Adrenergic & Antiadrenergic Drugs Flashcards
(19 cards)
Where do adrenergic drugs act?
How does norepinephrine act on receptors?
On the sympathetic nervous system of the autonomic nervous system.
Fight or Flight
1) Tyrosine is converted to dopamine. Dopamine enters vesicles and is converted to NE.
2) Calcium influx causes vesicles to fuse with the membrane, releasing NE.
3) NE binds to adrenergic receptors on the postsynaptic cell, producing a physiological effect.
4) Most NE is taken back up into the presynaptic neuron via norepinephrine transporter (NET)
5) NE is metabolized by: COMT (Catechol-O-methyltransferase) and MAO (Monoamine oxidase) These enzymes help terminate NE’s action.
Catecholamines vs Non-catecholamines
What are catecholamines?
What are its characteristics?
List the endogenous and synthetic drugs?
Why are they called noncatecholamines?
Why do they have a longer half life?
Give examples.
Catecholamines a subset of sympathomimetic amines such as epinephrine, norepinephrine and dopamine. These are endogenous.
They have High potency, Rapid inactivation and Poor penetration into the CNS.
Isoproterenol, Dobutamine are synthetic catecholamines.
Noncatecholamines lack the catechol hydroxyl groups and have longer half-lives because they are not inactivated by COMT.
e.g. Amphetamine, Phenylephrine, Ephedrine,
Characteristics of catecholamines.
Characteristics of noncatecholamines.
- Have a catechol nucleus.
- Cannot be given orally because it is natural/endogenous.
- Shorter duration of action due to metabolism by COMT and MAO.
- Cannot cross BBB so it doesn’t stimulate CNS.
- Act directly on adrenergic receptors.
- No catechol nucleus.
- Can be given orally.
- Longer duration of action
- Cross BBB to stimulate CNS
- Acts directly, indirectly and via mixed action on receptors.
Where are alpha 1 and 2 receptors found?
What are the responses when agonist bind to alpha receptors?
Where are beta 1 and 2 receptors found?
What are the responses when agonist bind to beta receptors?
Alpha1-Adrenergic Receptors
Located on postsynaptic effector cells.
Alpha2-Adrenergic Receptors
Located on presynaptic nerve terminals.
Control the release of neurotransmitters
agonist responses are Vasoconstriction and CNS stimulation
Beta-Adrenergic Receptors
All are located on postsynaptic effector cells
Beta1-adrenergic receptors located primarily in the heart
Beta2-adrenergic receptors located in smooth muscle of the bronchioles, arterioles, and visceral organs
agonist response results in Bronchial, GI, and uterine smooth muscle relaxation
Glycogenolysis
Cardiac stimulation
What is the order of affinity for agonists at the alpha receptors?
What is the order of affinity for agonists at the beta receptors?
Give an example of an antagonist at each receptor.
Agonist affinity of Alpha (α): (ANI)
Adrenaline > Noradrenaline > Isoprenaline
Antagonist: Phenoxybenzamine
Agonist affinity of beta (β): (IAN)
Isoprenaline > Adrenaline > Noradrenaline
Antagonist: Propranolol
Norepinephrine binds to which receptors?
Epinephrine binds to which receptors?
How are they administered?
NE is a direct acting non–selective adrenergic agonist which acts on all adrenoceptors except β2
EP is a direct acting non-selective adrenergic agonist in all receptors.
Both are given parenterally because catecholamines are not given orally.
Uses of epinephrine.
- In bronchial asthma
It is given SC to act on β2 receptors to cause bronchodilation
Side effects-tachycardia and arrhythmia - In cardiogenic shock
It is given I.V to increase SBP(systolic blood pressure), BP, HR and CO. - In anaphylactic shock
It is given SC to act on
α1 cause Vasoconstriction, lead to increase BP & relief of congestion
β1 cause increase HR leading to increase CO, so, increase BP
β2 cause bronchodilation so, relieve bronchospasm
What are the Adverse effects of EP?
Compare the effects of EP when given in low vs high doses?
CNS DISTURBANCE: Includes: anxiety, fear, tension, headache, and tremor.
HEMORRHAGE
CARDIAC ARRYTHMIAS
PULMONARY EDEMA
At low doses, β effects (vasodilation) on the vascular system predominate, whereas at high doses, α effects (vasoconstriction) are strongest.
Dopamine
DA
non–selective adrenergic agonist
At low doses it acts directly on DA receptors
cause vasodilatation and treats shock to save these vital organs from hypoxia.
At medium doses it stimulates β1 receptors to increase HR, CO and BP.
At high doses it stimulates α1 receptors (direct + Via release of NE) to cause VC leading to increase BP and decrease organ perfusion
Isoprenaline
Synthetic Adrenergic agonists.
directly acting only on β–receptors.
Stimulate B1 to increase HR, arrhythmia and cardiac arrest.
Stimulate B2 causing vasodilation, decreases BP.
I.V must be given carefully because overdoses cause cardiac arrest.
only used now to reverse the heart block which is produced by overdoses of β–blockers
Dobutamine
direct acting β 1 selective agonist.
tolerance to its action
Given only parenterally
increases in CO
It has less arrhythmogenic effects than dopamine
Uses: Inotropic agent for Heart Failure; in septic and cardiogenic shock.
Amphetamine
non-selective adrenergic agonist
acts indirectly via enhancing NE release and DA.
non-catecholamine so can be given orally
used in In ADHD, narcolepsy (it can stimulate CNS to keep patient awake)
Side effects with chronic use
Tolerance
Dependence
Addiction
Paranoia
Psychosis
Hypertension
Centrally Acting Adrenergic Blockers
Clonidine, Methyldopa
They are agonists but block the release of norepinephrine.
Stimulate Alpha-2 receptors.
Adverse effects are sedation, dry mouth, decreased libido, Parkinson’s-like movement and bradycardia/sinus arrest.
Clonidine is used to treat Hypertension and Attention deficit hyperactivity disorder.
Salbutamol, Salmeterol
β2 selective agonist
orally, IV and by inhalation
used for bronchial asthma by β2 stimulation, which leads to relaxation of bronchial smooth muscle and bronchodilation.
Treatment of refractory hyperkalemia (I.V)
Ritodrine
β2 – selective agonist
used to delay premature labour because it causes relaxation of uterine smooth muscle leading to delay of labour
Adverse effects of adrenergic drugs.
CARDIAC ARRHYTHMIAS
HEADACHE
HYPERACTIVITY
INSOMIA
NAUSEA
TREMORS
Alpha 1 selective blockers
Prazosin, Terazosin, Doxazocin, Tamsulosin
prevent vasoconstriction and arteriolar constriction, which leads to vasodilation. Reduces peripheral resistance and BP.
prevents the normal dilation of the pupil (mydriasis), leading instead to miosis, or constriction of the pupil.
relaxing smooth muscle in the bladder neck and prostate allow for improved urine flow. useful in patients with benign prostatic hyperplasia (BPH) or urinary retention.
Uses: Raynaud’s Phenomenon, Prazosin/Tamsulosin is most commonly used in BPH.
Side effects: Nasal Congestion, Hypotension
Beta blockers (Beta 1 selective)
Non Selective Beta blockers
Cardioselective Beta Blockers, decreases HR.
Atenolol, Betaxolol, Esmolol (short half life), Acebutalol, Metoprolol
Bronchospasms and Decrease in HR
Propranolol, Timolol (Decreases aqueous humor production used in Open Angle glaucoma), Pindolol
Contraindicated in Asthmatics
Beta Blockers used for HTN, Angina, arrhythmias, MI, migraine, Thyrotoxicosis, Congestive cardiac failure (carvedilol and labetolol)
Side effects of Beta blockers: Beta 2 → Exacerbation of Asthma, Masks the sign of a hypoglycemic episode, Bradycardia
Sympathetic Nerves (“Fight or Flight”)
Dilate pupils
Inhibit salivation
Increase heartbeat
Relax airways
Inhibit activity of stomach
Stimulate release of glucose; inhibit gallbladder
Inhibit activity of intestines
Secrete epinephrine and norepinephrine
Relax bladder
Promote ejaculation and vaginal contraction
