In the ANS acetylcholine is the major autonomic nerve transmitter in all the preganglionic fibers and the parasympathetic postganglionic fibers and the sympathetic postganglionic fibers supplied to the sweat glands.
Acetylcholine is acting on the nicotinic receptors in the preganglionic level of both sympathetic and parasympathetic systems, and muscarinic receptors at the postganglionic level.
This can be detailed as follows:-
1.Preganglionic fibers of autonomic ganglia (Nn)
2.Preganglionic fibers that supplied to the adrenal medulla (Nn)
3.Postganglionic fibers of the parasympathetic system (M)
4.Postganglionic fibers of the sympathetic system that supplied to the sweat glands(M)
Nn means the nicotinic receptor at the neuronal level the name earned because it was first identified by nicotine.
M means the muscarinic receptor because it was first identified by using muscarine.
Here we deal with drugs that mimic acetylcholine's cholinergic stimulant actions.
These drugs are known as cholinomimetics and are categorized as follows:-
1.Direct Acting Stimulants (Agonists)
These are acting by chemically binding with the acetylcholine's nicotinic and muscarinic receptors in the body.
a.Acetylcholine
This is the natural endogenous prototype drug secreted within our body and affects almost every system in our body. This can be summarised as follows:-
Cardiovascular system In this system if acetylcholine dominates by acting on its muscarinic receptors in the parasympathetic postganglionic level as in rest and sleep, it decreases heart rate, B.P., and contractility.
Digestive system Increases intestinal motility
Urinary system Increases contractility of the bladder
Pulmonary system It increases pulmonary secretions.
The eye In the eyes it causes pupillary constriction (miosis)
Periphery It causes contraction of the muscles by its somatic nicotinic receptors(Nm) at the neuromuscular junction
Endocrine system It causes the release of adrenaline from the adrenal medulla by its nicotinic action.
As a medicine, this drug is very rarely used to produce miosis in the eyes and its use is very limited as it has widespread unwanted actions and is rapidly destroyed by acetylcholinesterase and eliminated by the body.
Side effects
Diarrhea and Decreased BP
Urination
Miosis
Bronchial secretions and Bradycardia
Excitation of the bone muscles
Lacrimation
Salivation
The side effects can be easily memorized by the anagram 'DUMBELS'
b.Bethanechol
It is chemically a carbamic acid ester.
It acts mainly on muscarinic receptors
Therapeutically it can be used to relieve constipation and urinary retention.
Side effects
Similar to that of acetylcholine
c.Carbachol
It is also similar to bethanechol a carbamic ester but because of more side effects due to nicotinic effects the drug is very rarely usedto produce miosis during eye surgery and in glaucoma
Acting on both muscarinic and nicotinic receptors
Side effects similar to that of acetylcholine
d.Pilocarpine
Pilocarpine is an alkaloid from the leaves of typical south American shrubs from the genusPiocarpus
Causes,
miosis
decreased heart rate
bronchial contractions
increase salivary, lacrimal and sweat secretions
The drug is unaffected by the enzyme acetylcholinesterase and hence yield prolonged action.
This is the drug of choice for the treatment of glaucoma
It has the advantage of acting primarily on muscarinic receptors only.
Side effects
Similar to acetylcholine but in addition to that it can enter the CNS to give effects like migraine,delusions, dizziness, etc.
e.Methacholine
Because of its short duration of action, it can be used for diagnosing asthma and bronchial hyperactivity.
Acting mainly on muscarinic receptors.
Side effects are due to generalized cholinergic stimulation.
In general, our nervous system is divided into two branches such as 1.Central Nervous System(CNS) which is centered at the brain systems and highly protected by the blood-brain barrier and skull.
2. Peripheral Nervous System(PNS) which is centered outside the brain midbrain, and spinal cord and is not much protected as CNS. Hence PNS is highly prone to be injured by toxins and mechanical means.
PNS is acting as a mediator between the end organs with the CNS.
The PNS is again divided into two such as 1. The Somatic nervous system supplied to the skeletal muscles to express our voluntary desired movements to the brain by sending and receiving back and forth the impulses and commands from the brain accordingly.
2. Autonomous Nervous System is an involuntary control of smooth muscles such as the heart, lungs, and liver etc.etc.
The system is connected to the CNS in two different physiological networks known as the sympathetic and parasympathetic nervous systems.
The autonomic nervous system is defined as a collection of nuclei, cell bodies, nerves ganglia, and plexuses that provides afferent and efferent nerves supplied to the smooth muscles and visceral organs that carries commands from the brain and stimuli or impulses to the brain by the end involuntary smooth muscles and organs.75% of the ANS nerve networks are linked with the CNS through the medulla oblongata.
The autonomic nervous system is so important as it regulates involuntary functions such as blood pressure, heart rate, and the digestive system. As in the diagram above the ANS is divided anatomically into two major components as follows:- 1.ParasympatheticNervous System in which there is a long preganglionic fiber that snaps with a short postganglionic fiber at the ganglion situated somewhere nearby the target organ as in the diagram shown above. The preganglionic fibers originate from cranial nerve nuclei III, VII, IX, and X as well as the III and IV sacral spinal roots and this system is known as craniosacral outflow 2.Sympathetic Nervous System in which there are short preganglionic fibers that snap with the long postganglionic fibers at the ganglia to form a sympathetic ganglionic chain adjacent to the spinal cord. All preganglionic fibers of the sympathetic nervous system originate in the thoracolumbar portion of the spinal cord and it is known as thoracolumbar outflow Pharmacologically acetylcholine is the nerve transmitter in the preganglionic fibers of both the systems and postganglionic fibers of the parasympathetic nervous system.
Norepinephrine is the major nerve transmitter at the postganglionic nerves in the sympathetic nervous system except the postganglionic sympathetic nerve supply in which acetylcholine is the nerve transmitter. Responses of the effector organs to the autonomic nervous system can give us an outline of predicting various drugs that mimic or antagonize the actions of these nerves. The two divisions of the ANS are generally antagonizing each other in some sites like the heart and digestive system and synergizing in some sites such as in sex organs.
General Functions Of ANS
Generally, the combined functions of the ANS are important in regulating the activities of vital organs which are functioning involuntarily below the level of consciousness. Thus respiration, circulation, digestion, body temperature, metabolism, sweating, and endocrine secretions of hormones are all regulated and controlled in part or entirely by ANS.
Specific Functions Of ANS
The specific functions of the two divisions of the ANS can be emphasized as follows:-
1. The sympathetic nervous system is the predominant one in normal situations as the majority of the combined nerve supply to various parts of our body belongs to this anatomical division of ANS. This nervous system is active even at rest but becomes dominant during stress by its adrenergic postganglionic activity. For example, if you feel danger or angry, or any other mind provoking thoughts, your heart rate increases, blood pressure rises, eyes dilate, blood sugar rises, lungs expand with more oxygen demand, and the face and parts of the body reddened as the blood flow shifts from the skin to skeletal muscle in order to get ready for a fight or flight.
The effector organs are responding to sympathetic(adrenergic) stimulations by the following receptors such as alpha-1,alpha-2;
beta-1,beta-2;and dopamine receptors.
In contrast, the parasympathetic nervous system which is not much innervated in our body is predominant at rest, sleep, and the situation of calmness. It is a nervous system of peace and tranquil. Stimulation of this nervous system in which the postganglionic fibers are 100% cholinergic slows heart rate, lower blood pressure, increase intestinal motility, constrict the pupil(miotic) and empty the urinary bladder. In general, this is a peace and digestive system.
The effector organs respond to this system(Cholinergic) at the receptors such as nicotinic(Nm, Nn) and muscarinic(m-1 to m-5)
The two systems are working and active all the time. Their action is antagonized to each other according to the situations. For example, the heart rate is normally under the influence of cholinergic. But when the situation gets tense the heart rate goes under the influence of the adrenergic sympathetic nervous system.
Nerve Transmitters
Apart from the anatomical sympathetic division of ANS, a pharmacological division of ANS is more convenient to understand their activities by means of the autonomical transmitters as follows:-
1.Cholinergic Nervous System in which the transmitter at the target organ is Acetylcholine
2.Adrenergic Nervous System in which the transmitter at the target organ is Norepinephrine.
The calcium ion is required to release the transmitters from their storage vesicles.
HD is a dominantly inherited disorder characterized by the gradual onset of mobility disorders followed by mental insufficiency. The condition is very common at a young age to mid-age.
Symptoms start insidiously either as a mobility disorder or a cognitive and personality disorder or both. The movement disorders consist of a brief jerk like movements of the extremities, trunk, face, and neck(chorea).
Motor incoordination and impairment of rapid eye movements are the early symptoms. If the onset of the disease occurs in the early 20s the choreic movements are less prominent but instead, bradykinesia(slow neuromuscular response) and dystonia (involuntary contract movement of muscles) are the prominent features.
As the disease progresses the dystonic muscle movements are more frequent and severe, leads to dysarthria(Arthritis like pain and speech difficulty), followed by dysphagia(pain and difficulty in swallowing), and balance to stand or walk is impaired.
Cognitive disorder slowly onset by slow mental processing and difficulty in organizing complex tasks.
Memory in distance and long ago may be impaired but short memories and memory of family friends, close relatives, and immediate incidences may be spared. Hence such persons always seem to be irritant anxious and depressed.
Less frequently paranoia and delusions may manifest.
Over a course of 20 to 30 years, the affected person becomes totally disabled and unable to communicate and require full-time care.
Death ensues from the complications of immobility.
Neurology
In general similar to the other neurological disorders, the HD also caused by the neuronal degeneration at the forebrain in which the reward system is present. The damages are mainly at the nerve nucleus known as caudate nucleus along with the round-shaped nerve capsule known as putamen composed parts of the basal ganglia, at the forebrain.HD is purely a genetic disorder due to a single defect on chromosome-4.
Treatments
There is no cure for the disease but medicines are used in a limited sense because of the side effects to control the symptoms.
1. Depression can be treated with antidepressant drugs such as tricyclic antidepressants(Amitriptyline, imipramine) but their anticholinergic effects which may exacerbate chorea. should be excluded.
SSRIs such as Fluoxetine can be employed to treat depression and irritability with a safe profile.
Antiepileptics such as Carbamazepine has also been tried successfully to relieve depression.
Neuroleptics such as clozapine and risperidone can be used but the doses should be lower than their dose employed in psychiatric disorders. At high doses, they may impair cognitive functions and mobility.
For those with large amplitude chorea causing frequent falls and injury can try antidopaminergic drugs such as haloperidol or tetrabenazine or reserpine. During the dopamine depleting drugs treatment patient should be watched for depression and hypotension.
Benzodiazepines like alprazolam, diazepam, or temazepam can be used to relieve anxiety and stress. Seizures can be controlled by anticonvulsants such as clonazepam or valproic acid
Alzheimer's Disease is a cognitive and memory disorder that usually occurs at the age of 60 and above. The onset of the disease is slow but with a definite progression. It may take 10 to 15 years to attain the fully developed stage at which the patient lost short and distant memories, inability to recognize anything, and become immobile with physical sufferings by infections. Death usually resulted in the cause of pneumonia or pulmonary embolism.
Pathophysiology
The major pathophysiology is the atrophy and damages of the cerebral cortex and subcortical neurons. Unlike PD, in AD, there are no much damages at the midbrain and hence there are no postural and extrapyramidal irregularities.
In the process of aging, there is a synthesis of neurons are progressed at the cerebral cortex usually in the grey matter. During the process, by-products are formed as plaques and deposited at the grey matter.
These deposits are larger in number and are mainly made of beta-amyloid. These plaques are neurotoxic and cause further degenerations of neurons in the cortex results in Alzheimer's Disease(AD).
Although small numbers of senile plaques and neurofibrillary tangles are common in normal individuals they are far more abundant in AD and the abundance is directly proportional to the cognitive impairment.
Unlike Parkinson's Disease in which the main pathophysiology is the loss of dopaminergic neurons in the midbrain but in Alzheimer's Disease, there is a major loss of cholinergic neurons with a hefty insufficiency of acetylcholine input at the cerebral cortex particularly at the basal forebrain that provide cholinergic innervation to the whole cerebral cortex. Also unlike in PD in AD, there is far more loss of neurotransmitter networks such as serotonin, glutamate, and neuropeptides to make it more complicated.
Treatments
One of the major basics of the treatment of the AD is to restore or normalize the acetylcholine input and to normalize the cholinergic innervation of the cortex. The approach with acetylcholine precursors such as choline chloride and lecithin was found with no expected benefits.
Direct injection of cholinergic agonists such as bethanechol into the intracerebroventricular region yield some benefits. But this is complicated with the need for surgical implantation of a reservoir connecting to the subarachnoid space(the space between the arachnoid mater and the pia mater ).
Later on, there are some more easy and improved methods such as the use of acetylcholinesterase inhibitors such as physostigmine a reversible inhibitor are developed. The use of physostigmine is limited because of its short half-life and side effects like a cholinergic crisis in therapeutic doses.
Recently the American FDA has approved a drug known as tacrine an acridine derivative for the treatment of AD. It is a potent centrally acting inhibitor of the enzyme AchEsterase.An I.V.injection of tacrine is tried with major flaws
Laer on oral tacrine combined with lecithin is tried successfully.
Side effects of oral tacrine
1.Abdominal cramp
2.Nausea and vomiting
3.Diarrhea
4.Liver toxicity(elevation of serum transaminases)
but liver enzymes rapidly subsided by withdrawing the medicine.
We have already seen the idiopathic PD is incurable as its structure of inhibitory and excitatory irregularities in the midbrain is more complicated.
The general assumption is there is increased direct stimulation of the midbrain by the cerebral cortex through glutamate excitatory pathway with the result of increased inhibition of the thalamus through the inhibitory GABA pathway. This leads to a decreased thalamic stimulation to the cortex. In the middle of this, there are many complicated dopaminergic pathways irregularities that happened in the basal ganglia with the loss of dopaminergic nerve networks which leads to Parkinson's Disease.
Treatments:-
I.A table of commonly used medicines with some details:-
1.Carbidopa/Levodopa:-
25 /100mgs 2 to 3 times a day, to yield 200/ 1200 mg levodopa daily range.
C/L SR:-
50/ 200 mg.2 times/day.A daily range of 200 /1200 mg.
Bioavailability is 75% of the standard form
2.Pergolide:-
0.05 mg once daily with a daily range of 0.75 to 5 mg/day
3.Bromocriptine:-
1.25 mg twice a day.
A daily useful range is 3.75 to 40 mg. daily.
4.Selegiline:-
5 mg twice a day
A daily range of 2.5 to 10 mg.
5.Amantadine (Antiviral):-
100 mg twice a day.
A daily range of 200 mg.
6.Trihexyphenidyl HCl:-(Anticholinergic)
1 mg twice a day
A daily useful range is 2 to 15 mg.
II.A Comprehensive Study of Treatments
Classic PD is having many symptoms like hypercholinergic effects associated with impaired dopaminergic effects and extrapyramidal side effects like bradykinesia, akinesia, dyskinesia, etc.Hence all the effects should be antagonized to yield a comfortable relief.
The drugs are classified as follows:-
1.Anticholinergics (for tremors)
2.The precursor of Dopamine (Carbidopa/Levodopa)
3.Direct Dopamine agonists such as Bromocryptine, and Pergolide
4.Indirect Dopamine agonists such as i.By decrease dopamine reuptake (Amantadine)
ii.By decrease dopamine metabolism(Selegiline)
Also, there are associated symptoms like depression, action tremor, which can be treated as follows:-
1.Tricyclic Antidepressants can be used as they also have mild anticholinergic and dopaminergic effects.
2.Beta-blockers like nonselective propranolol is useful to control the action tremor as it is highly fat-soluble and can pass easily the blood-brain barrier.
3.Benzodiazepines and Primidone are also very well effective in solving the action tremor.
4.Antihistamines such as Diphenhydramine a common ingredient in the cough suppressant syrups is have a value in controlling the action tremor by its mild anticholinergic effects.
General Principles of The Treatments:-
As a rule treatment of PD should be stared with a low dose with a slow gradual increase.The response should be within a few days.If not with the doctor's advice try with another class of medicine.
If an additional drug is added then reduce the dose of the first medicine to minimize the side effects.
Drug therapy should never be discontinued suddenly because sudden withdrawal may relapse the symptoms with exacerbation.
When the therapy started the following unwanted effects should be watched and corrected by dosage adjustments or a change in drug recipe.
Dyskinesias are the facial symptoms with irregular jerky movements.
On-Off effects are the sudden changes in mobility from no symptoms to full PD symptoms in a matter of minutes.
End dose effects usually occur at the latter part of the dosing interval can be improved by shortening the dosing interval.
Drug holiday Prolonged and continued use of dopamine direct agonists like levodopa may desensitize the dopaminergic receptor network at the midbrain(neostriatum -substantia nigra network)and a drug holiday gap can resensitize the striatal nigra dopamine receptors.But risk and care should be exercised under the doctor's supervision when a holiday is imposed.
Individual Drugs
Anticholinergic and antihistaminic Drugs
They are used mostly for tremors, rigidity, and kinetic irregularities.Resting tremors are more responding to anticholinergics.They have no effects on postural irregularities.
These drugs are acting by decreasing the excitatory acetylcholine inflow to the basal ganglia in the midbrain.
Caution should be taken when using these medicines in patients with GI and urinary tract obstructions, narrow-angle glaucoma, or severe cardiovascular defects.
Alcohol and other CNS depressants should be avoided.
Side effects
Peripheral side effects such as dry mouth(chewing gum may be helpful), decreased sweating(beware of summer), urinary retention, constipation, increased intraocular tension.
CNS side effects are dizziness, delirium, disorientation, anxiety, agitation,
hallucination, and impaired memory.
Cardiovascular side effects are hypotension,and orthostatic hypotension.
Drug Interactions
Anticholinergic action will be dangerously potentiated by the concurrent use of antihistamines and phenothiazines.
Anticholinergics will interfere with digoxin metabolism and increase its plasma levels.
1)Dopamine Precursor (Levodopa/Carbidopa)-Sinemet
In this combination, only levodopa is the active medicine, and carbidopa is only to prevent levodopa to be converted into dopamine before it enters into the blood-brain barrier.
Dopamine cannot enter into the blood-brain barrier which is necessary for the purpose of action.Levodopa can enter but if administered alone it will be rapidly decarboxylated to dopamine which cannot enter into CNS and produce many unwanted peripheral effects. To prevent this carbidopa is included which is a dopa decarboxylase inhibitor and prevents the conversion of levodopa into dopamine at the periphery.
Levodopa after entering into the CNS will be converted to dopamine by the enzyme dopa decarboxylase to produce the dopaminergic effect.
The dose of carbidopa should be at least 100 mg/day depending on the conditions.
If the patient is still complaining about the peripheral effects plain carbidopa can be given with a doctor's supervision.
Precautions
1.In narrow-angle glaucoma
2.Malignant melanoma
Side effects
1.Anorexia, nausea and vomiting
2.Postural hypotension, tachycardia
3.Dystonia
4.Confusion,depression and psychoses.
5.Hemolytic anemia,leucopenia, and rarely agranulocytosis.
Drug Interactions
1.Antacids
2.Hydantoin
3.Methionine
4.Metoclopramide
5.MAOIs and Furazolidone
6.Papaverine
7.Food will interfere with the absorption.Hence a protein-free food is advisable.
2.Direct Acting Dopaminergic Agents
1.Bromocriptine.
It is directly stimulating the dopamine receptors at the neostriatum and substantia nigra at the midbrain.It can be used as adjunct with L-dopa therapy if the patient is decreasing response to it and also to patients who cannot tolerate levodopa in higher doses.
Initially start with 1/2 tablet twice daily which is later increased to one twice daily.
Side effects
1.First dose effects may cause sudden cardiac collapse (Careful with MIs, and arrhythmias)
2.CNS effects similar to levodopa
3.Lung effects
2.Pergolide
Similar to bromocryptine but stimulating more towards the excitatory D-1 receptors while bromocriptine to inhibitory D-2 receptors and hence this medicine is more potent.
3.Indirect-Acting Dopamine Agonists.
Selegiline
The mechanism of action is selegiline inhibit selectively the MAO-B which is responsible for metabolizing dopamine in the CNS.
2.Amantadine
The mechanism is this antiviral drug decrease the presynaptic reuptake and increase the synthesis of dopamine.
In general, due to the excessive loss of dopaminergic nerve network in the basal ganglia and the depletion of dopamine input into the midbrain leads to the distinctive motor disability known as Parkinson's disease. TYPES OF PARKINSONISMS
1.Idiopathic or Primary:- This is also known as Classic typeor paralysis agitans The etiology is unknown and even the treatment is palliative the classic form is incurable.90% of the cases are of this type. But there is some hypothesis of the etiology of this type. They are assumed as prolonged exposure to potent neurotoxins such as carbon monoxide, N-methyl-4-phenyl-1,2,3,6 tetrahydro pyridine(MPTP), and manganese. But these are only assumptions as some of the pathologic conditions produced by these toxins can be curedby proper therapies. Exposure to these agents along with the age of nervous weakness or degeneration may be the cause for this incurable type. Another hypothesis is exposure to free radicals. Dopamine is catabolized by Monoamine oxidase (MAO) an enzyme abundantly available at the mitochondria of the ganglia which results in the formations of toxic free radicals such as OH-, Fe3+along with hydrogen peroxide(H2O2). If any deficiency of our body's natural protective mechanism against these free radicals or lack of supply antioxidants such as vitamin-C and E or hypersecretion of dopamine may lead to the suicide of its own nerve network in substantia nigra compacta at the midbrain. 2.Non-Classical or Secondary This type is rare and uncommon and curable as mostly this type occurs with known causes. This type is mostly caused by drug abuses such as:- Dopamine antagonists such as Phenothiazines(Chlorpromazine, perphenazine) Butyrophenones(Haloperidol) Reserpine Poisoning by chemicals such as CO poisoning Heavymetal poisoning (Manganese, mercury) MPTP, a commercial product used in the making of synthetic heroin-like narcotics. Infections such as Viral Encephalitis. Syphilis Other physiological disorders such as Arteriosclerosis Progressive supranuclear palsy(A nervous degenerative defects) Wilson's disease (A metabolic disorder) Symptoms of Parkinsonism Tremor, starts with action tremor followed by resting tremor(First symptom) Limb rigidity is clinically detected by when the arm responds with a rachet-like(e.g. Cog wheeling) movement when the limb is moved passively Akinesia or Bradykinesia, Akinesia is characterized by difficulty in initiating movement and bradykinesia a slow response of the muscle for a move. Gait and Postural Difficulties are detected by the patient's walk with a stooped flexed posture; a shuffling stride and an irresponsive and irregular rhythm of arm movements with the legs. Changes in mental state including 50% depression and 25% dementia There are five stages of the disease as follows:- 1.Unilateral involvement 2.Bilateral involvement but no postural abnormalities 3. Mild postural imbalance with bilateral involvement and patient can lead an independent life 4. Bilateral involvement with postural instability, require substantial help 5. Severe fully developed disease and patient restricted to bed and chair. Diagnosis Tests such as MRI scans should be carried out to rule out the secondary type of the disease. The latest technology of imaging such as Positron Emission Tomography is carried out in order to estimate the extent of the neuronal loss and to visualize the dopamine uptake in the substantia nigra.
Some times after attending late-night superb parties offered by friends in marriage functions or company bonus parties with a variety of spicy delicious foods when we return home at bed we feel a fullness of stomach with a prickly burning sensation at the heart. Commonly known as Heartburn is nothing but acid reflux from the stomach to the esophagus by the irregular behavior of the gastroesophageal valve. Technically this condition is known as Gastro-Esophageal-Reflux-Disease or simply known as GERD
The esophagus is the food passage down from the larynx the portion down next from the oral or buccal cavity. Food, after chewed and swallowed by the mouth, is pushed down to the esophagus through the larynx then passes down through it to reach the stomach by opening the valve gate known as the Lower esophageal sphincter(LES) which should open downwards into the stomach.
Esophagus the food passage has no protection from the acid attacks. Heavy food and spicy unbearable filling of the stomach may lead to an irregular upward opening of the lower esophageal sphincter and the acidic stomach juice refluxed up rapidly into the esophagus to cause heartburn.
This may not be a disease if it happened occasionally. But the frequent and prolonged stay of the acidic stomach contents effluxed into the esophagus may cause damages to the esophageal tissues (Reflux Esophagitis) and heartburn.
Symptoms
A burning sensation or pain focused at the lower chest can slowly radiate upwards to the left side and make confusion with the pain of a heart attack.
Symptoms usually occur soon after a meal and when lying on the bed.
Severe mucosal damage may cause pain during swallowing.
Complications
Patients with severe uncontrolled GERD may suffer from bleeding due to esophageal ulcerations, and respiratory complications due to the entry of the refluxed acid materials into the lungs through the upper airways.
Patients who have pain in swallowing(Dysphagia) may have esophageal ulcers, strictures, or cancer.
Etiology
Many people with GERD have a weak LES. As a result, the high pressure in the stomach (by taking full stomach or spicy foods) produces enough force to overcome the weak squeeze of the LES and allows the content to elude upward and causes reflux.
The following other factors also may weaken LES tone, delaying gastric emptying, increasing acid secretions, or impairing the gastroesophageal pressure gradient as follows:-
1.Calcium channel blockers like Amlodipine, nifedipine, verapamil, and diltiazem
2.Nitrates like nitroglycerin, sodium nitroprusside,
3.Anticholinergics like tricyclic antidepressants(amitriptyline,imipramine,clomipramine)antihistamines
antihistamines(Diphenhydramine, chlorpheniramine)
4.Oral contraceptives and estrogen.
Treatments
A.Nonpharmacological
1. Elevate the head of the bed about 5 inches by some mechanical means.
2. Eat night meals at least 2 hours before going to sleep
3. Avoid foods that reduce LES tones such as chocolate, mint and high-fat foods
4. Avoid the following foods that irritate the esophagus like tomato preparations, coffee, citrus juice, spicy foods.
5. Take small meals
6. Avoid bed soon after the meals
7. Stop smoking
8. Avoid alcohol
9.Reduce obesity
10. Avoid tight clothing.
B.Pharmacologic
Generally, the approach should follow first the nonpharmacologic procedures.
The pharmacologic procedure contains the antacids, the OTC H-2 Receptor Antagonists, with the nonpharmacological procedures as the first step.
1.Antacids
Antacids may reduce the acidity of the stomach contents by increasing its pH, and reduce the pressure on LES.
Generally, they reduce the heartburn in 10 to 15 minutes. The duration may range from 1 to 3 hours.
Repeated doses may require the maximum 5 times per day because of the short duration of action.
40 to 80 mEq is the daily dose should be taken after each meal and at bedtime.
a)Sodium bicarbonate should be used carefully because of its sodium content (12mEq/gm).
It is not suitable in patients with edema, CHF, kidney failure, cirrhosis in the liver, and hypertension.
b)Calcium carbonate is also good for GERD but may cause constipation.
c)Aluminum hydroxide may cause constipation but avoid to be used in patients with hemorrhoids, with constipation.
d)Magnesium hydroxide may frequently cause diarrhea. To prevent this a mixture of Aluminium and Magnesium hydroxide is better.
In general Kidney, patients should avoid all antacids
Cardiac patients can use under doctors' advice magnesium and potassium hydroxide mixtures.
The maximum daily dose is 500 mEq ANC (Acid Neutralizing Capacity) of antacids.
Antacids may interfere with the absorption of many drugs such as
Tetracyclines
Quinolones such as ciprofloxacin, ofloxacin
Iron preparations
Digoxin
2.Alginic acid
This is a safe medication for GERD as unlike antacids it works differently as follows. Alginic acid reacts with sodium bicarbonate of saliva to form viscous sodium alginate which when going into the stomach float above the stomach content so that the content cannot efflux upward beyond this viscous float and the effluxed sodium alginate will not irritate the esophagus.
Alginic acid tablets must be chewed before swallowing along with one or two glasses of water
It works well in patients with an upright position.
These products should not be taken at bedtime or just before lying into the bed.
3.OTC H-2 Receptor Antagonists
These products minimize the acid secretions by completely blocking the H-2 receptors of the histamine in the parietal cells of the stomach. The onset of the action is 1 to 2 hours.
These agents are giving effects >90%.
Very useful in healing gastric and duodenal ulcers.
All these medicines are equally effective but differ in their other untoward effects.
a)Cimetidine The adult dose is 200 mg.twice daily.
Side effects are liver problems, by interfering with the liver metabolisms of warfarin, phenytoin, and theophylline and thereby increase the plasma concentrations of these drugs dangerously.
b)Famotidine The adult dose is10 mg twice daily To be taken 1 hour before food. A 10 mg dose has an effect of 8 hours.
Fortunately, famotidine does not interfere with hepatic metabolisms of other drugs.
c)Ranitidine The adult dose is 75 mg up to twice daily.
Compared with cimetidine, ranitidine impairs hepatic metabolism of other drugs 10 times lesser.
d)Nizatidine The adult dose is 75 mg up to twice daily.
Fortunately, it does not impair the hepatic metabolism of other drugs.
The dosages of the OTC medications mentioned above should be increased only by a doctor's supervision
Side effects of H-2 RAs
1.Nausea
2.Headaches
3.Reversible gynecomastia(Male increased breast size)
4.Elevated serum prolactin results in galactorrhea
5.Altered estrogen metabolism in male
6.Inhibition of hepatic p-450 enzyme metabolism(Cimetidine and Ranitidine)
4.Proton Pump Inhibitors
These are prescription-only powerful medicines to treat GERD. Their duration of action is up to 3 days. The act by inhibiting the hydrogen-potassium ATPase pump on the surface of the parietal cells of the stomach.
1.Omeprazole
2.Lansoprazole
These medicines can be used in the following conditions:-
