Adrenoceptors Flashcards
General functions of Adr and NA
BP control
Myocardial contractility
Airway reactivity
Metabolic and CNS functions
Order of potency for B-ADRs
Isoprenaline
Adrenaline
Noradrenaline
Greater than or equal to for last two
Order of potency for a-ADRs
Adrenaline
Noradrenaline
Isoprenaline
(Greater than or equal to for all three)
Selective a-ADRs antagonist
Phenoxybenzamine
Selective antagonist for b-ADRs
Propanolol
Why did adrenaline cause a fall in arterial pressure after animal pre-treatment with ergot derivative?
The derivative is an a-ADR antagonist and the receptor’s blockade caused transition to b-ADR agonist effects.
Explain Ahlquist’s receptor name designations
a-ADRs on smooth muscles where catechol amines produce excitatory responses and b-ADEs where inhibitory responses are produced. GIT is an exception because it is relaxed by both agonist action
Adrenoceptor subtypes
Alpha-1A, 1B, 1D, (1L)
Alpha-2A, 2B, 2C, (2D)
Beta-1
Beta-2
Beta-3
Beta-4
Alpha-1 location and actions
Vascular smooth muscle - Increased vascular resistance
Eye - Mydriasis
Pilomotor - Hair erection
Liver - Glycolgenolysis
Vas Deferens - Ejaculation
Alpha-2 location and actions
Adrenergic and cholinergic nerve terminals - Inhibits transmitter release
Platelets - Stimulates aggregation
Some vascular smooth muscle - Contraction
Pancreas- Decreased insulin release
Beta-1 location and actions
Heart - Stimulates rate and force
Juxtaglomerular cells - Stimulates renin release
Beta-2 location and actions
Bronchioles - Dilation
Uterus - Relaxation
Vascular smooth muscle - Vasodilation
Liver - Glycogenolysis
Pancreatic B cells - Insulin release
Skeletal muscles - Tremors
Beta-3 location and actions
Fat cells (with B-1 and 2) - Lipolysis
Alpha 1 agonists
4MPTOX
Mephentermine
Methoxamine
Metaraminol
Midodrine
Phenylephrine
Tetrahydrozoline
Xylometazoline
Non-selective adrenergic agonists
Adrenaline (all)
NA (all except B3 and B4, less at B2)
Isoprenalol (B1 and B2)
Peculiarities of Alpha-1 agonists
Mephentermine and Metaraminol also act indirectly to release NA
Midodrine is a pro-drug
PPA of Alpha 1 agonists
Vasoconstriction
PTU of Alpha 1 agonists
- Pressor agents in treatment of of
hypotension & shock –) - Nasal decongestants
Which Alpha 1 agonists are used as pressor agents in the treatment of hypotension & shock?
Methoxamine & Phenylephrine
Which Alpha 1 agonists are used as treat nasal congestion?
Oxymetazoline
Tetrahydrozoline,
Xylometazoline
Naphazoline
Some preparations of phenylephrine
Adverse Effects (AEs) of Alpha 1 agonists
Hypertension
Headache
Reflex bradycardia
Excitability
Restlessness
Dry mouth
Sedation
Rebound hypertension ff. abrupt withdrawal
Alpha 2 agonists
A2C2GBAD
Apraclonidine
Clonidine
Clenbuterol
Guanfacine
Guanabenz,
Brimonidine
α-methyldopa
Dexmedetomidine
Peculiarities of Alpha 2 agonists
- Apraclonidine & Brimonidine are used topically for glaucoma
and ocular hypertension. - Methyldopa is converted in CNS to α-methylNA (α2 agonist).
- Used very occasionally as centrally-acting sympatholytic vasodilators for the Rx of hypertension.
Which Alpha 2 agonists are used topically for glaucoma and ocular hypertension?
Apraclonidine & Brimonidine
PPA of Alpha 2 agonists
Reduced sympathetic outflow resulting in reduced peripheral
vascular resistance and reduced production of aqueous humour.
PTU of Alpha 2
- Adjunct therapy in shock
- Hypertension
- To reduce sympathetic response to withdrawal from narcotics,
alcohol & tobacco - Glaucoma treatment
AE of Alpha 2 agonists
Sedation
Dry mouth & nasal mucosa
Bradycardia
Orthostatic hypotension
Impotence
Constipation
Nausea & gastric upset
Bradyarrythmia
Reduced cardiac output
Hypotension
Beta 1 agonists
DDX
Dobutamine
Denopamine
Xamoterol.
Caution for Beta 1 agonists
Use with caution in patients with hypertension or cardiac
arrhythmias; used only IV.
PPAs of Beta 1 agonists
Increases cardiac contractility
Increased heart rate
Increased atrioventricular conduction.
Peculiarities of Beta 1 agonists
Dobutamine has strong inotropic effect with little chronotropic
effect = increase in CO without significant increase in HR.
PTU of Beta 1 agonists
Short-term treatment of impaired cardiac function after
cardiac surgery, congestive heart failure, and myocardial infarction.
AEs of Beta 1 agonists
Increased BP and HR
Beta 2 agonists
MIFFAB2SPTR (Miffab2EsPita)
Metaproterenol
Isoetharine
Fenoterol
Formoterol
Albuterol
Bitolterol
Salmeterol
Salbutam
Procaterol
Terbutaline
Ritodrine
Which Beta 2 agonists are long-acting?
Salmeterol and Salbutamol
Which Beta 2 agonists are intermediate-acting?
All expect 2S
Peculiarities of B2 agonists
Use with caution in patients with CV disease (reduced by
inhalational administration; as aerosols); minimal side
effects → intermediate acting.
PPAs of Beta 2 agonists
- Relaxation of bronchial smooth muscle
- Relaxation of
uterine SM - Activation of other β2Rs after systemic
administration.
PTUs of Beta 2 agonists
- Asthma & chronic obstructive pulmonary disease
- Acute bronchospasm (short & intermediate acting drugs)
- Premature labour (Ritodrine)
- Prophylaxis (long acting agents).
AEs of Beta 2 agonists
Headache
Anxiety
Nausea
Muscle tremors
Nervousness
Palpitations
β3 agonists
Amibegron
Mirabegron
Ro40-2148,
Solabegron
Vibegron
α-non selective antagonists
Phenoxybenzamine
Phentolamine
Tolazoline
Ergot alkaloids
α1-selective antagonists
BPITTDAUNT
- Prazosin (1st agent)
- Terazosin (longer half-life)
- Doxazosin (longer half-life)
- Alfuzosin
- Tamsulosin
- Indoramin
- Urapidil
- Bunazosin
- Trimazosin
- Niguldipine.
PPAs of Alpha 1 selective antagonists
- Decreased peripheral vascular resistance (promote vasodilation);
- Relax smooth muscles in neck of bladder & in prostate.
PTUs of Alpha 1 antagonists
- Primary hypertension
- Urinary retention
- Increased urine flow in Benign Prostate Hyperplasia
AEs of alpha 1 antagonists
- Postural hypotension when therapy is instituted
- Reflex tachycardia
α2-selective antagonists
Yohimbine
Imiloxan
Idazoxan
PPAs of alpha-1 antagonists
- Blockade of decreased sympathetic outflow (aka increased sympathetic outflow) & potentiates release of NA
from nerve endings; i.e. effects opposite of clonidine - Enters CNS =>
increased sympathetic output => increased HR and BP. - Results in activation of α1 & β1 Rs in the heart & peripheral vasculature
PTUs of alpha-1 antagonists
- Ingredient in many weight loss products
- Extensive use in
treatment of male sexual dysfunction
AEs of alpha-1 antagonists
Increased HR, BP and can cause severe tremors
Non-selective β antagonists
Nadolol
Penbutolol
Pindolol
Propranolol
Timolol
Carteolol
Carvedilol
Bucindolol
Labetalol
Carvedilol & Labetalol also block…
…α1Rs
β1-selective antagonists
Acebutolol
Atenolol
Bisoprolol,
Esmolol (quick onset/short duration => used in urgent settings),
MetoprololBetaxolol
Celiprolol
Nebivolol
β-2 selective antagonists
Butoxamine
PPAs of B-blockers
↓ HR
↓ contractility
↓ CO; slow conduction in atria & AV node
↑ refractory period, AV node
Bronchoconstriction;
Prolonged hypoglycaemia
↓ plasma free fatty acids
↓ HDLc
↑ LDLc & triglycerides
Hypokalemia
PTUs of B-blockers
Angina pectoris
Hypertension
Cardiac arrhythmias
CHF
Pheochromocytoma
Glaucoma
Hypertropic obstructive cardiomyopathy
Hyperthyroidism
Migraine prophylaxis
Acute panic symptoms
Substance withdrawal
Variceal bleeding in portal hypertension
AEs of B-blockers
Bradycardia
-ve ionotropic effect
↓ CO
Bradyarrythmia
↓ AV conduction
Bronchoconstriction
Fatigue
Sleep disturbances (insomnia, nightmares
Prolongation of hypoglycemia
Sexual dysfunction in men
Drug interactions.
3rd generation non-selective agents
Carteolol
Carvedilol
Bucindolo
Labetalol
PPAs of 3rd generation B-blockers
membrane
stabilizing effect; ISA (intrinsic sympathomimetic activity);
vasodilation.
Mechanism of action of B-blockers
α1 antagonism
β2 agonism
Release of NO
Ca2+ channel blockade
Opening of K+ channels
