ANS-2 Flashcards
Vasomotor reversal (VMR) of Dale
BP variation in a living system when epinephrine + α blocker is given
No rise in BP initially
Delayed decrease due to β2
Dopamine and dose dependent property
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
Major effects of dopamine at various concentrations
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
Dopamine is DoC in
- Oliguria with CHF
2. Cardiogenic shock (over norepinephrine)
Route of administration of dopamine
Side effect of dopamine
Continuous IV infusion (like dobutamine) since it has a very low half life
Arrhythmia (β1 stimulation)
Dobutamine
Uses
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
Fenoldopam
- α2 agonist➡️ decreases NE➡️ decreases bp
- D1 agonist (like dopexamine)➡️ diuresis➡️ decreases bp
So used in hypertensive emergency (like dopexamine) via IV route
Dopexamine
- β2 agonist➡️ decreases bp
- D1 agonist (like fenoldopam)➡️ diuresis ➡️ decreases bp
So used in hypertensive emergency (like fenoldopam)
Isoprenaline or isoproterenol
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)
Droxedopa
Prodrug of NE
Treatment of neurogenic postural hypotension
Drugs which are α1 receptor agonists
- Phenylephrine-
- Tetrahydrozoline and xylometazoline-nasal decongestant
- Midodrine-postural hypotension
- Metarminol-
- Mephenteramine
- Methoxamine
Phenylephrine
α1 (vasoconstriction) receptor agonist
- Treatment of anaesthetic agent induced hypotension
- Mydriatic
- Nasal decongestant (like xylometazoline and tetrahydrozoline)
Xylometazoline and tetrahydrozoline
α1 (vasoconstriction) receptor agonist like phenylephrine
Nasal decongestant
Midodrine
α1 (vasoconstriction) receptor agonist like phenylephrine, xylometazoline and tetrahydrozoline
DoC for postural hypotension
Metarminol
α1 receptor agonist like phenylephrine,…
Treatment of hypotension caused by spinal anaesthesia
Mephenteramine
α1 receptor agonist like phenylephrine,…
Treatment of hypotension caused by arrhythmia
Methoxamine
α1 receptor agonist like phenylephrine,…
Treatment of shock
Examples of α2 receptor agonist
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,..
Clonidine
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
Side effects of clonidine
α2 receptor agonist Withdrawal hypotension (treated by IV phentolamine)
Dexmedetomidine
α2 receptor agonist like clonidine but highly potent Used as a pre anaesthetic agent 1. Sedation 2. Analgesia 3. Decreased secretions
Apraclonidine and Brimonidine
α2 receptor agonist
Treating glaucoma
Tizanidine
α2 receptor agonist
Used as a muscle relaxant in disorders like ALS (Amyotrophic lateral sclerosis)
Lofexidine
α2 receptor agonist
Treating opioid dependence
Moxonidine and Rilmenidine
Imidazole receptor (decreases bp), α2 receptor agonist
Uses:
1. Resistant hypertension in elderly
2. Treating neuropathic pain
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
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)
Mirabegron
β3 agonist
Used in urge incontenence
Under trial for treatment of CHF
Side effects:
- Decrease bp
- Head ache
- UTI
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)
LABA
Long acting β2 agonists
Duration: 12 hours
Salmeterol-slow acting
Formoterol-fast acting
Given via inhalation
VLABA
Very long acting β2 agonists
Duration: 24 hours
Carmoterol Indicaterol Olodaterol Vilanterol Given via inhalation for COPD
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
Uses of LABA
- Prophylaxis of bronchial asthma
- Prophylaxis of exercise induced asthma
- With ICS for persistent bronchial asthma
- Along with anticholinergics for COPD
- Nocturnal asthma
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
Side effects of β2 agonists
- Tremors (most common)
- Palpitations
- Potassium levels:
Open K+ channels ➡️ transient hyperkalemia
Increases insulin ➡️ hypokalemia
So used in treatment of hyperkalemia - Hyperglycaemia
Tyramine
NE depletor
Dietary amine
Present in cheese and red wine
Can cause cheese reaction
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)
NE depletors
- Tyramine : cheese reaction
- Ephedrine (…) and Pseudoephedrine (nasal decongestant)
- Norephedrine: was used for obesity
- Methylphenidate
- Amphetamine and dextroamphetamine
- Guanedrel and Guanethidine
Ephedrine
- NE depletor
- Agonist of α and β receptor
So mixed acting sympathomimetic - DoC of hypotension in:
pregnancy
anaesthetic agents - Mydriatic
- Nasal decongestant (along with it’s derivative pseudoephedrine)
Phenyl propanolamine or norephedrine
NE depletor
Was used for treatment of obesity
Now banned because associated with stroke
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
Use of a NE depletor in ADHD
Methylphenidate is the DoC in ADHD except in:
- ADHD with Tourette’s syndrome where it worsens tics
- 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)
Modafinil
DoC for:
- Narcolepsy (Solriamfetol, a DNRI -dopamine NE reuptake inhibitor, can also be used)
- Shift workers disease
- Sleepiness associated with OSA -obstructive sleep apnea
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
Methamphetamine
Drug of abuse
Also called Cristal meth
Why are amphetamines contraindicated in pregnancy
Amphetamines are teratogenic:
- IUGR
- Cardiac defect
- Cleft lip
- Biliary atresia
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)
Anti glaucoma drugs
- Miotic agents: increase trabecular outflow
- Prostaglandin analogues: increases the uveoscleral outflow
- Sympathomimetics
- β blockers (selective or non-selective): decrease aqueous production
- CA inhibitors
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
Side effects of using miotic agents as anti glaucoma drugs
Stimulates M3 receptors
- Ciliary body or accommodation spasm
- Induced myopia
- Retinal detachment
- Corneal oedema
- ACHE inhibitors like physostigmine and echothiophate when given typically cause cataract (so contraindicated in phacic patients)
- Echothiophate can cause iris cysts or NLD obstruction
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
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
Contraindications of prostaglandin used as anti glaucoma drugs
Contraindicated in patients with:
- Uveitis
- Herpetic keratitis
Sympathomimetics used as anti glaucoma drugs
- Epinephrine
- Dipivephrine (prodrug of epinephrine)
- α2 agonists like apraclonidine and ovimonidine
Used via topical route for open angle glaucoma
Mechanism of anti glaucoma action of sympathomimetics
1° mechanism of action is decreased aqueous production
2° mechanism of action increased uveoscleral outflow
Side effects of sympathomimetic used as anti glaucoma drugs
- Common side effect is ocular allergy
- Epinephrine and Dipivephrine cause conjunctival pigmentation
- Apraclonidine-(α1 and) α2 agonist:
α1 stimulation ➡️ mydriasis, lid retraction, conjunctival blanching - Brimonidine α2 agonist which crosses BBB so:
sedation, drowsiness and fatigue
apnea in neonates
dry mouth, hypertension
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)
How β blockers act as anti glaucoma drugs
When are they used
Decrease aqueous production
2nd line drug for open angle glaucoma after latanaprost,…
Side effects of β blockers as anti glaucoma drugs
- Contraindicated with systemic β blockers
- Contraindicated with patients with bronchial asthma or COPD, esp non selective β blockers
- Timolol can cause NLD obstruction and ocular cicatricial penphigoidnd
- Metripranolol can cause granulomatous anterior uveitis
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
Side effects of CA inhibitors as anti glaucoma drugs
Systemic (acetazolamide):
- Metabolic acidosis
- Hypokalemia
- Hyperammonemia
- Nephrolithiasis
Local (Brinzolamide, Dorzolamide):
- Transient myopia
- Periorbital dermatitis
- Corneal oedema
Netarsudil
Approved recently
Rho kinase inhibitor➡️ increases trabecular outflow
For treatment of open angle glaucoma
Latanaprost and Netarsudil fixed combination
Sympatholytic drug classification
A. α-receptor blockers: 1. Non selective (reversible and irreversible) 2. Selective B. β-receptor blockers
Tolazoline
Reversible, non-selective α receptor blocker Peripheral vasodilator Used in: 1. Raynaud’s disease 2. Vasodilator in angiography
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
Drugs used in erectile dysfunction
Phentolamine pyar Bremelanolatide bhi Naltrexone nahi Ketanserin kar S. Sildenafil (DoC) A. Alprostadil K. T. Trazodone A. AlVIPtadil
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
Phenoxybenzamine
Irreversible non-selective α-receptor blocker
DoC for preoperative HTN in pheochromocytoma
Treatment of choice for pheochromocytoma
α-blockers followed by β-blockers to avoid HTN emergency
Subtypes of α1 receptors
Significance
α1a: prostatic urethra, iris
α1b: blood vessels
α1d: blood vessels
Non-selective α1 blockers
Uses
- Vasodilation and prostatic urethra dilation
- They increase HDL and decrease LDL
DoC for: - Benign prostatic hyperplasia and HTN.
But the vasodilation is non selective (veins also dilated) ➡️ postural hypotension (1st dose effect) ➡️ night time dosing. - HTN with dyslipidemia
Non selective α1 blockers
Examples
- Terazosin
- Doxazosin
- Prazosin- Scorpion bite induced HTN or pulmonary oedema
- Alfuzodin-BPH
Drugs used for HTN: - Bunozosin
- Inforamin
- Urapidil
Scorpion bite pharmacological treatment
Prazosin: Non selective α1 blockers Scorpion bite induced HTN or pulmonary oedema Midazolone: CNS excitation Atropine: bradycardia
DoC for HTN with BPH or dyslipidemia
Examples:
Non selective α1 blockers
- Terazosin
- Doxazosin
- Prazosin (scorpion bite)
Selective α1 blockers (α1a blockers)
Silodosin
Tamsulosin-most selective
DoC for BPH benign prostatic hyperplasia
Side effects of α1 blockers
Prostatic urethra block ➡️ ejaculation abnormalities
Floppy iris
Side effects are maximum in tamsulosin
They are more in α1a blockers
Uses of β blockers
- 2nd line drug for hyperreninemic HTN
- Prophylaxis of migraine
- Hyperthyroidism
- Anxiety
- Stable angina
Propranolol is DoC for the above 4 conditions if they occur with HTN - Chronic CHF
- History of MI
- DoC for HOCM (digoxin is CI)
- DoC for aortic dissection
- Glaucoma
Non-selective β blockers
First generation β blockers
Blocks β1 and β2 receptors
Effects of non-selective β blockers/first generation β blockers
(and hence CI in)
Blocks:
- Bronchodilation (bronchial asthma)
- Vasodilation (Raynaud’s disease,variant angina)
- Symptoms of hypoglycaemia except sweating (DM)
- Glycogenolysis and gluconeogenesis in skeletal muscle-decreased muscle capacity
Selective β blockers
Block β1 only, less side effects
- Propranolol
- Oxprenolol
- Pindolol
- Timolol
- Nadolol
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
Third generation β blockers
Cardioselective or (non cardioselective + vasodilation effect) β1 blocker
Third generation β blocker with α1 blocking action
Labetolol
Carvedolol
Bevantolol
Bucindolol
Features of carvedilol
Third generation β1 blocker with α1 blocking action Calcium channel blocker Antioxidant (like Nebivolol) Anti inflammatory Blocks LDL oxidation
β1 blocker and β2 agonist
Bopindolol
Third generation β blocker which increases the release of NO
N. Nipradilol
N. Nebivolol (antioxidant)- most cardioselective
Third generation β blocker with K+ channel opening activity
Tilisolol
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
β blockers which are partial agonist and intrinsic sympathomimetic effect
Properties
- Less bradycardia
- Not used in:
migraine prophylaxis
MI
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)
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
Water soluble β blocker
Properties
CI in renal failure
Do not cross BBB, no central side effects like insomnia, depression or nightmares
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)
Longest acting β blocker
Nadolol
Water soluble selective first generation β blocker
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
β blocker with maximum plasma protein binding
Carvedilol
- Third generation β blockers
- Na+ channel blockers and has local anaesthetic and membrane stabilising effect
- α1 blocking action
- Calcium channel blocker
- Antioxidant (like Nebivolol)
- Anti inflammatory
- Blocks LDL oxidation
- Minimum bioavailability
β protein with minimum plasma protein binding
Celiprolol
3rd generation water soluble cardioselective β blocker
Has partial agonist and intrinsic sympathomimetic effect
β blockers with maximum (100%) bioavailability
Penbutolol Pindolol (1st generation selective β blocker) Both these drugs partial agonist and intrinsic sympathomimetic effect
β blockers with minimum (30%) bioavailability
Carvedilol Propranolol (1st generation, max Na+ channel blocking, local anaesthetic and membrane stabilising effect)
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
