Pharmacology of moderate sedation Flashcards
1
Q
What are the most common type of receptors?
A
Cell membrane receptors
2
Q
Are cell membrane receptors easy to isolate?
A
no
3
Q
Types of cell membrane receptors
A
- Cell wall
- Cytoplasmic
- Nuclear
4
Q
The most significant portion of the plasma membrane
A
Phospholipid bilayer
5
Q
Parts of transmembrane receptors
A
Intracellular
Extracellular
6
Q
Types of receptors
A
Ion channel linked
G protein linked
Enzyme linked
Intracellular
7
Q
What kind of receptors do local anaesthetics work on?
A
Ion channel linked
8
Q
What are the kinds of Ion channel linked receptors?
A
Voltage gated
Ligand gated
9
Q
What kind of receptor do sedatives work on?
A
G protein linked
10
Q
What kind of receptor does insulin work on?
A
Enzyme linked
11
Q
What kind of receptors do steroids work on?
A
Intracellular
12
Q
Examples of voltage gated channel linked receptors
A
Sodium channels with LA
SA Node
13
Q
How do ligand gated channels work?
A
They are activated after ligand-drug binding
14
Q
G-protein-linked receptors aka
A
Metabotropic receptors
15
Q
How do G-protein linked receptors work
A
They amplify biologic signal by G protein activation
16
Q
What system is integral to the function of G protein linked receptors
A
Second messenger system
17
Q
Activity of what enzyme triggers the second messenger system?
A
Adenyl cyclase
18
Q
What enzyme causes increase in intracellular function?
A
Protein Kinase A
19
Q
What receptors form half of ALL drug binding sites?
A
G protein linked receptors
20
Q
Give an example of a drug that uses G-protein linked receptors
A
Epinephrine
21
Q
Gs?
A
Stimulatory
22
Q
Gi?
A
Inhibitory
23
Q
What kinds of receptors are Beta 1 receptors?
A
Gs - G-protein linked stimulatory receptors
24
Q
What works on Beta 1 receptors?
A
Norepinephrine
25
How do B1 receptors work?
Norepinephrine acts on B1 receptors to increase heart rate
26
Where are Beta 1 receptors located?
Heart
27
Give an example of a Gi Receptor
Alpha 2 receptors
28
Role of Alpha 2 receptors
Autoregulation of Norepinephrine ---> vasoconstriction
29
Gq receptors - example
Alpha 1 receptors
30
Location of Alpha 1 receptors
Arterioles
31
What is the significance of G-protein linked receptors in dentistry?
LA activates Beta 1 receptors (Gs) and Alpha 1 receptors (Gq) leading to increased heart rate and increased vasoconstriction
32
What kinds of receptors act very quickly?
Enzyme linked receptors
33
How do enzyme linked receptors work?
Binding site on cell membrane activates cytoplasmic enzymatic activity
34
What receptors do cytokines work on?
Enzyme linked receptors
35
What receptors do growth factors work on?
Enzyme linked receptors
36
What kind of receptors act slowly?
Intracellular receptors
37
Why do intracellular receptors act slowly?
Their activation leads to increase in DNA activity
38
What kind of receptors do glucocorticoids work on?
Intracellular receptors
39
What kind of receptors do mineralocorticoids work on?
Intracellular receptors
40
What kind of receptors do sex steroids work on?
Intracellular receptors
41
What basic kinds of substances act on intracellular receptors?
Lipophilic substances
42
How long does it take for the effect of an orally administered drug to be evident when acting on intracellular receptors?
1 day
43
Duration required for evidence of action of IV administered drug to be apparent when acting on intracellular receptors
several hours
44
What drugs are receptor independent?
NSAIDs
45
How do NSAIDs work?
They alter enzyme activity
46
How do receptor independent drugs work?
They work on enzymes to produce natural ligands for receptors
47
Demonstrate downstream effect with NSAIDs
NSAIDs ---> Inhibit COX ---> inhibit production of prostaglandins ---> inhibit inflammatory response
48
Where does arachidonic acid come from?
Cell wall
49
Types of receptor independent drugs
- Alteration of enzyme activity
- Chemically reactive
- Physically active
- Counterfeit biochemical substances
50
Example of physically active drug
Hydrogen peroxide
51
Name agonists of BZD receptors
Diazepam, Lorazepam, Midazolam
52
How does Flumazenil interact with BZD receptor?
Competitive antagonist
53
What kind of drugs elicit responses that are the same as natural ligands?
Agonists
54
Example of a full agonist
Dobutamine - epinephrine
55
What is the difference between full agonists and partial agonists?
Full agonists don't have a ceiling response
56
What is the difference between partial agonists and partial antagonists?
Semantics
57
What is the difference between agonists and antagonists?
Antagonists have no intrinsic activity
58
A drug that blocks agonist or natural ligand is a....
An antagonist
59
What are the different kinds of antagonists?
Competitive and non-competitive
60
What are the most dangerous kinds of antagonists?
Non-competitive antagonists
61
Examples of non-competitive antagonists
Serin nerve gas
| Malathion
62
Why are non-competitive antagonists so dangerous?
They bind and sit at the receptor forever - and are therefore lethal
63
What kind of drug is used to reverse the toxic effects of an agonist?
Competitive antagonist, because it displaces the agonist or ligand.
64
What kind of drug is flumazenil
it is the competitive antagonist of diazepam
65
How do you treat diazepam toxicity?
Flumazenil
66
IS standard dose the same for everyone?
No
67
Why does standard dose vary?
Some people are super-responders and some are slow-responders
68
How effective is titration of drug?
Very hard with orally administered drugs, easier with IV activity and Nitrous oxide.
69
What is therapeutic index?
LD50 / ED50
70
What does CSM Stand for
Certain safety margin
71
How is TI related to the quality of the drug?
Greater the TI better the drug
72
How are TI and CSM related?
High TI and low CSM for the same drug is bad because that means that the drug has an overlapping region for maximum efficacy and the beginning of the lethal dose
73
Give an example of supra additive drugs
Benzodiazepines (valium, versad) and opioids (Fentanyl, Demirol, Morphine)
74
Give an example of potentiation
Epinephrine and SNRI's
75
SNRI's
Serotonin norepinephrine reuptake inhibitors
76
Potentiation
Prevention of reuptake of drug from synapse leading to prolonged action
77
Massive rebound hypertension
On stoppage of beta blockers after chronic usage, receptor downregulation leads to massive hypertension.
78
What is the major mechanism of drug absorption
Passive diffusion
79
Aquaporins
very small water soluble drugs
80
How do lipid soluble drugs get absorbed?
Transcellular diffusion aided by thin capillary walls
81
How do small hydrophilic drugs get absorbed?
Paracellular diffusion across intercellular clefts
82
Specialty of the Blood brain barrier
Very tight endothelial junctions, meaning only lipophilic drugs can cross
83
How are drugs transported away from the brain
Extensive transporter system to export drugs, prominently P-glycoprotein
84
Which part of the placenta protects it from drug entry?
Trophoblastic membrane
85
2 superfamilies of transporters (active transport)
SLC
| ABC
86
SLC transporters
Solute carriers
87
ABC transporters
ATP binding cassette transporters
88
Which drug is used in Parkinson's to bypass the BBB?
Levodopa
89
Which transporters are bidirectional?
SLC family - cotransport with Sodium potassium ATPase pump
90
Which transporters are unidirectional?
ABC family - primary active transport using ATP
91
Major plasma proteins to bind drugs
Albumin (over 200 ionised functional groups)
| Alpha acid glycoprotein (basic drug binding)
92
Protein binding of Diazepam
98%
93
Protein binding of Midazolam
95%
94
Protein binding of Fentanyl
85%
95
Protein binding of Meperidine
60%
96
Tissue reservoirs
VRG (vessel rich group)
Muscle
Fat
Vessel poor group
97
Hangover effect
Clinical effectiveness of a drug is based on its tissue redistribution and not its metabolism
98
Descending order of blood flow of tissue reservoirs
VRG (75% )> Muscle (19%) > Fat (6%) > Vessel poor group (<1%)
99
Lipid solubility
Directly proportional to:
1. Potency
2. Speed of onset
3. Fraction in CNS
Inversely proportional to:
1. Peripheral toxicity
2. Duration of action
100
Phases of Hepatic drug metabolism
```
Phase I:
Oxidation (CYP 450)
Reduction
Hydrolysis
Dehalogenation
```
Phase II:
Conjugation reactions
101
What type of protein is cyp 450?
Hemoprotein
102
CYP Isozymes
CYP3A > CYP2D6 > CYP2C > CYP1A2 > CYP2E1
103
Drugs that can have an effect on CYP are of what types?
1. Enzyme substrate
2. Enzyme inducer
3. Enzyme inhibitor
104
What other reactions can be affected by drugs that affect CYP450?
None except glucuronidation
105
Enzyme inducer
increases CYP enzyme activity
106
List CYP 3A4 inhibitors
- Antiarrhythmics
- Antifungals
- Antiinfectives
- Calcium channel blockers
- Proton pump inhibitors
- Protease inhibitors
- SSRI's
- Leukotriene modifiers
- Cannabinoids
107
Depending on prevalence of CYP2D6, classify people
- Extensive metabolism
- Ultrarapid metabolism
- Intermediate metabolism
- Poor metabolism
108
What sedative drugs are at high risk of interaction with CYP3A4 inhibitors?
Midazolam and triazolam
109
What sedative is not CYP metabolised and hence can be given alongside CYP inhibitors without adverse reaction?
Lorazepam
110
What sedative drug is metabolised with multiple CYP enzymes?
Diazepam
111
beta half life
time it takes for drug to leave body after equilibration has occurred
112
alpha half life
redistribution half life
113
Why are subsequent IV doses lesser than the first dose?
1. Plasma Protein loading
| 2/ Residual receptor occupancy
114
clinical sedation time vs residual sedation
Clinicall determined by redistribution and residual (hangover) based on elimination
115
Drug interaction types
Pharmacodynamic (action of drug)
Pharmacokinetic (distribution of drug)
Pharmaceutical (mixture of drugs)
116
Pharmacodynamic interactions
1. Drug receptor interactions (agonist + antagonist)
| 2. Receptor independent actions (block reuptake or affect enzyme activity)
117
How many doses at the end of each beta half life does it take for steady state drug concentration?
4
118
Terminal elimination half time
6 half times required for close to 100% of the drug being eliminated
