ANS-2 Flashcards
1
Q
Vasomotor reversal (VMR) of Dale
A
BP variation in a living system when epinephrine + α blocker is given
No rise in BP initially
Delayed decrease due to β2
2
Q
Dopamine and dose dependent property
A
Dopamine is selective towards certain receptors in certain concentrations
0-2 mcg/kg/min ➡️ D1
2-10 mcg/kg/min ➡️ β1
>10 mcg/kg/min ➡️ α1
3
Q
Major effects of dopamine at various concentrations
A
0-2 mcg/kg/min ➡️ D1 ➡️ diuresis ➡️ oliguria
2-10 mcg/kg/min ➡️ β1 ➡️ increased cardiac contraction ➡️ CHF
> 10 mcg/kg/min ➡️ α1 ➡️ vasoconstriction ➡️ cardiogenic shock
4
Q
Dopamine is DoC in
A
- Oliguria with CHF
2. Cardiogenic shock (over norepinephrine)
5
Q
Route of administration of dopamine
Side effect of dopamine
A
Continuous IV infusion (like dobutamine) since it has a very low half life
Arrhythmia (β1 stimulation)
6
Q
Dobutamine
Uses
A
Exogenous catecholamine
Agonist of β1»_space;> β2
No net effect at α1 (the 2 isomers of the racemic mixture cancel each other)
Uses:
1. Inotrope of choice in acute CHF (without oliguria)
2. Stress echocardiography
7
Q
Fenoldopam
A
- α2 agonist➡️ decreases NE➡️ decreases bp
- D1 agonist (like dopexamine)➡️ diuresis➡️ decreases bp
So used in hypertensive emergency (like dopexamine) via IV route
8
Q
Dopexamine
A
- β2 agonist➡️ decreases bp
- D1 agonist (like fenoldopam)➡️ diuresis ➡️ decreases bp
So used in hypertensive emergency (like fenoldopam)
9
Q
Isoprenaline or isoproterenol
A
Agonist of β1 and β2 receptors
Uses:
1. β1 ➡️ treating bradycardia and AV nodal block
2. β2 ➡️ bronchial asthma
SBP remains normal or increases slightly
DBP decreases
Significant increase in HR (action + feedback regulation due to vasodilation)
10
Q
Droxedopa
A
Prodrug of NE
Treatment of neurogenic postural hypotension
11
Q
Drugs which are α1 receptor agonists
A
- Phenylephrine-
- Tetrahydrozoline and xylometazoline-nasal decongestant
- Midodrine-postural hypotension
- Metarminol-
- Mephenteramine
- Methoxamine
12
Q
Phenylephrine
A
α1 (vasoconstriction) receptor agonist
- Treatment of anaesthetic agent induced hypotension
- Mydriatic
- Nasal decongestant (like xylometazoline and tetrahydrozoline)
13
Q
Xylometazoline and tetrahydrozoline
A
α1 (vasoconstriction) receptor agonist like phenylephrine
Nasal decongestant
14
Q
Midodrine
A
α1 (vasoconstriction) receptor agonist like phenylephrine, xylometazoline and tetrahydrozoline
DoC for postural hypotension
15
Q
Metarminol
A
α1 receptor agonist like phenylephrine,…
Treatment of hypotension caused by spinal anaesthesia
16
Q
Mephenteramine
A
α1 receptor agonist like phenylephrine,…
Treatment of hypotension caused by arrhythmia
17
Q
Methoxamine
A
α1 receptor agonist like phenylephrine,…
Treatment of shock
18
Q
Examples of α2 receptor agonist
A
These drugs decrease bp and have sedative effect
- Clonidine
- Dexmedetomidine: pre anaesthetic agent
- Apraclonidine and Brimonidine: glaucoma
- Tizanidine: muscle relaxant
- Lofexidine: opioid dependence
- Moxonidine and Rilmenidine
- α-methyl DOPA
- Guanfacine and Guanabenz: ADHD,..
19
Q
Clonidine
A
α2 receptor agonist
- DoC in treatment of hypertensive emergency
- DoC in tics associated with mild and moderate Taurette’s syndrome (otherwise Haloperidol)
- ADHD
- Prophylaxis of migraine
- Treating hot flashes
- Treating dependence of smoking, alcohol and opioids
- Diarrhoea associated with DM
- Used for pre anaesthetic medication
20
Q
Side effects of clonidine
A
α2 receptor agonist Withdrawal hypotension (treated by IV phentolamine)
21
Q
Dexmedetomidine
A
α2 receptor agonist like clonidine but highly potent Used as a pre anaesthetic agent 1. Sedation 2. Analgesia 3. Decreased secretions
22
Q
Apraclonidine and Brimonidine
A
α2 receptor agonist
Treating glaucoma
23
Q
Tizanidine
A
α2 receptor agonist
Used as a muscle relaxant in disorders like ALS (Amyotrophic lateral sclerosis)
24
Q
Lofexidine
A
α2 receptor agonist
Treating opioid dependence
25
Moxonidine and Rilmenidine
Imidazole receptor (decreases bp), α2 receptor agonist
Uses:
1. Resistant hypertension in elderly
2. Treating neuropathic pain
26
Methyl dopa
Prodrug which is converted into α-methyl NE
α2 receptor agonist and NE depletor
Treating PIH (pregnancy induced hypertension)
The DoC for PIH is oral labetalol
Side effect:
Haemolysis
27
Guanabenz
| Guanfacine
α2 receptor agonist
Both are used in treating ADHD
Guanfenacine is the DoC for treating tics associated with Taurette’s syndrome (along with clonidine)
28
Mirabegron
β3 agonist
Used in urge incontenence
Under trial for treatment of CHF
Side effects:
1. Decrease bp
2. Head ache
3. UTI
29
SABA examples
Short acting β2 agonists
Duration: 2-4 hours
Terbutaline-subcutaneous
Pirbuterol - inhalation
Albuterol (Salbutamol)- inhalation
These drugs are fast acting (along with formoterol)
30
LABA
Long acting β2 agonists
Duration: 12 hours
Salmeterol-slow acting
Formoterol-fast acting
Given via inhalation
31
VLABA
Very long acting β2 agonists
Duration: 24 hours
```
Carmoterol
Indicaterol
Olodaterol
Vilanterol
Given via inhalation for COPD
```
32
Fast acting β2 agonists and their uses
The fast acting β2 agonists are SABAs and formoterol
| There are used via inhalational route for the treatment of acute attacks of bronchial asthma
33
Uses of LABA
1. Prophylaxis of bronchial asthma
2. Prophylaxis of exercise induced asthma
3. With ICS for persistent bronchial asthma
4. Along with anticholinergics for COPD
5. Nocturnal asthma
34
The GINA (global initiative for asthma) guidelines
```
Age:
0-5 years: SABA
6-11 years: SABA+ICS
>11 years: ICS+ Formoterol (ToC)
(if not then SABA+ICS)
ICS decreases the severity of exacerbation of bronchial asthma
```
35
Side effects of β2 agonists
1. Tremors (most common)
2. Palpitations
3. Potassium levels:
Open K+ channels ➡️ transient hyperkalemia
Increases insulin ➡️ hypokalemia
So used in treatment of hyperkalemia
4. Hyperglycaemia
36
Tyramine
NE depletor
Dietary amine
Present in cheese and red wine
Can cause cheese reaction
37
Cheese reaction
Patient on MAO blockers (anti depressants) consumes wine or cheese ➡️ tyramine Increases ➡️ NE released into synapse ➡️ stimulates α1 receptors ➡️ hypertensive emergency
DoC: IV Phentolamine (α1 receptor blocker)
38
NE depletors
1. Tyramine : cheese reaction
2. Ephedrine (...) and Pseudoephedrine (nasal decongestant)
4. Norephedrine: was used for obesity
5. Methylphenidate
6. Amphetamine and dextroamphetamine
7. Guanedrel and Guanethidine
39
Ephedrine
1. NE depletor
2. Agonist of α and β receptor
So mixed acting sympathomimetic
1. DoC of hypotension in:
pregnancy
anaesthetic agents
2. Mydriatic
3. Nasal decongestant (along with it’s derivative pseudoephedrine)
40
Phenyl propanolamine or norephedrine
NE depletor
Was used for treatment of obesity
Now banned because associated with stroke
41
Methylphenidate
NE depletor and stimulant
Uses:
1. DoC for ADHD with 2 exceptions where the DoC is Atomoxetine
2. In narcolepsy where the DoC is Modafinil
42
Use of a NE depletor in ADHD
Methylphenidate is the DoC in ADHD except in:
1. ADHD with Tourette’s syndrome where it worsens tics
2. ADHD with family history of drug abuse due to risk of drug abuse
In these two cases Atomoxetine (an anti depressant which is a NE reuptake inhibitor)
43
Modafinil
DoC for:
1. Narcolepsy (Solriamfetol, a DNRI -dopamine NE reuptake inhibitor, can also be used)
2. Shift workers disease
3. Sleepiness associated with OSA -obstructive sleep apnea
44
Amphetamines
```
NE depletor and Stimulant
So is used are similar to methylphenidate:
1. ADHD
2. Narcolepsy
3. Obesity because it causes anorexia
```
It’s derivative dextroamphetamine is specific for central action so it is more preferred
45
Methamphetamine
Drug of abuse
| Also called Cristal meth
46
Why are amphetamines contraindicated in pregnancy
Amphetamines are teratogenic:
1. IUGR
2. Cardiac defect
3. Cleft lip
4. Biliary atresia
47
Guanethidine and guanadrel
NE depletor
Can be used for hypertension
These are contraindicated in pheochromocytoma (because of initial sympathomimetic effect leading to a cheese reaction like situation)
48
Anti glaucoma drugs
1. Miotic agents: increase trabecular outflow
2. Prostaglandin analogues: increases the uveoscleral outflow
3. Sympathomimetics
4. β blockers (selective or non-selective): decrease aqueous production
5. CA inhibitors
49
Miotic agents as anti glaucoma drugs
Miotic agents like pilocarpine, physostigmine, echothiophate, carbochol used in closed (and open) angle glaucoma to increase trabecular outflow
Stimulate M3 receptors
DoC for closed angle is pilocarpine
50
Side effects of using miotic agents as anti glaucoma drugs
Stimulates M3 receptors
1. Ciliary body or accommodation spasm
2. Induced myopia
3. Retinal detachment
4. Corneal oedema
5. ACHE inhibitors like physostigmine and echothiophate when given typically cause cataract (so contraindicated in phacic patients)
6. Echothiophate can cause iris cysts or NLD obstruction
51
Prostaglandin analogues and glaucoma
Latanoprost, Bimatoprost, Travoprost are PGF2α analogues
Increases the uveoscleral outflow
Given OD topically at night
DoC for open angle and normal tension glaucoma
52
Side effects of prostaglandin analogues
P. Pigmentation of iris or (heterochromia iridis), eyebrow and periorbital skin (increases effect of tyrosinase)
C. Cystoid macular oedema (careful in DM)
O. Overgrowth of eyelashes (trichomegaly): so bimatoprost is used in hypotrichosis (anti cancer drug)
S. Sandy or dry eyes
53
Contraindications of prostaglandin used as anti glaucoma drugs
Contraindicated in patients with:
1. Uveitis
2. Herpetic keratitis
54
Sympathomimetics used as anti glaucoma drugs
1. Epinephrine
2. Dipivephrine (prodrug of epinephrine)
3. α2 agonists like apraclonidine and ovimonidine
Used via topical route for open angle glaucoma
55
Mechanism of anti glaucoma action of sympathomimetics
1° mechanism of action is decreased aqueous production
| 2° mechanism of action increased uveoscleral outflow
56
Side effects of sympathomimetic used as anti glaucoma drugs
1. Common side effect is ocular allergy
2. Epinephrine and Dipivephrine cause conjunctival pigmentation
3. Apraclonidine-(α1 and) α2 agonist:
α1 stimulation ➡️ mydriasis, lid retraction, conjunctival blanching
4. Brimonidine α2 agonist which crosses BBB so:
sedation, drowsiness and fatigue
apnea in neonates
dry mouth, hypertension
57
β blockers as anti glaucoma drugs, examples
```
Non selective β blockers like:
Timolol (most potent)
Levobunolol
Metipranolol
Carteolol
And selective β blockers like Betaxolol (longest acting)
```
58
How β blockers act as anti glaucoma drugs
| When are they used
Decrease aqueous production
| 2nd line drug for open angle glaucoma after latanaprost,...
59
Side effects of β blockers as anti glaucoma drugs
1. Contraindicated with systemic β blockers
2. Contraindicated with patients with bronchial asthma or COPD, esp non selective β blockers
3. Timolol can cause NLD obstruction and ocular cicatricial penphigoidnd
4. Metripranolol can cause granulomatous anterior uveitis
60
CA inhibitors used as anti glaucoma drugs
```
1. Systemic drugs - acetazolamide:
Oral or IV
For acute congestive glaucoma
2. Topical drugs -
Brinzolamide, Dorzolamide
For open angle glaucoma
```
61
Side effects of CA inhibitors as anti glaucoma drugs
Systemic (acetazolamide):
1. Metabolic acidosis
2. Hypokalemia
3. Hyperammonemia
4. Nephrolithiasis
Local (Brinzolamide, Dorzolamide):
1. Transient myopia
2. Periorbital dermatitis
3. Corneal oedema
62
Netarsudil
Approved recently
Rho kinase inhibitor➡️ increases trabecular outflow
For treatment of open angle glaucoma
Latanaprost and Netarsudil fixed combination
63
Sympatholytic drug classification
```
A. α-receptor blockers:
1. Non selective
(reversible and irreversible)
2. Selective
B. β-receptor blockers
```
64
Tolazoline
```
Reversible, non-selective α receptor blocker
Peripheral vasodilator
Used in:
1. Raynaud’s disease
2. Vasodilator in angiography
```
65
Phentolamine
Reversible, non-selective α receptor blocker
DoC in:
1. Clonidine withdrawal hypertension
2. Cheese reaction
3. Intraoperative HTN in pheochromocytoma
Used in:
1. Treating erectile dysfunction
66
Drugs used in erectile dysfunction
```
Phentolamine pyar
Bremelanolatide bhi
Naltrexone nahi
Ketanserin kar
S. Sildenafil (DoC)
A. Alprostadil
K.
T. Trazodone
A. AlVIPtadil
```
67
Bremenelotide
Melanocortin peptide receptor agonist
1. α-MSH melanocortin ➡️ MC1R ➡️ pigmentation
2. ACTH ➡️ MC2R
3. Miscellaneous ➡️ MC3,4,5R ➡️ central sexual arousal
treatment of HSDD, erectile dysfunction
68
Phenoxybenzamine
Irreversible non-selective α-receptor blocker
| DoC for preoperative HTN in pheochromocytoma
69
Treatment of choice for pheochromocytoma
α-blockers followed by β-blockers to avoid HTN emergency
70
Subtypes of α1 receptors
| Significance
α1a: prostatic urethra, iris
α1b: blood vessels
α1d: blood vessels
71
Non-selective α1 blockers
| Uses
1. Vasodilation and prostatic urethra dilation
2. They increase HDL and decrease LDL
DoC for:
1. Benign prostatic hyperplasia and HTN.
But the vasodilation is non selective (veins also dilated) ➡️ postural hypotension (1st dose effect) ➡️ night time dosing.
2. HTN with dyslipidemia
72
Non selective α1 blockers
| Examples
1. Terazosin
2. Doxazosin
3. Prazosin- Scorpion bite induced HTN or pulmonary oedema
4. Alfuzodin-BPH
Drugs used for HTN:
5. Bunozosin
6. Inforamin
7. Urapidil
73
Scorpion bite pharmacological treatment
```
Prazosin:
Non selective α1 blockers
Scorpion bite induced HTN or pulmonary oedema
Midazolone: CNS excitation
Atropine: bradycardia
```
74
DoC for HTN with BPH or dyslipidemia
| Examples:
Non selective α1 blockers
1. Terazosin
2. Doxazosin
3. Prazosin (scorpion bite)
75
Selective α1 blockers (α1a blockers)
Silodosin
Tamsulosin-most selective
DoC for BPH benign prostatic hyperplasia
76
Side effects of α1 blockers
Prostatic urethra block ➡️ ejaculation abnormalities
Floppy iris
Side effects are maximum in tamsulosin
They are more in α1a blockers
77
Uses of β blockers
1. 2nd line drug for hyperreninemic HTN
2. Prophylaxis of migraine
3. Hyperthyroidism
4. Anxiety
5. Stable angina
Propranolol is DoC for the above 4 conditions if they occur with HTN
6. Chronic CHF
7. History of MI
8. DoC for HOCM (digoxin is CI)
9. DoC for aortic dissection
10. Glaucoma
78
Non-selective β blockers
First generation β blockers
| Blocks β1 and β2 receptors
79
Effects of non-selective β blockers/first generation β blockers
(and hence CI in)
Blocks:
1. Bronchodilation (bronchial asthma)
2. Vasodilation (Raynaud’s disease,variant angina)
3. Symptoms of hypoglycaemia except sweating (DM)
4. Glycogenolysis and gluconeogenesis in skeletal muscle-decreased muscle capacity
80
Selective β blockers
Block β1 only, less side effects
1. Propranolol
2. Oxprenolol
3. Pindolol
4. Timolol
5. Nadolol
81
Cardioselective β blockers
```
Blocks β1 >> β2
My. Metoprolol
B. Bisoprolol, ‘Betaxolol’
E. Esmolol
T. aTenolol
A. Acebutolol
O.
N. ‘Nebivolol’-most cardioselective
C. ‘Celiprolol’
E.
‘These 3 are’ 3rd generation
Remaining are 2nd generation
```
82
Third generation β blockers
```
Cardioselective
or
(non cardioselective + vasodilation effect) β1 blocker
```
83
Third generation β blocker with α1 blocking action
Labetolol
Carvedolol
Bevantolol
Bucindolol
84
Features of carvedilol
```
Third generation β1 blocker with α1 blocking action
Calcium channel blocker
Antioxidant (like Nebivolol)
Anti inflammatory
Blocks LDL oxidation
```
85
β1 blocker and β2 agonist
Bopindolol
86
Third generation β blocker which increases the release of NO
N. Nipradilol
| N. Nebivolol (antioxidant)- most cardioselective
87
Third generation β blocker with K+ channel opening activity
Tilisolol
88
β blockers which are partial agonist and intrinsic sympathomimetic effect
Examples
C. Celiprolol (cardioselective), Carteolol
L. Labetolol
A. Acebutolol (cardioselective)
P. Pindolol (maximum intrinsic sympathomimetic effect), Penbutolol
89
β blockers which are partial agonist and intrinsic sympathomimetic effect
Properties
1. Less bradycardia
2. Not used in:
migraine prophylaxis
MI
90
β blockers which are Na+ channel blockers and has local anaesthetic and membrane stabilising effect
Examples
Can. Carvedilol (max Na+ channel blocking action)
Blow. Betaxolol (min ... effect, cardioselective)
L. Labetolol
A. Acebutolol (cardioselective)
M. Metoprolol
P. Pindolol, Propranolol (max Na+ channel blocking action)
91
β blockers which are Na+ channel blockers and has local anaesthetic and membrane stabilising effect
Properties
Not used as topical agents against glaucoma (except cardioselective Betaxolol)
Due to their anaesthetic effect
92
Water soluble β blocker
| Properties
CI in renal failure
| Do not cross BBB, no central side effects like insomnia, depression or nightmares
93
Water soluble β blockers examples
```
B. Betaxolol (cardioselective, bisoprolol
A. Atenolol (cardioselective)
N. Nadolol
A.
N. Nebivolol (most cardioselective)
A. Acebutolol (cardio selective)
S. Sotalol
Chips-Celiprolol (cardioselective)
```
94
Longest acting β blocker
Nadolol
| Water soluble selective first generation β blocker
95
Shortest acting β blocker
| Uses
Esmolol
2nd generation cardioselective β blocker metabolised by esterase of RBCs
Used in:
1. Emergency in PVST (paraoxysmal supraventricular tachycardia)
2. Intraoperative use
96
β blocker with maximum plasma protein binding
Carvedilol
1. Third generation β blockers
2. Na+ channel blockers and has local anaesthetic and membrane stabilising effect
3. α1 blocking action
4. Calcium channel blocker
5. Antioxidant (like Nebivolol)
6. Anti inflammatory
7. Blocks LDL oxidation
8. Minimum bioavailability
97
β protein with minimum plasma protein binding
Celiprolol
3rd generation water soluble cardioselective β blocker
Has partial agonist and intrinsic sympathomimetic effect
98
β blockers with maximum (100%) bioavailability
```
Penbutolol
Pindolol (1st generation selective β blocker)
Both these drugs partial agonist and intrinsic sympathomimetic effect
```
99
β blockers with minimum (30%) bioavailability
```
Carvedilol
Propranolol (1st generation, max Na+ channel blocking, local anaesthetic and membrane stabilising effect)
```
100
Metabolic effects of different generations of β blockers
```
1. 1st generation: negative effect
Increased insulin resistance
Hyperglycaemic
Increased LDL/HDL ratio
2. 2nd generation: neutral
3. 3rd generation: positive effect
Opposite of 1st generation
```
