

A

Reduced protein synthesis

Urinary protein loss

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47
Q 
What is the metabolism type of:
acetaminophen
morphine
diazepam
sulfathiazole
digoxin
digitoxin ?
A

Glucoronidation

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48
Q

What amines are acetylated?
How can some genetically differ in this metabolism?
What kind of inheritance?

A
  1. Isoniazid
  2. Hydralazine
  3. Procainamide
    “Slow acetylators”
    Autosomal Recessive gene
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49
Q

What is succinyl choline metabolized by?
What does succinyl choline do?
How do some people differ in this metabolism?

A

Plasma cholinesterase (butyryl cholinesterase)
Neuromuscular blocking drug
1/2500 people, cholinesterase works slower (paralysis for hours)

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50
Q

What are the types of metabolism that can be affected by genetics?

A
  1. Hydrolysis of esters
  2. Acetylation of amines
  3. Oxidation
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51
Q 
What is the metabolism type of 
sulfonamides
isoniazid
clonazepam
mescaline
dapsone
hydralazine
procainamide ?
A

Acetylation

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52
Q

What is the metabolism type of
ethacrynic acid
reactive phase 1 metabolite of acetaminophen?

A

Glutathione conjugation

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53
Q

What do P-gp inhibitors do to bioavailability?
Ex?
What drugs are usually at toxic plasma [ ] with P-gp inhibitor?

A 
Increase it
----
Verapamil
Mibefradil
Furanocoumarin (GF juice)
---
digoxin
cyclosporine
saquinavir
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54
Q

What are suicide inhibitors?

Examples?

A 
They are metabolized to products that irreversibly inhibit the metabolizing enzyme
Ethinyl estradiol
norethindrone
spironolactone
secobarbital
allopurinol
fluroxene
propylthiouracil
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55
Q

What are the most common inhibitors of drug metabolism involved in serious drug interactions?

A 
Amiodarone
Cimetidine
Furanocoumarins (GF juice)
Ketoconazole
HIV protease inhibitor Ritonavir
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56
Q

How does enzyme induction work?

What are the most common inducers in serious drugs interactions?

A 
It increases the synthesis of cytochrome p450-dependent drug-oxidizing enzymes in liver
Carbamazepine
Phenobarbital
Phenytoin
Rifampin
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57
Q

Why is lipid solubility of drugs unfavourable in removal from body?

A

Favorable for absorption across membranes therefore it is reabsorbed from the urine in the renal tubule

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58
Q 
How are 
barbiturates
amphetamines
phenylbutazone
phenytoins
metabolized?
A

P450 dependent hydroxylation

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59
Q

What are the phase 1 metabolic reactions?

A
  1. Oxidation (esp. by cytochrome p450 aka mixed function oxidases)
  2. Reduction
  3. Deamination
  4. Hydrolysis
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60
Q 
How is
morphine
caffeine
theopylline
metabolized?
A

P450 dependent N-dealkylation

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61
Q

How is codeine metabolized?

A

P450 dependent O-dealkylation

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62
Q 
How is 
acetaminophen
nicotine
methaqualone
metabolized?
A

P450 dependent N-oxidation

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63
Q 
How is 
thioridazine
cimetidine
chlorpromazine
metabolized?
A

P450 dependent S-oxidation

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64
Q

How is
amphetamine
diazepam
metabolized?

A

P450 dependent deamination

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65
Q

How is epinephrine metabolized?

A

Amine oxidation

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66
Q

How is
ethanol
chloral hydrate
metabolized?

A

dehydrogenation

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67
Q 
How is 
chloramphenicol
clonazepam
dantrolene
naloxone
metabolized?
A

Reduction

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68
Q

Which drug has a higher first-pass metabolism in men than in women?

A

Ethanol

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69
Q 
How is 
procainamide
lidocaine
indomethacin
metabolized?
A

Amide hydrolysis

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70
Q 
How is
procaine
succinylcholine
aspirin
clofibrate
metabolized?
A

Ester hydrolysis

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71
Q

How does smoking increase metabolism of some drugs?

Example of a drug?

A

It induces enzymes in liver and lung

Theopylline

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72
Q

What are ALL the ways acetaminophen is metabolized?

A
  1. P450 dependent N-oxidation
  2. Glucoronidation
  3. Sulfate conjugation
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73
Q

What are ALL the ways amphetamine is metabolized?

A
  1. P450 dependent hydroxylation

2. P450 dependent deamination

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74
Q

What are ALL the ways morphine is metabolized?

A
  1. P450 dependent N-alkylation

2. Glucoronidation

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75
Q

What are ALL the ways epinephrine is metabolized?

A
  1. Amine oxidation

2. Methylation

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76
Q 
What is the metabolism type of
epinephrine
norepinephrine
dopamine
histamine?
A

Methylation

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77
Q

What is the metabolism type of
acetaminophen
methyldopa
estrone?

A

Sulfate conjugation

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78
Q

What is the metabolism type of
salicylic acid
nicotinic acid (niacin)
deoxycholic acid ?

A

Glycine conjugation

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79
Q

What does probenecid do?
By what mechanism?
What is it an example of?

A
  1. It is used to increase excretion of uric acid in gout
  2. It inhibits transport of uric acid, penicillin, and weak acids.
  3. It is an example of selective inhibitor of transport by special carrier
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80
Q

What do P-glycoprotein transport molecules cause?

Where have they been found?

A
  1. Cancer drug resistance

2. Epithelium of GI tract and BBB

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81
Q

How do B12 and Iron enter cells?

A

Endocytosis by complexing with special proteins.
B12 with intrinsic factor
Iron with transferrin

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82
Q

What is the equation for FIck’s Law and what does it predict?

A

Rate= (C1-C2) x permeation coeff./thickness x area

It predicts the rate of movement of molecules across a barrier

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83
Q

What are the variables in Fick’s Law?

A
  1. [ ] gradient
  2. Permeation coefficient
  3. Thickness and area of barrier
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84
Q

Why can’t anticoagulants be given intramuscularly?

A

They can cause bleeding (hematomas) in muscle

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85
Q

When taken in normal doses, what is acetaminophen conjugated to?

A

Harmless glucoronide and sulfate metabolites

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86
Q

In acetaminophen overdose, which phase metabolism dominates?
What does it convert it to?
What is it conjugated with? To what?

A

Phase 1
Reactive intermediate (N-acetyl-p-benzoquineimine)
Glutathione- harmless product

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87
Q

What happens if glutathione stores are exhausted in phase 1 acetaminophen metabolism?

A

The reactive intermediate binds with essential hepatic proteins, resulting in cell death

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88
Q

What can be life-saving after acetaminophen overdose?

Ex?

A

Other sulfhydryl donors

Ex: acetylcysteine

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89
Q

How do enzyme inducers affect acetaminophen toxicity?

Why?

A

Increase it

Because they would increase phase 1 metabolism which would results in increased production of reactive intermediates

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90
Q

Biotransformation usualy results in what form of the drug?

A

Less lipid-soluble (more water soluble)

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91
Q

What does induction of drug metabolism do to the SER?

Why?

A

It increases it

Because the SER contains the mixed function oxidase drug-metabolizing enzymes (cyt. P450 group of enzymes)

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92
Q

What effect does phenobarbital have on drug action?

Why?

A

It decreases duration of drug action

Because it is an inducer of drug-metabolizing enzymes

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93
Q

What effects does Cimetidine have?

A

Inhibition of P450 enzymes and decreasing hepatic blood flow

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94
Q

What are the effects of treatment with phenobarbital along with smoking?

A

Higher drug metabolism and LOWER blood levels of the drug

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95
Q

Which drugs slow the metabolism of older non-sedating antihistamines?

A

Ketoconazole
Itraconazole
Erythromycin
GF juice

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96
Q

What effect does Ritonavir have?

What has this permitted?

A

Inhibits hepatic drug metabolism

Dose reductions of other HIV protease inhibitors

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97
Q

What is teratogenesis?

A

Induction of developmental defects in the somatic tissues of the fetus

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98
Q

How is teratogenesis studied?

A

By treating pregnant female of at least 2 species during early pregnancy (organogenesis) with drug and later examining neonates for abnormalities

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99
Q

What are the drugs known for teratogenesis?

A 
Thalidomide
Isoretinoin
Valproic acid
Ethanol
Glucocorticoids
Warfarin
Lithium
Androgens
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100
Q

What is mutagenesis?

A

Changes in the genetic material of animals of any age, induction of heritable abnormalities

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101
Q

What are the two ways to test for mutagenesis?

A

Ames test and dominant lethal test

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102
Q

Describe the Ames test

In vitro/in vivo?

A

Uses salmonella, which usually depends on certain nutrients to grow. Loss of this dependence= mutation
In vitro

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103
Q

Describe the dominant lethal test

In vitro/in vivo?

A

Male mice are exposed to drug before mating, look for abnormalities in subsequent mating (loss of embryos, deformed fetuses)= mutation
In vivo

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104
Q

What carcinogens have mutagenic effects?

A

Aflatoxin
Cancer chemo drugs
Others that bind to DNA

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105
Q

How is carcinogenesis tested for?

A

Ames test, there is a high correlation between mutagenesis and carcinogenesis.

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106
Q

What are some known carcinogens?

A 
Coal tar
Aflatoxin
Dimethylnitrosamine
Urethane
Vinylchloride
Polycyclic aromatic hydrocarbons in tobacco smoke (benzo (a) pyrene)
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107
Q

What is an example of a polycyclic aromatic hydrocarbon in tobacco smoke?

A

Benzo (a) pyrene

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108
Q

How many clinical trial phases must be completed to submit an NDA?

A

3

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109
Q

What are the spinal roots for parasympathetic preganglionic fibers?

A

CN nuclei 3, 7, 9, and 10

and sacral segments (S2-S4)

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110
Q

What are the spinal roots for sympathetic preganglionic fibers?

A

T1-T12

and L1-L5

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111
Q

Where are parasympathetic ganglia located?

A

In the organs innervated

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112
Q

Are the parasympathetic preganglionic long or short?

Postganglionic?

A

Long

Short

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113
Q

Where are the sympathetic ganglia located?

A

In 2 paravertebral chains that lie along the spinal column (a few in the anterior aspect of abdominal aorta)

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114
Q

Are the sympathetic preganglionic long or short?

Postganglionic?

A

Short

Long

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115
Q

What are some uninnervated receptors for autonomic drugs?

A

Muscarinic receptors on endothelium of blood vessels

Some presynaptic receptors

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116
Q

Where is acetylcholine a primary transmitter?

A

In all autonomic ganglia

At the parasympathetic postganglionic-neuron-effector cell synapses

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117
Q

What is Ach synthesized from?

By what enzyme?

A

Acetyl CoA and choline

By Choline acetyl transferase

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118
Q

What is the rate limiting step of Ach synthesis?

What is it inhibited by?

A

Transport of choline into nerve terminal

Hemicholinium

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119
Q

Acetylcholine is actively transported into vesicles for storage. What inhibits this step?

A

Versamicol

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120
Q

What does the release of Ach from vesicles require?

A

Entry of Calcium

Triggering of reaction between proteins on vesicles and proteins on the nerve ending membrane

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121
Q

What are the proteins on vesicles?

A

VAMPs (vesicle-associated membrane proteins)
synaptobrevin
synaptotagmin

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122
Q

What are the proteins on the nerve ending membrane?

A

SNAPs (synaptosome-associated proteins)
SNAP25
syntaxin

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123
Q

What does the interaction between vesicle proteins and nerve ending membrane proteins cause?

A

Fusion of vesicles membranes and nerve ending membranes
Opening of pore to EC
Release of transmitter

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124
Q

What can inhibit release of Ach?

A

Botulinum toxin

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125
Q

Which protein can botulinum toxin enzymatically alter?

A

Synaptobrevin

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126
Q

How is Ach action terminated?

By what enzyme?

A

Metabolism of Ach into acetate and choline

Acetylcholinesterase

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127
Q

Where is NE a primary transmitter?

A

At the sympathetic postganglionic neurone-effector cell synapses in MOST tissues

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128
Q

What sympathetic postganglionic neuron effector cell synapses is NE NOT the primary transmitter of?
What is the primary transmitter?

A

1.Sympathetic fibers to thermoregulatory (eccrine) sweat glands
2. Vasodilator sympathetic fibers in skeletal muscle
They release Ach

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129
Q

What is the vasodilator of renal blood vessels?

A

Dopamine

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130
Q

What is the rate-limiting step of NE synthesis?
By what enzyme?
What is it inhibited by?

A

Tyrosine hydroxylation to DOPA
By tyrosine hydroxylase
Inhibited by Metyrosine

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131
Q

What is the second step of NE synthesis?
Where is the product transported to?
What inhibits this step?

A

DOPA decarboxylated to dopamine
Brought into vesicles
Inhibited by Reserpine

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132
Q

What is the last step of NE synthesis?

A

Dopamine hydroxylated to norepinephrine

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133
Q

Where are MAO’s found?

What do they do?

A

On mitochondria in adrenergic nerve ending

Inactivate portion of dopamine and NE in cytoplasm

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134
Q

What effect do MAO inhibitors have?

A

They increase the stores of dopamine and NE

AKA increase stores of catecholamines

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135
Q

Outside of the cleft, what are NE and Dopamine (catecholamines) metabolized by?

A

MAO

COMT (catechol-o-methyltransferase)

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136
Q

What happens to the products of enzymatic reactions of NE and Dopamine (catecholamines)?

A

Excreted

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137
Q

The 24-hour excretion of what drugs are useful indicators in diagnosing diseases like pheochromocytoma because they are an indicator of total body production of catecholamines?

A

Metanephrine
Normetanephrine
VMA

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138
Q

What drug inhibits the release of catecholamines?

A

Guanethidine

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139
Q

Where are cotransmitters found and what is their function?

A

In vesicles

They modulate synaptic transmission

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140
Q

Examples of cotransmitters

A 
ATP
enkephalins
Vasoactive Intestinal Peptide (VIP)
neuropeptide Y
Substance P
Neurotensin
Somatostatin
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141
Q

What are the two types of cholinoceptors? What transmitter do they respond to?

A

Muscarinic and Nicotinic

Ach and its analogs

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142
Q

What transmitters do muscarinic receptors respond to?

A

Muscarine and Ach

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143
Q

What do the effects of activating muscarinic receptors resemble?

A

Postganglionic parasympathetic nerve stimulation

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144
Q

Where are muscarinic receptors primarily located?

A 
On autonomic effector cells:
Heart
Vascular endothelium
Smooth muscle
Presynaptic nerve terminals
Exocrine glands
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145
Q

What transmitters do Nicotinic receptors respond to?

A

Nicotine and Ach

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146
Q

Where are nicotinic receptors located?

A

In ganglia and skeletal muscle end plates

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147
Q

What are the two types of adrenoceptors?

A

alpha and beta

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148
Q

What are the subtypes of alpha receptors?

Where are they found?

A 
Alpha-1 and Alpha-2
Vascular endothelium
Presynaptic nerve terminals
Blood platelets
Fat cells (lipocytes)
Neurons in brain
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149
Q

What is the difference between alpha 1 and alpha 2 adrenoceptors?

A

They are different families and utilize different G proteins

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150
Q

What are the subtypes of beta receptors?

Where are they found?

A 
Beta 1, 2, and 3
Most smooth muscle
Cardiac muscle
Some presynaptic nerve terminals
Lipocytes
Brain
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151
Q

What is the difference between Beta 1, 2, and 3 adrenoceptors?

A

Similar, use same G protein

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152
Q

Where are dopamine receptors found?

A

Usually in renal and splanchnic vessels

Brain

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153
Q

What is the most important peripheral effector-cell dopamine receptor?

A

D1

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154
Q

Where are D2 receptors found?

A

On presynaptic nerve terminals

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155
Q

What are the 3 types of NANC (Nonadrenergic, Noncholinergic) transmissions?

A
  1. Cause the release of ATP and possibly other purines
  2. Releases peptides as primary transmitters
  3. Have anatomic characteristics of sensory fibers and contain peptides such as substance P
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156
Q

What is mydriasis?

What ANS branch controls it? At what receptor?

A

Dilation of pupils
Sympathetic
Alpha

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157
Q

What does sympathetic discharge do to renal vessels?

A

Causes constriction of renal resistance vessels so there is a fall in renal blood flow

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158
Q

What are muscarinic receptors blocked by?

Where?

A

Atropine
At smooth muscle effector cells
At postganglionic nerve terminals

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159
Q

What nerves innervate thermoregulatory (eccrine) sweat glands?

A

Sympathetic cholinergic nerves

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160
Q

Where are nicotinic cholinoceptors found?

A

Both types of ganglia
Skeletal muscle neuromuscular junction
Adrenal medulla

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161
Q

What facilitates the release of catecholamine transmitters from the sympathetic nerve endings?

A

Amphetamine

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162
Q

What is the prototype for the direct-acting cholinomimetic drug acting on both muscarinic and nicotinic receptors?

A

Ach

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163
Q

What is the prototype for indirect-acting cholinomimetic drug?

A

Neostigmine

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164
Q

How does a direct-acting cholinomimetic work?

A

Acts directly on Ach receptors

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165
Q

How does an indirect-acting cholinomimetic work?

A

It inhibits cholinesterase

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166
Q

What are the direct-acting cholinomimetic choline esters?

A

Ach
Methacholine
Carbachol
Bethanechol

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167
Q

What are the direct-acting cholinomimetic alkaloids?

A

Muscarine
Pilocarpine
Nicotine
Lobeline

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168
Q

How do choline esters differ from alkaloids?

A
  1. Spectrum of action (amount of muscarinic vs nicotinic stimulation)
  2. Pharmacokinetics
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169
Q

What are M1 and M3 receptors coupled to?

A

Gq protein

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170
Q

What is Gq protein coupled to?

A

Phospholipase C

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171
Q

What is the mechanism of M1 and M3 receptors?

A

Gq protein coupled to phospholipase C which leads to release of 2nd messengers DAG and IP3

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172
Q

What does DAG do?

A

Modulated action of protein kinase C (important enzyme in secretion)

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173
Q

What is protein kinase C important for?

A

Secretion

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174
Q

What does IP3 do?

A

Evokes release of Calcium from intracellular storage sites= contraction

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175
Q

What are M2 receptors coupled to?

A

Gi inhibitory protein and potassium channels in the heart

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176
Q

What are Gi proteins coupled to?

A

Adenylyl cyclase

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177
Q

What is the mechanism of M2 Gi linked protein receptors?

A

Decrease CAMP production

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178
Q

What is the mechanism of M2 potassium channel linked receptors?

A

Muscarinic agonists open these channels in the heart

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179
Q

Where are nicotinic receptors located?

A

On channel protein that is selective for Na+K+

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180
Q

What is the nicotinic mechanism?

A

When receptor on channel protein that is selective for Na+K+ is activated, the channel opens and depolarization of cell occurs= EPSP

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181
Q

Where are Ach nicotinic receptors located?

A

Both sympathetic and parasympathetic ganglion cells (Nn)

Neuromuscular end plate (Nm)

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182
Q

Is vasodilation a parasympathomimetic response?

A

No

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183
Q

What does vasodilation result from?

What is it mediated by?

A

EDRF (endothelium-derived relaxing factor) and NO in the vessels which is mediated by UNINNERVATED muscarinic receptors on endothelial cells

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184
Q

Why does injection of small to medium amounts of direct-acting muscarinic cholinomimetics cause TACHYCARDIA?

A

Baroreceptor reflex

The decrease in BP, stimulated sympathetic response

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185
Q

Cholinomimetics stimulate sweating which is usually a ______ effect

A

Sympathetic cholinergic effect

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186
Q

Blood vessels are dominated by _____ innervation, therefore nicotinic receptor activation results in _____

A

Sympathetic

Vasoconstriction mediated by sympathetic postganglionic nerve discharge

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187
Q

The gut is dominated by ______control, therefore nicotinic drugs ____ motility and secretion because of _____ postganglionic neuron discharge

A

Parasympathetic
Increase
Parasympathetic

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188
Q

What does nicotinic end plate activation by direct-acting drugs result in?

A

Fasciculations and spasm of muscles

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189
Q

What are the effects of muscarinic toxicity?

A 
CNS stimulation
Miosis
Spasm of accommodation
Bronchoconstriction
Increased GI and genitourinary smooth muscle activity
Increased secretory activity
Vasodilation
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190
Q

What are the effects of nicotinic toxicity?

A

CNS stimulation followed by depression
Ganglionic stimulation and block
Neuromuscular end plate depolarization

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191
Q

What are the two major classes and 1 minor class of indirect-acting cholinergic agonists?

A

Carbamic Acid Esters
Phosphoric Acid Ester
Edrophonium

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192
Q

Example of Carbamic acid ester

Prototype

A

Carbamate

Neostigmine

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193
Q

Example of phosphoric acid ester

Prototype

A

Phosphates, organophosphates

Echothiopate

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194
Q

What is edrophonium?

A 
The only member in its class of indirect-acting cholinomimetic.
Alcohol with very short duration of action
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195
Q

Mechanism of carbamate and organophosphates

A

Bind to cholinesterase and undergo prompt hydrolysis

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196
Q

What happens to the alcohol portion of carbamate and organophosphate after hydrolysis?
The acid portion?

A 
Alcohol portion promptly released
Acid portion (carbamate ion or phosphate ion) released much more slowly thus preventing the binding and hydrolysis of acetylcholine
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197
Q

Duration of carbamates

A

2-8 hours

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198
Q

Duration of organophosphates

A

Days to weeks

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199
Q

What are the effects of carbamates and organophosphates?

A
  1. Inhibit cholinesterase
  2. Amplify action of endogenous Ach
    by:
    Increasing [ ]
    Increasing half life
    Increasing actions of Ach in synapses
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200
Q

Examples of carbamates

A

Neostigmine
Physostigmine
Ambenonium
Pyridostigmine

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201
Q

Which indirect-acting cholinomimetic is used more commonly in therapeutic? Especially in treatment of myasthenia

A

Carbamates

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202
Q

What are the three organophosphates used in medicine and for what conditions?

A
  1. Echothiopate- Glaucoma
  2. Malathion- Scabicide
  3. Metrifonate- Helminths
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203
Q

What is the pneumonic for cholinomimetic toxicity?

A 
DUMBBELSS
Diarrhea
Urination
Miosis
Bronchoconstriction
Bradycardia
Excitation of skeletal muscle and CNS followed by resp. and cardiac depression
Lacrimation
Salivation
Sweating
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204
Q

Difference between physostigmine and bethanechol

A

Physostigmine is indirect-acting cholinomimetic- cholinesterase is at all cholinergic synapses- increased Ach effects at nicotinic as well as muscarinic receptors
Bethanechol is direct-acting cholinomimetic- selective for muscarinic receptors

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205
Q

How are -thion organophosphates activated?

A

By conversion to -oxon

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206
Q

-thion organophosphates are ____ stable than DDT and thus ___ persisten in the environment

A

Less and less

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207
Q

Parathion is ____ toxic than Malathion

A

More

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208
Q

How can Parathion toxicity be partly reversed?

A

Pralidoxine

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209
Q

What drug is used to distinguish between cholinergic crisis and myasthenia crisis?
Why?

A

Edrophonium
Because it is the shortest acting cholinesterase inhibitor
If it is indeed cholinergic crisis, you want something short acting because the symptoms will worsen

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210
Q

What is the most common cause of death in cholinesterase inhibitor toxicity?

A

Respiratory failure (from neuromuscular paralysis or CNS depression)

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211
Q

Cholinesterase inhibition is typically associated with _____ bowel activity

A

Increased

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212
Q

Long acting cholinesterase inhibitors (organophosphates) (Ex. Echothiophate) are associated with what condition when they are given the drugs for glaucoma?

A

Higher incidence of cataracts

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213
Q

What is cyclospasm?
What causes it?
What is the results?

A

Opposite of paralysis of accommodation (aka cycloplegia)
Cholinomimetics
In open angle glaucoma, this results in increase in outflow of aqueous humour and decrease in IOP

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214
Q
  • direct-acting cholinomimetic
  • lipid-soluble
  • frequently used for glaucoma
A

Pilocarpine

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215
Q
  • indirect-acting cholinomimetic
  • charged substance with poor lipid solubility
  • duration: 2-4 hours
A

Neostigmine

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216
Q
  • direct-acting cholinomimetic alkaloid
  • mood-elevating properties
  • insecticide
A

Nicotine

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217
Q
  • indirect-acting cholinomimetic

- plant alkaloid, therefore lipid soluble, therefore enters CNS readily

A

Physostigmine

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218
Q

All the muscarinic antagonists in the US are nonselective/selective?

A

Nonselective

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219
Q

What are the primary target organs of muscarinic antagonists?

A

CNS
Eye
Bronchi
GI or genitourinary system

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220
Q

What is the major determinant of lipid solubility in antimuscarinics?

A

Presence or absence of permanently charged (quaternary) amine group in the drug
The charged molecule is more polar, therefore less likely to penetrate lipid barrier

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221
Q

What is the prototypical nonselective muscarinic blocker?

A

Atropine
Tertiary amine
Lipid soluble

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222
Q

What is the mechanism of action of antimuscarinic drugs?

What can they be overcome by?

A

Competitive antagonists

Overcome by higher [ ] of muscarinic agonists

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223
Q

What are the effects of muscarinic antagonists?

A
  • Sedation
  • Decrease motion sickness
  • Decreases signs of parkinsonism
  • Decreases heart rate
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224
Q

What kind of drug is scopolamine?

What is it used for?

A

Antimuscarinic

Motion sickness

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225
Q 
What kind of drugs are
benztropine
biperiden
trihexyphenidyl ?
What are they used for?
A

Antimuscarinic

Anti parkinsonism

226
Q

What effect do antimuscarinincs have on the eye?

A 
Dilate the pupil (mydriasis)
Paralyze accommodation (cyclopegia)
227
Q

What are the antimuscarinics that work on the eye?

A 
CHAT
Cyclopentate
Homatropine
Atropine
Tropicamide
228
Q

What is the antimuscarinic drug that works on bronchi?
How is it administered?
How does it work?

A

Ipratropium
Inhalation
Promotes bronchodilation in asthma and COPD

229
Q

What are the antimuscarinic drugs that work on the gut?

How does it work?

A 
MAP
Methscopolamine
Atropine
Propantheline
Decreases gastric acid secretion (not as effective as H2 blockers or proton pump inhibitors)
230
Q

What are the antimuscarinic drugs that work on the bladder?

How do they work?

A 
Glycopyrolate
Oxybutynin
Methscopolamine
Tolterodine
Reduces urgency in mild cystisis and reduces bladder spasms following urologic surgery.
231
Q

“Dry as a bone, red as a beet, mad as a hatter”

Is the toxicity for what drugs?

A

Antimuscarinic drug toxicity

232
Q

What is the most dangerous effect of antimuscarinic drugs?

A

Hyperthermia
“Dry as a bone”
Because of increased sweating, salivation, and lacrimation

233
Q

What are the CNS effects of antimuscarinic toxicity?

A

Sedation, amnesia, delirium, and hallucinations

“Mad as a hatter”

234
Q

What are the cardiac effects of antimuscarinic toxicity?

A

Dilation of cutaneous vessels of arms, head, neck, and trunk

“Red as a beet”

235
Q

What are the two subtypes of nicotinic antagonists?

A

Ganglion-blocking and neuromuscular-blocking

236
Q

What was the first successful drug developed for hypertension?

A

Ganglion-blocking nicotinic antagonist

237
Q

Where do nicotine and mecamylamine (ganglion-blocking drugs) have receptors?
What do they help with?

A

CNS

Nicotine addiction and Tourette’s

238
Q

What drugs interrupt sympathetic control of venous tone?
What does this cause?
What is the major manifestation of these drugs?

A

Ganglion-blocking antinicotinic drugs
Marked venous pooling
Postural hypotension

239
Q

What drugs are important for complete skeletal relaxation during surgery?

A

Neuromuscular-blocking antinicotinic drugs

240
Q

What are the two subgroups of neuromuscular-blocking antinicotinic drugs?

A

Nondepolarizing and depolarizing groups

241
Q

What is the prototype for non-depolarizing neuromuscular-blocking antinicotinic drugs?

A

Tubocurarine

242
Q

How do non-depolarizing neuromuscular antinicotinic drugs work?
What do they result in?

A 
By completely blocking at the end plate of nicotinic receptors
Flaccid paralysis (30-60min)
243
Q

What are some non-depolarizing neuromuscular-blocking antinicotinic drugs? (Other than the prototype Tubocurarine)

A

PAV
Pancuronium
Atracurium
Vecuronium

244
Q

How do the depolarizing neuromuscular-blocking antinicotinic drugs work?

A

They are actually nicotinic agonists but also cause flaccid paralysis

245
Q

What is the name of a depolarizing neuromuscular-blocking antinicotinic drug?
What effect does it have?
What is it hydrolyzed by?

A

Succinylcholine
Produces fasciculations during induction (patients may complain of pain after)
Plasma cholinesterase

246
Q

What kind of antagonists are cholinesterase inhibitors?

A

Chemical antagonists

247
Q

How does the oxime group in cholinesterase regenerators work?

A

It has a higher affinity for phosphorus atom in organophosphate insecticides than cholinesterase does. So active enzyme is regenerated

248
Q

What is an example of a cholinesterase regenerator?

What is it used for?

A

Pralidoxine

Used for exposure to insecticides (Parathion)

249
Q

In young children, what is the most dangerous effect of Belladonna Alkaloids?

A

Belladonna Alkaloid= atropine
Atropine= Prototypical nonselective muscarinic blocker
Hyperthermia

250
Q

Is atropine well absorbed?

A

Yes

251
Q

Drug with long duration, especially as an anti motion sickness drug

A

Scopolamine

252
Q

Drug with quaternary amino group (so permanently charged), poorly absorbed from airways

A

Ipatropium

253
Q

Drug with tertiary amino group, lipid soluble, so penetrates CNS well

A

Benztropine

254
Q

Drug that is well absorbed from conjuctival sac into the eyes

A

Cyclopentolate

255
Q

What two subgroups of drugs have both of these effects?
Mydriasis (dilation of the pupil)
Increased heart rate
Blurred vision
Dry mouth
Constipation
Only one of them causes postural hypotension. Which one and why?

A

Antimuscarinics and antinicotinics

Antinicotinics (sympathetic blockade)

256
Q

All _____ cause cyclopegia (paralysis of accommodation)

_______ have the opposite effect (cyclospasm)

A

Antimuscarinics

Cholinomimetics

257
Q

Why can ordinary doses of atropine be hazardous in the elderly?

A

Because atropine can elevate IOP in patients with glaucoma

258
Q 
What are 
-motion sickness
-parkinson's
-post operative bladder spasm
-wanting to produce mydriasis and cyclopegia
therapeutic indications for use of?
A

Antimuscarinics

259
Q

What is NOT responsive to antimuscarinics

A

Hypertension

260
Q

What effect do muscarinic M1 and M3 receptors evoke?

Where?

A

Increase in IP3 and DAG in target tissues

Intestine and salivary glands

261
Q

What effect do muscarinic M2 receptors evoke?

A

Decrease in cAMP and increase in K+ permeability

262
Q

What drug causes vasodilation by activating muscarinic receptors on endothelium blood vessels?
What blocks this?

A

Bethanechol

Atropine

263
Q

What is a common source of antimuscarinic drug poisoning?

A

Jimson Weed (Datura stramonium)

264
Q

What are the two ways that sympathomimetics work?

A

Directly activate adrenoreceptors or

indirectly by increasing [ ] of catecholamines in synapse

265
Q

How do amphetamine derivatives and tyramine work?

What type of sympathomimicry is this?

A

Cause release of stored catecholamines

Indirect

266
Q

How do cocaine and tricyclic antidepressants work?

A

They inhibit reuptake of catecholamines by nerve terminals

267
Q

How do you block sympathomimetic metabolism?

A

By blocking MAO and COMT

268
Q

What effect do MAO inhibitors have?

A

Increase stores of catecholamines thus may potentiate action of indirect sympathomimetics

269
Q

What are the three endogenous adrenoreceptor agonists?

What type of drugs are they?

A

Epinephrine
NE
Dopamine
Catecholamines

270
Q

What are the endogenous adrenoreceptor catecholamines (Epinephrine, NE, and Dopamine) metabolized by?
Are they active by the oral route?

A

Metabolized my COMT and MAO

271
Q

What is the mechanism of alpha-1 agonists?

What kind of G protein are the receptors they coupled to?

A

Coupled to Gq protein
Gq activated
Alpha moiety causes release of IP3 and DAG from membrane lipids
Calcium released from smooth muscle cell stores

272
Q

What G protein are alpha-2 receptors coupled to?

What is the results of activation?

A

Gi protein

Results in inhibition of adenylyl cyclase= decrease in cAMP

273
Q

What G protein are B-1, 2, and 3 receptors coupled to?

What is the result of activation?

A

Gs protein

Results in stimulation of adenylyl cyclase= increase cAMP

274
Q

Where are dopamine receptors mostly?
D1-
D2-

A

D1- activate adenylyl cyclase in neurons and vascular smooth muscle
D2- brain

275
Q

How do smooth muscles of pupillary dilator respond to topical phenylephrine and alpha agonists?

A

Mydriasis (dilation)

276
Q

How do alpha-1 and alpha-2 agonists differ in their mechanism of lower IOP?

A

alpha-1: facilitate outflow of aqueous humor

alpha-2: reduce synthesis of aqueous humor

277
Q

How do smooth muscle of bronchi respond to B-2 agonists?

A

Relax

278
Q

What are the most effective drugs for bronchospasm?

A

B-2 agonists

279
Q

What effect does activation of either alpha or beta receptors have on Gi tract?

A

Relaxation of smooth muscle

280
Q

What effect do alpha-2 agonists have on GI tract?

A

Decrease salt and water secretion into intestine

281
Q

Where are the alpha receptors in the genitourinary tract?

What effect does their activation have?

A

In bladder trigone and sphincter area

Mediate contraction of sphincter (sympathomimetics increase sphincter tone)

282
Q

Where are B-2 receptors found in the genitourinary tract?

What effect does their activation have?

A

Uterus

Uterine relaxation in pregnant women

283
Q

What is an example of an alpha-1 agonist in the vascular system?

A

Phenylephrine

284
Q

What effects does an alpha-1 agonist (such as phenylephrine) have on the vascular system?

A

Constricts skin and splanchnic blood vessels
Increases peripheral vascular resistance
Increases venous P

285
Q

What kind of response do alpha-1 agonists evoke in the vascular system?

A

Compensatory bradycardia

286
Q

What is an example of an alpha-2 agonist in the vascular system?

A

Clonidine

287
Q

What effects does an alpha-2 agonist (such as Clonidine) have on the vascular system?

A

Vasoconstriction (IV or nasal)

When IV, accumulates in CNS and REDUCES sympathetic outflow and BP

288
Q

What is an example of a B agonist in the vascular system?

A

Terbutaline

289
Q

What kind of response does a B agonist (ex. Terbutaline) evoke in the vascular system?

A

Decrease in arteriolar tone in skeletal muscle vascular bed
Decrease in peripheral vascular resistance
Decrease in arterial BP

290
Q

What effect does Dopamine have in the vascular system?

A

Vasodilation in splanchnic and renal vascular beds by activating D1 receptors

291
Q

What receptors does the heart have a lot of?

A

B1 and B2

292
Q

What is an example of a sympathomimetic with both alpha and beta effects?

A

NE

293
Q

Why does NE cause an increase in vagal outflow?

A

Because it increases BP and evokes a baroreceptor reflex

294
Q

What does a slow NE infusion result in ( cardio ) ?

A

Increased BP and bradycardia

295
Q

If the baroreceptor reflex is blocked (by a ganglion blocker) what will happen with NE administration?

A

NE will cause a direct B1-mediated tachycardia

296
Q

What is an example of a pure alpha agonist?

A

Phenylephrine

297
Q

What cardiac effects does a pure alpha agonist have?

A

Slows heart rate via baroreceptor reflex

298
Q

What is an example of a pure B agonist?

A

Isoproterenol

299
Q

What cardiac effects does a pure B agonist have?

A

Increase in HR

300
Q

What are the metabolic and hormonal effects of B1 agonists?

A

-Increased renin secretion
- Increased insulin secretion
- Increased glycogenolysis
Resulting hyperglycemia countered by increased insulin levels

301
Q

All of these drugs appear to stimulate lipolysis

A

B agonists

302
Q

What is the number one drug used for anaphylaxis?

A

Epinephrine

303
Q

What can epinephrine be supplemented with for anaphylactic shock?

A

Antihistamines and corticosteroids

304
Q

Used for:
Narcolepsy
ADHD
Weight reduction

A

Phenylisopropylamines such as amphetamines

305
Q

What effects do alpha agonists have on the eye?

A 
Produce mydriasis (dilating of the pupil)
Reduce conjunctival itching and allergy
Reduce aqueos humor (alpha 2 selectives)
306
Q

What drugs treat acute bronchospasm?

A

B2 selectives

307
Q

What are the short-acting drugs used for bronchospasm?

What kind of drugs are they?

A

Terbutaline
Albuterol
Metaproterol
B2 selectives

308
Q

What are the long-acting B agonists used for prophylaxis of bronchi?

A

Long-acting B agonists

Salmeterol

309
Q

What drugs are used in chronic heart failure and shock?

Why?

A

B1 agonists

Because increase cardiac contractility

310
Q

What drugs are used in spinal shock and orthostatis hypotension?
Why?

A

Alpha-1 agonists

Vasoconstriction

311
Q

What drugs are used to suppress premature labor?

What kind of drugs are they?

A

Ritodrine
Terbutaline
B2 selectives

312
Q

Main manifestations of the following toxicities:
Alpha 1 agonists
B1 agonists
B2 agonists

A

Hypertension
Tachycardia and arrhythmia
Skeletal muscle tremor

313
Q

Which drug acts on all A1, A2, B1, and B2 receptors?

A

Epinephrine

314
Q

Long-acting indirect sympathomimetic
Oral route
Urinary incontinence in children
Also in herb Ma-huang and energy supplements

A

Ephedrine

315
Q

What is the difference between antimuscarinic and alpha sympathomimetic effects on the eye?

A

Antimuscarinic: mydriatic (dilation of pupil) and cycloplegic (paralysis of accommodation)
Alpha sympathomimetic: Only mydriatic

316
Q

What kind of drug is Pilocarpine?

What effect does it have on the eye?

A

Indirect-acting cholinomimetic

Miosis (contriction of the pupil)

317
Q

Relax uterine and bronchiolar smooth muscle

A

B2 agonists

318
Q

What is a common side effect of B2 agonists?

A

Tremor

319
Q

Blood vessels in the skin have almost exclusively ___ receptors

A

Alpha (vasoconstrictor)

320
Q

Stimulation of renin is a ___ effect

A

B1

321
Q

Increase in cAMP in heart muscle
Increase in FFA in blood
Increase of glc in blood
Increase of lactate in blood

A

Epinephrine

322
Q

What is the basis for the widespread use of alpha agonists (ex. phenylephrine) as topical decongestants?

A

Vasoconstriction in the nasal mucosa

323
Q

What will cause reflex bradycardia in an intact heart but not in a heart transplant patient?

A

A pure alpha agonist

intact innervation vs not

324
Q

What is an example of an irreversible, long lasting adrenoceptor blocker?
What is the mechanism of action?

A

Phenoxybenzamine

Binds covalently to alpha receptor

325
Q

What is an example of a reversible, short-acting, and non-selective adrenoceptor blocker?
What is the moa?

A

Phentolamine

Competitive pharmacological antagonist (effects surmounted by more agonist)

326
Q 
What are
Prazosin
Doxazosin
Trazosin
Tamsulosin ?
A

Alpha 1 selective blockers

327
Q

What are
Yohimbine
Rauwolscine ?

A

Alpha 2 selective blockers

328
Q

What system do non-selective alpha blockers have the most important effects on?
What are those effects?
Do they cause a baroreceptor reflex?

A

Cardiovascular system
Reduce vascular tone with reduction of both arterial and venous pressure
Yes, cause reflex-mediated tachycardia as a result of the drop in MAP

329
Q

What is epinephrine reversal?

A

The use of it with an alpha blocker changes its effect from pressor (alpha receptor) to depressor (B2 receptor)

330
Q

Example of alpha1 selective blocker

What do selective alpha blockers cause much less of?

A

Prazosin

Tachycardia (when reducing bp)

331
Q

What are the clinical uses of nonselective alpha blockers?

A

Presurgical management of pheochromocytoma

OD with amphetamine, cocaine, or phenylpropanolamine

332
Q

What nonselective alpha blocker is used in the presurgical treatment of pheochromocytoma?
Why?

A

Phenoxybenzamine

Patients have severe hypertension and low blood volume

333
Q

OD with amphetamine, cocaine, or phenylpropanolamine may lead to what condition?
What does this condition respond well to?

A

Hypertension

Alpha blockers

334
Q

What selective alpha-1 blockers are used in hypertension?

A

Prazosin
Doxazosin
Terazosin

335
Q 
Prazosin
Doxazosin
Terazosin
Tamsulosin
Used in?
A

Urinary hesitancy and prevention of urinary retention in men with BPH

336
Q

What kind of antagonists are beta blockers?

What is the prototype drug?

A

Competitive pharmacologic antagonists

Propanolol

337
Q 
What are 
Acebutolo
Atenolo
Esmolol
Metoprolol ?
A

B-1 selective blockers

338
Q

When are B1 selective blockers an advantage?

A

When treating asthma

339
Q

Nadolol
Propranolo
Timolo

A

non selective B blockers

340
Q

Labetaolol

Carvedilol

A

Both alpha and beta action

341
Q

Which beta blockers are partial agonists?

Why could they be an advantage?

A

Pindolol
Acebutolol
When treating asthma because even at max dosage they cause some bronchodilation

342
Q

Which beta blocker has local anaesthetic activity?

When is it a disadvantage?

A

Propanolol

When used topically in the eye because it lowers protective reflexes and increases risk of corneal ulceration

343
Q

What is the longest-acting beta blocker?

A

Nadolol

344
Q

What are the clinical uses for B blockers?

A 
Hypertension
Angina
Arrhythmias
CHF
Pheochromocytoma and glaucoma ( uses both alpha and beta)
345
Q

What are the manifestations of b blocker toxicity?

A 
Bradycardia
AV blockade
HF
asthma attacks
Masking of premonitory hypoglycemic symptoms
346
Q 
What drugs block these:
Cardiac stimulation
Increase in cAMP in fat
Relaxation of bronchial smooth muscle
Relaxation of uterus
A

B blockers

347
Q

Alpha blockers used in hypotension and reflex tachycardia

A

Phentolamine and phenoxybenzamine

348
Q

What is the most important contraindication in the use of beta blockers?

A

AV block

349
Q

What are the adverse effects of beta blockers?

A

Bronchoconstriction
Impaired blood sugar responses
Sleep disturbances
Heart failure exacerbation

350
Q

What is an adverse effect of alpha blockers in the eye?

A

Increased IOP

351
Q

What is the only autonomic receptor blocker in clinical use that binds covalently with its receptor?

A

Phenoxybenzamine with is alpha receptor

352
Q

Synthesized in the body from AA precursors

Eliminated by amine oxidation

A

Histamine and Serotonin

353
Q

What receptors do ergo alkaloids interact with?

A

Serotonin receptors
Dopamine receptors
Alpha receptors

354
Q

What is histamine formed from? Where is it stored?

What is it metabolized by?

A

Histidine, mast cells

MAO and DAO

355
Q

What is histamine measured by in the urine?

A

Its major metabolite: imidazoleactic acid

356
Q

What is histamine released from mast cells in response to?

A

IgE-mediated allergic reactions

357
Q 
What plays a pathophysiological role in 
Rhinitis (hay fever)
Urticaria
Angioneurotic edema
(Also important as NT and in control of acid secretion in stomach)
A

Histamine

358
Q

What kind of receptor is the H1 receptor? What are its second messengers? Where are they important?

A

Gq-coupled
IP3 and DAG
In smooth muscle (especially those caused by IgE-mediated effects)

359
Q

What is the typical response to activation of the H1 receptor?

A

Bronchoconstriction

Vasodilation

360
Q

What is the vasodilation as a result of activation of the H1 receptor caused by?

A

Release of NO from EDRF

361
Q

On top of releasing EDRF, the capillaries do what in response to activation of H1 receptor?

A

Contract

362
Q

What does contraction of capillary endothelial cells cause?

A

Opening gaps in permeation barrier= edema

363
Q

What kind of receptor is the H2 receptor? What’s its second messenger? What does it mediate?

A

Gs-couples to adenylyl cyclase
cAMP
Gastric acid secretion by parietal cells in the stomach

364
Q

Which histamine receptor mediates:
Gastric acid secretion by parietal cells in the stomach
Cardiac stimulant effect
Negative feedback on mast cells

A

H2

365
Q

Where are H3 receptors found?

A

Mainly in presynapatic modulation of histaminergic neurotransmission in the CNS

366
Q

What are
diphenhydramine
doxylamine ?
What are their defining qualities?

A

Old 1st generation histamine-1 antagonists

highly sedating with autonomic receptor-blocking effects

367
Q

What are
chlorpheniramine
cyclizine ?
What are their defining qualities?

A

New 1st generation histamine-1 antagonists

Less sedating, less autonomic effects

368
Q 
What are 
fexofenadine
loratadine
cetirizine ? 
What are their defining qualities?
A

2nd generation histamine-1 anatagonists

Far less lipid soluble than 1st generation thus, non-sedating, no autonomic effects

369
Q

What kind of antagonists are histamine -1 antagonists?

A

Competitive pharmacologic antagonists at the H1 receptor?

370
Q

Why are 1st generation H1 antagonists potent antagonists at autonomic receptors?

A

Because their structure closely resembles muscarinic and alpha adrenoreceptor blockers

371
Q

Most of these are sedating
Some work for anti-motion sickness
Many are potent local anaesthetics

A

H1 antagonists

372
Q

What are the two clinical uses for H1 antagonists?

A

Immediate-type allergies and anti-motion sickness

373
Q

What are immediate-type allergies caused by?

Examples?

A

Caused by antigens acting on IgE antibody-sensitized mast cells
Hay fever and urticaria

374
Q 
What are these H1 antagonists used for?
diphenhydramine
dimenhydrinate
cyclizine
meclizine
promethazine ?
A

Anti-motion sickness drugs

375
Q

Drug used for chemotherapy-induced vomiting

A

Diphenhydramine

376
Q

What is common with these H1 antagonist drugs?
Diphenhydramine
Doxylamine
Promethazine

A

Sedation

377
Q

What are the anti muscarinic effects H1 anagonists have?

A

Dry mouth

Blurred vision

378
Q

What are the alpha-blocking effecs that H1 antagonists have?

A

Orthostatic hypotension

379
Q

Excessively high concentrations of either anti-histamine will result in?

A

Lethal arrhythmias

380
Q 
What are these drugs?
Cimetidine (prototype)
Ranitidine
Famotidine
Nizatidine
A

H2 antagonists

381
Q

What is the mechanism of H2 blockers?

What is their effect?

A

Surmountable blockade of H2 receptor

Decreases gastric acid secretion

382
Q

What are the clinical uses of H2 antagonists?

What is more effective for these uses?

A 
For acid-peptic ulcer (esp. duodenal)
For gastric peptic ulcers
Zollinger-Ellison syndrome
GERD
PPI
383
Q

What is a potent inhibitor of hepatic drug-metabolizing enzymes?
What happens with its toxicity?

A

Cimetidine
May reduce hepatic blood flow
Has antiandrogen effects

384
Q

What is serotonin produced from?
Where is it stored?
What is it metabolized by?
What is excess production (carcinoid) detected by in the urine?

A

Tryptophan
Vesicles in the enterochromaffin cells of the gut and neurons of the CNS, and platelets
MAO
It’s metabolite: 5HIAA

385
Q

What is the only serotonin agonist?

A

5HT1D receptor

386
Q

What are the serotonin antagonists?

A

5HT2 and 5HT3 receptors

387
Q

Where is the 5HT1 receptor most important?
What does it do there?
What kind of receptor is it?

A

In the brain (less importantly: sm. m. tissues)
It mediates synaptic inhibition via increased potassium conductance in brain (in tissues: both excitatory and inhibitory)
Gi protein-coupled receptor

388
Q

Where are 5HT2 receptors found?
What do they mediate at each place?
What symptoms do they mediate in a carcinoid tumor?

A

In brain and peripheral tissues
Mediate synaptic excitation in the CNS and smooth muscle contraction in the gut, bronchi, uterus and vessels
Dilation: in the vessels
In carcinoid tumor: vasodilation, diarrhea, and bronchoconstriction

389
Q

Where are 5HT3 receptors found?
What receptors are they?
What kind of drugs are they?

A

CNS, especially the chemoreceptive area and vomiting center. Also, peripheral sensory and enteric nerves
5HT gated ion channels
Antiemetic drugs

390
Q

What are examples of 5HT1D agonists?

What are they used for?

A

Sumatriptan (prototype)
Naratriptan
other “-triptans”
Acute migraines and cluster headache attacks

391
Q

What are SSRIs used as?

How do they work?

A

Antidepressants

Work by increasing activity at serotonergic synapses by inhibits reuptake carrier for 5HT

392
Q

What are these drugs?
Ketanserin
Phenoxybenzamine
Cyproheptadine

A

5HT2 blockers

393
Q 
What are these drugs?
Ondansetron
Granisetron
Dolasetron
Alosetron
A

5HT3 blockers

394
Q

What are 5HT partial agonists?

A

Ergot alkaloids

395
Q

What kind of antagonists are ketanserin and cyproheptadine?

A

Competitive pharmacologic 5HT2 antagonists

396
Q

What kind of antagonist is phenoxybenzamine?

A

Irreversible blocker of 5HT2

397
Q

What are the uses of ketanserin?

A

antihypertensive and carcinoid tumor

398
Q 
What are the uses of 
ketanserin
cyproheptadine
phenoxybenzamine ?
What kind of drugs are these?
A

For symptoms of carcinoid tumour

5HT2 blockers

399
Q

What are the symptoms of a carcinoid tumor?

A

Diarrhea
Bronchocontriction
Flushing

400
Q

What is Ondansetron used for?

What kind of drug is it?

A

Post chemo and post op vomiting

5HT3 blocker

401
Q

What is Alosetron used for?

What kind of drug is it?

A

Women with IBS

5HT3 blocker

402
Q

What are the adverse effects of ketanserin?

A

Those of alpha blockade and H1 blockade

403
Q

What are the adverse effects of
Ondansetron
Granisetron
Dolasetron ?

A

Diarrhea and headache

404
Q

What are ergot alkaloids produced by?
What were the symptoms called in the middle ages?
How do they work?

A

Fungus found in wet or spoiled grain
“St. Anthony’s fire”- ergotism
Partial agonists at alpha adrenoreceptors and 5HT receptors

405
Q

What effects do ergot alkaloids have on vessels?
What’s the prototype for these effects?
What happens with OD of this drug?

A

Prolonged alpha receptor-mediated vasoconstriction
Ergotamine
Ischemia and gangrene

406
Q

What effects do ergot alkaloids have on the uterus?
What’s the prototype for these effects?
Which ergot alkaloids are used post partum? For what?

A

Powerful contractions, especially near term. If happen earlier on= sufficient to cause abortion
Ergonovine
Ergonovine and Ergotamine, they produce USEFUL contraction to reduce blood loss

407
Q

What effects do ergot alkaloids have on the brain?

What are some examples, and which receptors do they work on?

A

Hallucination
LSD works as 5HT2 blocker in peripheral tissues and CNS effects are due to dopamine receptors
Bromocriptine and pergolide work on dopamine receptors

408
Q

What is LSD?

A

A semisynthetic ergot derivative

409
Q

What receptors do bromocriptine and pergolide work on? What are their effects?

A

Dopamine D2 receptors in the pituitary

Inhibit prolactin secretion

410
Q

Which ergot alkaloids are used for migraines? What are their effects?

A

Ergotamine used for acute attacks

Methysergide and Ergonovine used prophylactically

411
Q

Which ergot alkaloids are used for obstetric bleeding?

A

Ergonovine and Ergotamine

412
Q

Which ergot alkaloids are used for hyperprolactinemia and parkinsonism?

A

Bromocriptine and Pergolide

413
Q

Which ergot alkaloid is used for carcinoid tumor symptoms?

A

Methysergide

414
Q

What systems do ergot alkaloid toxicity affect? What are the symptoms?

A 
Vascular= severe prolonged vasoconstriction=gangrene and ischemia
GI= nausea, vomiting, diarrhea
Uterine= contractions
CNS= hallucinations and psychosis
415
Q

What is an effective antagonist of ergot alkaloid vascular toxicity?

A

Nitroprusside

416
Q

What can long term use of methysergide lead to ?

A

Hyperplasia of connective tissue

417
Q

What respiratory symptom does serotonin cause?

A

Bronchospasm

418
Q

What kind of drug is Sumatripan?

A

5HT1D agonist

419
Q 
What drug has these effects?
Antimuscarinic reduction in bladder tone
Local anaesthetic where injected
Anti motion sickness effect
Sedation
A

H1 blockers

420
Q

What happens if you block an H2 receptor? Why?

A

Decrease in cAMP because it is a Gs protein-coupled receptor

421
Q

What is P450 inhibition a sign of toxicity of?

Example of a drug

A

H2 toxicity

Cimetidine (potent CYP3A4 inhibitor)

422
Q

What kind of drug is Ondansetron?

A

Antiemetic

423
Q

What is an antiandrogenic and a CYP3A4 inhibitor? (P450 enzymes)

A

Cimetidine (H2 blocker)

424
Q

Which antihistamine is used for hay fever?

A

Cetirizine (2nd gen. H1 blocker)

425
Q

Which ergot alkaloid dopamine agonist is used for hyperprolactinemia?

A

Bromocriptine

426
Q

What kind of blocker is Cimetidine?

A

H2

427
Q

What kind of agonist is Sumatriptan? What is it used to treat?

A 
5HT1D agonist (serotonin)
Acute migraines
428
Q

What is an irreversible antagonist for treatment of carcinoid tumors? What kind of blocker is it?

A

Phenoxybenzamine (5HT2)

429
Q

What is Angiotensin 1 produced from? By what enzyme? Where is this enzyme released from?

A

Angiotensinogen
Renin
From juxtaglomerular apparatus in kidney

430
Q

What is the inactive decapeptide vasoactive peptide?

A

Angiotensin 1

431
Q

What is the active octapeptide vasoactive peptide?

A

Angtiotensin 2

432
Q

What converts Angiotensin 1 to Angiotensin 2?

A

ACE

433
Q

What is Angiotenin 2 rapidly degraded by?

A

Peptidases

434
Q

What are the effects of AT2?

A

Potent vasoconstrictor and stimulant of aldosterone release

Also facilitates release of NE

435
Q

Direct effects of AT2

A

Increase peripheral resistance

436
Q

Indirect (through aldosterone) effects of AT2

A

Causes renal Na retention

437
Q

What is AT2 clinically used for?

A

Hypertension and HF

438
Q

What are
captopril
enalapril
What are they used for?

A

ACE inhibitors

Hypertension and HF

439
Q

What are
losartan
valsartan

A

AT2 receptor blockers

440
Q

What kind of AT2 antagonists are there?

What is their action accompanied by?

A

ACE inhibitors
A2 receptors blockers
Accompanied by compensatory increase in renin and AT1

441
Q

What is bradykinin (all kinins) produced from? By what enzyme?

A

From kininogen

By kallikreins

442
Q

Causes production of IP3, DAG, cAMP, NO, and PGs in tissue
One of the most potent vasodilators
Involved in inflammation (causes edema and pain when released or injected into tissue)

A

Bradykinin

443
Q

Where are natriuretic peptides synthesized and stored? What is the stimulus that causes their release?

A

Cardiac atria of mammals

Released from atria in response to distention of chambers

444
Q

What are the effects of natriuretic peptides?

A

Activate guanylyl cyclase
Act as vasodilators and natriuretic (Na-excretion-enhancing agents)
Increase GFR, decrease proximal tubule Na reabsorption, inhibitory effect on renin secretion
Inhibit AT2 and aldosterone

445
Q

What is nesiritide?

A

BNP for HF

446
Q

What are peptide vasoconstrictors?

A

Endothelins

447
Q

Where are endothelins formed in and released by?

A

Endothelial cells in blood vessels

448
Q

What receptors are responsible for vasoconstriction by endothelins ?

A

ET-A receptor

449
Q

How are endothelins compared to NE as vasoconstrictors?

A

Much more potent and long-lasting

450
Q

What is Bosentan? What is it used for?

A

Endothelin antagonist. Pulmonary hypertension

451
Q

VIP is an extremely potent _____ and neutrotransmitter

A

Vasodilator

452
Q

Potent vasodilator action on arterioled and neurotransmitter
Potent stimulant of veins and intestinal and airway smooth muscles
Local hormone in GI tract
High concentrations found in part of nervous system that contains pain neurons

A

Substance P

453
Q

What is Capsaicin? What does it release? What is its clinical use?

A

“hot” component of chilli peppers
releases substance P in nerve endings
Topical use on arthritic joints and post herpitic neuralgia

454
Q

What are neurokinins A and B used for?

Example?

A

Depression, nausea, and vomiting

Aprepitant

455
Q

Where is CGRP found in high concentrations?

Where in less?

A

Thyroid

Smooth muscle tissues

456
Q

What is the most potent hypotensive (vasodilator) agent discovered?
What does it cause?

A

CGRP

Reflex tachycardia

457
Q

What is NPY? What does it stimulate?

A

Potent vasoconstrictor

Stimulates heart

458
Q

Potent vasodilator with pain and edema-inducing effects and inactivated by ACE

A

Bradykinin

459
Q

Arterial vasodilator
Constrictor of veins and airway smooth muscle
Found in afferent pain fibers

A

Substance P

460
Q

Inhibited by Captopril
Also degrades kinins
As well as AT1—>AT2

A

ACE

461
Q

Endothelin antagonist used for pulmonary hypertension

A

Bosentan

462
Q

Antagonist of peptide (neurokinin)

Decreases nausea and vomiting (chemo)

A

Aprepitant

463
Q

Peptide cotransmitter found in autonomic nerve endings

Vasoconstrictor

A

NPY

464
Q

Potent vasoconstricor peptide synthesized in endothelium of blood vessels

A

Endothelin

465
Q

Which are the cyclized arachidonic acid derivatives?

A

Prostacyclin
Prostaglandins
Thromboxane

466
Q

Which are the straight-chain arachidonic acid derivatives?

A

Leukotrienes

467
Q

What does an injury or immune reaction stimulus activate? What does it then release?

A

Activates phospholipases in cell membrane or cytoplasm

Membrane phospholipids then release arachidonic acid

468
Q

What can arachidonic acid be metabolized by? What are the products?

A

Lipoxygenase= straight chain leukotrienes

COX- cyclized prostacyclin, prostaglandins, and thromboxane

469
Q

Where is COX2 primarily found?

A

Inflammatory cells

470
Q

Where is thromboxane preferentially synthesized?

A

Platelets

471
Q

Where is prostacyclin preferentially synthesized?

A

Endothelial cells of vessels

472
Q

What comprise the important mediator of bronchoconstriction ( slow-reacting substance of anaphylaxis- SRS-A)?

A

LTC4 and LTD4

473
Q

Which eicosanoid is a chemotactic factor important in inflammation?

A

LTB4

474
Q

Which eicosanoids are endogenous vasodilators?

A

PGE2 and prostacyclin

475
Q

What effect does PGE1 have on gastric mucosa? What is the mechanism?

A

Protective effect

By increasing secretion of bicarb and mucus and decreasing acid secretion

476
Q

Which eicosanoids relax vascular and other smooth muscles?

A

PGE1 and PGE2

477
Q

Which eicosanoid is a natural vasodilator that maintains the patency of ductus arterioles during fetal development?

A

PGE2

478
Q

Which eicosanoids are released from endometrium during menstruation?

A

PGE2 and PGF2-alpha

479
Q

Which eicosanoid is involved in physical ripening of cervix at term?

A

PGE2

480
Q

What is associated with uterine contractions induced by prostaglandins?

A

Dysmenorrhea

481
Q

Which eicosanoid is platelet aggregation strongly activated by?

A

Thromboxane

482
Q

Which eicosanoid reduced IOP?

A

PGF2-alpha

483
Q

What are the effects of PGE2 and PGF2-alpha in obstetrics?

What is dinoprostone? What does it do?

A

Contraction of uterus
PGE2
Ripens cervix at term (before induction of labor with oxytocin)

484
Q

Which eicosanoids have been used as abortifacients in 2nd trimester of pregnancy?

A

PGE2 and PGF2-alpha

485
Q

What is misoprostol? What is it used for?

A

PGE1 analog

Abortifacient and against peptic ulcer associated with NSAID use

486
Q

What is PGE1 used for in Pediatrics?

A

As infusion- maintains patency of ductus arteriosus in infants with transposition of the great vessels (until surgery)

487
Q

What is prostacyclin (PGI2) used for in pulmonary hypertension and dialysis? As what drug?

A

As hypotensive agent in pulmonary hypertension and prevents platelet aggregation in dialysis machine
As epoprostenol

488
Q

What is PGE1 used for in urology? As what drug?

A

To treat impotence

As alprostadil

489
Q

What are PGF2-alphas used for in opthalmology?
What are the drugs?
How do they work?

A 
Glaucoma
Latanoprost
Bimatoprost
Travoprost
Noprostone
Increase outflow of aqueous humour, thus decrease IOP
490
Q

What does Zileuton inhibits?

A

Lipoxygenase

491
Q

What do Zafirlukast and Montelukast inhibit? What are they used for?

A

LTD4 receptor, used for treatment of asthma

492
Q

What two processes do corticosteroids inhibit?

A

Production of arachidonic acid by phospholipases in the membrane and synthesis of COX-2

493
Q

What do NSAIDs inhibit?

What are the COX2 selective NSAIDs

A

COX

Rofecoxib and Celecoxib and Valdecoxib

494
Q

What makes aspirin unique as an NSAID?

A

It binds COX irreversibly

495
Q

What is the mechanism of aspirin allergy?

A

Results from diversion of arachidonic acid to the leukotriene pathway when COX prostaglandin pathway is blocked
The increase in leukotrienes results in bronchoconstriction

496
Q

What does the increase in leukotrienes in aspirin allergy manifest as?

A

Bronchocontriction

497
Q

What action of aspirin results from the inhibition of thromboxane?

A

Antiplatelet action

498
Q

Which eicosanoid is a potent vasodilator?

A

Prostacyclin (PGI2)

499
Q 
What do all of these have in common?
AT2
Methysergide
PGF2-alpha
Thromboxane
A

Vasoconstrictors

500
Q

What is a uterine stimulant derived from membrane lipid in endometrium?

A

PGE2

501
Q

Why aren’t eicosanoids used in hypertension?

A

They don’t have a long enough duration of action

502
Q

Which eicosanoids are used in glaucoma?

A

PGF2-alpha and analogs

503
Q

What are the nonselective NSAIDs with moderate effectiveness?

A

Ibuprofen and Naproxen

504
Q

What are the nonselective NSAIDs with greater anti-inflammatory effectiveness?

A

Indomethacin

505
Q

What are the nonselective NSAIDS with greater analgesic effectiveness?

A

Ketorolac

506
Q

What is the mechanism of action of aspirin and older non-selective NSAIDs?

A

Inhibit both isoforms of cox non-selectively , thus decrease prostaglandin and thromboxane synthesis

507
Q

What are these the effects of?
Decreased inflammation
Decreased PG-mediated cytoprotection in the GI tract and autoregulation of renal transcription

A

COX inhibitors

508
Q

What are these the effects of?

Decreased prostaglandin synthesis stimulated by pyrogens

A

NSAIDS

509
Q

What does low dose aspirin do?

A

Reduces platelet aggregation

510
Q

What does intermediate dose aspirin do?

A

Antipyretic and analgesic effects

511
Q

What does high dose aspirin do?

A

Anti inflammatory effects

512
Q

What are the benefits of Naproxen and Piroxicam as NSAIDs?

A

Have long half lives, less frequent dosing

513
Q

What are COX2 inhibitors used for?

A

Inflammatory diseases

514
Q

What is used to treat
Dysmenorrhea
Headache
Patent ductus arteriosus in premies ?

A

NSAIDs

515
Q

What is the only NSAID available parenterally and used mainly as a systemic analgesic?

A

Ketorolac

516
Q

Which drug reduces polyp formation in FAP?

A

Ketorolac

517
Q

Which drug’s chronic use toxicity includes
Gastric upset
Upper GI bleeding
Gastric ulcerations
Renal effects (acute failure and nephritis)
Increased bleeding time ?

A

Aspirin

518
Q 
Which drug's high dose toxicity includes:
Tinnitus
Vertigo
Hyperventilation
Respiratory alkalosis
A

Aspirin

519
Q 
Which drug's very high dose toxicity includes:
Metabolic acidosis
Dehydration
Hyperthermia
Collapse, coma, death
A

Aspirin

520
Q

What are the toxic effects of non selective NSAIDs?

A

Gi and renal damage

521
Q

Which drugs don’t have as profound GI effects as other NSAIDs, aren’t cardioprotective, and shouldn’t be used during renal dysfunction?

A

COX2 inhibitors

522
Q

What are anti inflammatories that show evidence of slowing or reversal of joint damage called? How long does it take for them to work?

A

Disease-modifying, Slow-acting Antirheumatic Drugs
(DMARDs, SAARDs)
6 weeks to 6 months

523
Q

What kind of drug is methotrexate? How does it work?

A

Cytotoxic

Decreases the number of immune cells

524
Q 
Which drug:
Interferes with T cell activity
Decreases leukocyte chemotaxis
Stabilizes lysosomal membranes
Interferes with DNA and RNA synthesis
Traps free radicals
What drug does is this similar to?
A

Hydroxychloroquine

Penicillin

525
Q

What is a prodrug that is rapidly metabolized to a compound that inhibits dihydroorotate dehydrogenase?
Why is this enzyme important?

A

Leflunomide
It is an enxyme required by activated lymphocytes for synthesis of the pyrimidines that are needed for RNA synthesis. When you block this enzyme- cell cycle arrest

526
Q

What happens when you inhibit dihydroorate dehydrogenase?

A

Cell cycle arrest, no synthesis of pyrimidines needed for RNA synthesis

527
Q

What are monoclonal antibodies that bind to and prevent action of TNF-alpha

A

Inflixamib and adalimumab

528
Q

When are DMARDs used?

A

In RA patients that aren’t responding to other agents. Also in SLE and other immunologic disorders

529
Q

Which DMARDs are taken orally?

A 
Sulfalazine
Hydroxychloroquine
Methotrexate
Cyclosporine
Penicillamine
Leftunomide
530
Q

How are anti TNF-alphas administered?

A

Injection

531
Q

What is the only OTC non-antiinflammatory analgesic?

A

Acetaminophen

532
Q

What effects do acetaminophens have? Which ones don’t they have?

A

Analgesis and Antipyretic

Lack anti inflammatory and antiplatelet effects

533
Q

What kind of people are acetaminophens good for?

A

People with aspirin intolerance (same as intermediate dose aspirin effects)

534
Q

What does acetaminophen toxicity require? When does this happen? What drug can be lifesaving in acetaminophen OD?

A

Oxidation to cytotoxic intermediates by phase I cyt. P450 enzymes
When substrates for phase II reactions are lacking
Acetylcysteine (sulfhydryl donor)

535
Q

What are the phase II reaction substrates?

A

Acetate and glucoronide

536
Q

What is the increase in serum uric acid?

A

Gout

537
Q

What is joint inflammation initiated by precipitation of uric acid crystals?

A

Acute gout attack

538
Q

What are the three ways to treat gout?

A
  1. Decrease inflammation during acute attack
  2. Accelerate renal excretion
  3. Decrease conversion of purines to uric acid via xanthine oxidase
539
Q

What is used to decrease inflammation during an acute attack of gout?

A

Colchicine
NSAIDs
Glucocorticoids

540
Q

What is used to accelerate renal excretion of uric acid in gout?

A

Probenecid

Sulfinpyrazone

541
Q

What is used to decrease the conversion of purines to uric acid via xanthine oxidase?

A

Allopurinol

542
Q

What is an example of a potent NSAID used in the treatment of gout?

A

Indomethacin

543
Q

What is the mechanism of potent NSAIDs in the treatment of gout?

A

Inhibit inflammation of acute gouty arthritis by decreasing PG formation and inhibiting crystal phagocytosis by macrophages

544
Q

What is the mechanism of Colchicine in treatment of gout?

A

Selective inhibitor of microtubule assembly, it decreases leukocyte migration and phagocytosis

545
Q

What are the effects of NSAIDs and glucocorticoids in gout?

A

Decrease synthesis of mediators of inflammation by inflammatory cells in the gouty joint

546
Q

What are the effects of Colchicine in gout?

A

It is a general mitotic poison since tubulin is necessary for normal cell division, motility, and other processes and Cochicine inhibits microtubule assembly

547
Q

Which drugs are preferred for acute gouty arthritis?

Which drug used in low doses is used to prevent gout attacks? Why not in high doses?

A

Indomethacin and glucocorticoids
Colchicine
Because of GI problems

548
Q

Example of uricosuric drugs

A

Probenecid

Sulfinpyrazone

549
Q

What is the mechanism of uricosuric drugs?

A

They are weak acids that compete with uric acid for reabsorption by weak acid transport in proximal tubules
At low doses, may compete with uric acid for secretion by the tubule

550
Q

What are the effects of uricosuric drugs?

A

Inhibits secretion of a large number of other weak acids (penicillin and methotrexate)
Inhibits reabsorption of uric acid

551
Q

What are the preferred drugs for treatment of chronic gout?

A

Uricosuric drugs or allopurinol

552
Q

What does Xanthine Oxidase do?

A

Converts allopurinol to oxypurinol
And hypoxanthine to xanthine
and
xanthine to uric acid

553
Q

What are irreversible suicide inhibitors of xanthine oxidase?

A

Allopurinol and oxypurinol

554
Q

What are the effects of allopurinol?

A

Inhibits XO which
Increases concentration of hypoxanthine and xanthine and
Decreases concentration of uric acid

555
Q

What are some other effects of allopurinol (toxicities) ?

A

Inhibits metabolism of mercaptopurine and azathiopine (which depend on XO) for elimination

556
Q

Indomethacin is used in the closure of patent ductus arteriosus , how does it do this?

A

By blocking PGE production in the ductus arteriosus of the newborn- by inhibiting COX

557
Q

What is primary dysmenorrhea caused by? What should it be treated with?

A

Production of PGs including PGF2-alpha

NSAIDs that block COX

558
Q

What is the advantage of using Ketorolac over aspirin?

A

It is a parenteral agent (IM or IV)

559
Q

Why is it better to indomethacin than cochicine to treat acute gout?

A

Because at the doses of colchicine needed to treat acute gout it causes GI upset

560
Q

Why use a selective COX2 inhibitor in RA?

A

To avoid GI toxicity

561
Q

Recombinant protein that binds TNF

Prevents inflammatory effects

A

Etanercept

Pharmacology (2 decks)

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