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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
What are the two pharmacological antagonists?
Competitive and irreversible
26
In the presence of an agonist, a partial agonist acts as a ?
Inhibitor
27
The two most important plasma proteins with binding capacity
1. Albumin | 2. Orosomucoid (alpha 1-acid glycoprotein)
28
How do inert binding sites contribute to the concentration gradient of a drug? Why?
1. They buffer the concentration gradient | 2. Because the bound drug does not contribute to the concentration gradient that drives diffusion
29
How are spare receptors determined?
By comparing the concentration for 50% of max effect (EC50) and concentration for 50% of max binding (Kd)
30
Dose that causes the specified response in 50% of population
EC50 in quantal dose-response
31
What is potency determined by?
Affinity of receptor for drug
32
Define potency
The amount of drug needed to produce an effect | EC50 in graded-response
33
What does the quantal dose-response relationship measure?
Minimum dose required to produce specific response | AKA statistical distribution of sensitivity to a drug
34
What is Kd? What does it measure? The smaller the Kd...
The concentration of drug required to bind 50% of receptor sites Affinity of a drug to a binding site The higher the affinity
35
Define efficacy
Max effect an agonist can produce if dose taken at very high levels
36
The smaller the EC50 the greater the...
potency
37
What is the loading dose equation?
loading dose= VD x desired P [ ] / bioavailability
38
What is the adjusted dosage equation?
Corrected dose= Avg. dose x patient's creatinine CL/100ml/min
39
What is the maintenance dosage equation?
Dosing rate= CL x desired P [ ] / bioavailabity
40
What is half-life completely determined by? | Equation?
Vd and CL | t1/2= 0.693 x Vd/ CL
41
What does clearance measure? | Equation?
Relates rate of elimination to plasma [ ] | CL= rate of elimination / plasma drug [ ]
42
What does the volume of distribution measure? | Equation?
Amount of drug in body compared to plasma [ ] | Vd= Amount of drug in body/ Plasma drug [ ]
43
``` A drug reaches __% of steady state [ ] at 1? 2? 3? 4? half lives ```
``` 1= 50% 2= 75% 3= 87.5% 4= 93.75% ```
44
Clearance of a particular drug by individual organ depends on what 2 factors?
1. Extraction capability of that organ for that drug | 2. Rate of delivery of drug to the organ (blood flow)
45
How is bioavailability lowered in the intestine?
Expulsion by P-glycoprotein transporter
46
How can liver disease alter the Vd of drugs that are normally bound to plasma proteins? Kidney disease?
Reduced protein synthesis | Urinary protein loss
47
``` What is the metabolism type of: acetaminophen morphine diazepam sulfathiazole digoxin digitoxin ? ```
Glucoronidation
48
What amines are acetylated? How can some genetically differ in this metabolism? What kind of inheritance?
1. Isoniazid 2. Hydralazine 3. Procainamide "Slow acetylators" Autosomal Recessive gene
49
What is succinyl choline metabolized by? What does succinyl choline do? How do some people differ in this metabolism?
Plasma cholinesterase (butyryl cholinesterase) Neuromuscular blocking drug 1/2500 people, cholinesterase works slower (paralysis for hours)
50
What are the types of metabolism that can be affected by genetics?
1. Hydrolysis of esters 2. Acetylation of amines 3. Oxidation
51
``` What is the metabolism type of sulfonamides isoniazid clonazepam mescaline dapsone hydralazine procainamide ? ```
Acetylation
52
What is the metabolism type of ethacrynic acid reactive phase 1 metabolite of acetaminophen?
Glutathione conjugation
53
What do P-gp inhibitors do to bioavailability? Ex? What drugs are usually at toxic plasma [ ] with P-gp inhibitor?
``` Increase it ---- Verapamil Mibefradil Furanocoumarin (GF juice) --- digoxin cyclosporine saquinavir ```
54
What are suicide inhibitors? | Examples?
``` They are metabolized to products that irreversibly inhibit the metabolizing enzyme Ethinyl estradiol norethindrone spironolactone secobarbital allopurinol fluroxene propylthiouracil ```
55
What are the most common inhibitors of drug metabolism involved in serious drug interactions?
``` Amiodarone Cimetidine Furanocoumarins (GF juice) Ketoconazole HIV protease inhibitor Ritonavir ```
56
How does enzyme induction work? | What are the most common inducers in serious drugs interactions?
``` It increases the synthesis of cytochrome p450-dependent drug-oxidizing enzymes in liver Carbamazepine Phenobarbital Phenytoin Rifampin ```
57
Why is lipid solubility of drugs unfavourable in removal from body?
Favorable for absorption across membranes therefore it is reabsorbed from the urine in the renal tubule
58
``` How are barbiturates amphetamines phenylbutazone phenytoins metabolized? ```
P450 dependent hydroxylation
59
What are the phase 1 metabolic reactions?
1. Oxidation (esp. by cytochrome p450 aka mixed function oxidases) 2. Reduction 3. Deamination 4. Hydrolysis
60
``` How is morphine caffeine theopylline metabolized? ```
P450 dependent N-dealkylation
61
How is codeine metabolized?
P450 dependent O-dealkylation
62
``` How is acetaminophen nicotine methaqualone metabolized? ```
P450 dependent N-oxidation
63
``` How is thioridazine cimetidine chlorpromazine metabolized? ```
P450 dependent S-oxidation
64
How is amphetamine diazepam metabolized?
P450 dependent deamination
65
How is epinephrine metabolized?
Amine oxidation
66
How is ethanol chloral hydrate metabolized?
dehydrogenation
67
``` How is chloramphenicol clonazepam dantrolene naloxone metabolized? ```
Reduction
68
Which drug has a higher first-pass metabolism in men than in women?
Ethanol
69
``` How is procainamide lidocaine indomethacin metabolized? ```
Amide hydrolysis
70
``` How is procaine succinylcholine aspirin clofibrate metabolized? ```
Ester hydrolysis
71
How does smoking increase metabolism of some drugs? | Example of a drug?
It induces enzymes in liver and lung | Theopylline
72
What are ALL the ways acetaminophen is metabolized?
1. P450 dependent N-oxidation 2. Glucoronidation 3. Sulfate conjugation
73
What are ALL the ways amphetamine is metabolized?
1. P450 dependent hydroxylation | 2. P450 dependent deamination
74
What are ALL the ways morphine is metabolized?
1. P450 dependent N-alkylation | 2. Glucoronidation
75
What are ALL the ways epinephrine is metabolized?
1. Amine oxidation | 2. Methylation
76
``` What is the metabolism type of epinephrine norepinephrine dopamine histamine? ```
Methylation
77
What is the metabolism type of acetaminophen methyldopa estrone?
Sulfate conjugation
78
What is the metabolism type of salicylic acid nicotinic acid (niacin) deoxycholic acid ?
Glycine conjugation
79
What does probenecid do? By what mechanism? What is it an example of?
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
80
What do P-glycoprotein transport molecules cause? | Where have they been found?
1. Cancer drug resistance | 2. Epithelium of GI tract and BBB
81
How do B12 and Iron enter cells?
Endocytosis by complexing with special proteins. B12 with intrinsic factor Iron with transferrin
82
What is the equation for FIck's Law and what does it predict?
Rate= (C1-C2) x permeation coeff./thickness x area | It predicts the rate of movement of molecules across a barrier
83
What are the variables in Fick's Law?
1. [ ] gradient 2. Permeation coefficient 3. Thickness and area of barrier
84
Why can't anticoagulants be given intramuscularly?
They can cause bleeding (hematomas) in muscle
85
When taken in normal doses, what is acetaminophen conjugated to?
Harmless glucoronide and sulfate metabolites
86
In acetaminophen overdose, which phase metabolism dominates? What does it convert it to? What is it conjugated with? To what?
Phase 1 Reactive intermediate (N-acetyl-p-benzoquineimine) Glutathione- harmless product
87
What happens if glutathione stores are exhausted in phase 1 acetaminophen metabolism?
The reactive intermediate binds with essential hepatic proteins, resulting in cell death
88
What can be life-saving after acetaminophen overdose? | Ex?
Other sulfhydryl donors | Ex: acetylcysteine
89
How do enzyme inducers affect acetaminophen toxicity? | Why?
Increase it | Because they would increase phase 1 metabolism which would results in increased production of reactive intermediates
90
Biotransformation usualy results in what form of the drug?
Less lipid-soluble (more water soluble)
91
What does induction of drug metabolism do to the SER? | Why?
It increases it | Because the SER contains the mixed function oxidase drug-metabolizing enzymes (cyt. P450 group of enzymes)
92
What effect does phenobarbital have on drug action? | Why?
It decreases duration of drug action | Because it is an inducer of drug-metabolizing enzymes
93
What effects does Cimetidine have?
Inhibition of P450 enzymes and decreasing hepatic blood flow
94
What are the effects of treatment with phenobarbital along with smoking?
Higher drug metabolism and LOWER blood levels of the drug
95
Which drugs slow the metabolism of older non-sedating antihistamines?
Ketoconazole Itraconazole Erythromycin GF juice
96
What effect does Ritonavir have? | What has this permitted?
Inhibits hepatic drug metabolism | Dose reductions of other HIV protease inhibitors
97
What is teratogenesis?
Induction of developmental defects in the somatic tissues of the fetus
98
How is teratogenesis studied?
By treating pregnant female of at least 2 species during early pregnancy (organogenesis) with drug and later examining neonates for abnormalities
99
What are the drugs known for teratogenesis?
``` Thalidomide Isoretinoin Valproic acid Ethanol Glucocorticoids Warfarin Lithium Androgens ```
100
What is mutagenesis?
Changes in the genetic material of animals of any age, induction of heritable abnormalities
101
What are the two ways to test for mutagenesis?
Ames test and dominant lethal test
102
Describe the Ames test | In vitro/in vivo?
Uses salmonella, which usually depends on certain nutrients to grow. Loss of this dependence= mutation In vitro
103
Describe the dominant lethal test | In vitro/in vivo?
Male mice are exposed to drug before mating, look for abnormalities in subsequent mating (loss of embryos, deformed fetuses)= mutation In vivo
104
What carcinogens have mutagenic effects?
Aflatoxin Cancer chemo drugs Others that bind to DNA
105
How is carcinogenesis tested for?
Ames test, there is a high correlation between mutagenesis and carcinogenesis.
106
What are some known carcinogens?
``` Coal tar Aflatoxin Dimethylnitrosamine Urethane Vinylchloride Polycyclic aromatic hydrocarbons in tobacco smoke (benzo (a) pyrene) ```
107
What is an example of a polycyclic aromatic hydrocarbon in tobacco smoke?
Benzo (a) pyrene
108
How many clinical trial phases must be completed to submit an NDA?
3
109
What are the spinal roots for parasympathetic preganglionic fibers?
CN nuclei 3, 7, 9, and 10 | and sacral segments (S2-S4)
110
What are the spinal roots for sympathetic preganglionic fibers?
T1-T12 | and L1-L5
111
Where are parasympathetic ganglia located?
In the organs innervated
112
Are the parasympathetic preganglionic long or short? | Postganglionic?
Long | Short
113
Where are the sympathetic ganglia located?
In 2 paravertebral chains that lie along the spinal column (a few in the anterior aspect of abdominal aorta)
114
Are the sympathetic preganglionic long or short? | Postganglionic?
Short | Long
115
What are some uninnervated receptors for autonomic drugs?
Muscarinic receptors on endothelium of blood vessels | Some presynaptic receptors
116
Where is acetylcholine a primary transmitter?
In all autonomic ganglia | At the parasympathetic postganglionic-neuron-effector cell synapses
117
What is Ach synthesized from? | By what enzyme?
Acetyl CoA and choline | By Choline acetyl transferase
118
What is the rate limiting step of Ach synthesis? | What is it inhibited by?
Transport of choline into nerve terminal | Hemicholinium
119
Acetylcholine is actively transported into vesicles for storage. What inhibits this step?
Versamicol
120
What does the release of Ach from vesicles require?
Entry of Calcium | Triggering of reaction between proteins on vesicles and proteins on the nerve ending membrane
121
What are the proteins on vesicles?
VAMPs (vesicle-associated membrane proteins) synaptobrevin synaptotagmin
122
What are the proteins on the nerve ending membrane?
SNAPs (synaptosome-associated proteins) SNAP25 syntaxin
123
What does the interaction between vesicle proteins and nerve ending membrane proteins cause?
Fusion of vesicles membranes and nerve ending membranes Opening of pore to EC Release of transmitter
124
What can inhibit release of Ach?
Botulinum toxin
125
Which protein can botulinum toxin enzymatically alter?
Synaptobrevin
126
How is Ach action terminated? | By what enzyme?
Metabolism of Ach into acetate and choline | Acetylcholinesterase
127
Where is NE a primary transmitter?
At the sympathetic postganglionic neurone-effector cell synapses in MOST tissues
128
What sympathetic postganglionic neuron effector cell synapses is NE NOT the primary transmitter of? What is the primary transmitter?
1.Sympathetic fibers to thermoregulatory (eccrine) sweat glands 2. Vasodilator sympathetic fibers in skeletal muscle They release Ach
129
What is the vasodilator of renal blood vessels?
Dopamine
130
What is the rate-limiting step of NE synthesis? By what enzyme? What is it inhibited by?
Tyrosine hydroxylation to DOPA By tyrosine hydroxylase Inhibited by Metyrosine
131
What is the second step of NE synthesis? Where is the product transported to? What inhibits this step?
DOPA decarboxylated to dopamine Brought into vesicles Inhibited by Reserpine
132
What is the last step of NE synthesis?
Dopamine hydroxylated to norepinephrine
133
Where are MAO's found? | What do they do?
On mitochondria in adrenergic nerve ending | Inactivate portion of dopamine and NE in cytoplasm
134
What effect do MAO inhibitors have?
They increase the stores of dopamine and NE | AKA increase stores of catecholamines
135
Outside of the cleft, what are NE and Dopamine (catecholamines) metabolized by?
MAO | COMT (catechol-o-methyltransferase)
136
What happens to the products of enzymatic reactions of NE and Dopamine (catecholamines)?
Excreted
137
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?
Metanephrine Normetanephrine VMA
138
What drug inhibits the release of catecholamines?
Guanethidine
139
Where are cotransmitters found and what is their function?
In vesicles | They modulate synaptic transmission
140
Examples of cotransmitters
``` ATP enkephalins Vasoactive Intestinal Peptide (VIP) neuropeptide Y Substance P Neurotensin Somatostatin ```
141
What are the two types of cholinoceptors? What transmitter do they respond to?
Muscarinic and Nicotinic | Ach and its analogs
142
What transmitters do muscarinic receptors respond to?
Muscarine and Ach
143
What do the effects of activating muscarinic receptors resemble?
Postganglionic parasympathetic nerve stimulation
144
Where are muscarinic receptors primarily located?
``` On autonomic effector cells: Heart Vascular endothelium Smooth muscle Presynaptic nerve terminals Exocrine glands ```
145
What transmitters do Nicotinic receptors respond to?
Nicotine and Ach
146
Where are nicotinic receptors located?
In ganglia and skeletal muscle end plates
147
What are the two types of adrenoceptors?
alpha and beta
148
What are the subtypes of alpha receptors? | Where are they found?
``` Alpha-1 and Alpha-2 Vascular endothelium Presynaptic nerve terminals Blood platelets Fat cells (lipocytes) Neurons in brain ```
149
What is the difference between alpha 1 and alpha 2 adrenoceptors?
They are different families and utilize different G proteins
150
What are the subtypes of beta receptors? | Where are they found?
``` Beta 1, 2, and 3 Most smooth muscle Cardiac muscle Some presynaptic nerve terminals Lipocytes Brain ```
151
What is the difference between Beta 1, 2, and 3 adrenoceptors?
Similar, use same G protein
152
Where are dopamine receptors found?
Usually in renal and splanchnic vessels | Brain
153
What is the most important peripheral effector-cell dopamine receptor?
D1
154
Where are D2 receptors found?
On presynaptic nerve terminals
155
What are the 3 types of NANC (Nonadrenergic, Noncholinergic) transmissions?
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
156
What is mydriasis? | What ANS branch controls it? At what receptor?
Dilation of pupils Sympathetic Alpha
157
What does sympathetic discharge do to renal vessels?
Causes constriction of renal resistance vessels so there is a fall in renal blood flow
158
What are muscarinic receptors blocked by? | Where?
Atropine At smooth muscle effector cells At postganglionic nerve terminals
159
What nerves innervate thermoregulatory (eccrine) sweat glands?
Sympathetic cholinergic nerves
160
Where are nicotinic cholinoceptors found?
Both types of ganglia Skeletal muscle neuromuscular junction Adrenal medulla
161
What facilitates the release of catecholamine transmitters from the sympathetic nerve endings?
Amphetamine
162
What is the prototype for the direct-acting cholinomimetic drug acting on both muscarinic and nicotinic receptors?
Ach
163
What is the prototype for indirect-acting cholinomimetic drug?
Neostigmine
164
How does a direct-acting cholinomimetic work?
Acts directly on Ach receptors
165
How does an indirect-acting cholinomimetic work?
It inhibits cholinesterase
166
What are the direct-acting cholinomimetic choline esters?
Ach Methacholine Carbachol Bethanechol
167
What are the direct-acting cholinomimetic alkaloids?
Muscarine Pilocarpine Nicotine Lobeline
168
How do choline esters differ from alkaloids?
1. Spectrum of action (amount of muscarinic vs nicotinic stimulation) 2. Pharmacokinetics
169
What are M1 and M3 receptors coupled to?
Gq protein
170
What is Gq protein coupled to?
Phospholipase C
171
What is the mechanism of M1 and M3 receptors?
Gq protein coupled to phospholipase C which leads to release of 2nd messengers DAG and IP3
172
What does DAG do?
Modulated action of protein kinase C (important enzyme in secretion)
173
What is protein kinase C important for?
Secretion
174
What does IP3 do?
Evokes release of Calcium from intracellular storage sites= contraction
175
What are M2 receptors coupled to?
Gi inhibitory protein and potassium channels in the heart
176
What are Gi proteins coupled to?
Adenylyl cyclase
177
What is the mechanism of M2 Gi linked protein receptors?
Decrease CAMP production
178
What is the mechanism of M2 potassium channel linked receptors?
Muscarinic agonists open these channels in the heart
179
Where are nicotinic receptors located?
On channel protein that is selective for Na+K+
180
What is the nicotinic mechanism?
When receptor on channel protein that is selective for Na+K+ is activated, the channel opens and depolarization of cell occurs= EPSP
181
Where are Ach nicotinic receptors located?
Both sympathetic and parasympathetic ganglion cells (Nn) | Neuromuscular end plate (Nm)
182
Is vasodilation a parasympathomimetic response?
No
183
What does vasodilation result from? | What is it mediated by?
EDRF (endothelium-derived relaxing factor) and NO in the vessels which is mediated by UNINNERVATED muscarinic receptors on endothelial cells
184
Why does injection of small to medium amounts of direct-acting muscarinic cholinomimetics cause TACHYCARDIA?
Baroreceptor reflex | The decrease in BP, stimulated sympathetic response
185
Cholinomimetics stimulate sweating which is usually a ______ effect
Sympathetic cholinergic effect
186
Blood vessels are dominated by _____ innervation, therefore nicotinic receptor activation results in _____
Sympathetic | Vasoconstriction mediated by sympathetic postganglionic nerve discharge
187
The gut is dominated by ______control, therefore nicotinic drugs ____ motility and secretion because of _____ postganglionic neuron discharge
Parasympathetic Increase Parasympathetic
188
What does nicotinic end plate activation by direct-acting drugs result in?
Fasciculations and spasm of muscles
189
What are the effects of muscarinic toxicity?
``` CNS stimulation Miosis Spasm of accommodation Bronchoconstriction Increased GI and genitourinary smooth muscle activity Increased secretory activity Vasodilation ```
190
What are the effects of nicotinic toxicity?
CNS stimulation followed by depression Ganglionic stimulation and block Neuromuscular end plate depolarization
191
What are the two major classes and 1 minor class of indirect-acting cholinergic agonists?
Carbamic Acid Esters Phosphoric Acid Ester Edrophonium
192
Example of Carbamic acid ester | Prototype
Carbamate | Neostigmine
193
Example of phosphoric acid ester | Prototype
Phosphates, organophosphates | Echothiopate
194
What is edrophonium?
``` The only member in its class of indirect-acting cholinomimetic. Alcohol with very short duration of action ```
195
Mechanism of carbamate and organophosphates
Bind to cholinesterase and undergo prompt hydrolysis
196
What happens to the alcohol portion of carbamate and organophosphate after hydrolysis? The acid portion?
``` Alcohol portion promptly released Acid portion (carbamate ion or phosphate ion) released much more slowly thus preventing the binding and hydrolysis of acetylcholine ```
197
Duration of carbamates
2-8 hours
198
Duration of organophosphates
Days to weeks
199
What are the effects of carbamates and organophosphates?
1. Inhibit cholinesterase 2. Amplify action of endogenous Ach by: Increasing [ ] Increasing half life Increasing actions of Ach in synapses
200
Examples of carbamates
Neostigmine Physostigmine Ambenonium Pyridostigmine
201
Which indirect-acting cholinomimetic is used more commonly in therapeutic? Especially in treatment of myasthenia
Carbamates
202
What are the three organophosphates used in medicine and for what conditions?
1. Echothiopate- Glaucoma 2. Malathion- Scabicide 3. Metrifonate- Helminths
203
What is the pneumonic for cholinomimetic toxicity?
``` DUMBBELSS Diarrhea Urination Miosis Bronchoconstriction Bradycardia Excitation of skeletal muscle and CNS followed by resp. and cardiac depression Lacrimation Salivation Sweating ```
204
Difference between physostigmine and bethanechol
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
205
How are -thion organophosphates activated?
By conversion to -oxon
206
-thion organophosphates are ____ stable than DDT and thus ___ persisten in the environment
Less and less
207
Parathion is ____ toxic than Malathion
More
208
How can Parathion toxicity be partly reversed?
Pralidoxine
209
What drug is used to distinguish between cholinergic crisis and myasthenia crisis? Why?
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
210
What is the most common cause of death in cholinesterase inhibitor toxicity?
Respiratory failure (from neuromuscular paralysis or CNS depression)
211
Cholinesterase inhibition is typically associated with _____ bowel activity
Increased
212
Long acting cholinesterase inhibitors (organophosphates) (Ex. Echothiophate) are associated with what condition when they are given the drugs for glaucoma?
Higher incidence of cataracts
213
What is cyclospasm? What causes it? What is the results?
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
214
- direct-acting cholinomimetic - lipid-soluble - frequently used for glaucoma
Pilocarpine
215
- indirect-acting cholinomimetic - charged substance with poor lipid solubility - duration: 2-4 hours
Neostigmine
216
- direct-acting cholinomimetic alkaloid - mood-elevating properties - insecticide
Nicotine
217
- indirect-acting cholinomimetic | - plant alkaloid, therefore lipid soluble, therefore enters CNS readily
Physostigmine
218
All the muscarinic antagonists in the US are nonselective/selective?
Nonselective
219
What are the primary target organs of muscarinic antagonists?
CNS Eye Bronchi GI or genitourinary system
220
What is the major determinant of lipid solubility in antimuscarinics?
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
221
What is the prototypical nonselective muscarinic blocker?
Atropine Tertiary amine Lipid soluble
222
What is the mechanism of action of antimuscarinic drugs? | What can they be overcome by?
Competitive antagonists | Overcome by higher [ ] of muscarinic agonists
223
What are the effects of muscarinic antagonists?
- Sedation - Decrease motion sickness - Decreases signs of parkinsonism - Decreases heart rate
224
What kind of drug is scopolamine? | What is it used for?
Antimuscarinic | Motion sickness
225
``` What kind of drugs are benztropine biperiden trihexyphenidyl ? What are they used for? ```
Antimuscarinic | Anti parkinsonism
226
What effect do antimuscarinincs have on the eye?
``` Dilate the pupil (mydriasis) Paralyze accommodation (cyclopegia) ```
227
What are the antimuscarinics that work on the eye?
``` CHAT Cyclopentate Homatropine Atropine Tropicamide ```
228
What is the antimuscarinic drug that works on bronchi? How is it administered? How does it work?
Ipratropium Inhalation Promotes bronchodilation in asthma and COPD
229
What are the antimuscarinic drugs that work on the gut? | How does it work?
``` MAP Methscopolamine Atropine Propantheline Decreases gastric acid secretion (not as effective as H2 blockers or proton pump inhibitors) ```
230
What are the antimuscarinic drugs that work on the bladder? | How do they work?
``` Glycopyrolate Oxybutynin Methscopolamine Tolterodine Reduces urgency in mild cystisis and reduces bladder spasms following urologic surgery. ```
231
"Dry as a bone, red as a beet, mad as a hatter" | Is the toxicity for what drugs?
Antimuscarinic drug toxicity
232
What is the most dangerous effect of antimuscarinic drugs?
Hyperthermia "Dry as a bone" Because of increased sweating, salivation, and lacrimation
233
What are the CNS effects of antimuscarinic toxicity?
Sedation, amnesia, delirium, and hallucinations | "Mad as a hatter"
234
What are the cardiac effects of antimuscarinic toxicity?
Dilation of cutaneous vessels of arms, head, neck, and trunk | "Red as a beet"
235
What are the two subtypes of nicotinic antagonists?
Ganglion-blocking and neuromuscular-blocking
236
What was the first successful drug developed for hypertension?
Ganglion-blocking nicotinic antagonist
237
Where do nicotine and mecamylamine (ganglion-blocking drugs) have receptors? What do they help with?
CNS | Nicotine addiction and Tourette's
238
What drugs interrupt sympathetic control of venous tone? What does this cause? What is the major manifestation of these drugs?
Ganglion-blocking antinicotinic drugs Marked venous pooling Postural hypotension
239
What drugs are important for complete skeletal relaxation during surgery?
Neuromuscular-blocking antinicotinic drugs
240
What are the two subgroups of neuromuscular-blocking antinicotinic drugs?
Nondepolarizing and depolarizing groups
241
What is the prototype for non-depolarizing neuromuscular-blocking antinicotinic drugs?
Tubocurarine
242
How do non-depolarizing neuromuscular antinicotinic drugs work? What do they result in?
``` By completely blocking at the end plate of nicotinic receptors Flaccid paralysis (30-60min) ```
243
What are some non-depolarizing neuromuscular-blocking antinicotinic drugs? (Other than the prototype Tubocurarine)
PAV Pancuronium Atracurium Vecuronium
244
How do the depolarizing neuromuscular-blocking antinicotinic drugs work?
They are actually nicotinic agonists but also cause flaccid paralysis
245
What is the name of a depolarizing neuromuscular-blocking antinicotinic drug? What effect does it have? What is it hydrolyzed by?
Succinylcholine Produces fasciculations during induction (patients may complain of pain after) Plasma cholinesterase
246
What kind of antagonists are cholinesterase inhibitors?
Chemical antagonists
247
How does the oxime group in cholinesterase regenerators work?
It has a higher affinity for phosphorus atom in organophosphate insecticides than cholinesterase does. So active enzyme is regenerated
248
What is an example of a cholinesterase regenerator? | What is it used for?
Pralidoxine | Used for exposure to insecticides (Parathion)
249
In young children, what is the most dangerous effect of Belladonna Alkaloids?
Belladonna Alkaloid= atropine Atropine= Prototypical nonselective muscarinic blocker Hyperthermia
250
Is atropine well absorbed?
Yes
251
Drug with long duration, especially as an anti motion sickness drug
Scopolamine
252
Drug with quaternary amino group (so permanently charged), poorly absorbed from airways
Ipatropium
253
Drug with tertiary amino group, lipid soluble, so penetrates CNS well
Benztropine
254
Drug that is well absorbed from conjuctival sac into the eyes
Cyclopentolate
255
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?
Antimuscarinics and antinicotinics | Antinicotinics (sympathetic blockade)
256
All _____ cause cyclopegia (paralysis of accommodation) | _______ have the opposite effect (cyclospasm)
Antimuscarinics | Cholinomimetics
257
Why can ordinary doses of atropine be hazardous in the elderly?
Because atropine can elevate IOP in patients with glaucoma
258
``` What are -motion sickness -parkinson's -post operative bladder spasm -wanting to produce mydriasis and cyclopegia therapeutic indications for use of? ```
Antimuscarinics
259
What is NOT responsive to antimuscarinics
Hypertension
260
What effect do muscarinic M1 and M3 receptors evoke? | Where?
Increase in IP3 and DAG in target tissues | Intestine and salivary glands
261
What effect do muscarinic M2 receptors evoke?
Decrease in cAMP and increase in K+ permeability
262
What drug causes vasodilation by activating muscarinic receptors on endothelium blood vessels? What blocks this?
Bethanechol | Atropine
263
What is a common source of antimuscarinic drug poisoning?
Jimson Weed (Datura stramonium)
264
What are the two ways that sympathomimetics work?
Directly activate adrenoreceptors or | indirectly by increasing [ ] of catecholamines in synapse
265
How do amphetamine derivatives and tyramine work? | What type of sympathomimicry is this?
Cause release of stored catecholamines | Indirect
266
How do cocaine and tricyclic antidepressants work?
They inhibit reuptake of catecholamines by nerve terminals
267
How do you block sympathomimetic metabolism?
By blocking MAO and COMT
268
What effect do MAO inhibitors have?
Increase stores of catecholamines thus may potentiate action of indirect sympathomimetics
269
What are the three endogenous adrenoreceptor agonists? | What type of drugs are they?
Epinephrine NE Dopamine Catecholamines
270
What are the endogenous adrenoreceptor catecholamines (Epinephrine, NE, and Dopamine) metabolized by? Are they active by the oral route?
Metabolized my COMT and MAO
271
What is the mechanism of alpha-1 agonists? | What kind of G protein are the receptors they coupled to?
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
What G protein are alpha-2 receptors coupled to? | What is the results of activation?
Gi protein | Results in inhibition of adenylyl cyclase= decrease in cAMP
273
What G protein are B-1, 2, and 3 receptors coupled to? | What is the result of activation?
Gs protein | Results in stimulation of adenylyl cyclase= increase cAMP
274
Where are dopamine receptors mostly? D1- D2-
D1- activate adenylyl cyclase in neurons and vascular smooth muscle D2- brain
275
How do smooth muscles of pupillary dilator respond to topical phenylephrine and alpha agonists?
Mydriasis (dilation)
276
How do alpha-1 and alpha-2 agonists differ in their mechanism of lower IOP?
alpha-1: facilitate outflow of aqueous humor | alpha-2: reduce synthesis of aqueous humor
277
How do smooth muscle of bronchi respond to B-2 agonists?
Relax
278
What are the most effective drugs for bronchospasm?
B-2 agonists
279
What effect does activation of either alpha or beta receptors have on Gi tract?
Relaxation of smooth muscle
280
What effect do alpha-2 agonists have on GI tract?
Decrease salt and water secretion into intestine
281
Where are the alpha receptors in the genitourinary tract? | What effect does their activation have?
In bladder trigone and sphincter area | Mediate contraction of sphincter (sympathomimetics increase sphincter tone)
282
Where are B-2 receptors found in the genitourinary tract? | What effect does their activation have?
Uterus | Uterine relaxation in pregnant women
283
What is an example of an alpha-1 agonist in the vascular system?
Phenylephrine
284
What effects does an alpha-1 agonist (such as phenylephrine) have on the vascular system?
Constricts skin and splanchnic blood vessels Increases peripheral vascular resistance Increases venous P
285
What kind of response do alpha-1 agonists evoke in the vascular system?
Compensatory bradycardia
286
What is an example of an alpha-2 agonist in the vascular system?
Clonidine
287
What effects does an alpha-2 agonist (such as Clonidine) have on the vascular system?
Vasoconstriction (IV or nasal) | When IV, accumulates in CNS and REDUCES sympathetic outflow and BP
288
What is an example of a B agonist in the vascular system?
Terbutaline
289
What kind of response does a B agonist (ex. Terbutaline) evoke in the vascular system?
Decrease in arteriolar tone in skeletal muscle vascular bed Decrease in peripheral vascular resistance Decrease in arterial BP
290
What effect does Dopamine have in the vascular system?
Vasodilation in splanchnic and renal vascular beds by activating D1 receptors
291
What receptors does the heart have a lot of?
B1 and B2
292
What is an example of a sympathomimetic with both alpha and beta effects?
NE
293
Why does NE cause an increase in vagal outflow?
Because it increases BP and evokes a baroreceptor reflex
294
What does a slow NE infusion result in ( cardio ) ?
Increased BP and bradycardia
295
If the baroreceptor reflex is blocked (by a ganglion blocker) what will happen with NE administration?
NE will cause a direct B1-mediated tachycardia
296
What is an example of a pure alpha agonist?
Phenylephrine
297
What cardiac effects does a pure alpha agonist have?
Slows heart rate via baroreceptor reflex
298
What is an example of a pure B agonist?
Isoproterenol
299
What cardiac effects does a pure B agonist have?
Increase in HR
300
What are the metabolic and hormonal effects of B1 agonists?
-Increased renin secretion - Increased insulin secretion - Increased glycogenolysis Resulting hyperglycemia countered by increased insulin levels
301
All of these drugs appear to stimulate lipolysis
B agonists
302
What is the number one drug used for anaphylaxis?
Epinephrine
303
What can epinephrine be supplemented with for anaphylactic shock?
Antihistamines and corticosteroids
304
Used for: Narcolepsy ADHD Weight reduction
Phenylisopropylamines such as amphetamines
305
What effects do alpha agonists have on the eye?
``` Produce mydriasis (dilating of the pupil) Reduce conjunctival itching and allergy Reduce aqueos humor (alpha 2 selectives) ```
306
What drugs treat acute bronchospasm?
B2 selectives
307
What are the short-acting drugs used for bronchospasm? | What kind of drugs are they?
Terbutaline Albuterol Metaproterol B2 selectives
308
What are the long-acting B agonists used for prophylaxis of bronchi?
Long-acting B agonists | Salmeterol
309
What drugs are used in chronic heart failure and shock? | Why?
B1 agonists | Because increase cardiac contractility
310
What drugs are used in spinal shock and orthostatis hypotension? Why?
Alpha-1 agonists | Vasoconstriction
311
What drugs are used to suppress premature labor? | What kind of drugs are they?
Ritodrine Terbutaline B2 selectives
312
Main manifestations of the following toxicities: Alpha 1 agonists B1 agonists B2 agonists
Hypertension Tachycardia and arrhythmia Skeletal muscle tremor
313
Which drug acts on all A1, A2, B1, and B2 receptors?
Epinephrine
314
Long-acting indirect sympathomimetic Oral route Urinary incontinence in children Also in herb Ma-huang and energy supplements
Ephedrine
315
What is the difference between antimuscarinic and alpha sympathomimetic effects on the eye?
Antimuscarinic: mydriatic (dilation of pupil) and cycloplegic (paralysis of accommodation) Alpha sympathomimetic: Only mydriatic
316
What kind of drug is Pilocarpine? | What effect does it have on the eye?
Indirect-acting cholinomimetic | Miosis (contriction of the pupil)
317
Relax uterine and bronchiolar smooth muscle
B2 agonists
318
What is a common side effect of B2 agonists?
Tremor
319
Blood vessels in the skin have almost exclusively ___ receptors
Alpha (vasoconstrictor)
320
Stimulation of renin is a ___ effect
B1
321
Increase in cAMP in heart muscle Increase in FFA in blood Increase of glc in blood Increase of lactate in blood
Epinephrine
322
What is the basis for the widespread use of alpha agonists (ex. phenylephrine) as topical decongestants?
Vasoconstriction in the nasal mucosa
323
What will cause reflex bradycardia in an intact heart but not in a heart transplant patient?
A pure alpha agonist | intact innervation vs not
324
What is an example of an irreversible, long lasting adrenoceptor blocker? What is the mechanism of action?
Phenoxybenzamine | Binds covalently to alpha receptor
325
What is an example of a reversible, short-acting, and non-selective adrenoceptor blocker? What is the moa?
Phentolamine | Competitive pharmacological antagonist (effects surmounted by more agonist)
326
``` What are Prazosin Doxazosin Trazosin Tamsulosin ? ```
Alpha 1 selective blockers
327
What are Yohimbine Rauwolscine ?
Alpha 2 selective blockers
328
What system do non-selective alpha blockers have the most important effects on? What are those effects? Do they cause a baroreceptor reflex?
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
What is epinephrine reversal?
The use of it with an alpha blocker changes its effect from pressor (alpha receptor) to depressor (B2 receptor)
330
Example of alpha1 selective blocker | What do selective alpha blockers cause much less of?
Prazosin | Tachycardia (when reducing bp)
331
What are the clinical uses of nonselective alpha blockers?
Presurgical management of pheochromocytoma | OD with amphetamine, cocaine, or phenylpropanolamine
332
What nonselective alpha blocker is used in the presurgical treatment of pheochromocytoma? Why?
Phenoxybenzamine | Patients have severe hypertension and low blood volume
333
OD with amphetamine, cocaine, or phenylpropanolamine may lead to what condition? What does this condition respond well to?
Hypertension | Alpha blockers
334
What selective alpha-1 blockers are used in hypertension?
Prazosin Doxazosin Terazosin
335
``` Prazosin Doxazosin Terazosin Tamsulosin Used in? ```
Urinary hesitancy and prevention of urinary retention in men with BPH
336
What kind of antagonists are beta blockers? | What is the prototype drug?
Competitive pharmacologic antagonists | Propanolol
337
``` What are Acebutolo Atenolo Esmolol Metoprolol ? ```
B-1 selective blockers
338
When are B1 selective blockers an advantage?
When treating asthma
339
Nadolol Propranolo Timolo
non selective B blockers
340
Labetaolol | Carvedilol
Both alpha and beta action
341
Which beta blockers are partial agonists? | Why could they be an advantage?
Pindolol Acebutolol When treating asthma because even at max dosage they cause some bronchodilation
342
Which beta blocker has local anaesthetic activity? | When is it a disadvantage?
Propanolol | When used topically in the eye because it lowers protective reflexes and increases risk of corneal ulceration
343
What is the longest-acting beta blocker?
Nadolol
344
What are the clinical uses for B blockers?
``` Hypertension Angina Arrhythmias CHF Pheochromocytoma and glaucoma ( uses both alpha and beta) ```
345
What are the manifestations of b blocker toxicity?
``` Bradycardia AV blockade HF asthma attacks Masking of premonitory hypoglycemic symptoms ```
346
``` What drugs block these: Cardiac stimulation Increase in cAMP in fat Relaxation of bronchial smooth muscle Relaxation of uterus ```
B blockers
347
Alpha blockers used in hypotension and reflex tachycardia
Phentolamine and phenoxybenzamine
348
What is the most important contraindication in the use of beta blockers?
AV block
349
What are the adverse effects of beta blockers?
Bronchoconstriction Impaired blood sugar responses Sleep disturbances Heart failure exacerbation
350
What is an adverse effect of alpha blockers in the eye?
Increased IOP
351
What is the only autonomic receptor blocker in clinical use that binds covalently with its receptor?
Phenoxybenzamine with is alpha receptor
352
Synthesized in the body from AA precursors | Eliminated by amine oxidation
Histamine and Serotonin
353
What receptors do ergo alkaloids interact with?
Serotonin receptors Dopamine receptors Alpha receptors
354
What is histamine formed from? Where is it stored? | What is it metabolized by?
Histidine, mast cells | MAO and DAO
355
What is histamine measured by in the urine?
Its major metabolite: imidazoleactic acid
356
What is histamine released from mast cells in response to?
IgE-mediated allergic reactions
357
``` What plays a pathophysiological role in Rhinitis (hay fever) Urticaria Angioneurotic edema (Also important as NT and in control of acid secretion in stomach) ```
Histamine
358
What kind of receptor is the H1 receptor? What are its second messengers? Where are they important?
Gq-coupled IP3 and DAG In smooth muscle (especially those caused by IgE-mediated effects)
359
What is the typical response to activation of the H1 receptor?
Bronchoconstriction | Vasodilation
360
What is the vasodilation as a result of activation of the H1 receptor caused by?
Release of NO from EDRF
361
On top of releasing EDRF, the capillaries do what in response to activation of H1 receptor?
Contract
362
What does contraction of capillary endothelial cells cause?
Opening gaps in permeation barrier= edema
363
What kind of receptor is the H2 receptor? What's its second messenger? What does it mediate?
Gs-couples to adenylyl cyclase cAMP Gastric acid secretion by parietal cells in the stomach
364
Which histamine receptor mediates: Gastric acid secretion by parietal cells in the stomach Cardiac stimulant effect Negative feedback on mast cells
H2
365
Where are H3 receptors found?
Mainly in presynapatic modulation of histaminergic neurotransmission in the CNS
366
What are diphenhydramine doxylamine ? What are their defining qualities?
Old 1st generation histamine-1 antagonists | highly sedating with autonomic receptor-blocking effects
367
What are chlorpheniramine cyclizine ? What are their defining qualities?
New 1st generation histamine-1 antagonists | Less sedating, less autonomic effects
368
``` What are fexofenadine loratadine cetirizine ? What are their defining qualities? ```
2nd generation histamine-1 anatagonists | Far less lipid soluble than 1st generation thus, non-sedating, no autonomic effects
369
What kind of antagonists are histamine -1 antagonists?
Competitive pharmacologic antagonists at the H1 receptor?
370
Why are 1st generation H1 antagonists potent antagonists at autonomic receptors?
Because their structure closely resembles muscarinic and alpha adrenoreceptor blockers
371
Most of these are sedating Some work for anti-motion sickness Many are potent local anaesthetics
H1 antagonists
372
What are the two clinical uses for H1 antagonists?
Immediate-type allergies and anti-motion sickness
373
What are immediate-type allergies caused by? | Examples?
Caused by antigens acting on IgE antibody-sensitized mast cells Hay fever and urticaria
374
``` What are these H1 antagonists used for? diphenhydramine dimenhydrinate cyclizine meclizine promethazine ? ```
Anti-motion sickness drugs
375
Drug used for chemotherapy-induced vomiting
Diphenhydramine
376
What is common with these H1 antagonist drugs? Diphenhydramine Doxylamine Promethazine
Sedation
377
What are the anti muscarinic effects H1 anagonists have?
Dry mouth | Blurred vision
378
What are the alpha-blocking effecs that H1 antagonists have?
Orthostatic hypotension
379
Excessively high concentrations of either anti-histamine will result in?
Lethal arrhythmias
380
``` What are these drugs? Cimetidine (prototype) Ranitidine Famotidine Nizatidine ```
H2 antagonists
381
What is the mechanism of H2 blockers? | What is their effect?
Surmountable blockade of H2 receptor | Decreases gastric acid secretion
382
What are the clinical uses of H2 antagonists? | What is more effective for these uses?
``` For acid-peptic ulcer (esp. duodenal) For gastric peptic ulcers Zollinger-Ellison syndrome GERD PPI ```
383
What is a potent inhibitor of hepatic drug-metabolizing enzymes? What happens with its toxicity?
Cimetidine May reduce hepatic blood flow Has antiandrogen effects
384
What is serotonin produced from? Where is it stored? What is it metabolized by? What is excess production (carcinoid) detected by in the urine?
Tryptophan Vesicles in the enterochromaffin cells of the gut and neurons of the CNS, and platelets MAO It's metabolite: 5HIAA
385
What is the only serotonin agonist?
5HT1D receptor
386
What are the serotonin antagonists?
5HT2 and 5HT3 receptors
387
Where is the 5HT1 receptor most important? What does it do there? What kind of receptor is it?
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
Where are 5HT2 receptors found? What do they mediate at each place? What symptoms do they mediate in a carcinoid tumor?
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
Where are 5HT3 receptors found? What receptors are they? What kind of drugs are they?
CNS, especially the chemoreceptive area and vomiting center. Also, peripheral sensory and enteric nerves 5HT gated ion channels Antiemetic drugs
390
What are examples of 5HT1D agonists? | What are they used for?
Sumatriptan (prototype) Naratriptan other "-triptans" Acute migraines and cluster headache attacks
391
What are SSRIs used as? | How do they work?
Antidepressants | Work by increasing activity at serotonergic synapses by inhibits reuptake carrier for 5HT
392
What are these drugs? Ketanserin Phenoxybenzamine Cyproheptadine
5HT2 blockers
393
``` What are these drugs? Ondansetron Granisetron Dolasetron Alosetron ```
5HT3 blockers
394
What are 5HT partial agonists?
Ergot alkaloids
395
What kind of antagonists are ketanserin and cyproheptadine?
Competitive pharmacologic 5HT2 antagonists
396
What kind of antagonist is phenoxybenzamine?
Irreversible blocker of 5HT2
397
What are the uses of ketanserin?
antihypertensive and carcinoid tumor
398
``` What are the uses of ketanserin cyproheptadine phenoxybenzamine ? What kind of drugs are these? ```
For symptoms of carcinoid tumour | 5HT2 blockers
399
What are the symptoms of a carcinoid tumor?
Diarrhea Bronchocontriction Flushing
400
What is Ondansetron used for? | What kind of drug is it?
Post chemo and post op vomiting | 5HT3 blocker
401
What is Alosetron used for? | What kind of drug is it?
Women with IBS | 5HT3 blocker
402
What are the adverse effects of ketanserin?
Those of alpha blockade and H1 blockade
403
What are the adverse effects of Ondansetron Granisetron Dolasetron ?
Diarrhea and headache
404
What are ergot alkaloids produced by? What were the symptoms called in the middle ages? How do they work?
Fungus found in wet or spoiled grain "St. Anthony's fire"- ergotism Partial agonists at alpha adrenoreceptors and 5HT receptors
405
What effects do ergot alkaloids have on vessels? What's the prototype for these effects? What happens with OD of this drug?
Prolonged alpha receptor-mediated vasoconstriction Ergotamine Ischemia and gangrene
406
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?
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
What effects do ergot alkaloids have on the brain? | What are some examples, and which receptors do they work on?
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
What is LSD?
A semisynthetic ergot derivative
409
What receptors do bromocriptine and pergolide work on? What are their effects?
Dopamine D2 receptors in the pituitary | Inhibit prolactin secretion
410
Which ergot alkaloids are used for migraines? What are their effects?
Ergotamine used for acute attacks | Methysergide and Ergonovine used prophylactically
411
Which ergot alkaloids are used for obstetric bleeding?
Ergonovine and Ergotamine
412
Which ergot alkaloids are used for hyperprolactinemia and parkinsonism?
Bromocriptine and Pergolide
413
Which ergot alkaloid is used for carcinoid tumor symptoms?
Methysergide
414
What systems do ergot alkaloid toxicity affect? What are the symptoms?
``` Vascular= severe prolonged vasoconstriction=gangrene and ischemia GI= nausea, vomiting, diarrhea Uterine= contractions CNS= hallucinations and psychosis ```
415
What is an effective antagonist of ergot alkaloid vascular toxicity?
Nitroprusside
416
What can long term use of methysergide lead to ?
Hyperplasia of connective tissue
417
What respiratory symptom does serotonin cause?
Bronchospasm
418
What kind of drug is Sumatripan?
5HT1D agonist
419
``` What drug has these effects? Antimuscarinic reduction in bladder tone Local anaesthetic where injected Anti motion sickness effect Sedation ```
H1 blockers
420
What happens if you block an H2 receptor? Why?
Decrease in cAMP because it is a Gs protein-coupled receptor
421
What is P450 inhibition a sign of toxicity of? | Example of a drug
H2 toxicity | Cimetidine (potent CYP3A4 inhibitor)
422
What kind of drug is Ondansetron?
Antiemetic
423
What is an antiandrogenic and a CYP3A4 inhibitor? (P450 enzymes)
Cimetidine (H2 blocker)
424
Which antihistamine is used for hay fever?
Cetirizine (2nd gen. H1 blocker)
425
Which ergot alkaloid dopamine agonist is used for hyperprolactinemia?
Bromocriptine
426
What kind of blocker is Cimetidine?
H2
427
What kind of agonist is Sumatriptan? What is it used to treat?
``` 5HT1D agonist (serotonin) Acute migraines ```
428
What is an irreversible antagonist for treatment of carcinoid tumors? What kind of blocker is it?
Phenoxybenzamine (5HT2)
429
What is Angiotensin 1 produced from? By what enzyme? Where is this enzyme released from?
Angiotensinogen Renin From juxtaglomerular apparatus in kidney
430
What is the inactive decapeptide vasoactive peptide?
Angiotensin 1
431
What is the active octapeptide vasoactive peptide?
Angtiotensin 2
432
What converts Angiotensin 1 to Angiotensin 2?
ACE
433
What is Angiotenin 2 rapidly degraded by?
Peptidases
434
What are the effects of AT2?
Potent vasoconstrictor and stimulant of aldosterone release | Also facilitates release of NE
435
Direct effects of AT2
Increase peripheral resistance
436
Indirect (through aldosterone) effects of AT2
Causes renal Na retention
437
What is AT2 clinically used for?
Hypertension and HF
438
What are captopril enalapril What are they used for?
ACE inhibitors | Hypertension and HF
439
What are losartan valsartan
AT2 receptor blockers
440
What kind of AT2 antagonists are there? | What is their action accompanied by?
ACE inhibitors A2 receptors blockers Accompanied by compensatory increase in renin and AT1
441
What is bradykinin (all kinins) produced from? By what enzyme?
From kininogen | By kallikreins
442
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)
Bradykinin
443
Where are natriuretic peptides synthesized and stored? What is the stimulus that causes their release?
Cardiac atria of mammals | Released from atria in response to distention of chambers
444
What are the effects of natriuretic peptides?
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
What is nesiritide?
BNP for HF
446
What are peptide vasoconstrictors?
Endothelins
447
Where are endothelins formed in and released by?
Endothelial cells in blood vessels
448
What receptors are responsible for vasoconstriction by endothelins ?
ET-A receptor
449
How are endothelins compared to NE as vasoconstrictors?
Much more potent and long-lasting
450
What is Bosentan? What is it used for?
Endothelin antagonist. Pulmonary hypertension
451
VIP is an extremely potent _____ and neutrotransmitter
Vasodilator
452
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
Substance P
453
What is Capsaicin? What does it release? What is its clinical use?
"hot" component of chilli peppers releases substance P in nerve endings Topical use on arthritic joints and post herpitic neuralgia
454
What are neurokinins A and B used for? | Example?
Depression, nausea, and vomiting | Aprepitant
455
Where is CGRP found in high concentrations? | Where in less?
Thyroid | Smooth muscle tissues
456
What is the most potent hypotensive (vasodilator) agent discovered? What does it cause?
CGRP | Reflex tachycardia
457
What is NPY? What does it stimulate?
Potent vasoconstrictor | Stimulates heart
458
Potent vasodilator with pain and edema-inducing effects and inactivated by ACE
Bradykinin
459
Arterial vasodilator Constrictor of veins and airway smooth muscle Found in afferent pain fibers
Substance P
460
Inhibited by Captopril Also degrades kinins As well as AT1--->AT2
ACE
461
Endothelin antagonist used for pulmonary hypertension
Bosentan
462
Antagonist of peptide (neurokinin) | Decreases nausea and vomiting (chemo)
Aprepitant
463
Peptide cotransmitter found in autonomic nerve endings | Vasoconstrictor
NPY
464
Potent vasoconstricor peptide synthesized in endothelium of blood vessels
Endothelin
465
Which are the cyclized arachidonic acid derivatives?
Prostacyclin Prostaglandins Thromboxane
466
Which are the straight-chain arachidonic acid derivatives?
Leukotrienes
467
What does an injury or immune reaction stimulus activate? What does it then release?
Activates phospholipases in cell membrane or cytoplasm | Membrane phospholipids then release arachidonic acid
468
What can arachidonic acid be metabolized by? What are the products?
Lipoxygenase= straight chain leukotrienes | COX- cyclized prostacyclin, prostaglandins, and thromboxane
469
Where is COX2 primarily found?
Inflammatory cells
470
Where is thromboxane preferentially synthesized?
Platelets
471
Where is prostacyclin preferentially synthesized?
Endothelial cells of vessels
472
What comprise the important mediator of bronchoconstriction ( slow-reacting substance of anaphylaxis- SRS-A)?
LTC4 and LTD4
473
Which eicosanoid is a chemotactic factor important in inflammation?
LTB4
474
Which eicosanoids are endogenous vasodilators?
PGE2 and prostacyclin
475
What effect does PGE1 have on gastric mucosa? What is the mechanism?
Protective effect | By increasing secretion of bicarb and mucus and decreasing acid secretion
476
Which eicosanoids relax vascular and other smooth muscles?
PGE1 and PGE2
477
Which eicosanoid is a natural vasodilator that maintains the patency of ductus arterioles during fetal development?
PGE2
478
Which eicosanoids are released from endometrium during menstruation?
PGE2 and PGF2-alpha
479
Which eicosanoid is involved in physical ripening of cervix at term?
PGE2
480
What is associated with uterine contractions induced by prostaglandins?
Dysmenorrhea
481
Which eicosanoid is platelet aggregation strongly activated by?
Thromboxane
482
Which eicosanoid reduced IOP?
PGF2-alpha
483
What are the effects of PGE2 and PGF2-alpha in obstetrics? | What is dinoprostone? What does it do?
Contraction of uterus PGE2 Ripens cervix at term (before induction of labor with oxytocin)
484
Which eicosanoids have been used as abortifacients in 2nd trimester of pregnancy?
PGE2 and PGF2-alpha
485
What is misoprostol? What is it used for?
PGE1 analog | Abortifacient and against peptic ulcer associated with NSAID use
486
What is PGE1 used for in Pediatrics?
As infusion- maintains patency of ductus arteriosus in infants with transposition of the great vessels (until surgery)
487
What is prostacyclin (PGI2) used for in pulmonary hypertension and dialysis? As what drug?
As hypotensive agent in pulmonary hypertension and prevents platelet aggregation in dialysis machine As epoprostenol
488
What is PGE1 used for in urology? As what drug?
To treat impotence | As alprostadil
489
What are PGF2-alphas used for in opthalmology? What are the drugs? How do they work?
``` Glaucoma Latanoprost Bimatoprost Travoprost Noprostone Increase outflow of aqueous humour, thus decrease IOP ```
490
What does Zileuton inhibits?
Lipoxygenase
491
What do Zafirlukast and Montelukast inhibit? What are they used for?
LTD4 receptor, used for treatment of asthma
492
What two processes do corticosteroids inhibit?
Production of arachidonic acid by phospholipases in the membrane and synthesis of COX-2
493
What do NSAIDs inhibit? | What are the COX2 selective NSAIDs
COX | Rofecoxib and Celecoxib and Valdecoxib
494
What makes aspirin unique as an NSAID?
It binds COX irreversibly
495
What is the mechanism of aspirin allergy?
Results from diversion of arachidonic acid to the leukotriene pathway when COX prostaglandin pathway is blocked The increase in leukotrienes results in bronchoconstriction
496
What does the increase in leukotrienes in aspirin allergy manifest as?
Bronchocontriction
497
What action of aspirin results from the inhibition of thromboxane?
Antiplatelet action
498
Which eicosanoid is a potent vasodilator?
Prostacyclin (PGI2)
499
``` What do all of these have in common? AT2 Methysergide PGF2-alpha Thromboxane ```
Vasoconstrictors
500
What is a uterine stimulant derived from membrane lipid in endometrium?
PGE2
501
Why aren't eicosanoids used in hypertension?
They don't have a long enough duration of action
502
Which eicosanoids are used in glaucoma?
PGF2-alpha and analogs
503
What are the nonselective NSAIDs with moderate effectiveness?
Ibuprofen and Naproxen
504
What are the nonselective NSAIDs with greater anti-inflammatory effectiveness?
Indomethacin
505
What are the nonselective NSAIDS with greater analgesic effectiveness?
Ketorolac
506
What is the mechanism of action of aspirin and older non-selective NSAIDs?
Inhibit both isoforms of cox non-selectively , thus decrease prostaglandin and thromboxane synthesis
507
What are these the effects of? Decreased inflammation Decreased PG-mediated cytoprotection in the GI tract and autoregulation of renal transcription
COX inhibitors
508
What are these the effects of? | Decreased prostaglandin synthesis stimulated by pyrogens
NSAIDS
509
What does low dose aspirin do?
Reduces platelet aggregation
510
What does intermediate dose aspirin do?
Antipyretic and analgesic effects
511
What does high dose aspirin do?
Anti inflammatory effects
512
What are the benefits of Naproxen and Piroxicam as NSAIDs?
Have long half lives, less frequent dosing
513
What are COX2 inhibitors used for?
Inflammatory diseases
514
What is used to treat Dysmenorrhea Headache Patent ductus arteriosus in premies ?
NSAIDs
515
What is the only NSAID available parenterally and used mainly as a systemic analgesic?
Ketorolac
516
Which drug reduces polyp formation in FAP?
Ketorolac
517
Which drug's chronic use toxicity includes Gastric upset Upper GI bleeding Gastric ulcerations Renal effects (acute failure and nephritis) Increased bleeding time ?
Aspirin
518
``` Which drug's high dose toxicity includes: Tinnitus Vertigo Hyperventilation Respiratory alkalosis ```
Aspirin
519
``` Which drug's very high dose toxicity includes: Metabolic acidosis Dehydration Hyperthermia Collapse, coma, death ```
Aspirin
520
What are the toxic effects of non selective NSAIDs?
Gi and renal damage
521
Which drugs don't have as profound GI effects as other NSAIDs, aren't cardioprotective, and shouldn't be used during renal dysfunction?
COX2 inhibitors
522
What are anti inflammatories that show evidence of slowing or reversal of joint damage called? How long does it take for them to work?
Disease-modifying, Slow-acting Antirheumatic Drugs (DMARDs, SAARDs) 6 weeks to 6 months
523
What kind of drug is methotrexate? How does it work?
Cytotoxic | Decreases the number of immune cells
524
``` 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? ```
Hydroxychloroquine | Penicillin
525
What is a prodrug that is rapidly metabolized to a compound that inhibits dihydroorotate dehydrogenase? Why is this enzyme important?
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
What happens when you inhibit dihydroorate dehydrogenase?
Cell cycle arrest, no synthesis of pyrimidines needed for RNA synthesis
527
What are monoclonal antibodies that bind to and prevent action of TNF-alpha
Inflixamib and adalimumab
528
When are DMARDs used?
In RA patients that aren't responding to other agents. Also in SLE and other immunologic disorders
529
Which DMARDs are taken orally?
``` Sulfalazine Hydroxychloroquine Methotrexate Cyclosporine Penicillamine Leftunomide ```
530
How are anti TNF-alphas administered?
Injection
531
What is the only OTC non-antiinflammatory analgesic?
Acetaminophen
532
What effects do acetaminophens have? Which ones don't they have?
Analgesis and Antipyretic | Lack anti inflammatory and antiplatelet effects
533
What kind of people are acetaminophens good for?
People with aspirin intolerance (same as intermediate dose aspirin effects)
534
What does acetaminophen toxicity require? When does this happen? What drug can be lifesaving in acetaminophen OD?
Oxidation to cytotoxic intermediates by phase I cyt. P450 enzymes When substrates for phase II reactions are lacking Acetylcysteine (sulfhydryl donor)
535
What are the phase II reaction substrates?
Acetate and glucoronide
536
What is the increase in serum uric acid?
Gout
537
What is joint inflammation initiated by precipitation of uric acid crystals?
Acute gout attack
538
What are the three ways to treat gout?
1. Decrease inflammation during acute attack 2. Accelerate renal excretion 3. Decrease conversion of purines to uric acid via xanthine oxidase
539
What is used to decrease inflammation during an acute attack of gout?
Colchicine NSAIDs Glucocorticoids
540
What is used to accelerate renal excretion of uric acid in gout?
Probenecid | Sulfinpyrazone
541
What is used to decrease the conversion of purines to uric acid via xanthine oxidase?
Allopurinol
542
What is an example of a potent NSAID used in the treatment of gout?
Indomethacin
543
What is the mechanism of potent NSAIDs in the treatment of gout?
Inhibit inflammation of acute gouty arthritis by decreasing PG formation and inhibiting crystal phagocytosis by macrophages
544
What is the mechanism of Colchicine in treatment of gout?
Selective inhibitor of microtubule assembly, it decreases leukocyte migration and phagocytosis
545
What are the effects of NSAIDs and glucocorticoids in gout?
Decrease synthesis of mediators of inflammation by inflammatory cells in the gouty joint
546
What are the effects of Colchicine in gout?
It is a general mitotic poison since tubulin is necessary for normal cell division, motility, and other processes and Cochicine inhibits microtubule assembly
547
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?
Indomethacin and glucocorticoids Colchicine Because of GI problems
548
Example of uricosuric drugs
Probenecid | Sulfinpyrazone
549
What is the mechanism of uricosuric drugs?
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
What are the effects of uricosuric drugs?
Inhibits secretion of a large number of other weak acids (penicillin and methotrexate) Inhibits reabsorption of uric acid
551
What are the preferred drugs for treatment of chronic gout?
Uricosuric drugs or allopurinol
552
What does Xanthine Oxidase do?
Converts allopurinol to oxypurinol And hypoxanthine to xanthine and xanthine to uric acid
553
What are irreversible suicide inhibitors of xanthine oxidase?
Allopurinol and oxypurinol
554
What are the effects of allopurinol?
Inhibits XO which Increases concentration of hypoxanthine and xanthine and Decreases concentration of uric acid
555
What are some other effects of allopurinol (toxicities) ?
Inhibits metabolism of mercaptopurine and azathiopine (which depend on XO) for elimination
556
Indomethacin is used in the closure of patent ductus arteriosus , how does it do this?
By blocking PGE production in the ductus arteriosus of the newborn- by inhibiting COX
557
What is primary dysmenorrhea caused by? What should it be treated with?
Production of PGs including PGF2-alpha | NSAIDs that block COX
558
What is the advantage of using Ketorolac over aspirin?
It is a parenteral agent (IM or IV)
559
Why is it better to indomethacin than cochicine to treat acute gout?
Because at the doses of colchicine needed to treat acute gout it causes GI upset
560
Why use a selective COX2 inhibitor in RA?
To avoid GI toxicity
561
Recombinant protein that binds TNF | Prevents inflammatory effects
Etanercept

Pharmacology (2 decks)

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