Pharm 1 Flashcards
(125 cards)
1
Q
_ stimulates salivation by the submaxillary gland. _ blocks it
A
Pilocarpine
Atropine
2
Q
Pilocarpine and atropine produce their effects by acting on _ proteins of _
A
Muscarinic acetylcholine receptor proteins of salivary glands
3
Q
Which antagaonists can produce xerostomia?
A
Muscarinic
4
Q
Like pilocarpine and atropine, _ and _ have the same relationship but with a chicken gastrocnemius muscle
A
Nicotine and curare
5
Q
A and B with respect to Y compete based on what two things
A
How much of each is present
How well each can bind to receptor
6
Q
Dissociation constant =
A
[R] [L] / [RL]
7
Q
Interaction of a drug with a receptor is based on the law of _
A
Mass action
8
Q
Kd happens at _ binding to the receptor
A
1/2
9
Q
What is EC50?
A
The dose of the drug that produces 1/2 maximal effect
10
Q
What is a dose response curve?
A
Dose on x, change on Y
Shows pharmacological effect
11
Q
What are partial agonists?
A
Agonists that activate a low % of receptors and produce a partial effect
12
Q
What is drug efficacy and what is drug potency?
A
Efficacy: ability to confer the response after binding
Potency: ability of a drug to confer an effect
Potency = affinity and efficacy
13
Q
What are receptor gene families and why are they important in understanding pharmacology?
A
Receptors that differ in responsiveness to similar structures
One drug can elicit different effects in different contexts.
Explain why we need receptor specific agonists and antagonists and explains complexity of drug action
14
Q
EC50 vs. Keq
A
EC50 produces 1/2 maximal EFFECT
Keq produces 1/2 maximal BINDING
15
Q
Drugs with insufficient efficacy will be _ no matter how high their affinity
A
Partial agonists
16
Q
Antagonists efficacy
A
0
17
Q
4 types of signaling receptors
A
Ligand activated ion channels
G protein coupled
Ligand activated transcription factors
Tyrosine kinase receptors
18
Q
40% of all drugs are agonists or antagonists of _
A
A G protein coupled receptor
19
Q
The basis of transmission of nerve impulses is _
A
Activating and inhibiting ligand activated plasma membrane ion channels
20
Q
Ca release from the ER is mediated by
A
IP3
21
Q
4 steps in the G protein cycle
A
- Ligand binds to GPCR, GDP-GTP exchange
- complex falls apart into Galpha and GBetagamma
- Galpha hydrolyzes GTP to GDP and Pi
- Complex reassembles
22
Q
Which parts of the GPCR are the major and minor parts
A
Major is Galpha
Minor is GBetagamma
23
Q
What does adenylate Cyclase do
A
ATP -> cAMP + PPi
cAMP -> protein kinase A -> phosphorylation of many proteins causing many effects
24
Q
Activation of glycogenolysis is mediated by _
A
PKA
25
How do GPCR liberate signaling molecules from within phospholipids
Activate phospholipases which free them up
26
_ is the source of eicosinoid signaling molecules and prostaglandins
Arachidonic acid
27
Cleavage of _ by phospholipase C yields DAG and _
PIP2
| IP3
28
What turns off GPCR
Desensitization
29
Two fates of endocytosed receptor
Recycling
| Degradation
30
How does signaling by receptor tyrosine kinase work? (Steps)
```
Binding of ligand ->
dimerization of receptor (homo/hetero) ->
transphosphorylation of receptors ->
docking of signaling molecules ->
different cascades of signaling ->
Change in gene expression in cells
```
31
STAT proteins mediate _
Biological response to cytokines
32
Class 1 vs class 2 nuclear receptors
Class 1: binds to ligand on complex, complex falls apart, forms homodimer, binds to DNA
Class 2: binds to target DNA or corepressors, switches from corepressor to coactivator
33
Patient factors influencing drug effects
```
Body weight/composition
Age
Sex
Pregnancy
Environmental
Diet
Physiologic differences
Pathologic conditions
Genetic factors
```
34
Pharmacokinetic vs. pharmacodynamic tolerance
Kinetic: effective drug conc is diminished
Dynamic: response is diminished
35
Acute pharmacodynamic tolerance is called _
Tachyphylaxis
36
How does warfarin work?
Inhibits synthesis of vit. K dependent clotting factors (II, VII, IX, X)
Can lead to hemorrhaging
37
5 categories of drugs during pregnancy
A - no risks in humans
B - no risks in humans BUT animal studies bad OR no human studies, animal studies clear
C - no human and either no animal studies, or bad news animal studies
D - human fetal risk
X - human or animals BAD BAD. Risks outweigh benefit
38
Pharmacokinetic vs pharmacodynamic variations
Kinetic: response changes with drug concentration
Dynamic: diff response to drug
39
Most important oxidation polymorphic enzyme
CYP2D6
40
Why is CYP2D6 important
Poor metabolizers have higher incidence of bad effects (cevimeline isn’t metabolized as fast as it should be)
Need it to convert tamoxifen to endoxifen. W/o it, tamoxifen is less effective for breast cancer tx
Converts codeine to morphine
41
What do ryanodine receptors do?
Defect causes what
Mediate Ca mediated Ca release from SR in muscle
Malignant hyperthermia
42
% of americans that:
Take 1 prescription drug
At least 2
5+
70%
50%
20%
43
How does drug potentiation occur
```
One drug:
-Enhances absorption
-Alters distribution
-Inhibits elimination
Of another drug.
```
44
Types of pharmaceutical interactions
```
Antagonism
Potentiation
Unexpectation
Summation
Synergism
```
45
Pharmacokinetic interactions
Absorption
Distribution
Metabolism
Excretion
46
Most drugs metabolized in liver by _
Microsomal P450 enzymes
47
When does net efflux of K end
When the chemical force leading K outside is balanced by the electrical force bringing it back
48
Nernst equation
Vk = -60 mV log ([K]in/[K]out)
49
_ and _ are primarily responsible for maintaining homeostasis
Autonomic nervous sys
And
Endocrine
50
Synthesis of catecholamine NTMs
```
Tyrosine
DOPA
Dopamine -> norepinephrine -> epinephrine
I
V
Noradrenalin
```
51
Adrenergic vs cholinergic transmission at synapse. What happens to NTM
A: NE transported back into presynaptic terminal
C: Ach hydrolyzed in synapse
52
Rate limiting step of catecholamine synthesis
Tyrosine hydroxylase (tyrosine -> L-DOPA)
53
Alpha 1 receptors do what
Where are they
Increase Ca
Increase activity of myosin light chain kinase
Increase myosin light chain phosphorylation
Increase muscle contractility
Smooth muscle cells
54
Increasing Ca in the smooth muscle cell will do what to the cell
Constrict
55
Alpha 2 receptors are where and do what
Presynaptic termini
| Inhibit epinephrine and NE release
56
Beta 2 receptors on smooth muscle do what
```
Increase PKA
Phosphorylation and inhibit MLCK
Lower Ca levels
Inhibit MLCK
Diminish phosphorylation of MLC
Decrease muscle contractility
```
57
Beta 1 receptors on cardiac muscle cells do what
Activate PKA
Activate L type Ca channels
Increase Ca levels
Increase muscle contractility
58
Drugs that activate B1 in heart are used to do what
Improve contractility of failing heart
59
NE doesn’t activate _ receptors, but epinephrine does
B2
Epi activates a, B1 and B2
60
Why use NE or epi with local anesthetic
Keep anesthetic around longer due to vasoconstriction
61
Alpha1 receptor agonists do what
Produce contraction of vascular smooth muscle
| -increase BP
62
_ is sometimes used as a vasoconstrictor in conjunction with a local anesthetic
Levonordefrin
63
3 reasons to use a vasoconstrictor with a local anesthetic?
Which is the most common and second most common
1. Prolong duration of nerve block, increase success
2. Diminish systemic toxicity of anesthetic
3. Minimize blood loss during surgical procedure
64
What do alpha2 receptor agonists do
Inhibit epi and NE release from presynaptic termini in CNS
65
Beta1 agonists do what
Tx of heart failure and cardiogenic shock
66
Beta2 receptor agonists do what
Produce smooth muscle relaxation. Treat asthma, relax uterine wall
67
Adverse effects come from what 4 things
Too large a dose
Accidental intravascular injection
Heightened sensitivity
Patient with cardiovascular disease
68
Alpha 1 antagonists are used to treat what
Hypertension
Hemodynamics shock
Raynaud’s disease
69
3 alpha1 antagonists
Prazosin
Alfuzosin
Tamulosin
70
_ is used to reverse soft tissue numbness after local anesthetic
It is a _
Phentolamine
Non-selective alpha adrenergic receptor antagonist
71
Beta blockers are mostly used to block out _
What do they do
Beta1
Decrease heart rate and force of contraction
72
Beta blockers diminish _ release from the kidney
Renin
73
What is ISA and how does it affect beta blockers
Intrinsic sympathomimetic activity
(Partial agonists)
Low beta stimulation when using blockers. Don’t depress cardiac function as well but still attenuate agonist driven increases.
74
Therapeutic uses of beta blockers
```
Hypertension
Ischemic heart disease (reduce oxygen consumption by reducing CO)
Post MI
Congestive heart failure
Treat arrhythmias
```
75
A patient taking a beta blocker could have what kind of conditions
Moderate, well controlled
Serious disease
Anything in between
76
What can treat glaucoma
Beta blockers
77
Two drugs are alpha and beta receptor antagonists
Labetalol
| Carvedilol
78
```
Adverse effects of Beta blockers
Heart
Smooth muscle
Metabolic
CNS
```
Heart: bradycardia, AV block
Smooth muscle: reduce vasodilator responses, increase bronchospasms
Metabolic: hypoglycemia
CNS: depression, fatigue, sleep disturbances, hallucinations, dizziness
79
Alpha blockers can cause _ hypotension
Orthostatic
80
Who is at risk of a hypertensive episode after receiving local anesthetic with a vasoconstrictor?
Why?
Patient taking non-selective beta blocker
Doesn’t get B2 mediated vasodilation to counteract alpha mediated vasoconstriction
81
-zosin
Alpha1 adrenergic receptor blocker
82
-olol
Beta-adrenergic receptor blocker
83
-ilol, -alol
Beta-adrenergic receptor blocker with alpha1 activity
84
Two types of cholinergic receptors
Nicotinic and muscarinic
85
Nicotinic AcCHRs bind what?
What kind of receptor is it?
Structure of receptor?
Bind nicotine
Ligand activated ion channel
Receptors contain 5 subunits and bind two molecules of agonist
86
Difference in adult vs infant nicotinic receptors
Both have 2 alpha1, one Beta, one delta
Adult has one epsilon
Infant has one gamma
87
How many muscarinic receptors are there
They are _ receptors
5
G protein coupled receptors
88
M_, _, _ are linked to Galphaq
| M_, _ are linked to Galphai
M1,3,5 G-alpha-q
| M2,4 G-alpha-i
89
How can we figure out whether an Ach receptor is nicotinic or muscarinic?
Ask whether we want to depolarize across a membrane (nicotinic) or activate G protein coupled receptor (musc)
90
Two types of cholinergic agonists, how do they work
Direct: bind to nicotinic/muscarinic AcCh receptor or both
Indirect: cholinesterase inhibitor
91
Acetylcholinesterase breaks Ach into _ and _
Acetate
| Choline
92
Which is hydrolyzed faster b/t ach and methacoline? What is the effect
Ach is hydrolyzed faster, shorter duration
93
4 steps in neuromuscular transmission
Nicotinic Ach receptors activated, post-synaptic membrane de polarized
Local depolarization leads to action potential
Post synaptic depolarization leads to release of Ca from SR
Ca leads to muscle contraction
94
How do troponin and tropomyosin work?
Ca binds to troponin complex
Troponin causes tropomyosin to shift exposing myosin binding sites
Myosin binds actin
95
Muscle cross bridge cycle stops when
Ca levels drop
96
Which muscarinic receptors are stimulatory, which are inhibitory
1,3,5 are stimulatory
2,4 are inhibitory
97
_ receptors on the sphincter muscle mediate pupil constriction
M3 muscarinic
98
Cardiac muscle contains _ receptors and parasympathetic innervation. Activation of these receptors _
M2
| Reduce cardiac output
99
Most arteries and veins in the body are innervated by _ nerves
Sympathetic adrenergic
100
Vascular endothelial cells express _ receptors. When activated they produce vasodilation
M3
101
_ on the bronchial muscle mediate muscle constriction
M3 muscarinic receptors
102
Secretory glands are activated by _ receptors
M3
103
_ receptors mediate detrusor muscle contraction (voids bladder)
M3
104
3˚ vs 4˚ amine, which is better absorbed? Why?
3˚
| Pass through biological membranes better
105
Muscarinic agonists have what effect
SLUD
| Salivation, lacrimation, urination, defecation
106
Which anticholinesterases act in a completely irreversible manner
Malathion
Sarin
(Both organophosphate)
107
Anticholinesterases produce an effect that is similar to _
Direct acting cholinergic agonists
108
T/F anticholinesterases produce muscarinic mediated vasodilation
FALSE. They do not.
| Not much parasymp innervation of vascular endothelium
109
What is physostigmine and what does it do
Tertiary amine
| Produces vasodilator effects through action in the CNS
110
_ and _ (drugs) are frequently used to treat dry mouth
Pilocarpine
| Cevimeline
111
5 therapeutic used of cholinergic agonists and anticholinesterases
1. Glaucoma
2. Xerostomia
3. Reversal of neuromuscular block
4. ACE for treatment of Myasthenia Gravis
5. ACE cross BBB to improve cognitive function in Alzheimer’s
112
_ have the potential to cause significant CNS impairment
Antimuscarinics
113
Antimuscarinics usually place the target under control by _
Except _
Symp NS
Sweat glands (both S and PS act on muscarinic)
114
Anti-muscarinics cause _ in the eye
Pupil dilation
115
Anti-muscarinics are used to produce _ in the lungs
Bronchodilation
116
Heart and urinary respond how to antimuscarinics
Mild bradycardia
| Urinary retention
117
Quaternary amine anti-cholinergics are _ absorbed, have a _ therapeutic margin, and are _ tolerated
Poorly absorbed
Wide therapeutic margin
Well tolerated
118
Anti-cholinergic toxidrome
Hot, blind, dry, mad
119
_ receptors are important mediators in the CNS
Nicotinic Ach
120
Desensitization especially happens at _ receptors
Ach
121
Non-depolarizing blockers are competitive antagonists of _
Ach
122
Non-polarizing vs polarizing blockers onset of action and duration
Depolarizing has rapid onset and shorter duration
123
Intravenous infusion of neuromuscular blocking agents induces _
Flaccid paralysis
124
Neuromuscular blockers are used how in dentistry
Muscle relaxation for surgery
125
Adverse effects of neuromuscular blockers
Respiratory failure
