Pharmacology Revision

[amna.]

I'm following you Saif.

[Saifullah]

On the first page i went through cholinergic agonist. Now i will talk about cholinergic antagonists

CHOLINERGIC ANTAGONISTS

Ill just quickly recap that cholinergic is used for neurons which have acetylcholine as their neurotransmitter. If an agent is able to enhance the effects acetylcholine on the receptors (muscarinic and nicotinic) then it is called cholinergic agonist. These mimic the parasympathetic action

This diagram helps us to understand



What this shows is the pre-ganglionic receptors and post-ganglionic receptors. In brackets are the receptors and on top is the neurotransmitter.

So we said acetylcholine (cholinergic) agonists are like parasympathetic activity coz as we see in this diagram acetylcholine is present both in pre and post ganglionic neurons!!

[Saifullah]

Now the classification of the CHOLINERGIC ANTAGONIST is based upon the receptors it block

-ANTIMUSCARINIC-Block the muscarinic receptors
-GANGLION BLOCKERS-Block the nicotinic receptors (both sympathetic and parasympathetic preganglionic)
-NEUROMUSCULAR BLOCKERS-Block the nicotinic receptor only at the striated muscles (muscles)

[Saifullah]

Now wat are the actions of anti-muscarinic. Well it is opposite to what the actions of the cholinergic agonist were.

In the eye it causes mydriasis (dilation of pupil)
Cycloplegia (inability to focus near vision)

In the GI it is used as an antispasmodic to reduce activity of GI tract.

In urinary system it causes urinary retention

It blocks the salivary glands, producing drying effect on oral mucosa (XEROSTOMIA). Sweat and lacrimal glands are also affected.

Therapeutic uses

Usually it is used in the eye to create a mydriatic and cycloplegic effect,.

It is used as an anti spasmodic to relax the GI tract and bladder.

Antidote for cholinergic agonists, if you get overdose of insecticides and some mushroom poisoning you can use massive doses on the antagonist to counteract the poisons.

IT is anti secretory agent helps in blocking secretions in upper and lower respiratory tracts prior to surgery.

[Saifullah]

Adverse effects

You can guess this again by just thinking about the cholinergic agonists, it is the opposite mainly.

-Mydriasis (pupil dilation)
-Blurred vision (cycloplegia, out of focus on near vision)
These two effects may make glucoma worse

-Constipation
-Confusion
-Dry mouth

A list of antimuscarinic drugs

-ATROPINE...Has all the effects mentioned above of antimuscarinics

-CYCLOPENTOLATE...Used in opthalmic solutions
-IPRATROPIUM...Used in asthma for those who can't take other drugs
-SCOPOLAMINE....Anti-motion sickness drug
-TROPICAMIDE...used in opthalmic solutions

[Saifullah]

NEW UNIT-DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM

Neurodegenerative diseases
The main two diseases are:
-Parkinsons disease
-and Alzheimers disease

Let us go through Parkinsons disease firstly.

It is a progressive neurological disorder of muscle movenement, characterised by tremors and muscular rigidity, bradykinesia (slowness in initiating movement) and postural and gait abnormalities. Most commonly occurs in age of 65 and above.

Etiology (cause)

It is unknown for most patients. The disease is linked to the destruction of dopaminergic neurons in the substantia nigra (located in brainstem) with consequent reduction of dopamine actions in the corpus striatum (brains basal ganglia-involved in motor control). The loss of dopamine neurons in the substantia nigra is shown by diminished overall uptake of dopamine precursors in this region, which can be visualised.

Genetic factors do not play a dominant role in etiology of the disease, although it may contribute to susceptibility of the disease. Also environmental facotrs.

[Saifullah]

DRUGS USED IN PARKINSON'S DISEASE

To understand this first let me explain the role of substantia nigra in Parkinsons disease. There is a a circuit where the substantia nigra interacts with the neostriatum. The job of substantia nigra is to cause inhibition in neostriatum to decrease the acetylcholine released. This then stops unwanted extra movements, but if this is affected then the inhibition from substanita nigra stop and more acetylcholine is released in neostriatum causing a chain of abnormal signaling leading to impaired mobility.

Now you can then see what kind of drugs are needed, they should increase the level of dopamine in any way whether directly or indirectly from substantia nigra, to antagonise the cholinergic activity in neostriatum (cholinegic excitatory neurons)

[Mayana]

Jazakullah Khairan. Keep it up, Saifullah. =)

[Saifullah]

Continuation of Parkinson Disease and wat drugs are used

Let me classify the drugs so you can better understand

-DOPAMINE PRECURSOR
-DOPAMINE AGONIST
-COMT inhibitors (catechol-O-methyltransferase inhibitors)
-MAO-B INHIBITORS (mono amine oxidase B inhibitors)

Dopamine precursors
Levodopa-This enhances doaminergic neurotransmission in the corpus striatum by enhancing synthesis of dopamine in the surviving neurons of the substantia nigra. In patients with the early disease the number of residual neurons (dopaminergic) is adequate for conversion of levopdopa to dopamine.

Parkinson results from insufficient dopamine in specific regions of the brain. Dopamine itself does not cross blood brain barrier, but levodopa its precursor does and is converted in the brain to dopamine. Most of the drug is decarboxylated to dopamine in the periphery so to stop this from happening another drug called carbidopa (a dopa decarboxylase inhibitor) is used. This means that levodopa is not gonna go to the periphery to cause side effects but most of it will be converted to dopamine in the brain.

Adverse effects of levodopa

Anorexia, vomiting and nausea as stimulation of chemotrigger zone of medulla Tachycardia due to dopaminergic effect on heart.

Can lead to depression, mood changes, anxiety and psychosis. This is due to over activity of dopamine at receptors in basal ganglia.

[eyeliner]

dopamine and serotonin are associated with depression and other psychological disorders

[Saifullah]

Yes (also norepinephrine)

That is why first line drugs for depression are called selective serotonin re-uptake inhibitors..it stops the re-uptake of serotonin, making more serotonin available at the neurons.

Schizophrenia is a problem where there is too much dopamine and drugs used are meant to lower levels of dopamine.

So Schizophrenia and Parkinsons are related in a way, because the treatment of one involves lowering dopamine whereas the other increases level of dopamine. So sometimes with treatment of schizophrenia you get parkinsonism as an adverse effect

[eyeliner]

^ i heard that they were not sure whether it was too little or too much dopamine that caused it.

[Saifullah]

DOPAMINE AGONISTS
A dopamine agonist is a compound that activates dopamine receptors in the absence of dopamine.

These include bromocriptine, cabergoline, ropinirole, pramipexole and rotigotine. They have longer duration of action compared to levodopa. Used in advanced stages of the disease.

[Saifullah]

^ i heard that they were not sure whether it was too little or too much dopamine that caused it.

Schizophrenia-High dopamine levels
Depression-Low serotonin levels is main theory used (or what they call catecholamines dopamine and norepinephrine)
Parkinson-Low dopamine levels

Drugs for parkinson increase dopamine level
Drugs for treatment of depression include increase serotonin level (SSRI's)
Drugs for treatment of schizophrenia include lowering dopamine levels

This is a simple way of classifying it

[eyeliner]

drugs for depression are valium now known as diazipham, i forgot the other one. Did you know that valium had caused a lot of mothers to give birth to stillborn babies, (source psychology lol)