KAPLAN Flashcards
1
Q
What processes do pharmacokinetics concern?
A
Absorption
Storage/distribution
Metabolism
Excretion
2
Q
What processes do pharmacodynamics concern?
A
Dynamics/mechanisms of action of drugs
Side effects of drugs
3
Q
What do pharmacokinetics describe?
A
What body does to drug
4
Q
What do pharmacodynamics describe?
A
What drug does to body
5
Q
What factors does drug permeation depend on?
A
Solubility
Concentration gradient
Surface area and vascularity
6
Q
Where are drugs more rapidly absorbed? Stomach or large intestine? Why?
A
Small intestine based on larger surface area and microvilli
7
Q
How are drugs more rapidly absorbed? IM or subQ? (Muscles vs. Fat) Why?
A
IM because muscles are a more vascular tissue
8
Q
What are common weak acid drugs?
A
Aspirin
Penicillins
Cephalosporins
Loop and thiazide diuretics
9
Q
What are common weak base drugs?
A
Morphine
Local aenesthetics
Amphetamines
PCP
10
Q
If you want to get rid of a weak base, put it in____
A
Acid
11
Q
If you want to get rid of a weak acid, put it in____
A
Base
12
Q
If you want to absorbs a drug, put it in ____
A
“like”
13
Q
If you want to absorb a weak acid put it in ____
A
Acid
14
Q
If you want to absorb a weak base, put it in ____
A
Base
15
Q
What is stomach pH?
A
1-2
16
Q
What is small intestine pH?
A
6
17
Q
What is blood pH?
A
7.4
18
Q
What is urine pH?
A
5.8
19
Q
How is lactulose useful in hepatic encephalopathy?
A
Gut bacteria convert it to lactic acid which acidifies fecal masses and traps NH3 in the form of NH4+. Decreases levels of circulating NH3, NH4+ clears.
20
Q
Gut bacteria convert this drug to lactic acid which acidifies fecal masses and traps NH3 in the form of NH4+. Decreases levels of circulating NH3, NH4+ clears.
A
Lactulose
21
Q
What forms of drug are filtered?
A
Free
Unbound
Both ionized and nonionized
22
Q
Which form of a drug undergoes active secretion and active or passive reabsorption?
A
Nonionized
23
Q
Acidification of urine—>Increases ionization of___—->Increases _____
A
Weak bases
Renal elimination
24
Q
Alkalinization of urine—>Increases ionization of___—->Increases _____
A
Weak acids
Renal elimination
25
What do you use to acidify urine?
NH4Cl
Vitamin C
Cranberry juice
26
```
What do you use
NH4Cl
Vitamin C
Cranberry juice
for?
```
Acidification of urine
27
What do you use to alkalinize urine?
NaHCO3
| Acetazolamide (historically)
28
What do you use
NaHCO3
Acetazolamide (historically)
for?
Alkalinization of urine
29
The glomerulus is a good size filter, but a poor ___ filter
charge
30
Any system that uses a carrier can be ______
Saturated
31
What is
Tubular secretion of penicillins and diuretics in proximal tubule
an example of?
Active transport
32
IV administration does not involve _______
Absorption
| There is no loss of drug
33
What is bioavailability through IV?
100%
34
What is the fastest route of absorption?
Inhalation
35
How do you know if administration is extravascular?
It gets absorbed
36
What two drugs are examples of oral administration first-pass effect?
Lidocaine
| Nitroglycerin
37
How is Lidocaine administered to avoid first-pass effect? Nitroglycerin?
IV
| Sublingual
38
Competition between drugs for plasma protein-binding sites may increase the _____, possibly enhancing the effects of the _____
Free fraction
| Drug displaced
39
What two drugs are involved in the development of kernictus in neonates? What is the MOA?
Sulfonamides and Bilirubin
Both bind to albumin, when add sulfonamides they displace the bilirubin and increase bilirubin [ ] = kernictus = brain dysfunction
40
Warfarin is usually ____% protein-bound
| What do warfarin and sulphonamides compete for? What are the effects of this competition
98%
Albumin
Sulfonamides displace the warfarin and thus increase warfarin [ ] in the blood= warfarin toxicity= bleeding and bruising
41
What is the better barrier, placenta or brain?
Brain
42
What does the placental barrier let through?
Most small molecular weight drugs
43
What does the BBB let through?
Only lipid soluble drugs or those of very low molecular weight
44
If the drug can cross the BB, it easily crosses the ____
Placenta
45
What factors make a drug safer in pregnancy?
Water-soluble
Large
Protein-bound
46
What happens when thyroid meds cross the placental barrier?
Cretinism
47
What are the manifestations of cretinism?
Decrease in size
Limbs
Retardation
48
What are the effects of anticonvulsants when cross the placental barrier?
Examples:
Teratogenicity
Phenytoin
Carbamazepine
Valproic acid
49
Volume of Distribution equation
```
Vd= Dose/C0
Co= plasma concentration at time zero
```
50
Vd is low when a high percentage of a drug is _____
Bound to plasma proteins
51
VD is high when a high percentage of a drug is _____
Sequestered in tissues
52
If most of the drug is in plasma, Vd is ____
Low
53
If most of drug is outside of plasma, Vd is ____
High
54
Why is thiopental's (IV anaesthetic) half life 9 hours when it reaches the brain in less than a minute?
Redistribution: Drug goes into the brain quickly, leaves quickly, gets redistributed into the fat where sequestered for a long time (does not have an effect during this time)
55
What are the phase I reactions of biotransformation?
Oxidation
Reduction
Hydrolysis
56
Where are CytP450 enzymes located?
| What do they have an absolute requirement for?
SER
| Oxygen and NADPH
57
Substrate example of 1A2
Theophylline
| Acetaminophen
58
Theophylline
| Acetaminophen
Substrate example of 1A2
59
Inducers of 1A2
```
Aromatic hydrocarbons (smoke) (benzopyrenes)
Cruciferous vegetables
```
60
```
Aromatic hydrocarbons (smoke) (benzopyrenes)
Cruciferous vegetables
```
Inducers of 1A2
61
Inhibitors of 1A2
Quinolones
| Macrolides
62
Quinolones
| Macrolides
Inhibitors of 1A2
63
2C9 substrate examples
Phenytoin
| Warfarin
64
Phenytoin
| Warfarin
2C9 substrate examples
65
Inducers of 2C9
General Inducers
66
What are the general inducers?
Anticonvulsants: barbiturates (phenobarbital), phenytoin, carbamazepine
Antibiotics (rifampin)
Chronic alcohol
Glucocorticoids
67
Anticonvulsants: barbiturates (phenobarbital), phenytoin, carbamazepine
Antibiotics (rifampin)
Chronic alcohol
Glucocorticoids
General Inducers
68
2D6 substrate examples
Many CV and CNS drugs
69
Many CV and CNS drugs
2D6 substrate examples
70
Inhibitors of 2D6
Haloperidol
| Quinidine
71
3A4 substrate examples
60% of drugs
72
Inducers of 3A4
General Inducers
73
General inducers induce:
2C9 and 3A4
74
Inhibitors of 3A4
General Inhibitors + GF juice
75
What are general inhibitors?
Antiulcer medications (cimetidine, omeprazole)
Antibiotics (chloramphenicol, macrolides (erythromycin), ritonavir (protease inhibitors in HIV), ketoconazole (antifungal),
Acute alcohol
76
What compounds are metabolized by hydrolysis?
What kind of genetics polymorphism exists with this kind of metabolism?
What does this result in?
Esterases and Amidases
Pseudocholinesterase
Increased [ ] of succinylcholine which is a sk. m. relaxant (that is metabolized by pseudocholinesterase)
77
What do MAOs metabolize?
```
Endogenous amine neurotransmitters (dopamine, serotonin, and NE)
Exogenous compounds (Tyramine)
```
78
Where is tyramine found?
Found in beer, red wine, cheese, and fish
79
What are the types of conjugation in phase II metabolism?
Glucoronidation
Acetylation
Glutathione conjugation
80
What are morphine and chloramphenicol metabolized by?
Phase II Glucoronidation
81
What is chloramphenicol toxicity a result of?
The inability of a neonate to effectively metabolize the drug because neonate has low levels of glucoronyl transferase so can't metabolize effectively
82
What diseases are as a result of a deficiency in glucoronyl transferase?
Gilbert and Crigler-Najjar syndrome
83
What is drug-induced SLE caused by?
By slow acetylators in the use of hydralazine, pracainamide, and isoniazid
84
Caused by slow acetylators in the use of hydralazine, pracainamide, and isoniazid
Drug-induced SLE
85
What's the commonality and the difference between drug-induced and non-drug induced SLE?
Commonality: butterfly malar rash
Difference: non induced has +ANA and antihistones
86
What is acetaminophen hepatotoxicity associated with?
Depletion of GSH in the liver
87
A constant amount of drug is eliminated per unit time
Zero-order elimination
88
Rate of elimination is independent of plasma concentration
Zero-order elimination
89
No fixed half-life
Zero-order elimination
90
Drugs with zero-order elimination
Phenytoin
Ethanol
Aspirin
91
A constrant fraction of the drug is eliminated per unit time
First-order elimination
92
Half life is constant
First-order elimination
93
Rate of elimination is directly proportional to plasma level- the higher the amount, the more rapid the elimination
First-order elimination
94
What is zero-order elimination due to?
Saturation of elimination mechanisms
95
Rate of elimination equation
= GFR + active secretion - reabsorption
96
CL=GFR when?
There is no reabsorption or secretion and no plasma protein binding
97
CL=
free fraction x GFR
98
If CL< GFR then
drug is reabsorbed
99
if CL> GFR then
drug is actively secreted
100
Maintenance dose equation
C (steady state) x CL x tau / f
101
The time to reach steady state is dependent ONLY on
Elimination half life
102
```
How many half lives does it take to get to
50% steady state
90% steady state
95% steady state
100% steady state
```
1 half life
3.3 half lives
4-5 half lives
>7 half lives
103
CLINICAL steady state is accepted to be reached at how many half lives?
4-5 half lives
104
Loading dose equation
= Vd x plasma conc. / f
105
Half life equation
= .7 x Vd/CL
106
Infusion rate equation
= CL x Conc. (steady state)
107
What does a partial agonist act as in the presence of an agonist?
Antagonist
108
What is an example of a partial agonist that acts as an antagonist in the presence of epinephrine?
Pindolol (B blocker)
109
Causes a parallel shift to the right in the D-R curve
Can be reversed by increasing the dose of the agonist
Appears to decrease the potency of the agonist
Competitive antagonist
110
Cause a nonparallel shift to the right
Can be only partially reversed by increasing the dose of the agonist
Appear to decrease the efficacy of the agonist
Noncompetitive antagonist
111
Examples of noncompetitive antagonists
```
Phenoxylbenzamine (alpha blocker)
Digoxin (blocks Na K ATPase)
Allopurinol- XO
PPIs- proton pump
Aspirin- COX
```
112
```
Phenoxylbenzamine (alpha blocker)
Digoxin (blocks Na K ATPase)
Allopurinol- XO
PPIs- proton pump
Aspirin- COX
```
Examples of noncompetitive antagonists
113
Drugs with low therapeutic index (dangerous)
Theophylline
Digoxin
Warfarin
Lithium
114
Theophylline
Digoxin
Warfarin
Lithium
Drugs with low therapeutic index (dangerous)
115
Therapeutic index equation
| What does it mean
TI= Therapeutic Dose 50/ Effective Dose 50
| x how many recommended doses you can take before toxicity
116
Examples of intracellular receptors
Glucocorticoids
Thyroid hormones
Gonadal steroids
Vitamin D
117
Glucocorticoids
Thyroid hormones
Gonadal steroids
Vitamin D
Examples of intracellular receptors
118
Examples of membrane receptors directly coupled to ion channels
Nicotinic receptor for ACh coupled to Na+K+ ion channel
| GABA receptor in the CNS coupled to a chloride channel
119
```
Receptors for:
Catecholamines (Beta)
Dopamine (D1)
Glucagon
Histamine (H2)
Prostacyclin
Some serotonin subtypes
```
Gs protein drugs
120
Gs protein drugs
```
Receptors for:
Catecholamines (Beta)
Dopamine (D1)
Glucagon
Histamine (H2)
Prostacyclin
Some serotonin subtypes
```
121
Adrenoreceptors (alpha-2)
ACh (M2)
Dopamine (D2)
Opioid and serotonin subtypes
Gi protein drugs
122
Gi protein drugs
Adrenoreceptors (alpha-2)
ACh (M2)
Dopamine (D2)
Opioid and serotonin subtypes
123
Ach (M1 and M3)
NE (alpha 1)
Angiotensin II
Serotonin subtypes
Gq protein drugs
124
Gq protein drugs
Ach (M1 and M3)
NE (alpha 1)
Angiotensin II
Serotonin subtypes
125
M1 M3 A-1 receptor mechanism
Gq activation of phospholipase C
126
M2 A-2 D2 receptor mechanism
Gi inhibition of adenylyl cyclase
127
B-1 B-2 D1
Gs activation of adenylyl cyclase
128
Which ANS receptors use Gq activation of phospholipase C
M1 M3 A-1 receptor mechanism
129
Which ANS receptors use Gi inhibition of adenylyl cyclase
M2 A-2 D2 receptor mechanism
130
Which ANS receptors Gs activation of adenylyl cyclase
B-1 B-2 D1
131
Mechanism of vasodilators
Increase the synthesis of NO by endothelial cells. NO activates guanylyl cyclase thus increasing cGMP in smooth muscle. cGMP facilitates dephospho rylation of myosin light chains, preventing their interaction with actin and thus causing vasodilation.
132
How does cGMP cause vasodilation?
facilitates dephospho rylation of myosin light chains, preventing their interaction with actin and thus causing vasodilation.
133
facilitates dephospho rylation of myosin light chains, preventing their interaction with actin and thus causing vasodilation.
cGMP
134
Drugs activating NO
Nitrates (Nitroglycerin)
| M receptor agonists (Bethanechol)
135
Nitrates (Nitroglycerin)
| M receptor agonists (Bethanechol)
Drugs activating NO
136
Endogenous compounds activating NO
Bradykinin and histamine
137
Bradykinin and histamine
Endogenous compounds activating NO
138
If see increase in secretions =
Muscarinic agonist
139
If see drying out of secretions (dry mouth, no sweating) =
Muscarinic blocker
140
Hormone which can work on both innervated and non innervated tissues
Epinephrine
141
B2 receptors are generally not innervated so what hormone will work on them and which one will never work on them?
Epinephrine and NE (or other NTs)
142
Neurotransmitter at both nicotinic and muscarinic receptors in tissues that are innervated
All direct transmission from CNS (preganglionic and motor) uses this NT
ACh
143
ACh
Neurotransmitter at both nicotinic and muscarinic receptors in tissues that are innervated
All direct transmission from CNS (preganglionic and motor) uses this NT
144
NT at most adrenoceptors in organs, as well as in cardiac and smooth muscle
NE
145
NE
NT at most adrenoceptors in organs, as well as in cardiac and smooth muscle
146
Activates receptors causing vasodilation in renal and mesenteric vascular beds
Dopamine
147
Dopamine
Activates D-1 receptors causing vasodilation in renal and mesenteric vascular beds
148
Activates most adrenoceptors and is transported in the blood
Epinephrine
149
Epinephrine
Activates most adrenoceptors and is transported in the blood
150
What is the direct way of increasing BP?
Ach-->Nn, NE-->B-1
151
What is the direct way of decreasing BP?
Ach-->Nn, Ach-->M (AV node)
152
What receptor increases TPR?
A-1
153
What receptor decreases TPR?
B-2
154
What happens when TPR increases?
By what NT on what receptor?
How do you block this?
Reflex bradycardia
ACh on M2
M2 blocker or ganglionic blocker
155
What happens when TPR decreases?
By what NT on what receptor?
How do you block this?
Reflex tachycardia
ACh on B-1
B-1 blocker or ganglionic blocker
156
Blood pressure system is ONLY affected by ____ in mean BP which results in ___ in renal blood flow
Decrease
| Decrease
157
Decreased renal pressure causes the release of ____ which promotes the formation of _____
Renin
| Angiotensins
158
Angiotensin II increases ____ release from the adrenal cortex, which increases blood volume by____
Angiotensin also causes ____ resulting in an ___TPR
Aldosterone
Acting to retain sodium and water
Vasoconstriction
Increase
159
Equation for BP
=TPR x CO
160
Equation for CO
= HR x SV
161
=TPR x CO
Equation for BP
162
= HR x SV
Equation for CO
163
When you give antihypertensive drugs, the body responds by the renin-angiotensin-aldosterone system and increases BV and thus BP, how do we fight off reflexes?
Tachycardia: B blocker
| Salt and water retention: diuretics or ACE inhibitor
164
What muscles in the eye are under muscarinic control?
Sphincter (contracts)
| Ciliary (contracts)
165
What effects does muscarinic stimulation have on the eye?
Miosis
| Accomodation (near vision)
166
Accomodation is purely a _____ response
PANS (muscarinic)
167
What effects does muscarinic antagonism have on the eye?
Mydriasis
| Accommodation to far vision (cyclopegia) (Paralysis of accommodation)
168
What does accommodation to far vision lead to?
Cyclopegia (Paralysis of accommodation)
169
What muscles in the eye are under adrenergic control? What receptors?
Radial (A-1) (Contracts)
170
What effects do A-1 agonists have on the eye?
```
Mydriasis
No cyclopegia (there are no A-1 receptors on ciliary muscle, only under M control)
```
171
Miosis + blurred vision=
M agonist
172
Mydriasis + blurred vision=
M antagonist
173
What does hemicholinium do?
Inhibits uptake of choline
174
Inhibits uptake of choline
hemicholinium
175
What does Botulinum toxin do?
| How?
Prevents Ach release by binding to synaptobrevin (which allows docking of vesicles onto membrane)
176
Prevents Ach release by binding to synaptobrevin (which allows docking of vesicles onto membrane)
Botulinum toxin
177
What does synaptobrevin do?
allows docking of vesicles onto membrane
178
Reversible AChE inhibitors
Edrophonium
Physostigmine
Neostigmine
179
Edrophonium
Physostigmine
Neostigmine
Reversible AChE inhibitors
180
Irreversible AChe inhibitors
Echothiophate
Malathion
Parathion
181
Echothiophate
Malathion
Parathion
Irreversible AChe inhibitors
182
What are the medical uses of botulinum toxin?
Blepharospam (involuntary contraction of eyelid)
Strabismus (lazy eye) (paralyzes extraocular muscles)
Hyperhydrosis (sweatiness) (decreases secretions by decreasing ACh)
Dystonia (painful menstrual cramps)
Cosmetics
183
Blepharospam (involuntary contraction of eyelid)
Strabismus (lazy eye) (paralyzes extraocular muscles)
Hyperhydrosis (sweatiness) (decreases secretions by decreasing ACh)
Dystonia (painful menstrual cramps)
Cosmetics
medical uses of botulinum toxin
184
Decreased CV function
Increased secretions
Increased smooth muscle contractions
M receptor activation
185
Results of M receptor activation
Decreased CV function
Increased secretions
Increased smooth muscle contractions
186
What M receptors are in the eye? What parts of the eye? What are they coupled to? How do they work?
What effect does agonism of these receptors have?
```
Sphincter m= M3
Ciliary m= M3
Gq-coupled
Increase Ca in smooth muscle= contraction
Miosis and Accommodation for near vision
```
187
What M receptors are in the heart? What parts of the heart? What are they coupled to? How do they work?
What effects does agonism of these receptors have? What changes on the EKG?
Where are sympathetic R NOT found in the heart (only sympathetic R)
```
SA node= M2
AV node= M2
Gi-coupled
Inhibit adenylyl cyclase
SA node= decrease heart rate (bradycardia)
AV node= decrease conduction velocity
Increases PR interval
Ventricular muscle
```
188
What M receptors are in the lungs? What parts of the lungs? What are they coupled to? How do they work?
What effects does agonism of these receptors have?
When shouldn't you use M agonists based on these effects?
```
Bronchioles=M3
Glands= M3
Gq-coupled
Increase Ca in smooth muscle= contraction
Bronchioles= Contraction=bronchospasm
Glands= Increased secretion
Decreases the FEV/FVC ratio
Those are COPD symptoms. Shouldn't use it on patients with asthma or CF
```
189
What M receptors are in the GI tract? What parts of the GI tract? What are they coupled to? How do they work?
What effects does agonism of these receptors have?
When shouldn't you use M agonists based on these effects?
```
Stomach= M3
Glands= M1
Intestine= M3
M1 and M3 coupled to Gq
Increase Ca in smooth muscle= contraction
Stomach= Increased motility-cramps
Glands= Increased acid production
Intestine= Contraction=diarrhea, involuntary defecation
Patients with PUD
```
190
What M receptors are in the bladder? What are they coupled to? How do they work?
What effects does agonism of these receptors have?
```
M3
Gq-coupled
Increase Ca in smooth muscle= contraction
Contraction in the detrusor
Relaxation in the trigone/sphincter
=
Voiding and urinary incontinence
```
191
What M receptors are in the sphincters?
What are they coupled to? How do they work?
What effects does agonism of these receptors have?
M3
Gq-coupled
Increase Ca in smooth muscle= contraction
Relaxation except lower esophageal which contracts
192
What M receptors are in the glands?
What are they coupled to? How do they work?
What effects does agonism of these receptors have?
All glands are M3 except in the GI tract (M1)
Gq-coupled
Increase Ca in smooth muscle= contraction
Secretion-sweat (thermoregulatory), salivation, and lacrimation
193
What M receptors are in the blood vessel endothelium?
What effects does agonism of these receptors have?
What is the exception to what can activate these receptors? Why?
M3
Dilation (via NO/EDRF)
Indirect agonists will NOT work because there is no parasympathetic innervation in vasculature, it is solely sympathetic. So, only direct M agonists will work.
194
What is the response of activating Nn receptors in the adrenal medulla?
Secretion of epinephrine and NE
195
What is the response of activating Nm receptors at the neuromuscular junction?
Stimulation- twitch/hyperactivity of skeletal muscle
196
Blood vessels are solely innervated by the _____, so stimulation of autonomic ganglia results in ______
SANS
| Vasoconstriction
197
GI tract is dominated by ____ so ganglionic stimulation causes ______
PANS
| Increased motility and secretions
198
What is ileus? When does it occur?
When does urinary retention occur?
What drug is used for these conditions? What kind of drug is it?
When the gut is not moving (no peristalsis) Post-op or neurogenic
As a result of peripheral neuropathy that diabetics suffer from
Bethanechol
DIRECT-ACTING Cholinomimetic working on M1 and M3
199
When is methacholine used?
| What kind of drug is it?
Used for diagnostic procedure: it triggers wheezing in a person with bronchial hyperreactivity
DIRECT-ACTING Cholinomimetic woking on M receptors
200
When is pilocarpinen used?
| What kind of drug is it?
In glaucoma (topical-eye drops)
Xerostomia (dry mouth)
Sjoger disease (fibrosis of lacrimal and salivary glands)
DIRECT-ACTING Cholinomimetic working on M receptors
201
What is myasthenia? What drugs are used for its differentiation from cholinergic crisis? What drugs are used for its treatment?
Autoimmune disease where auto antibodies block N receptors of skeletal muscles so patient has facial weakness and ptosis as a result of paralysis of muscles from lack of stimulation from ACh.
Edrophonium
Neostigmine and Pyridostigmine
202
What is characteristic of physostigmine?
| What is it used to treat?
```
Tertiary amine (enters CNS)
Glaucoma and antidote for atropine (M antagonist) overdose
```
203
```
Tertiary amine (enters CNS)
Used in Glaucoma and antidote for atropine (M antagonist) overdose
```
Physostigmine
204
What is characteristic of neostigmine and pyridostigmine?
| What are they used to treat?
```
Quaternary amines (cannot enter CNS)
Ileus
Urinary retention
Myasthenia
Reversal of nondepolarizing NM blockers
```
205
```
Quaternary amines (cannot enter CNS)
Used to treat:
Ileus
Urinary retention
Myasthenia
Reversal of nondepolarizing NM blockers
```
neostigmine and pyridostigmine
206
What are donepezil and tacrine used to treat?
Alzheimer's
207
What indirect-acting cholinomimetics are used to treat Alzheimer's?
donepezil and tacrine
208
What is characteristic of organophosphates?
| How are they used?
Irreversible inhibitors
Used in glaucoma (echothiophate)
Used as insecticides (malathion, parathion) and as nerve gas (sarin)
209
Irreversible inhibitors
Used in glaucoma (echothiophate)
Used as insecticides (malathion, parathion) and as nerve gas (sarin)
Organophosphates
210
Acute AChE inhibitor poisoning symptoms-Muscarinic effects
```
DUMBBELSS
Diarrhead
Urination
Miosis
Bradycardia
Bronchoconstriction
Excitation (CNS/muscle)
Lacrimation
Salivation
Sweating
```
211
```
DUMBBELSS
Diarrhead
Urination
Miosis
Bradycardia
Bronchoconstriction
Excitation (CNS/muscle)
Lacrimation
Salivation
Sweating
```
Acute AChE inhibitor poisoning symptoms- Muscarinic effects
212
Skeletal muscle excitation followed by paralysis
| CNS stimulation
Acute AChE inhibitor poisoning symptoms- Nicotinic effects
213
Acute AChE inhibitor poisoning symptoms- Nicotinic effects
Skeletal muscle excitation followed by paralysis
| CNS stimulation
214
How do you manage Acute AChE inhibitor toxicity?
Atropine (antimuscarinic) for muscarinic effects
| Pralidoxime (2-PAM) for the regeneration of AChE
215
How does 2-PAM work?
It takes the phosphate that attached to AChE and binds it to itself
216
How does chronic AChE inhibitor poisoning present itself?
Peripheral neuropathy causing muscle weakness and sensory loss
MS symptoms: foot drop, wrist drop, scanning speech, diplopia
217
Peripheral neuropathy causing muscle weakness and sensory loss
MS symptoms: foot drop, wrist drop, scanning speech, diplopia
are symptoms of?
chronic AChE inhibitor poisoning
218
What are the atropine side effects?
Decreased secretions (salivary, bronchiolar, sweat, dry mouth)
Mydriasis and cycloplegia
Hyperthermia (with resulting vasodilation)
Tachycardia
Sedation
Urinary retention and constipation
Behavioral excitation and hallucinations
219
Decreased secretions (salivary, bronchiolar, sweat)
Mydriasis and cycloplegia
Hyperthermia (with resulting vasodilation)
Tachycardia
Sedation
Urinary retention and constipation
Behavioral excitation and hallucinations
atropine side effects
220
When is the atropine side effect of decreased secretions used?
In allergies, colds, intubation
| side effect: dry mouth
221
When is the atropine side effect of mydriasis and cyclopegia used?
To check for retinopathies in diabetics
| Side effect: blurred vision (lack of accommodation)
222
When is the atropine side effect of urinary retention and constipation used?
In urinary incontinence and diarrhea
223
What are some other drugs with antimuscarinic pharmacology?
```
Antihistamines
TC antidepressants
Antipsychotics
Quinidine
Amantadine
Merepidine
```
224
```
Antihistamines
TC antidepressants
Antipsychotics
Quinidine
Amantadine
Merepidine
```
other drugs with antimuscarinic pharmacology
225
How do you treat acute atropy intoxication?
| Why this drug?
Symptomatic + physostigmine
| It is an AChE inhibitor that can cross the BBB
226
M blockers
```
BAITS
Benztropine, trihexyphenidyl
Atropine
Iptratropium
Tropicamide
Scopolamine
```
227
```
BAITS
Benztropine, trihexyphenidyl
Atropine
Iptratropium
Tropicamide
Scopolamine
```
M blockers
228
Clinical uses and/or characteristics of atropine
Antispasmodic, antisecretory, management of AChE inhibitor OD, antidiarrheal, ophthalmology
229
Antispasmodic, antisecretory, management of AChE inhibitor OD, antidiarrheal, ophthalmology
Clinical uses and/or characteristics of atropine
230
Clinical uses and/or characteristics of tropicamide
Opthalmology (topical)- dilates the pupil
231
Opthalmology (topical)- dilates the pupil
Clinical uses and/or characteristics of tropicamide
232
Clinical uses and/or characteristics of ipratropium
Asthma, COPD- no CNS entry, no change in mucus viscosity (decreases secretions in volume not viscosity)
Prevents bronchospasm
233
Asthma, COPD- no CNS entry, no change in mucus viscosity (decreases secretions in volume not viscosity)
Prevents bronchospasm
Clinical uses and/or characteristics of ipratropium
234
Clinical uses and/or characteristics of scopolamine
Used in motion sickness, causes sedation and short-term memory blocks (anterograde amnesia)
235
Used in motion sickness, causes sedation and short-term memory blocks (anterograde amnesia)
Clinical uses and/or characteristics of scopolamine
236
What do ganglionic blockers essentially do?
Wipe out ANS
| Prevent baroreceptor reflexes
237
What are endplate nicotinic receptor blockers?
Tubocuranine
Atracurium
Succinylcholine
238
What effectors are controlled by the SANS?
| What is the effect then of a ganglion blockade?
Arterioles- vasodilation, hypotension
Veins- Dilation, decreased venous return, decreased CO
Sweat glands- anhydrosis (lack of sweating)
239
What effectors are controlled by the PANS?
| What is the effect then of a ganglion blockade?
Heart- FIXED tachycardia (no more ANS regulation)
Iris- FIXED mydriasis
Ciliary muscle- Cycloplegia (blurred vision)
GI tract- Decreased tone and motility= constipation
Bladder- Urinary retention
Salivary glands- Xerostoma (dry mouth)
240
What step does methyl-p-tyrosine inhibit in catecholamine synthesis?
The rate-limiting step
| Tyrosine --> DOPA
241
What effect do MAO inhibitors and releasers have?
Increase the NE mobile pool= CV effects
242
What does reuptake of NE usually do? What do reuptake blockers do? What are they used for?
Create concentration gradient
Block this- thus get rid of conc. gradient
Depression (keep the NE in the junction!)
243
How do A-2 agonists work in the neuroeffector junction?
How does an A-2 blockade work?
Examples of A-2 agonists
They enhance negative feedback so decrease NE levels being released (used for hypertension)
Increase NE levels (cancels negative feedback)
Clonidine and methyldopa
244
What adrenergic receptors are found in the eye?
| What is the response to activation?
A-1 on radial (dilator) muscle
| Contraction= mydriasis (without cycloplegia- no blurred vision)
245
What adrenergic receptors are found in the arterioles (skin, viscera) ?
What is the response to activation?
A-1- makes the heart work harder
Contraction= increased TPR=increase in diastolic P, increase in after load (what the heart has to work against)
Useful in shock
246
What adrenergic receptors are found in the veins?
| What is the response to activation?
A-1
| Contraction=increased venous return=increased preload=increased systolic P
247
What adrenergic receptors are found in the bladder trigone and sphincter?
What is the response to activation?
A-1
| Contraction=urinary retention
248
What adrenergic receptors are found in the male sex organs?
| What is the response to activation?
A-1
Vas deferens- ejaculation
Why people don't like to take alpha blockers lawl
249
What adrenergic receptors are found in the liver?
| What is the response to activation?
A-1 and B-2
A-1= increased glycogenolysis
B-2= increased glycogenolysis, increased gluconeogenesis, increased lipolysis
Beta receptors are more sensitive (until high doses of A)
250
What adrenergic receptors are found in the kidney?
What is the response to activation?
A-1 and B-1
A-1= decreased renin release
B-1= increased renin release
Beta receptors are more sensitive (until high doses of A)
251
What adrenergic receptors are found in the pre junctional nerve terminals?
What is the response to activation?
A-2
| Decreased transmitter release and NE synthesis= decreased A-1 stimulation= decreased contraction
252
What adrenergic receptors are found in the platelets?
What is the response to activation?
What hormone works on these receptors?
When do you not want A-2 side effects? (AKA whom do you not want to prescribe A-2 agonist to?)
A-2
Aggregation
Epinephrine- plays role in aggregation of platelets and thrombosis during bleeding
If patient is hypertensive or has atherosclerotic plaques
253
What adrenergic receptors are found in the pancreas?
What is the response to activation?
When is it not best to give an A-2 agonist then?
A-2 and B-2
A-2= decreased insulin secretion
B-2= Increased insulin secretion
Beta receptors are more sensitive (until high doses of A)
To a diabetic patient if it further suppresses insulin secretion!
254
What adrenergic receptors are found in the heart?
What is the response to activation?
What can this cause?
B-1
SA node= Increase in HR
AV node= increase in conduction velocity
Atrial and Ventr. muscle= increased force of contraction, conduction velocity, CO and oxygen consumption
His-Purkinje= increased automaticity and conduction velocity
Worsen angina, worsen M.I, can't use chronically
255
What is characteristic of B-2 receptors?
What does this mean in terms of what can and cannot work on it?
What is the physiological basis for this?
They are mostly not innervated
Neurotransmitters (NE) cannot reach it
In fight or flight, NE constricts vessels= no O2 to the heart, brain, or muscles (which you need!)
Epinephrine opposes this silly reaction by vasodilating all the blood vessels
B-2 receptors are more sensitive than A-1 to stimulation
256
What adrenergic receptors are found in all blood vessels?
| What is the response to activation?
B-2 receptors
| Vasodilation- decrease in TPR=decrease in diastolic P=decrease in afterload
257
What adrenergic receptors are found in the uterus?
What is the response to activation?
When is it used?
B-2
Relaxation
To prevent premature labor
258
What adrenergic receptors are found in the bronchioles?
What is the response to activation?
When is it used?
B-2
Dilation
Asthma
259
What adrenergic receptors are found in skeletal muscle?
| What is the response to activation?
B-2
| Increased glycogenolysis= contractility (tremor)
260
Where are D-1 receptors found?
| What is the response to activation?
Renal, mesenteris, coronary vasculature
| Vasodilation- in kidney= increased RBF, increased GFR, increased Na secretion
261
What kind of drug is phenylephrine?
| What is it used for?
Direct A-1 agonist
| Nasal decongestant and ophthalmologic use (mydriasis without cycloplegia)
262
Direct A-1 agonist
| Nasal decongestant and ophthalmologic use (mydriasis without cycloplegia)
phenylephrine
263
What kind of drug is methoxamine?
| What is it used for?
Direct A-1 agonist
Paroxysmal atrial tachycardia through vagal reflex
Needs to slow SA and AV node so increases BP to get a reflex bradycardia
264
What kind of drugs are clonidine and methyldopa? What are they used for?
A-2 agonists
| Hypertension
265
```
What kind of drugs are
albuterol
salmeterol
terbutaline ?
What are they used for?
```
Selective B-2 agonists
| Asthma
266
What kind of a drug is ritodrine?
| When is it used?
Selective B-2 agonist
| Premature labor
267
What kind of a drug is isoproterenol?
| What it is used for?
B-1=B-2 agonist
| Used for bronchospasm, heart block, and bradyarrhythmias
268
Direct A-1 agonist
Paroxysmal atrial tachycardia through vagal reflex
Needs to slow SA and AV node so increases BP to get a reflex bradycardia
methoxamine
269
A-2 agonists
| Hypertension
clonidine and methyldopa
270
Selective B-2 agonist
| Premature labor
ritodrine
271
B-1=B-2 agonist
| Used for bronchospasm, heart block, and bradyarrhythmias
isoproterenol
272
What kind of a drug is dobutamine?
| When is it used?
B-1>B-2 agonist
| CHF
273
B-1>B-2 agonist
| CHF
dobutamine
274
What receptor does NE not work on?
| What does this mean?
B-2
| It can never lower BP
275
```
Out of this list of conditions, which ones are acted upon by NE, epi, or both? On what receptors?
Cardiac arrest
Adjunct to local anesthetic
Hypotension
Anaphylaxis
Asthma
```
```
Cardiac arrest- both (B-1)
Adjunct to local anesthetic-both (A-1)
Hypotension-both (A-1, B-1)
Anaphylaxis- just epi (B-2)
Asthma-just epi (B-2)
```
276
What are the two main categories of indirect-acting adrenergic agonists?
Releasers and reuptake inhibitors
277
Releasers and reuptake inhibitors
two main categories of indirect-acting adrenergic agonists
278
What are the three types of releasers?
| What is their drug interaction?
Tyramine
Amphetamines
Ephedrine
MAO inhibitors (do not mix!)
279
Tyramine
Amphetamines
Ephedrine
MAO inhibitors (do not mix!)
releasers
280
Where is tyramine found?
| What increases its bioavailability? What decreases it?
Red wine and cheese
MAO inhibition= hypertensive crisis
MAO-A metabolism in gut and liver
281
What is the clinical use of amphetamines?
Methyl phenidate in narcolepsy and ADHD
282
What are the two types of reuptake inhibitors?
Cocaine and TCAs
283
What is ephedrine used as?
Cold medication
284
What are the major uses of A blockers?
Hypertension (selective A-1)
Pheochromocytoma (non-selective)
BPH (selective A-1)
285
Hypertension (selective A-1)
Pheochromocytoma (non-selective)
BPH (selective A-1)
major uses of A blockers
286
What are two nonselective A-blockers?
| What is the difference between them?
Phentolamine- competitive inhibitor
| Phenoxybenzamine- non-competitive- choice for pheochromocytoma because binds irreversibly
287
```
What do all of these have in common?
Prazosin
Doxazosin
Terazosin
Tamsulosin
```
Selective A-1 blockers
288
Selective A-1 blockers
Prazosin
Doxazosin
Terazosin
Tamsulosin
289
What are these? What are their clinical uses?
Yohimbine
Mirtazapine
Selective A-2 blockers
Yohimbine- postural hypotension and impotence
Mirtazapine- antidepressant
290
What are the main effects of a B-1 blockade?
| What are the uses?
Decreased HR, SV, CO aka decreased O2 demand (decreased angina, decreased recurrence of MI
Decreased renin release (hypertension management)
Decreased aqueous humor production (decreased IOP, glaucoma)
291
A-->M beta blockers are
B-1 selective
292
B-1 selective blockers
Acebutolol
Atenolol
Metoprolol
293
P-->Z beta blockers are
non-selective
294
Non-selective B blockers
Pindolol
Propranolol
Timolol
295
What are the general uses of beta-blockers
Angina, hypertension, post MI
Antiarrhythmics (class 2: propranolol, acebutolol, esmolol)
Glaucoma (timolol, betaxolol)
Migraine, thyrotoxicosis, performance anxiety, essential tremor
296
Which drugs have combined A and B-blocking activity?
| What are they used for?
Labetalol and Carvedilol
| CHF
297
Which drug has K channel blockade and B-blocking activity?
Sotalol (class 2-antiarrhythmic)
298
Where is histamine released from?
| What triggers its release?
Mast cells, basophils, and platelets
| IgE-mediated allergic reactions, Type 1 hypersensitivity, drugs, venoms, and trauma
299
How can increased histamine production be detected?
Increased amounts of its metabolite imidazoleacetic (5HIAA) in the urine
300
Increased amounts of its metabolite imidazoleacetic (5HIAA) in the urine makes its over production detectable
histamine
301
What G protein are H1 receptors coupled to?
| What are the effects of H1 activation?
Gq protein
Increased capillary dilation (via NO)= decrease in BP (leads to shock in anaphylaxis)
Increased capillary permeability= increased edema
Increased bronchiolar sm. m contraction (via IP3 and DAG release)
Increased activation of peripheral nociceptive receptors= increased pain and pruritus (itching)
Decreased AV nodal conduction= bradycardia
302
What receptor activation is this?
Gq protein
Increased capillary dilation (via NO)= decrease in BP (leads to shock in anaphylaxis)
Increased capillary permeability= increased edema
Increased bronchiolar sm. m contraction (via IP3 and DAG release)
Increased activation of peripheral nociceptive receptors= increased pain and pruritus (itching)
Decreased AV nodal conduction= bradycardia
H1
303
What G protein is the H2 receptors coupled to?
| What are the effects of H2 activation?
Gs
Increased gastric acid secretion= increase in GI ulcers
Increased SA nodal rate, positive inotropism and automaticity- cardiac stimulation
Reduces histamine release from mast cells (neg feedback)
304
What receptor activation is this?
Gs
Increased gastric acid secretion= increase in GI ulcers
Increased SA nodal rate, positive inotropism and automaticity- cardiac stimulation
Reduces histamine release from mast cells (neg feedback)
H2
305
All of these are active by oral route
All require hepatic metabolism and most cross the placental barrier
Many of them are potent anesthetics because block activation of nociceptors
H1 antagonists
306
What are the major antihistamines?
Which ones are 1st generation, which ones 2nd?
What is the difference?
```
Diphenhydramine-1st
Promethazine-1st
Chlorpheniramine-1st
Meclizine-1st
Cetirizine-2nd
Loratadine-2nd
Fexofenadine-2nd
1st generation antihistamines cause drowsiness- are anti motion sickness, are muscarinic blockers and enter the CNS
2nd generation do not cause drowsiness, are not anti motion sickness, are not antimuscarinics and do not enter CNS
```
307
Which antihistamine is used for management of chemotherapy-induced vomiting?
Diphenhydramine
308
Which anti histamine is the most effective anti-motion sickness drug?
Meclizine
309
What are the uses for antihistamines?
Allergic reactions (hay fever, rhinitis, urticaria)
Motion sickness, vertigo (M blockers)
Nausea and vomiting with pregnancy (M blockers)
Preoperative sedation (M blockers)
OTC: sleep aids and cold medication (m blockers)
Parkinson disease
Acute EPSs
310
What drugs are used for these conditions?
Allergic reactions (hay fever, rhinitis, urticaria)
Motion sickness, vertigo (M blockers)
Nausea and vomiting with pregnancy (M blockers)
Preoperative sedation (M blockers)
OTC: sleep aids and cold medication (m blockers)
Parkinson disease
Acute EPSs
Antihistamines
311
By what mechanism do prostaglandins have a protective role in the stomach?
Inhibit proton pump
Improve mucus secretion to cover the lining of the stomach to protect from acid erosion
Enhance bicarb secretion to neutralize the acid
312
What are these mechanisms of?
Inhibit proton pump
Improve mucus secretion to cover the lining of the stomach to protect from acid erosion
Enhance bicarb secretion to neutralize the acid
Prostaglandin's protective role in the stomach
313
What are antacids?
Bases floating around in the stomach that neutralize the acids
314
Bases floating around in the stomach that neutralize the acids
Antacids
315
What is sucralfate and bismuth subsalicylate?
"sticky gel" that coats ulcer crater to protect it from further erosion by acids
316
"sticky gel" that coats ulcer crater to protect it from further erosion by acids
sucralfate and bismuth subsalicylate
317
What are examples of H2 antagonists?
| Which one is the only one that crosses the BBB?
```
Cimetidine
Ranitidine
Famotidine
Nizatidine
Only Cimetidine crosses the BBB
```
318
What is the MOA of H2 antagonists?
Suppress secretory responses to food stimulation and nocturnal secretion of gastric acid via their ability to indirectly decrease the activity of the proton pump
Also partially antagonize HCl secretion caused by vagally or gastrin-induced release of histamine from ECL-like cells
319
What drug's MOA is this?
Suppress secretory responses to food stimulation and nocturnal secretion of gastric acid via their ability to indirectly decrease the activity of the proton pump
Also partially antagonize HCl secretion caused by vagally or gastrin-induced release of histamine from ECL-like cells
H2 antagonists
320
What are the uses for H2 antagonists?
PUD
GERD
Zollinger-Ellison
321
What drugs are used for these conditions?
PUD
GERD
Zollinger-Ellison
H2 antagonists
322
What are the major side effects of Cimetidine?
Decrease in androgens= gynecomastia and decreased libido
323
Decrease in androgens= gynecomastia and decreased libido
| What are these side effects of?
Cimetidine
324
What is the MOA of PPIs?
What is an example of one?
What are their uses?
```
Irreversible direct inhibitors of the PP (K/H anti port) in the gastric parietal cell
Omeprazole (all -prazoles)
More effective than H2 clockers in PUD
Effective in GERD and Zollinger Ellison
Eradication regimen for H. pylori
```
325
What is the eradication regimen for H. pylori?
PPI
Clarithromycin (macrolide)
Amoxicillin
326
What is Barrett's? What does it result from? What does this increase the risk of?
Metaplastic transformation (squamous cells in lower third of esophagus turn into columnar mucus-producing cells)
From chronic GERD
Increases the risk of developing adenocarcinoma of esophagus
327
What is Misoprostol? What is it also known as? What is its MOA? What are its uses?
PGE1 analog- "antidote to aspirin-induced ulcers"
It is cytoprotective. It increases mucus and bicarbonate secretion and decreases HCl secretion.
It is used in NSAID-induced GI ulcers
328
Why is anything with -prost contraindicated in pregnancy?
Because it's a PGE1 analog which can induce contractions= abortion
329
PGE1 analog- "antidote to aspirin-induced ulcers"
It is cytoprotective. It increases mucus and bicarbonate secretion and decreases HCl secretion.
It is used in NSAID-induced GI ulcers
Misoprostol
330
What are examples of antacids?
| What are side effects?
Al(OH)3, Mg(OH)2, CaCo3
| Side effects: Constipation (Al+3), diarrhea (Mg+2)
331
Al(OH)3, Mg(OH)2, CaCo3
| Side effects: Constipation (Al+3), diarrhea (Mg+2)
Antacids
332
What do antacids increase the oral absorption of?
| Example
Weak bases (quinidine-dangerous anti arrhythmic=tachycardia)
333
What do antacids decrease the oral absorption of?
| Example
```
Weak acids (Warfarin- run the risk of thrombotic disorders)
Tetracycline (via chelation)
```
334
What are all the drugs used for nausea and vomiting? Examples of each
5HT3 antagonists: ondansetron (commonly used in cancer chemotherapy), granisetron
DA antagonists: prochlorperazine, metoclopramide
H1 antagonists: diphenhydramine, meclizine, promethazine (M blockers)
Muscarinic blockers: scopolamine
Cannabinoids: dronabinol
NK1-receptor antagonist: aprepitant
335
What are examples of neurokinins? What do they have to do with nausea and vomiting?
Substance P and bradykinin
| They are inflammatory mediators and pain mediators- pain-induced vomiting
336
Which 5HT3 antagonists are anti-nauseates?
ondansetron (commonly used in cancer chemotherapy), granisetron
337
Which DA antagonists are anti-nauseates?
prochlorperazine, metoclopramide
338
Which H1 antagonists are anti nauseates?
diphenhydramine, meclizine, promethazine (M blockers)
339
Which muscarinic blockers are anti nauseates?
Scopolamine
340
Where is serotonin synthesized and stored?
What is it metabolized by?
What is the marker for carcinoid?
GI cells, neurons, and platelets
MAO type A
Its metabolite- 5-hydroxyinolacetic acid (5HIAA)
341
Where are 5HT1 receptors found?
CNS (usually inhibitory) and smooth muscle (both)
342
What is buspirone?
Partial agonist at 5HT1a receptor-->anxiolytic for GAD (generalized anxiety disorder)
343
Partial agonist at 5HT1a receptor-->anxiolytic for GAD (generalized anxiety disorder)
buspirone
344
What is sumatriptan?
Agonist at 5HT1d receptor in cerebral vessels-->decrease migraine pain by vasoconstricting (contraindicated for people with CV problems)
D=dee worst headache of your life
345
Agonist at 5HT1d receptor in cerebral vessels-->decrease migraine pain by vasoconstricting (contraindicated for people with CV problems)
D=dee worst headache of your life
sumatriptan
346
Where are 5HT2 receptors found and what are activation effects?
CNS-excitatory
| Periphery- vasodilation, contraction of GI, bronchial, and uterine smooth muscle, and platelet aggregation
347
CNS-excitatory
| Periphery- vasodilation, contraction of GI, bronchial, and uterine smooth muscle, and platelet aggregation
5HT2 receptors
348
What is Olanzapine?
Antipsychotic
| Antagonist at 5HT2a receptors in the CNS-->decreases symptoms of psychosis
349
Antipsychotic
| Antagonist at 5HT2a receptors in the CNS-->decreases symptoms of psychosis
Olanzapine
350
What is cyproheptadine?
5HT2 antagonist used in carcinoid, other GI tumours, and postgastrectomy, also used for anorexia nervosa
Has marked H1-blocking action: used in seasonal allergies
351
5HT2 antagonist used in carcinoid, other GI tumours, and postgastrectomy, also used for anorexia nervosa
Has marked H1-blocking action: used in seasonal allergies
cyproheptadine
352
What is the drug of choice for carcinoid and other GI tumors? How does it work?
Octreotide- somatostatin analog
| Suppresses actual secretion of serotonin from the GI tumor
353
Where are 5HT3 receptors found? What is their MOA?
Area postrema, peripheral sensory and enteric nerves
| Activation opens ion channels
354
What is ondansetron? and other -setrons?
5HT3 antagonists-->decrease emesis in chemotherapy and radiation and postoperatively
355
5HT3 antagonists-->decrease emesis in chemotherapy and radiation and postoperatively
ondansetron and other -setrons
356
What is ergotamine? How does it work in migraines? What are the side effects?
Partial agonist at A and 5HT2 receptors in the vasculature and possibly CNS
Also agonists or partial agonists at dopamine receptors
Vasoconstrictive actions decreases pulsation in cerebral vessels may be relevant to acute actions of ergotamine during migraine attack
Used in acute attacks
GI distress, prolonged vasoconstriction-->ischemia and gangrene, abortion near term
357
Partial agonist at A and 5HT2 receptors in the vasculature and possibly CNS
Also agonists or partial agonists at dopamine receptors
Vasoconstrictive actions decreases pulsation in cerebral vessels may be relevant to acute actions of ergotamine during migraine attack
Used in acute attacks
GI distress, prolonged vasoconstriction-->ischemia and gangrene, abortion near term
ergotamine
358
What drugs are used for migraine prophylaxis?
Propranolol
Verapamil
Amitriptyline
Valproic acid
359
What is bromocriptine? How does it work?
Agonist of D2 receptor therefore decreases prolactin release
360
What is ergonovine used for?
To reduce postpartum bleeding by contracting the uterus
361
What is methysergide?
5HT2 antagonist used in carcinoid tumor
362
Cytoprotective in the stomach
Dilate renal vasculature
Contract the uterus
Maintain ductus arteriosus
Prostaglandins
363
What does Zileuton do? What is it used in?
Inhibits lipoxygenase
| Prophylaxis and treatment of asthma
364
What do -lukasts (Zafirlukast) do? What are they used in?
Block leukotriene receptors
| Treatment and prophylaxis of asthma
365
Inhibits lipoxygenase
| Prophylaxis and treatment of asthma
Zileuton
366
Block leukotriene receptors
| Treatment and prophylaxis of asthma
-lukasts
| Zafirlukast
367
Chemotactic factor important in inflammation
| MOA: inflammatory mediator-->neutrophil chemoattractant; activates PMNs; increases free radical formation-->cell damage
LTB4
368
LTB4
Chemotactic factor important in inflammation
| MOA: inflammatory mediator-->neutrophil chemoattractant; activates PMNs; increases free radical formation-->cell damage
369
Make up slow-reacting substance of anaphylaxis (SRS-A)
| Cause anaphylaxis and bronchoconstriction (role in asthma)
LTA4, LTC4, and LTD4
370
LTA4, LTC4, and LTD4
Make up slow-reacting substance of anaphylaxis (SRS-A)
| Cause anaphylaxis and bronchoconstriction (role in asthma)
371
Constitutive, Expressed in most tissues including platelets and stomach
Acts to synthesize thromboxane and cytoprotective prostaglandin, respectively
COX-1
372
COX-1
Constitutive, Expressed in most tissues including platelets and stomach
Acts to synthesize thromboxane and cytoprotective prostaglandin, respectively
373
Inducible, expressed in the brain and kidney and at sites of inflammation
COX-2
374
COX-2
Inducible, expressed in the brain and kidney and at sites of inflammation
375
What is misoprostol? What is it used for?
A PGE1 analog
| Used in the treatment of NSAID-induced ulcers (protective action on gastric mucosa)
376
A PGE1 analog
| Used in the treatment of NSAID-induced ulcers (protective action on gastric mucosa)
Misoprostol
377
What is Alprostadil? What is it used for?
PGE1
Maintains patency of ductus arterioles
Vasodilation; used in male impotence
378
PGE1
Maintains patency of ductus arterioles
Vasodilation; used in male impotence
Alprostadil
379
What is used to close a patent ductus arteriosus?
Indomethacin (most powerful NSAID)
380
PGE2 and PGF2-A are known mainly for
contraction of uterus and abortion
381
contraction of uterus and abortion
PGE2 and PGF2-A are known mainly for
382
What is the MOA of PGE2?
| Example of a drug and what it is used for
MOA: uterine smooth muscle contraction
| Dinoprostone; can be used for cervical ripening and as an abortifacient
383
MOA: uterine smooth muscle contraction
| Dinoprostone; can be used for cervical ripening and as an abortifacient
PGE2
384
What is the MOA of PGF2-A?
| Two examples of drugs and their uses
Uterine and bronchiolar smooth muscle contraction
Carboprost: abortifacient
Latanoprost: for treatment of glaucoma (reduced IOP)
385
Uterine and bronchiolar smooth muscle contraction
Carboprost: abortifacient
Latanoprost: for treatment of glaucoma (reduced IOP)
PGF2-A
386
How does Latanoprost work in glaucoma? What is a common side effect?
It vasodilates the canals of Schlemm, thereby improving outflow of aqueous humour (reducing IOP)
Causes dark pigmentation of the iris
387
It vasodilates the canals of Schlemm, thereby improving outflow of aqueous humour (reducing IOP)
Causes dark pigmentation of the iris
Latanoprost
388
Platelet stabilizer and vasodilator
Drug: epoprestenol
Uses: pulmonary hypertension
What prostaglandin is it and where is it found?
PGI2 (prostacyclin) found in endothelial cells
389
What does PGI2 do? Example drug? What is it used for?
Platelet stabilizer and vasodilator
Drug: epoprestenol
Uses: pulmonary hypertension
390
Which prostaglandins both increase in primary dysmenorrhea? What helps in primary dysmenorrhea?
PGE2 and PGF-A
| NSAID because block their synthesis
391
Platelet aggregator
| Inhibition of their synthesis underlies protective role of aspirin post MI
TXA2 (thromboxane)
392
TXA2 (thromboxane)
Platelet aggregator
| Inhibition of their synthesis underlies protective role of aspirin post MI
393
What is the prototypical NSAID?
Aspirin (ASA)
394
Causes irreversible inhibition of COX
Covalent bond via acetylation of a serine hydroxyl group near the active site
Actions are dose-dependent
Aspirin
395
Actions of aspirin
Causes irreversible inhibition of COX
Covalent bond via acetylation of a serine hydroxyl group near the active site
Actions are dose-dependent
396
What are the low-dose actions of aspirin (~80mg/day)
Antiplatelet aggregation
| The basis for post MI prophylaxis and to reduce the risk of recurrent TIAs
397
Antiplatelet aggregation
The basis for post MI prophylaxis and to reduce the risk of recurrent TIAs
are the actions of?
low dose aspirin (~80mg/day)
398
What are the moderate dose actions of aspirin? (~325mg)
Analgesia and antipyresis
399
Analgesia and antipyresis
| are the actions of?
Moderate dose aspirin (~325mg)
400
What are the high dose actions of aspirin? (~3-5 g/day)
Antiinflammatory
401
Antiinflammatory
| are the actions of?
High dose aspirin (3-5 grams/day)
402
How to low to moderate doses of aspirin work in uric acid elimination?
How do high doses work in uric acid elimination?
Aspirin=weak acid= competes with other acids for secretion
Low to moderate doses: decrease tubular secretion-->hyperuricemia (cannot use it for gout!)
High doses: decrease tubular reabsorption-->uricosuria
403
What happens to the acid-base and electrolyte balance at high doses of aspirin?
Mild uncoupling of oxidative phosphorylation--> increased respiration-->decreased pCO2-->respiratory alkalosis-->renal compensation-->increased HCO3 elimination-->compensated respiratory alkalosis (pH=normal, decreased pCO2, decreased HCO3)
404
What happens to the acid-base and electrolyte balance at toxic doses of aspirin?
Inhibits respiratory center-->decreased respiration-->increased pCO2-->respiratory acidosis (decreased pH, decreased HCO3, normalization of pCO2) plus inhibition of Krebs cycle and severe uncoupling of oxidative phosphorylation (decreased ATP) -->metabolic acidosis, hyperthermia, and hypokalemia
405
What are the side effects of aspirin toxicity?
GI irritation: gastritis, ulcers, bleeding
Salicylism: tinnitus, vertigo, decreased hearing
Bronchoconstriction: exacerbation of asthma
Hypersensitivity, especially the "triad" of asthma, nasal polyps, rhinitis
Reye syndrome: encephalopathy
Increased bleeding time (anti platelet)
Chronic use: associated with renal dysfunction
406
What are these side effects of?
GI irritation: gastritis, ulcers, bleeding
Salicylism: tinnitus, vertigo, decreased hearing
Bronchoconstriction: exacerbation of asthma
Hypersensitivity, especially the "triad" of asthma, nasal polyps, rhinitis
Reye syndrome: encephalopathy
Increased bleeding time (anti platelet)
Chronic use: associated with renal dysfunction
Aspirin toxicity
407
What are aspirin drug interactions?
Ethanol (increases GI bleeding)
OSUs and warfarin (increases their effects)
Uricosurics (decreases their effect)
408
Other NSAIDS
```
I-SINK
Ibuprofen
Sulindac
Indomethacin (most potent)
Naprox
Ketorolac (used for post-op pain)
```
409
```
I-SINK
Ibuprofen
Sulindac
Indomethacin (most potent)
Naprox
Ketorolac (used for post-op pain)
```
Other NSAIDS
410
Ketorolac
Analgesia
411
How do other NSAIDs compare to aspirin in analgesic effects?
Ketorolac>ibuprofen/naproxen>ASA
412
How do other NSAIDs compare to aspirin in GI irritation?
All < ASA
413
All NSAIDs < ASA
| in terms of what?
GI irritation
414
Which NSAID has no renal side effects?
Sulindac
415
What are the specific toxicities of indomethacin?
Thrombocytopenia
Agranulocytosis
and > CNS effects
416
Thrombocytopenia
Agranulocytosis
and > CNS effects
are toxicities of what drug?
Indomethacin
417
What are the specific toxicities of Sulindac?
Stevens-Johnson syndrome
| Hematotoxicity
418
Stevens-Johnson syndrome
Hematotoxicity
are toxicities of what drug?
Sulindac
419
What are the primary differences between nonselective COX inhibitors and the selective COX 2 inhibitors?
Selective COX-2 inhibitors have less GI toxicity and less antiplatelet action
420
What is the MOA of acetaminophen?
No COX inhibition in peripheral tissues and lacks significant anti-inflammatory effects
Equivalent analgesic and antipyretic activity to ASA due to inhibition of COX in CNS
421
Where is acetaminophen mainly metabolized?
What is the minor pathway and what does it result in? What is it inactivated by?
What happens in acetaminophen OD? Why?
Liver
via P450, a reactive metabolite
Glutathione
Hepatotoxicity.The finite stores of GSH are depleted. When this happens, the reactive metabolite reacts with hepatocytes= nausea, vomiting, abdominal pain, and ultimately liver failure due to centrilobular necrosis.
422
How do you manage acetaminophen OD-induced hepatotoxicity ? When should you do this?
With N-acetylcysteine (supplies -SH groups)
| Preferably within first 12 hours
423
What are examples of DMARDs? What are they used for?
```
Hydroxychloroquine
Methotrexate
Sulfalazine
Glucocorticoids
Gold salts
Penicilamine
Leflunomide
Etanercept
Inflixamib
Anakinra
```
RA
424
```
Hydroxychloroquine
Methotrexate
Sulfalazine
Glucocorticoids
Gold salts
Penicilamine
Leflunomide
Etanercept
Inflixamib
Anakinra
```
What are these?
DMARDs
425
What is the mechanism of hydroxychloroquine? What are its side effects?
MOA: Stabilizes lysosomes and decreases chemotaxis
Side effects: GI distress and visual dysfunction (cinchonism)
hemolysis in G6PD deficiency
426
MOA: Stabilizes lysosomes and decreases chemotaxis
Side effects: GI distress and visual dysfunction (cinchonism)
hemolysis in G6PD deficiency
hydroxychloroquine
427
What is the MOA of methotrexate? What are its side effects?
MOA: cytotoxic to lymphocytes
| Side effects: Hematotoxicity
428
MOA: cytotoxic to lymphocytes
| Side effects: Hematotoxicity
methotrexate
429
What is the MOA of sulfalazine? Side effects?
MOA: it is broken down by colonic bacteria in 5-ASA (antiinflammatory-possibly inhibits COX- with benefits in UC) and sulfapyridine which decreases B cell function
Side effects: Hemolysis in G6PD deficiency
430
MOA: it is broken down by colonic bacteria in 5-ASA (antiinflammatory-possibly inhibits COX- with benefits in UC) and sulfapyridine which decreases B cell function
Side effects: Hemolysis in G6PD deficiency
sulfalazine
431
What is the MOA of glucocorticoids? Side effects?
MOA: Decreases LTs, ILs, and platelet activating factor (PAF)
Side effects: ACTH suppression, cushingoid state, osteoporosis, GI distress, glaucoma
432
MOA: Decreases LTs, ILs, and platelet activating factor (PAF)
Side effects: ACTH suppression, cushingoid state, osteoporosis, GI distress, glaucoma
glucocorticoids
433
What is the MOA of gold salts? Side effects?
MOA: Decrease lysosomal and macrophage functions
| Side effects: Dermatitis, hematotoxicity, nephrotoxicity
434
MOA: Decrease lysosomal and macrophage functions
| Side effects: Dermatitis, hematotoxicity, nephrotoxicity
gold salts
435
What is the MOA of penicillamine? Side effects?
| Other use?
MOA: suppresses T cells and circulating rheumatoid factor
Side effects: Proteinuria, hematotoxicity, and autoimmune disease
**Also used in Wilson's disease (liver cirrhosis and CNS damage bc of Cu accumulation) because it is a chelator of Cu
436
MOA: suppresses T cells and circulating rheumatoid factor
Side effects: Proteinuria, hematotoxicity, and autoimmune disease
**Also used in Wilson's disease (liver cirrhosis and CNS damage bc of Cu accumulation) because it is a chelator of Cu
Penicillamine
437
What is the MOA of leflunomide? Side effects?
MOA: inhibits dihydro-orotic acid dehydrogenase (DHOD) --> decreased UMP-->decreased ribonucleotides-->arrests lymphocytes in G1
Side effects: Alopecia (baldness), rash, diarrhea, hepatotoxicity
438
MOA: inhibits dihydro-orotic acid dehydrogenase (DHOD) --> decreased UMP-->decreased ribonucleotides-->arrests lymphocytes in G1
Side effects: Alopecia (baldness), rash, diarrhea, hepatotoxicity
leflunomide
439
What is the MOA of etanercept? Side effects?
| What is another use?
MOA: Binds TNF; is a recombinant form of TNF receptor
Side effects: Infections
Also used in Crohn's
440
MOA: Binds TNF; is a recombinant form of TNF receptor
| Side effects: Infections
etanercept
441
What is the MOA of inflixamib? Side effects?
| What is another use?
MOA: Monoclonal antibody to TNF
Side effects: infections
Also used in Crohn's
442
MOA: Monoclonal antibody to TNF
| Side effects: infections
inflixamib
443
What is the MOA of anakinra? Side effects?
| What is another use?
MOA: IL-1 receptor antagonist
Side effects: infections
Also used in Crohn's
444
MOA: IL-1 receptor antagonist
Side effects: infections
Also used in Crohn's
anakinra
445
____ are used to treat the symptoms of RA, _____ are used to treat the disease
NSAIDS
| DMARDs
446
Which drug is recommended for mild arthritis?
| Which for moderate to severe?
Hydroxychloroquine
| Methotrexate
447
What is gout?
An increase in body stores of uric acid.
| Acute attacks involve joint inflammation and precipitation of uric acid crystals
448
An increase in body stores of uric acid.
| Acute attacks involve joint inflammation and precipitation of uric acid crystals
Gout
449
What are the three treatment strategies for gout?
1. Reducing inflammation with Colchicine, NSAIDs, or glucocorticoids
2. Accelerating renal excretion of uric acid with uricosuric drugs
3. Reducing conversion of purines to uric acid by inhibiting XO
450
1. Reducing inflammation with Colchicine, NSAIDs, or glucocorticoids
2. Accelerating renal excretion of uric acid with uricosuric drugs
3. Reducing conversion of purines to uric acid by inhibiting XO
treatment strategies for gout
451
What is the MOA of colchicine?
| What are its acute and chronic side effects?
MOA: binds to tubulin--> decreased mictrotubular polymerization; decreased LTB4 and decreased leukocyte and granulocyte migration
Acute side effects: diarrhea and GI pain
Chronic side effects: hematuria, alopecia, myelosuppression, gastritis, and peripheral neuropathy
452
MOA: binds to tubulin--> decreased mictrotubular polymerization; decreased LTB4 and decreased leukocyte and granulocyte migration
Acute side effects: diarrhea and GI pain
Chronic side effects: hematuria, alopecia, myelosuppression, gastritis, and peripheral neuropathy
colchicine
453
What is alloxanthine?
A suicide inhibitor: metabolite inhibits its own formation
It is the metabolite of allopurinol. Allopurinol is metabolized by xanthine oxidase into alloxanthine, and then alloxanthine inhibits xanthine oxidase
454
What are the drugs allopurinol and probenecid used for?
Prophylaxis of chronic gout
455
What is the action of allopurinol?
It is a prodrug converted by xanthine oxidase, forming alloxanthine, which inhibits the enzyme= decreased purine metabolism= decreased uric acid
456
What does xanthine oxidase do?
Metabolizes purines to uric acid
457
Metabolizes purines to uric acid
xanthine oxidase
458
What are the drug interactions of allopurinol?
| Describe this drug interaction
With 6-mercaptopurine (6-MP) (anti cancer)
6-MP is inactivated by xanthine oxidase. Allopurinol inhibits this. So you get a buildup of active anti-cancer drug- can cause tremendous toxicity from the bone marrow= suppressing effect
OR, if careful about it, allows you to decrease the dose of 6-MP by 2/3 with the same effect
459
What is the action of probenecid?
| Side effects?
MOA: Inhibits proximal tubule pumps that reabsorb and secrete - so inhibits proximal tubule reabsorption of urate (ineffective if GFR <50mL/min)
Also inhibits secretion of many acidic drugs (cephalosporins, fluroquinolones, penicillins)
Side effects: Crystallization if high excretion of uric acid
ASA may decrease effects by competing with urate for excretion= hyperuricemia
460
MOA: Inhibits proximal tubule pumps that reabsorb and secrete - so inhibits proximal tubule reabsorption of urate (ineffective if GFR
probenecid
461
What are the effects of glucocorticoids?
Decreased leukocyte migration (decrease in integrins)
Increased lysosomal membrane stability= decreased phagocytosis (decreased fusion of lysosomes and endosomes)
Decreased capillary permeability
Inhibit PLA2 (via lipocortin expression)= decreased PGs and LTs
Decreased expression of COX 2
Decreased PAF (thrombosis and inflammatory responses)
Decreased interleukins (mediators of stimulation of lymphocytes)
462
Decreased leukocyte migration (decrease in integrins)
Increased lysosomal membrane stability= decreased phagocytosis (decreased fusion of lysosomes and endosomes)
Decreased capillary permeability
Inhibit PLA2 (via lipocortin expression)= decreased PGs and LTs
Decreased expression of COX 2
Decreased PAF (thrombosis and inflammatory responses)
Decreased interleukins (mediators of stimulation of lymphocytes)
Are the effects of what?
Glucocorticoids
463
What do integrins do? How do glucocorticoids affects them?
Integrins are required for sticking of WBCs to endothelial wall (part of the immunoglobulin family).
Glucocorticoids decrease integrins which in turn decrease leukocyte migration. So someone on glucocorticoids= leukocytosis (increased WBC count)
464
Side effects of glucocorticoids
Suppression of ACTH: cortical atrophy, malaise, arthralgia, and fever- may result in a shock state with abrupt withdrawal
Iatrogenic (drug-induced) cushingoid syndrome= fat deposition, muscle weakness/atrophy, bruising, acne
Hyperglycemia due to increased gluconeogenesis (corticosteroids induce PEPCK-control enzyme of gluconeogenesis)= increased insulin demand and other adverse effects (caution in diabetic patients)
Osteoporosis: vertebral fractures- aseptic hip necrosis (because of increased osteoclast activity)
Increased GI acid and pepsin release= ulcers, GI bleeding (due to lack of PG) (bc of proteolysis and thinning of tissues= can have perforation)
Electrolyte imbalance: Na/water retention= edema and hypertension, hypokalemic alkalosis, hypocalcemia (caution with hypertensive patients)
Decreased skeletal growth in children
Decreased wound healing, increased infections (thrush from C. albicans)
Increased glaucoma, increased cataracts (via increased sorbitol) Sorbitol does osmotic damage to lens
Increased mental dysfunction
465
Suppression of ACTH: cortical atrophy, malaise, arthralgia, and fever- may result in a shock state with abrupt withdrawal
Iatrogenic (drug-induced) cushingoid syndrome= fat deposition, muscle weakness/atrophy, bruising, acne
Hyperglycemia due to increased gluconeogenesis (corticosteroids induce PEPCK-control enzyme of gluconeogenesis)= increased insulin demand and other adverse effects (caution in diabetic patients)
Osteoporosis: vertebral fractures- aseptic hip necrosis (because of increased osteoclast activity)
Increased GI acid and pepsin release= ulcers, GI bleeding (due to lack of PG) (bc of proteolysis and thinning of tissues= can have perforation)
Electrolyte imbalance: Na/water retention= edema and hypertension, hypokalemic alkalosis, hypocalcemia (caution with hypertensive patients)
Decreased skeletal growth in children
Decreased wound healing, increased infections (thrush from C. albicans)
Increased glaucoma, increased cataracts (via increased sorbitol) Sorbitol does osmotic damage to lens
Increased mental dysfunction
Side effects of glucocorticoids
466
What cells cause damage in asthma?
What is the main damage-causing agent?
How does the respiratory tract react?
What happens in the upper airways?
```
Eosinophils
Cationic protein in their membrane "MBP"- major basic protein, is what causes damage along the respiratory tract. Causes bronchial hyper reactivity (particularly bronchospasm )
With chronic inflammation and damage= hypertrophy and hyperplasia- thickening of bronchiolar wall
Increase in goblet cells= mucus secretion
```
467
What induces bronchoconstriction?
Acetylcholine
Adenosine
Leukotrienes
468
Acetylcholine
Adenosine
Leukotrienes
Inducers of bronchoconstriction
469
What inhibits acetylcholine (and thus inhibits bronchoconstriction)?
Ipratropium
470
What does Ipratropium do ?
Inhibits Acetylcholine and thus bronchoconstriction
471
What inhibits adenosine and thus bronchoconstriction?
Theophylline
472
What does theophylline do?
Inhibits adenosine and thus bronchoconstriction
473
What inhibits leukotrienes (and thus bronchoconstriction) and how?
-lukasts (zafirlukast) by blocking LTC4 and LTD4 receptors
| Zileuton by blocking the synthesis of LTC4 and LTD4 by blocking lipoxygenase
474
What drugs are widely used for relief of acute bronchoconstriction and in prophylaxis of exercise-induced asthma?
B-2 selective agonists (albuterol, metaproterenol, terbutaline)
475
These drugs used via inhalation cause bronchodilation in acute asthma, especially COPD patients, and they may be safer than B agonists in patients with CV disease
Ipratropium and other M blockers
476
What are the drugs of choice in bronchospasm caused by B blockers?
Ipratropium and other M blockers
477
What are the two ways in which theophylline bronchodilates?
1. Via inhibition of phosphodiesterase (PDE)= increase in cAMP
2. Antagonism of adenosine (a bronchoconstrictor)
478
What works in these ways to cause bronchodilation?
1. Via inhibition of phosphodiesterase (PDE)= increase in cAMP
2. Antagonism of adenosine (a bronchoconstrictor)
Theophylline
479
What is theophylline toxicity increased by?
Erythromycin
Cimetidine
Fluoroquinolones
480
Erythromycin
Cimetidine
Fluoroquinolones
Increase theophylline's toxicity
481
How do Cromolyn and Nedocromil work in asthma?
| MOA and prophylaxis:
MOA: Prevent degranulation of pulmonary mast cells and decrease release of histamine, PAF and LTC4 from inflammatory cells
Prophylaxis: decrease symptoms and bronchial hyperactivity (BHR), especially responses to allergens
482
MOA: Prevent degranulation of pulmonary mast cells and decrease release of histamine, PAF and LTC4 from inflammatory cells
Prophylaxis: decrease symptoms and bronchial hyperactivity (BHR), especially responses to allergens
How Cromolyn and Nedocromil work in asthma
483
What role to beclomethasone and flunisolide play in asthma?
They are surface-active drugs used via inhalation for both acute attacks and for prophylaxis
484
They are surface-active drugs used via inhalation for both acute attacks and for prophylaxis of asthma
beclomethasone and flunisolide
