Sympathomimetics (Adrenergic Agonists)

Question 1

What are the drugs affecting synthesis of catecholamines?

Answer 1

α-Methyltyroxine
α-Methyldopa

Question 2

Briefly discuss α-Methyltyroxine under:
MOA, use, adverse effects

Answer 2

MOA: It inhibits the enzyme tyroxine hydroxylase. The compounds competes at the active site of the enzyme.

Uses: The drug is useful in treating tumor of adrenal medulla.
When the drug is given, the tissues stores of NA is decreased.
Adverse effects: Circulating reflexes are with held and this could cause postural hypotension.

Question 2

Briefly discuss α-Methyldopa under:
MOA, use, adverse effects, brand name
Why is is known as a false neurotransmitter?

Answer 2

This drug is an analog of dopamine and a false neurotransmitter because it has a structure resembling DOPA.
It will be acted upon by DOPA to give α-methyldopamine.
The α-methyldopamine is rapidly taken into the storage vesicles and within the storage vesicles; it is converted to α-methyl nor-adrenaline by dopamine hydroxylase

The α-methyl nor-adrenaline is an extremely potent agonist of α2 receptors.
It will stimulate the α2-receptors to stop the extra release of adrenaline.
α-methyl DOPA is a useful anti-hypertensive drug.
This effect is central to the brain and not peripheral N.S.

Some of the unwanted effects of α-methyl DOPA are drowsiness, depression, retention, of salt and water by the kidney, it is marked as Aldomet(R).

Question 2

Examples of DRUG INHIBITING STORAGE OF NEUROTRANSMITTERS

Answer 2

Reserpine
Guanethidine

Question 2

Briefly discuss Cocaine under:
MOA, uses & adverse effect

Answer 2

MOA: This a prototye of drug that inhibits neuronal uptake.
It potentiates the action of directly acting sympathomimetics.

It has sympathomimetics effects which develops slowly e.g it causes mydriasis, constriction of conjuctival blood vessels.
the stimulants effect of cocaine on mood and behaviour are attributed to blockade.
its blockade of neurotransmitters uptake by adrenergic neurons in the CNS.

Question 2

Briefly discuss Reserpine under:
MOA, uses & adverse effects

Answer 2

Reserpine depletes the storage of Noradrenaline/ neutrotransmitter. It is rapidly taken up into the storage vesicles. It has an affinity for the storage vescicles of >10,000 times more than the cathecholamines for storage vesicles.

Depletion of stores of neurotransmitter is secondary to uptake by pushing out the transmitter.

It is useful as an antihypertensive drug. however, the drug does not have so much use today as one of the side effects is depression to suicidal tendency.

Question 2

Guanethidine
MOA, use

Answer 2

Displaces noradrenaline also and is useful in the management of hypertension.

Question 2

Example of a drug inhibiting neurotransmitter release

Answer 2

Prostagladins E1 and E2

Question 2

Briefly dicuss Prostagladins E1 and E2 under:
MOA, uses

Answer 2

They inhibit release of nor-adrenaline in response to stimulation of adrenergic nerves.

it is important to note that sympathetic nerve stimulations causes increase in synthesis and release of prostagladins E.

This interaction is called a negative feedback control of neurotransmitter release. The prostagladins E are useful in the induction of labour.

Question 3

Example of DRUGS INHIBITING NEURONAL UPTAKE

Answer 3

• Cocaine
• Tricyclic Despiramine and Imipiramine

Question 3

Briefly discuss TRICYCLIC DESPIRAMINE AND IMIPIRAMINE under:
MOA & use

Answer 3

Used in management of depression and potent inhibitors of neuronal uptake.

Question 3

Examples of DRUGS INHIBITING EXTRANEURONAL UPTAKE

Answer 3

Steroids

Question 4

Discuss steroids under:
MOA

Answer 4

The steroids inhibit extraneuronal uptake and increases the response to sympathomimetic.

The significance of this observation has not been fully elicidated.However, it is possible that the diverse action of corticosteroids may be linked to the inhibition of extraneuronal uptake.

Question 5

Example of ADRENERGIC NEURONE BLOCKING DRUG

Answer 5

Debrisoquine

Question 5

PHARMACOLOGICAL PROPERTIES OF NA
Heart, blood vessels. BP, GIT, uterus, brochial smooth muscle, eye, CNS and metabolic effect

Answer 5

HEART: NA causes contraction of the cardiac muscle (positive inotrophic effect) and positive chromotropic effect (heart rate) and increase in heart rate which is positive chromotropic effect.
The cardiac output is thereby increased and the rate of O2 consumption is also elevated.

BLOOD VESSELS: NA induces vasoconstriction.
stimulation of α1-adrenergic receptors resulting in increased peripheral resistance to blood pressure is also elevated.

BLOOD PRESSURE:Adrenaline is one of the potent vasopressor agent and produced BP elevation
The BP elevating effect of adrenaline is due to direct myocardiac stimulation.
increase in heart rate and vasoconstriction in many vasculatory beds.
However, the BP elevating effect of NA is mainly due to vasoconstriction effect.

BRONCHIAL SMOOTH MUSCLES:
Adrenaline is more potent than NA in causing bronchodilation (Dilation of bronchal smooth muscle)
The beneficial effect of adrenaline in asthmatic conditions, is related to bronchodilating effect and as a physiological antagonist to many substance that produce bronchoconstriction.

GIT SMOOTH MUSCLES:
The GIT smooth muscle are relaxed by adrenaline and NA and also isopenaline.
the intestinal tone, frequency, and amplitude of spontaneous contraction of the ion are reduced resulting in increased gastric emptying time.

EYE:
NA and adrenaline produce pupillary dilation without loss of accomodation

METABOLIC EFFCTS:
adrenaline produces elevation of the blood level of glucose and free fatty acid through stimulation of glycogenolysis and glycolisis
this effect is mediated through β-receptors

UTERUS:
during the last month of pregnancy and at birth, adrenaline is known to inhibit uterine tone and contraction.
β2-selective agonist are commonly used to delay premature labor.

CNS:
NA is a mild CNS stimulants.
it induces restlessness, tremor, and anxiety.
NA is involved in the regulation of mood and behavior.

URINARY BLADDER:
mediates relaxation of the urinary bladder which is mediated by β2 receptors.

Question 5

CLASSIFICATION OF ADRENERGIC RECEPTORS

Answer 5

Based on the use of agonists and antagonists specificity, dz receptors are classified into α and β receptors.

They are sub-classified into:

α- adrenergic receptors: which can be further subdivided into α1 and α2 adrenergic receptors
β-adrenergic receptors: which can be further subdivided into β1, β2 and β3 adrenergic receptors

Question 6

α2-receptors

Answer 6

they are mainly located presynaptically and may aslo be found postsynaptically in the liver cells
stimulants of presynaptic α2 receptors cause inhibition of biosynthesis and release of NA. it produce the β2 receptors and negative feedback regulation of sympathetic discharge
it is very important target for drug regulation.

Question 6

β3- receptors

Answer 6

β3- receptors
they are found mainly in adipose tissues .
they are involved in the mediation of glycolysis.

Question 6

Discuss Debrisoquine under:
MOA, use

Answer 6

MOA: they abolish the response to stimulation of post ganglionic adrenergic neurons.
they abolish the response to stimulation of post ganglionic adrenergic neurons.

The adrenergic neuron blockers can exert their effects by:
1. Being taken up preferentially into the neurons and stored in the storage vesicle.
2. Depletion of stores of neurotransmitter in the storage vesicles.
3. Some of them inhibit the synthesis of nor-adrenaline by inhibiting the enzyme dopamine β-hydroxylase

Use: these drugs are useful in the treatment of hypertension
All drugs in this category have local anasthetic activity because in one way or the other, they block the conduction of nerve implulses

Question 6

β1- adrenergic receptors

Answer 6

They are majorly found in the cardiac muscles, GIT and blood plateleta.
Activation of β1-receptors leads to contraction of the cardiac muscles and relaxation of GIT smooth muscle
they also promote platelets aggregation and glycolysis.

Signal tranduction: involves stimulation of GS proteins which results in the stimulation of adenylyl cyclase. this leads to increase in the production level of cyclic AMP and elevation of cell level of Ca2+.

Question 6

β2-receptors

Answer 6

They are found mainly in the bronchial smooth muscles, uterus, skeletal muscle sites.
They mediate bronchodilation, relaxation of the uterus and contraction of skeletal muscle
it prevents the release of histamine from mast cells.

Question 6

α1-receptors

Answer 6

predominantly found in the blood vessels, GIT and the liver, they produce vasoconstriction, relaxation of the GIT smooth muscles and glycogenolysis in the liver.