Indirect Sympathomimetics. Selective a1 agonists. Select alpha 2 agonists and drugs acting on the imidazoline receptors. Flashcards
1
Q
Indirect sympathomimetics: Name the Releasers
A
- Amphetamine
- Tyramine
- Ephedrine
- Norpseudoephedrine
- Modanifil
- Methylfenidate
- Dexmethylfenidate
2
Q
Amphetamine
- Action
- Clinical use
- Characteristics
A
- Amphetamine is an indirect sympathomimetic
- It promotes the release of NT from the nerve terminals
Action:
- Amphetamine increases the BP - (via a1 (vasculature) and b1 (heart) stimulation)
- Psychostimulant: it is a mood stimulant and increases alertness
- When it is abused it can result in euphoria
- Decreases appetite
Clinical use:
- ADHD
Characteristic:
- Orally active
- Long action of duration
- Enters CNS very easily and releases biological amines
3
Q
Tyramine:
- Clinical use
- Characteristics
- Treatment
A
- Tyramine is a releaser
Clinical use:
- It is not clinically used
Characteristics:
- Tyramine is present in foods such as cheese and red wine.
- It is metabolised and inactivated by MAO-A in the GIT
- On those in MAO-A inhibitors that injest tyramine means that tyramine is not inactivated by MAO-A and therefore tyramine reaches the systemic circulation and increases the sympathetic tone by releasing NE
- Results in hypertensive crisis
Treatment:
- Treatment of tyramine induced hypertensive crisis is Phentolamine (a non selective alpha receptor antagonist)
4
Q
Norpseudoephedrine:
- Clinical use
- Characteristic
A
- Norpseudoephedrine is a releaser
Clinical use:
- Nasal decongestant
Characteristics:
- Used with ibroprofen and antihistamines
5
Q
Modanifil
- Clinical use
A
- Modanifil is a releaser
Clinical use:
- Narcolepsy
6
Q
Methylfenidate
- Clinical use
A
- Methylfenidate is a releaser
Clinical use:
- ADHD
7
Q
Dexmethylfenidate
- Clinical use
A
- Dexmethylfenidate is a releaser
Clinical use:
- ADHD
8
Q
Cocaine:
- Action
- Clinical use
- Adverse effects
- Treatment
A
- Cocaine is a reuptake inhibitor
Action:
- It blocks dopamine and NE reuptake by blocking the Na+/K+ ATPase in the CNS and the periphery
- Its sympathomimetic actions in the CNS result in euphoria
Clinical use:
- Local anaesthetic
Adverse effects:
- Nasal septum perforation - this is because it also has intrinsic alpha 1 receptor agonist action and therefore causes vasoconstriction leading to nasal ischemia.
- Dilated cardiomyopathy
- Drug abuse
Treatment:
- Phentolamine
9
Q
TCA: Desipramine and Amitriptyline
- Action
- Clinical use
- Adverse effects
A
- TCAs are reuptake inhibitors
Action:
- They block NE reuptake in the CNS and the periphery
Clinical use:
- Depression
Adverse effects:
- Arrhythmias
- Change in BP
- alpha and M blockers may complicate their autonomic actions
10
Q
Name the TCA
A
- Amitryptyline
- Desipramine
11
Q
Name the irreversible non-selective MAO inhibitors
A
- Tranylcypromine
- Phenelzine
- Pargyline
12
Q
What is are Tranylcypromine, Phenelzine and Pargyline used for?
Why are they no longer recommended?
A
- Depression
- No longer used as they are non-selective MAO inhibitors so the ingestion of Tyramine can result in Hypertensive crisis
13
Q
Name the irreversible MAO-B inhibitors
A
Selegiline
14
Q
What is Selegiline used for?
A
Parkinsons
15
Q
What type of MAO inhibitor is Selegiline?
A
Irreversible MAO-B inhibitor
16
Q
What does MAO-A metabolise?
A
NE and serotonin
17
Q
What does MAO-B metabolise?
A
Dopamine and tyramine
18
Q
Name the reversible MAO-A inhibitors
A
Moclobemid
19
Q
What is Moclobemid used for?
A
Mental depression
20
Q
What type of MAO inhibitor is Moclobed?
A
Reversible MAO-A inhibitor
21
Q
What are the selective alpha 1 agonists?
A
Phenylephrine
Methoxamine
Midodrine
22
Q
Phenylephrine
- Action
- Clinical use
- Characteristics
A
Action:
- Phenylephrine is a selective alpha 1 receptor agonist
- It results in vasoconstriction which increases BP
Clinical use:
- Nasal decongestant (topical or oral)
- Ophthalmologic use (mydriasis without cycloplegia)
- Hypovolemia or shock: increased SBP and DBP results in reflex bradycardia
Characteristics:
- Not used as a systemic drug as it is dangerous
- It replaces pseudoephedrine as a nasal decongestant
- It is not inactivated by COMT as it is a catechol derivative
23
Q
What sort of drug is Phenylephrine?
A
It is a selective alpha 1 receptor agonist
24
Q
What are the clinical uses of Phenylephrine?
A
- Nasal decongestant (topical or oral)
- Hypovolemia or shock
- Ophthalmologic uses
25
What is the mechanism of action of Phenylephrine?
It results in vasoconstriction which increases BP
26
What is the mechanism of action of Methoxamine?
It results in vasoconstriction which increases BP
27
What is the mechanism of action of Midodrine?
It results in vasoconstriction which increases BP
28
When do we use Methoxamine?
- Paroxysmal atrial tachycardia (PAT) through the vagal reflex
29
How is Methoxamine administered?
- Parenteral use
30
Methoxamine:
- Action
- Clinical use
- Characteristic
Action:
- Methoxamine is a selective alpha 1 receptor agonist
- It results in vasoconstriction which increases the BP
Clinical use:
- PAT through the vagal reflex
Characteristic:
- Parenteral use
31
Midodrine:
- Action
- Clinical use
- Characteristcs
- Midodrine is a selective alpha 1 receptor agonist
- it results in vasoconstriction that increases the BP
Clinical use:
- Orthostatic hypotension due to impaired ANS
Characteristics:
- Prodrug that is enzymatically hydrolysed to desglymidodrine, which is a selective a1 agonist
Adverse effects:
- Hypertension when patient is supine
32
What is Midodrine used for?
Orthostatic hypotension due to impaired ANS
33
Which alpha 1 receptor agonist is a prodrug?
What is the prodrug converted to?
Midodrine
Desglymidodrine
34
What are the adverse effects of Midodrine?
Hypertension when the patient is supine
35
What are the selective alpha 2 agonists?
```
Clonidine
Methyldopa
Guaficine
Tizanidine
Dexmedetomidine
```
36
Clonidine:
- Action
- Clinical use
- Characteristics
- Adverse effects
- Clonidine is a selective alpha 2 agonist
Action:
- Centrally: it acts on the presynaptic alpha 2 receptors in the solitary tract nucleus of the medulla, resulting in a decrease in BP
- Peripherally:
- acts on alpha 2 receptors resulting in negative feedback
- It stimulates I1 receptors in rostral ventrolateral medulla which results in a decrease of SY outflow
Clinical use:
- Hypertension
- Nasal decongestant
- Perianesthetic medication
- Diarrhoea in diabetics
- ADHD
- Glaucoma
- Minimizes symptoms of withdrawal from opiates, tobacco and benzodiazepine
Characteristics:
- Imidazole derivative
- Do not use in sedation, xerostomia and constipation as they are parasympatholytic effects
Adverse effects:
- Lethargy
- Sedation
- Constipation
- Xerostomia
- Rebound HTN if there is abrupt discontinuation of the drug
37
What are the clinical uses of Clonidine?
- Hypertension
- Nasal decongestant
- Perianesthetic medication
- Diarrhoea in diabetics
- ADHD
- Glaucoma
- Minimizes symptoms of withdrawal from opiates, tobacco and benzodiazepine
38
What are the adverse effects of Clonidine?
- Lethargy
- Sedation
- Constipation
- Xerostomia
- Rebound HTN if there is abrupt discontinuation of the drug
39
What is the action of Clonidine?
- Centrally: it acts on the presynaptic alpha 2 receptors in the solitary tract nucleus of the medulla, resulting in a decrease in BP
- Peripherally:
- acts on alpha 2 receptors resulting in negative feedback
- It stimulates I1 receptors in rostral ventrolateral medulla which results in a decrease of SY outflow
40
What type of drug is Guaficine?
It is a selective alpha 2 agonist
41
What is the action of Guaficine?
Centrally acting selective alpha 2 agonist
42
What is Guaficine used for?
HTN
43
What type of drug is methyldopa?
It is a selective alpha 2 agonist
44
Methyldopa:
- Action
- Clinical use
- Characteristics
Action
- Methyldopa enhances the negative feedback at NE terminals
- It is a competitive inhibitor of DOPA-decarboxylase
Clinical use:
- Mild to moderate HTN
- HTN in pregnancy
45
What does Methyldopa inhibit?
It is a competitive inhibitor of DOPA-decarboxylase
46
What are the clinical uses of Methyldopa?
- Mild to moderate HTN
| - HTN in pregnancy
47
What type of drug is Tizanidine?
It is a selective alpha 2 receptor agonist
48
What is Tizanidine used for?
Centrally acting skeletal muscle relaxant
49
What are the adverse effects of Tizanidine?
Sedation
50
What type of drug is Dexmedetomidine?
It is a selective alpha 2 receptor agonist
51
What is Dexmedetomidine used for?
Sedation of initially intubated and mechanically ventilated patients during treatment in the ICU
52
Which drugs act on the Imidazoline receptors?
Moxonidine
| Rilmenidine
53
What is Moxonidine and Rilmenidine used for?
HTN
54
What is the action of Moxonadine and Rilmenidine?
- They decrease SY out flow
| - They have more selective binding to I1 receptors and less affinity to alpha 2 receptors
55
What are the adverse effects of Moxonadine and Rilmenidine?
- Dry mouth (but less than with Clonidine)
| - Sedation
