These are the drugs which used in treatment of major psychosis
They are also called a major tranquilizers, since they reduce agitation and disturbed behavior seen in schizophrenia
1. Phenothiazines
Chlorpromazine
Triflupromazine
Fluphenazine
Thioridazine
2. Butyrophenones
Haloperidol
Trifluperidol
3. Rauwolfia alkaloids
Reserpine
4. Thioxanthines
Chlorprothixene
Thiothixene
5. Indolic derivatives
Molindine
6. Miscellaneous
Oxypertine
Tetrabenazine
Pimozide
CHLORPROMAZINE (CPZ)
These are the most widely used compounds in the treatment of major psychoses
Phenothiazines are three ringed structures
In which two benzene rings are linked by a sulphur and a nitrogen atom
Chlorpromazine is the important phenothiazine and was synthesized in 1950
According to the chemical structure , phenothiazines could be predominantly antipsychotic c, ant cholinergic or antihistaminic
Mechanism of action
Phenothiazines and other antipsychotic drugs produce beneficial effects probably by affecting three of the major integrating systems in the brain
Mesolimbic system
Mesocortical system
Hypothalamus
Cause blockage mainly of postsynaptic dopaminergic (D2) receptors and to smaller extent 5-HT receptors
Modify the function of the mesolimbic system
Reduce the incoming sensory stimuli by acting on the brainstem reticular formation
Pharmacological actions
On CNS
When chlorpromazine is given to patients with psychosis , it produces
Psychomotor slowing
Emotional quietening
Decreased initiative
Decreased anxiety
Phenothiazines do not have as analgesic effect
But they potentate the analgesic effect of morphine
They don’t have anticonvulsant effect
Behavioral effects
In normal subjects CPZ reduces motor activity, produces drowsiness and indifference to surroundings
In psychotic agitated patients, it reduce aggression , initiative and motor activity, relieves anxiety and brings about emotional quietening and drowsiness
It normalizes the sleep disturbances characteristic of psychoses
Other CNS actions
Cortex
CPZ lowers seizure threshold and can precipitate convulsions in untreated epileptics
Hypothalamus
CPZ decreases gonadotrophin secretion and may result in amenorrhea in women
It increases the secretion of prolactin resulting ins galactorrhiea and gynaecomastia
Basal ganglia
CPZ acts as a dopamine antagonist and therefore results in extra-pyramidal motor symptoms ( drug induced parkinsonism)
Brainstem
Vasomotor reflexes are depressed leading to a fall in BP
Anti-emetic action
CPZ has a powerful anti emetic effect
These block the dopamine (DA) receptors in the CTZ
This effect is produced by depress the chemoreceptor trigger zone
On ANS
The actions on the ANS are complex
CPZ is an alpha adrenergic blocker
The alpha blocking potency varies with each neuroleptic
CPZ also has ant cholinergic properties which leads to side effects like dryness of mouth, blurred vision, reduced sweating, decreased gastric motility, constipation and urinary retention
The degree of anti cholinergic activity also varies with each drug
CVS
CPZ produce hypotension due to alpha blockade action and reflex tachycardia
It also has a direct myocardiac depressant effect like guanidine
It also has anti- fibrillatory effect
Local anesthetic effect
These has local anesthetic properties but is not used for the purpose since in is an irritant
Kidney
CPZ depresses ADH secretion and has weak diuretic effects
Tolerance develops to the sedative and hypertensive actions while no tolerance is seen to the anti psychotic actions
On endocrine glands
These produces inhibition of ovulation, amamenorrhea and lactation in females
In males, it produces loss of libido
These effect are produced by blocking the action of dopamine on hypothalamus and pituitary
Other actions
Inhibition of hiccough
Skeletal muscle relaxant effect
Pharmacokinetics
It is well absorbed after oral and parenteral administration
It is highly protein bound
High concentration is found in the lungs, liver and adrenal glands
It is subjected to enterohepatic circulation
This increases its duration of action
The half life period is 20 to 24 hours and is therefore given once a day
It is metabolized in the liver and the metabolic products are excreted in urine s
Adverse reaction
CNS effects
Drowsiness, excitement, psychotic reactions, confusion and parkinsonism
ANS effects
Blurred vision, constipation, nasal stuffiness and urinary retention
These occur due to the ant cholinergic effects
CVS effects
Hypotension, palpitation and tachycardia
Hemopoietic effects
Agranulocytosis, thrombocytopenia and aplastic anemia
Endocrine effects
Gymaecomastia, lactation and menstrual disturbances
Hypersensinitivity reactions
Jaundice, agranulocytosis and skin rashes
Drug interactions
CPZ enhance the sedative effects of CNS depressants, alpha blockers and of ant cholinergic drugs
When combined with these groups of drugs , the effects may be additive
These inhibit the actions of dopamine agonists and Levo dopa
Dose
Chlorpromazine tablets and syrup- 25 to 1000mg by mouth
Chlorpromazine injection-25 to 50 mg by intramuscular injection
Uses
These are given orally ( chlorpromazine 100 – 800mg)
In acute psychosis they may be given intramuscularly and response is seen in 24 hrs
While in chronic psychosis it takes 2-3 weeks of treatment to demonstrate the beginning of obvious response
It is used in the treatment of major psychosis
It is used to control aggressiveness in children
It is used as ant emetic
CPZ can control intractable hic- cough
It is used in pre- anesthetic medication
It used in neuropsychiatry disorders such as Huntington’s disease
Drug dependence
They are useful in the management of psychosis associated with chronic alcoholism but are contraindicated in acute withdrawal syndromes for fear of precipitating seizures
Haloperidol
This is a very potent drug, belonging go the class of butyrophenones but with similar clinical effects as piperzine phenothiazines
It is more effective in highly agitated or manic patients and has less prominent sedative and autonomic effects than chlorpromazine
Mechanism of action
It blocks postsynaptic dopamine D1 and D2 receptors in the mesolimbic system and decreases the release of hypothalamic and hypophyseal hormones
It produces calmness and reduces aggressiveness with disappearance of hallucinations and delusions
Treatment
It is given orally in the dose of 1.5 to 7.5mg , there times day
It can also be given IM in the dose of 2-10 mg, repeated every hour up to a total of 30 mg, in agitated and violent patients
Subcutaneous –Adult 5-15 mg given over 24 hrs
Depot injection preparation of haloperidol are also available
Interactions
Carbamazepine and rifampicin reduce plasma concentrations
The irreversible toxic encephalopathy has been reported in patients on lithium if they are given high doses of haloperidol
The other drugs of this series are trifluperidol and droperidol which are used in combination with fentamyl for neuroleptanalgesia
Adverse drug reactions
Anxiety, drowsiness , depression , anorexia, hypotension and leucopenia
Rauwolfia alkaloids
It is alkaloid obtained from a plant called Rauwolfia serpentine
In ancient Ayurvedic medicine, the extract of this plant has been claimed to be useful in cases of insomnia , insanity and snake bite
It is called serpentine because of the resemblances of the root to a snake
Mechanism of action
Reserpine is of great pharmacological interest because it produces depletion of endogenous catecholamine and 5-HTfron the brain and peripheral sites by interfering with amine storage
Such depletion can last for day or weeks
A single dose of 5 mg / kg body weight is sufficient to cause 90% reduction in brain nor adrenaline and 5-HT over a period of 10 days
This depletion of cerebral monoamines is believed to be responsible for its central actions
Pharmacological actions of reserpine
CNS
It has central antipsychotic action resembling those of phenothiazines
It differs from the latter compounds in that it has no antihistaminic, cholinergic blocking or direct adrenergic blocking effects
In man , it produces a similar calming effect as well as extra pyramidal action as those observed flowing chlorpromazine
It does not produce clouding of consciousness
Reserpine is less effective than phenothiazines in t he treatment of schizophrenia
It may cause mental depression precipitating suicidal tendencies , hence it is no more used as an antipsychotic drug
CVS
It is used as antihypertensive drug
Reserpine is less effective tam phenothiazines in the treatment of schizophrenia
But is commonly used as an antihypertensive drug
Clozapine
This antipsychotic drug, related to heterotricyclic compounds like imipramine , was synthesized in 1960
It was found to cause agranulocytosis and its use was abandoned
It has selective effects in the limbic, dopaminergic systems, its other actions include antiadrenergic , anti5-HT and ant cholinergic actions
It differs from phenothiazines in that it causes fewer EPRs and does not cause hyperprolactinemia
It given orally, it produces antipsychotic effects similar to other standard neuroleptics
Its major advantage is that the drug improves not only the positive symptoms but also the negative symptoms such as emotional withdrawal, bunted affect, retardation and social withdrawal
It is started in the dose of 12.5 mg once daily and gradually increased to 200- 450 mg / day in divided doses
Adverse reactions
These includes nausea, vomiting , sedation , hypotension , severe tachycardia , and confusion
Anti-depressant drugs
These are the drugs used for the treatment of mental depression
They are also called as psycho analeptics or mood elevators
Classification of Anti-depressant drugs
1. Monoamine oxidase inhibitors
Meclobemide
Phenelzine
Isocarboxazid
Nialamide
11. Try cyclic compounds
Imipramine
Desipramine
Amitriptyline
Nortriptyline
111. Selective Serotonin reuptake inhibitors
Fluoxetine
Citalopram
Escitalopram
Paroxetine
Sertaline
IV. Serotonin or nor epinephrine re-uptake inhibitors
Phenelzine
Tranyl -cypromine
1. Mono-amine oxidase inhibitors (MAOI)
Monoamine oxidase (MAO) is a mitochondrial enzyme found in nerve , liver and gut
In the neuron, MAO functions is to deaminate and inactivate any excess neurotransmitter molecules (nor epinephrine, dopamine and serotonin) that may leak out of synaptic vesicles when the neuron is at test
The MAO inhibitors may irreversibly or reversibly inactivate the enzyme, permitting neurotransmitter molecules to escape degradation and therefore to both accumulate within the presysaptic neuron and leak into the synaptic space
It enhance neuronal levels of nor-adrenaline , dopamine and 5-HT
This causes activation of nor- epinephrine and serotonin receptors and it may be responsible for the antidepressant action of these drugs
Two MAO inhibitors are currently available for treatment of depression- Phenelzine and tranylcypromine
The use of MAO inhibitors is now limited due to the complicated dietary restrictions required of patients taking MAO inhibitors
Antidepressant actions develop slowly over week’s of treatment
Because of the side effects and drug interactions, MAOI are not the preferred antidepressants
Mechanism of action
MAO inhibitors such as phenelzine form stable complex with enzyme, causing irreversible inactivation
These results in increased stores of nor epinephrine, serotonin and dopamine within the neuron and subsequent diffusion of excess neurotransmitter into the synaptic space
Pharmacological actions
1.Behavior
In case o f mental depression, these compounds elevate the mood
The patient feels more energetic and fresh
2. On CVS
No effect on heart or circulation at normal dose
3. Potentiation of sympathomimetic amines
These compounds potentiate the action of symathomimitic amines like amphetamine and tyramine
These have a mild amphetamine like stimulant effect
They interact with many drugs and food
Pharmacokinetics
These drugs are will absorbed on oral administration
Antidepressant effects require two to four week of treatment
MAO inhibitors are metabolized and excreted rapidly in the urine
Adverse effects
Behavioral effects
Headache, excitement and disturbed sleep
CNS effects
Twitching, ataxia and tremors
ANS effects
Dry mouth, constipation and blurred vision
Hypertension
Tyramine is met abolished by the enzyme MAO
In presence of MAOI , tyramine is not metabolized
These leads to accumulation of tyramine
Tyramine produces rise in blood pressure by releasing nor adrenaline
Uses
MAO inhibitors are indicated for depressed patients who are un- responsive or allergic to TCA or who experience strong anxiety
These drugs are also useful in the treatment of phobic state
s
MAO inhibitors also used in the treatment of a special subcategory of depression called atypical depression
Atypical depression is characterized by labile mood , rejection sensitivity and appetite disorders
Meclobemide
It is a MAO inhibitor
It is a reversible and selective inhibitor of the MAO isoenzyme inhibiting serotonin, nor epinephrine and dopamine metabolism result into an increase in the levels of neurotransmitters
Treatment
Adult - Initially , 300 mg daily in divided doses taken alter food, increased up to 600 mg in 2 divided doses given after 3 days and continued for 8- 12 weeks
Drug interactions
May decreases t he effects of antihypertensive
Adverse drug interactions
Dizziness, headache, anxiety , agitation ,irritability y , constipation , dry mouth , sleep disturbances and visual disturbances
11. Tricyclic antidepressants
These blocks nor epinephrine and serotonin uptake into the neuron
These drugs are voluble alternative for patients who do not respond to SSRIs
Mechanism of action
These are potent inhibitors of the neuronal re-uptake of nor epinephrine and serotonin into presynaptic nerve terminals
This produces increase in its concentration at the receptor sites
These contributes for the antidepressant action
TCAs also block serotonergic, alpha adrenergic ,histamine and muscarinic receptors
Pharmacological actions
1. Behavior
These elevate mood, improve mental alertness ,increase physical activity
The onset of the mood elevation is slow , requiring two weeks or longer
These drugs do not produce CNS stimulation or mood elevation in normal individuals
Physical and psychological dependence have been reported
The drugs can be used for prolonged treatment of depression without loss of effectiveness
2. CVS
No effect at normal dose
But toxic doses may produce cardiac arrhythmias
3. ANS
Imipramine produces anti cholinergic effects like dry mouth, constipation , palpitation and blurred vision
ADME
Imipramine is well absorbed on oral administration
Because of their lipophilic nature ,they are widely distributed and readily penetrate into the CNS
This lipid solubility also causes these drugs to have long half lives – 4 – 17 hours for imipramine
These drugs are metabolized by the hepatic microsomal system and conjugated with glucuronic acid
The TCA are excreted as inactive metabolites via the kidney
It actions are mediated through desmethyl-imipramine which is a metabolite product
Adverse reactions
CNS effects
Lethargy, headache and drowsiness
ANS effects
Dry mouth, constipation and tachycardia
CVS effects
Cardiac arrhythmias and hypotension
Allergic reactions
Skin rashes and photosensitivity
Uses
These are very effective in treating severe major depression
Some panic disorders also respond to TCA
Imipramine has been used to control bed- wetting in children by causing contraction of the internal sphincter of the bladder
TCAs , particularly amitriptyline , have been used to treat chronic pain
Imipramine
It inhibits noradrenalin re- uptake and to a lesser extent that of serotonin
It is is relatively less sedating then amitriptyline and reduces REM sleep
It has few anticholinergic action and can PR interval and flatten or inverse T wave
Treatment
Initially, 75 mg daily in divided doses increased gradually to 150—200 mg daily if necessary
300 mg daily given in severely depressed
Drug interactions
Barbiturates reduces plasma levels thereby reducing antidepressant effect
Cimetidine elevates serum immpramine concentration and consequently adverse effects causes drowsiness and impaired performance in combination with alcohol
Amitriptyline
Amitriptylin exerts its antidepressant action by blocking the neuronal re-uptake of Noradrenalin and serotonin
Treatment
Adults – 75 mg daily in divided doses or as a single dose at night , increased gradually , if necessary to 150 mg daily given in the late afternoon or evening
Alternatively 50- 100 mg a single dose at bedtime , increased by 25 – 50 mg
Child – 30 – 75 mg daily or in divided doses preferably at bedtime
Maximum dose
Adult – 150mg daily
Treatment of severs depression
200- 300 mg daily , maximum dose 300 mg daily
Drug inter action
Potentates sedative effect of alcohol, antiparkinson agents and antipsychotic drugs increase risk of ant cholinergic effects
Reduced effect of anti hypertensive
Potentates hypertensive effects of sympthomimetics
Marked hyperpyrexia , convulsions and coma wit h MAOIs
Clomipramine
It is a potent inhibitor of serotonin re-uptake in t he brain
Significant antagonism at cholinergic and alpha receptors
Weak antagonism at dopamine receptors
It has also antidepressant , sedative and anticholinergic effects
Dose
10 mg daily, gradually
250 mg daily given in severe cases
Doxepin
Doxepin inhibits serotonin and noradrenalin re-uptake by the presynaptic neuronal membrane increasing its synaptic concentration in the CNS
Dose
Initially 75 mg daily adjusted according to response, 300 mg daily in severely depressed patients
Pharmacological actions
1.Behavior
In case o f mental depression, these compounds elevate the mood
The patient feels more energetic and fresh
2. On CVS
No effect on heart or circulation at normal dose
3. Potentiation of sympathomimetic amines
These compounds potentiate the action of symathomimitic amines like amphetamine and tyramine
These have a mild amphetamine like stimulant effect
They interact with many drugs and food
Pharmacokinetics
These drugs are will absorbed on oral administration
Antidepressant effects require two to four week of treatment
MAO inhibitors are metabolized and excreted rapidly in the urine
Adverse effects
Behavioral effects
Headache, excitement and disturbed sleep
CNS effects
Twitching, ataxia and tremors
ANS effects
Dry mouth, constipation and blurred vision
Hypertension
Tyramine is met abolished by the enzyme MAO
In presence of MAOI , tyramine is not metabolized
These leads to accumulation of tyramine
Tyramine produces rise in blood pressure by releasing nor adrenaline
Uses
MAO inhibitors are indicated for depressed patients who are un- responsive or allergic to TCA or who experience strong anxiety
These drugs are also useful in the treatment of phobic state
s
MAO inhibitors also used in the treatment of a special subcategory of depression called atypical depression
Atypical depression is characterized by labile mood , rejection sensitivity and appetite disorders
Meclobemide
It is a MAO inhibitor
It is a reversible and selective inhibitor of the MAO isoenzyme inhibiting serotonin, nor epinephrine and dopamine metabolism result into an increase in the levels of neurotransmitters
Treatment
Adult - Initially , 300 mg daily in divided doses taken alter food, increased up to 600 mg in 2 divided doses given after 3 days and continued for 8- 12 weeks
Drug interactions
May decreases t he effects of antihypertensive
Adverse drug interactions
Dizziness, headache, anxiety , agitation ,irritability y , constipation , dry mouth , sleep disturbances and visual disturbances
11. Tricyclic antidepressants
These blocks nor epinephrine and serotonin uptake into the neuron
These drugs are voluble alternative for patients who do not respond to SSRIs
Mechanism of action
These are potent inhibitors of the neuronal re-uptake of nor epinephrine and serotonin into presynaptic nerve terminals
This produces increase in its concentration at the receptor sites
These contributes for the antidepressant action
TCAs also block serotonergic, alpha adrenergic ,histamine and muscarinic receptors
Pharmacological actions
1. Behavior
These elevate mood, improve mental alertness ,increase physical activity
The onset of the mood elevation is slow , requiring two weeks or longer
These drugs do not produce CNS stimulation or mood elevation in normal individuals
Physical and psychological dependence have been reported
The drugs can be used for prolonged treatment of depression without loss of effectiveness
2. CVS
No effect at normal dose
But toxic doses may produce cardiac arrhythmias
3. ANS
Imipramine produces anti cholinergic effects like dry mouth, constipation , palpitation and blurred vision
ADME
Imipramine is well absorbed on oral administration
Because of their lipophilic nature ,they are widely distributed and readily penetrate into the CNS
This lipid solubility also causes these drugs to have long half lives – 4 – 17 hours for imipramine
These drugs are metabolized by the hepatic microsomal system and conjugated with glucuronic acid
The TCA are excreted as inactive metabolites via the kidney
It actions are mediated through desmethyl-imipramine which is a metabolite product
Adverse reactions
CNS effects
Lethargy, headache and drowsiness
ANS effects
Dry mouth, constipation and tachycardia
CVS effects
Cardiac arrhythmias and hypotension
Allergic reactions
Skin rashes and photosensitivity
Uses
These are very effective in treating severe major depression
Some panic disorders also respond to TCA
Imipramine has been used to control bed- wetting in children by causing contraction of the internal sphincter of the bladder
TCAs , particularly amitriptyline , have been used to treat chronic pain
Imipramine
It inhibits noradrenalin re- uptake and to a lesser extent that of serotonin
It is is relatively less sedating then amitriptyline and reduces REM sleep
It has few anticholinergic action and can PR interval and flatten or inverse T wave
Treatment
Initially, 75 mg daily in divided doses increased gradually to 150—200 mg daily if necessary
300 mg daily given in severely depressed
Drug interactions
Barbiturates reduces plasma levels thereby reducing antidepressant effect
Cimetidine elevates serum immpramine concentration and consequently adverse effects causes drowsiness and impaired performance in combination with alcohol
Amitriptyline
Amitriptylin exerts its antidepressant action by blocking the neuronal re-uptake of Noradrenalin and serotonin
Treatment
Adults – 75 mg daily in divided doses or as a single dose at night , increased gradually , if necessary to 150 mg daily given in the late afternoon or evening
Alternatively 50- 100 mg a single dose at bedtime , increased by 25 – 50 mg
Child – 30 – 75 mg daily or in divided doses preferably at bedtime
Maximum dose
Adult – 150mg daily
Treatment of severs depression
200- 300 mg daily , maximum dose 300 mg daily
Drug inter action
Potentates sedative effect of alcohol, antiparkinson agents and antipsychotic drugs increase risk of ant cholinergic effects
Reduced effect of anti hypertensive
Potentates hypertensive effects of sympthomimetics
Marked hyperpyrexia , convulsions and coma wit h MAOIs
Clomipramine
It is a potent inhibitor of serotonin re-uptake in t he brain
Significant antagonism at cholinergic and alpha receptors
Weak antagonism at dopamine receptors
It has also antidepressant , sedative and anticholinergic effects
Dose
10 mg daily, gradually
250 mg daily given in severe cases
Doxepin
Doxepin inhibits serotonin and noradrenalin re-uptake by the presynaptic neuronal membrane increasing its synaptic concentration in the CNS
Dose
Initially 75 mg daily adjusted according to response, 300 mg daily in severely depressed patients
Anti- manic drugs
The following drug are used in the treatment of manic disorder
Lithium salts
Carbamazepine
Valproic acid
Lithium carbonates
It is a small monovalent cation
In 1949 it was found to be sedative in animals and to exert beneficial effects in manic patients
Mechanism of action
The mechanism of antimanic and mood stabilizing action of LI is not known
It has been proposed that
Lithium partly replaces body Na and is nearly equally distributed in and outside the cells ( contrast Na and K ) , this may affect ionic fluxes across brain cells or modify the property of cellular membranes
Lithium has been found to decrease the release of Na and DA in t he brain of treated animals without affecting 5 –HT release
This may correct imbalance in the turnover of brain monoamines
Pharmacological actions
On CNS
Lithium has practically no acute effects in normal individuals as well as in MDI patients
It is neither sedative nor euphorient, but on prolonged administration, It acts as a mood stabilser in bipolar disease
Given to patients in acute mania, it gradually suppresses the episode taking 1-2 weeks
The markedly reduced sleep time in manic patients is normalized
Other actions
Lithium inhibits action of ADH on distal tubules and causes a diabetes like state
It has some insulin like action on glucose metabolism
Leukocyte count is increased by lithium therapy
Lithium reduces thyroxin synthesis by interfering with iodination of tyrosine
Pharmacokinetics
Lithium is given orally and the ion is excreted by the kidney
It is neither protein bound nor metabolized
It first distributes in the extra cellular water and then gradually enters cells and slowly penetrates into the CNS , ultimately attaining a rather uniform distribution in total body water , apparent volume of distribution at steady- state averages 0.8 L/kg
The lithium is handled by the kidney in much the same way as Na ,
Most of the filtered Lithium is reabsorbed in the proximal convoluted tubule
When Na is restricted, a larger fraction of filtered Na is reabsorbed , so is Li
After a single dose of li urinary excretion of rapid for 10- 12 hours followed by a much slower phase is 16- 30 hours
Renal clearance of lithium is 1/5 of creatinine clearance
On repeated medication steady-state plasma concentrations achieved in 5-7 days
Levels are higher in older patients and in those with renal insufficiency
Peaks in plasma lithium level over and above the steady-state level occur after every dose and produce episodes of toxicity if steady-state level if high or the dose is large
Divided daily dosing in 2-4 portions is needed to avoid high peaks
Lithium is excreted in sweat and saliva also salivary concentration is proportionate to serum concentration and may be used for noninvasive monitoring
Lithium is secreted in breast milk
Mothers on lithium should not breastfeed
Adverse reaction
Side effects are common but are mostly tolerable
Toxicity occurs at levels only marginally higher than therapeutic levels
Nausea, vomiting and mild diarrhea occur initially, can be minimized by starting at lower doses
Thirst and polyuria are experienced by most, some fluid retention may occur initially but clears later
Fine tremors and rarely seizures are seen even at therapeutic concentrations
CNS toxicity – coarse tremors, giddiness, ataxia, motor in coordination, mental confusion, slurred speech,
On long term use some patients develop renal diabetes and goiter has been reported in about 4 %
Interactions
Diuretics ( thiazide, furosemide0 by causing ) Na loss promote proximal tubular reabsorption of Na as well as lithium – plasma levels of lithium rise
Tetracycline’s , indomethacin and ACE inhibitors can also cause lithium retention
Lithium reduces presser response to NA
Lithium tends to enhance insulin / sulfonylurea induced hypoglycemia
Succinyl-choline and pancuronium have produced prolonged paralysis in lithium treated patients
Haloperidol have been frequently used along with lithium without problem , sometimes , the combination of haloperidol and lithium produces marked tremor and rigidity
Dose
Lithium used as its carbonate salt because this is less hygroscopic and less gastric irritant than lithium chloride or other salts
It converted into chlorides in the stomach
It is generally stared at 600 mg/day and gradually increased to yields therapeutic plasma levels, mostly 600-1200 mg /day is required
Carbamaepines
Actions
It reduces the propagation of abnormal impulses in the brain by blocking sodium channels, thereby inhibiting the generation of repetitive action potential in the epileptic focus and preventing their spread
ADME
It is absorbed slowly following oral administration
It enters the brain rapidly because of its high lipid solubility
It induces the drug metabolizing enzymes in the liver
The enhanced hepatic cytochrome p450 system activity also increases the metabolism of many drugs including other antiepileptic drugs
It is an inducer of the cytochromep450 isozyme cyp3a4, which decrease the effects of drugs that are metabolized by his enzyme
Adverse effects
Chronic administration of carbamazepine can cause stupor, coma and respiratory depression
It also produces drowsiness, vertigo, ataxia, and blurred vision
The drug is irritating to the stomach and nausea and vomiting may occur
Drug interaction
The hepatic metabolism of carbamazepine is inhibited by several drugs
Toxic symptoms may arise if the dose is not adjusted
Therapeutic uses
It is effective in Temporal lobe epilepsy
Trigeminal neuralgia
Used in post hepatic pain
Hallucinogens
These are drugs which alter mood, behavior, thought and perception in a manner similar to that seen in psychosis
In appropriate doses these produce changes in visual, auditory perception, in smell and taste , broadly illusions and hallucinations
There will be alteration of the sense of time and space with personality changes
Memory is not affected
The drugs which possess their actions are cannabis, mescaline, LSE -25 , psilocybin , bufotenine and harmoline
Cannabis
It is obtained from cannabis indica or Indian hemp
Flowering tops (ganja), the leaves (bhang) , the resinous exudation (Charas) or the whole drug ( Hashish)
In U.S.A. it is called as marihuana
Cannabinal (chemically an alcohol) a red syrapy oil is said to be the active principle
It produces hallucinations of time , space, euphoria ( sense of well being), imagination, mental exaltation, impulsive behavior, delirium ( confusion and excitement), mania
( mental disorder)
Cannabis is not useful therapeutically
Mescaline
It is an alkaloid obtained from a cactus
When given orally the drug produces sympathomimetic effects and visual hallucinations and a sense of floating in space
It also produces excitement , restlessness, change of mood and intelligence
It is used only for experimental purposes to produce psychotic states
LSD – 25 ( Lysergic acid diethylamide)
This is a derivative of ergot alkaloid, now being used in psychiatric research
It induces psychotic states in which repressed memories form the subconscious mind are brought of light
It stimulates emotional activity producing the sense of lightness and withdrawal from reality
It brings about personality change
It may be used in obsessional thoughts and anxiety conditions accompanied by mental tension
It is orally active in a dose of 25 micro gram
But it is widely misused for its hallucinogenic effects
The person become disoriented and his activities disorganized
It is noticed that it can induce chromosomal abnormalities and fetal malformation and possibly leukemia and hence it I withdrawn even form research
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