Adrenergic Flashcards
(21 cards)
Classify alpha receptors blockers
a1 selective:
Prazosin
Terazosin
Doxazosin
Tamsulosin
Alfuzosin
Indoramin
a2 selective:
Tolazoline
Yohimbine
Non selective a blocker (reversible)
Phentolamine
Non selective a blocker (irreversible)
Phenoxybenzamine
Indications of alpha blockers
1.Moderate to severe hypertension. Prazosin- doc. It is highly selective
2.Benign hyperplasia of prostate. Tamsulosin- doc. (It has selective action on a1A subtype of alpha receptors that are located on prostatic smooth muscle
3.Raynauds phenomenon
4.Pheochromocytoma. Phenoxybenzamine is used to reduce symptoms of catecholamine excess.
5.Micturation incontinence in women.
6.Erectile dysfunction.
7.Anxiety disorder, panic disorder
Adverse effects of alpha blockers
A.Orthostatic hypotension
(Due to venous pulling of blood in periphery)
B.First dose phenomenon: alpha blockers like prazolin can cause severe hypotension and even loss of conciousness within 2 hrs of taking first dose of the drug due to peripheral pooling of blood. To avoid this adverse event, the first dose should be reduced (0.5-1 mg) and should be given at bedtime.
3.Reflex tachycardia: when non selective a blocker is used, it blocks a1 mediated vasoconstriction which leads to hypotension. It also blocks a2 presynaptic receptors. This excess release of norepinephrine will stimulate B receptors in the heart.
Classify b blockers
According to receptor selectivity:
A) non selective: propanolol, timolol, pindolol
2. Non selective (both alpha and beta)
Carvedilol, labetalol, bucindolol.
3.Cardio-selective (β₁-selective): Metoprolol, atenolol, bisoprolol, nebivolol, esmolol, acebutolol, betaxolol.
Mention distribution of β2 receptor. (DU-23N)
Smooth muscles of skeletal, splanchnic & renal blood vessels
Bronchial smooth muscle
Uterine smooth muscle
Skeletal muscle
Liver
Q. Name some clinically important adrenergic drugs. [DU-18M]
Clinically important adrenergic drugs:
Adrenaline.
Noradrenaline.
Dopamine.
Dobutamine.
Salbutamol (Albuterol).
Salmeterol.
Ephedrine.
α-methyldopa.
Outline the biosynthesis & fate of adrenergic neurotransmitters. (DU-14Ju)
Synthesis of Noradrenaline and Adrenaline:
Step 1: Tyrosine is transported from ECF to noradrenergic nerve terminal by Na dependent carrier.
Step 2: Tyrosine is converted to DOPA (Dihydroxyphenylalanine) by the process of hydroxylation with the help of enzyme tyrosine hydroxylase.
Step 3: DOPA is converted to dopamine by decarboxylation with the help of DOPA-decarboxylase.
Step 4: Dopamine is transported from cytoplasm to storage vesicle by antiporter.
Step 5: Within vesicle dopamine is converted to noradrenaline by dopamine β-hydroxylase.
Within adrenal medulla:
Noradrenaline is converted to adrenaline by the enzyme phenylethanolamine N-methyl transferase.
Fate of Noradrenaline:
Uptake I - Reuptaken by presynaptic nerve terminal (80 - 90%).
Uptake II - Extraneuronal uptake. Uptake into perisynaptic glia or adjacent smooth muscle cells. No involvement of receptors..
Metabolized by MAO & COMT.
Get attached with the corresponding receptors and produce effect.
Simple diffusion away from the receptor site into neighboring tissue by paracrine fashion and metabolized in the plasma and liver by COMT.
Classify catecholamines
Catecholamines: A catecholamine is an organic compound that has a catechol (benzene with two hydroxyl side groups) and a side chain amine. Catecholamines are derived from the amino acid tyrosine.
Types of catecholamines:
Endogenous:
Adrenaline (epinephrine).
Nor-adrenaline (nor-epinephrine).
Dopamine.
Synthetic:
Isoprenaline.
Dobutamine.
Dopexamine.
Classify adrenergic drugs
Classification of adrenergic drugs:
A. According to chemical structure:
Catecholamines
a. Natural: Adrenaline, Noradrenaline, Dopamine
b. Synthetic: Isoprenaline, Dobutamine, Ibupamine
Noncatecholamines
a. Ephedrine
b. Amphetamine
c. Phenylephrine
d. Methoxamine
e. Oxymetazoline, Xylometazoline
f. Tyramine
B. According to receptor selectivity:
Both α and β agonist
Adrenaline α₁, α₂, β₁, β₂ (α₁= α₂, β₁= β₂)
Noradrenaline α₁, α₂, β₁ (α₁ = α₂, β₁»_space; β₂)
α₁ agonist – Phenylephrine, Methoxamine, Ephedrine, Xylometazoline, Oxylometazoline
α₂ agonist – Clonidine
Both β₁ & β₂ agonist – Isoprenaline
β₁ selective – Dobutamine, Prenalterol, Xameterol
β₂ selective – Salbutamol, Terbutaline, Metaproterenol, Ritodrine, Fenolterol, Bitolterol, Salmeterol, Pirbuterol, Rimiterol
Explain the role of adrenaline in anaphylactic shock. [DU-22N, 18M, 15Ju
Role of Adrenaline in anaphylactic shock:
Adrenaline antagonizes (non-competitive & reversible) the pharmacological effects due to Histamine released massively in anaphylactic shock.
Explanation: In anaphylactic shock there is rupture of basophil & mast cell membrane. As a result massive amount of Histamine are released which cause bronchoconstriction & hypotension (mediated with H₁-receptors on bronchial tree & vascular smooth muscle). Adrenaline causes elevation of BP by binding with α₁-receptors & prevents bronchoconstriction (i.e. bronchodilation) by binding with β₂-receptors. So, Adrenaline is the drug of choice in anaphylactic shock.
Mention the role of Adrenaline & Dopamine and dobutamine in the management of shock.
1.Effects of Adrenaline on cardiogenic shock:
Adrenaline → also binds with α₂ receptor (in the renal vascular smooth muscle) → ↓ cAMP
→ renal vasoconstriction → ↓ RBF, ↓ GFR & ↓ Na⁺ excretion → hampers normal renal function → chance of renal failure (ARF / acute renal shut down).
Adrenaline → β₁-receptor on heart → positive inotropic effect → ↑ HR & ↑ BP
2.Effects of Dopamine on cardiogenic shock: Both of the following effects of Dopamine help to improve the condition of cardiogenic shock -
➤ Dopamine → D₁-receptor (in the renal vascular smooth muscle) →↑ cAMP → renal vasodilatation →↑ RBF, ↑ GFR & ↑ Na⁺ excretion → natriuresis → improved renal function.
Dopamine → β₁-receptor on heart → positive Inotropic effect →↑ HR & ↑ BP.
- Effect of Dobutamine: Its chemical structure resembles Dopamine, but its actions are mediated mostly
by activation of α & β receptors.
Dobutamine has a
positive inotropic action due to predominant β-receptor activity & no significant effect on vessels &
peripheral resistance.
➤ Dobutamine increases cardiac output and stroke volume usually without a marked increase in heart rate.
What are the adverse effects of Adrenaline? [DU-18M; RMU-22M,21M]
Adverse effects of Adrenaline:
CNS effects: Anxiety, fear, tension, headache, and tremor, cerebral haemorrhage.
CVS:
Cardiac arrhythmias, particularly if the patient is receiving digoxin,
Epinephrine can also induce pulmonary edema due to increased afterload caused by vasoconstrictive properties of the drug.
Increased blood pressure.
Angina, MI.
Increased blood glucose level: Epinephrine increases the release of endogenous stores of gluc
In diabetic patients, dosages of insulin may have to be increased.
Mechanism of action of β₂-selective agonists / Salbutamol (Albuterol) / Salmeterol: (Inhalational
Salbutamol produces significant bronchodilation within 15 min & effect persists for 3-4 hours)
Binds to B2 receptor present in bronchial smooth muscles and stimulates adenylyl cyclase and inc camp which relaxes bronchial smooth muscle and causes bronchodilation.
State current status of β-blockers in hypertension. [DU-19M]
Current status of B-blockers in hypertension:
Classic beta blockers are not indicated as first line treatment for essential hypertension.
Beta blockers are indicated in the treatment of hypertension in patients in whom cardioprotection is desirable, such as-
Heart failure with reduced ejection fraction.
Coronary artery disease.
Currently cardio-selective β-blockers are used as anti-hypertensive agent due to their less systemic side effects.
Q. Write short note on: α-methyldopa.
Alpha-methyldopa: It is the α-methyl analogue of L-dopa (dopa is the precursor of dopamine, Noradrenaline & Adrenaline).
Mechanism of action of α-methyldopa: [NA: Nor Adrenaline; NT: Neurotransmitter]
α-methyldopa converted to α-methyl NA in the brain → α-methyl NA is a false NT & a potent α₂-agonist → α-Methyl NA then binds with the pre-synaptic α₂ receptor → ↓ adrenergic outflow from brain → ↓ total peripheral resistance → ↓ BP.
Pharmacokinetics of α-methyldopa:
Indication of α-methyldopa: Hypertension in pregnancy.
Adverse effects α-methyldopa:
Common: Sedation, lethargy, reduced mental capacity.
Less common: dryness of mouth, nasal stuffiness, headache, weight gain and impotence.
Postural hypotension is generally mild.
Positive Coombs test.
Advantage of α - methyldopa:
Cardiac output is not decreased & blood flow to the vital organ (e.g. kidney) is not diminished.
So, it can be used in HTN with renal insufficiency.
Most CVS reflexes remain intact after administration of α-methyldopa. So, postural hypotension does not occur.
Discuss how β-blockers / β-antagonists Propranolol / Carvedilol/ atenolol [DU-19M] lowers blood pressure.
CVS effects:
Blocks B₁-receptors on heart → ↓ HR & ↓ FOC → ↓ CO → ↓ BP.
Blocks B1-receptor on JG cells of kidney → ↓ rennin secretion from kidney → ↓ production of angiotensin-II → vasodilatation → ↓ TPR → ↓ BP.
Blocks pre-synaptic β2-receptor → causes negative feedback regulation / auto-regulation → ↓ exocytosis of Adrenaline / NA from nerve terminal → ↓ blood pressure.
Blocks β2-receptor of vasomotor center (VMC) → ↓ sympathetic & ↑ parasympathetic discharge → vasodilatation → ↓ peripheral resistance → ↓ blood pressure.
Effects on kidney (B₁-mediated): ↓ Renin secretion → ↓ angiotensin-II → renal vasodilatation and ↓ salt & water retention → ↓ BP.
Effects on bronchial smooth muscle (B₁-mediated): Bronchoconstriction → aggravation of bronchial asthma.
Effects on metabolism: (B₁-mediated action)
Liver: ↓ Glycogenolysis & gluconeogenesis → ↓ blood glucose.
Fat cell: ↓ Lipolysis → ↓ FFA level → dyslipidaemia.
Effects on skeletal muscle (B₁-mediated): ↓ glycogenolysis & ↓ K⁺ release.
Effects on CNS: Depression.
Less significant effects;
✓ Effects on GIT (Insignificant effect): Contraction of GIT smooth muscle & relaxation of sphincters → diarrhoea.
✓ Effects on genito-urinary system (Insignificant effect): Contraction of Detrusor muscle of urinary bladder and relaxation of Trigone & relaxation of sphincter → urgency
Explain how Propranolol [DU-17J] / Atenolol [DU-14Ju; SUST-17N, 15J] reduce blood pressure?
Propranolol reduces blood pressure by blocking both β₁ & B₂ receptor, whereas
Atenolol reduces by blocking β₁ receptor only (Please see above for details).
Write down four (4) adverse effects of Propranolol. [DU-18N]
CVS adverse effects:
Bradycardia.
Hypotension.
Cardiac conduction abnormalities (cardiac arrhythmias).
Cold extremities (↓ Peripheral circulation).
Exercise intolerance (Dilation of muscular & large blood vessels).
CNS adverse effects:
Sedation.
Depression.
Sleep disturbance (Insomnia, nightmares).
Suicidal tendency (in case of long term use).
Others:
Bronchoconstriction.
Dyslipidaemia.
Prolongation of hypoglycaemia.
Sexual dysfunction in men.
Write down 04 (four) contraindications of propranolol [BUP-22N]
CVS contraindications:
Heart block.
Cardiac bradyarrhythmia / bradycardia.
Hypotension.
Peripheral vascular diseases (Raynaud’s phenomenon).
Other contraindications:
Bronchial asthma.
Explain the anti-anginal effects of propranolol [DU-16J; CU-18N] / Atenolol [CU-21M 15J].
Role of β-blockers in angina pectoris:
β-blockers blocks β₁-receptors on heart
↓
Heart rate & force of contraction (FOC)
↓
Cardiac work
↓
Reduction of cardiac O₂ demand
↓
Relief / prevention of angina pain
