Download Free Medical Antidepressants Mood stabilizers Psychostimulants Nootropic drugs and CNS stimulants PowerPoint Presentation

Antidepressants Mood stabilizers Psychostimulants Nootropic drugs and CNS stimulants PowerPoint Presentation

DOWNLOAD MEDICAL POWERPOINT PRESENTATION

About This Presentation

Description : Check out this medical presentation on Pharmacology, which is titled "Antidepressants, Mood stabilizers, Psychostimulants, Nootropic drugs, and CNS stimulants", to know about Antidepressants, Mood stabilizers, Psychostimulants, Nootropic drugs, and CNS stimulants.

Tags : Pharmacology, Antidepressants, Mood stabilizers, Psychostimulants, Nootropic drugs, CNS stimulants

Published on : Jul 18, 2021 | Views : 1302 | Downloads : 4

Shareable Url :

Embed Code :

Comment

Transcript

Slide 1-

Assoc. Prof. Iv. Lambev www.medpharm-sofia.eu Medical University of Sofia, Faculty of Medicine Department of Pharmacology and Toxicology Antidepressants Mood stabilizers Psychostimulants Nootropic drugs CNS stimulants (Abstract)
Slide 2-

Depression is a heterogeneous disorder. A simplified classification based on presumed origin is as follows: (1) brief reactive or secondary depression (most common), occurring in response to real stimuli such as grief, illness, etc; (2) major depression (melancholic and recurrent depression) a genetically determined biochemical disorder manifested by an inability to experience ordinary pleasure or to cope with ordinary life events; (3) manic-depressive depression (depression associated with bipolar affective disorder) Pharmacologic treatment of depressions is very important, although a continuing role for electroconvulsive therapy for severe forms of life-threatening depression is also noted.
Slide 3-

manic
Slide 4-

Depression is one of the most common psychiatric disorders. At any given moment, about 3–5% of the population is depressed, and an estimated 10% of people may become depressed during their lives. The symptoms of depression are often subtle and unrecognized both by patients and by physicians. Patients with vague complaints that resist explanation as manifestations of somatic disorders and those who might be simplistically described as “neurotic” should be suspected of being depressed. Soon after the introduction of reserpine (1948), it became apparent that the drug could induce depression by inhibiting the neuronal storage of amine neurotransmitters 5-HT and NE. Reserpine-induced depression and depleted stores of amine neuro- transmitters. It was reasoned, depression must be associated with decreased functional amine-dependent synaptic transmission.
Slide 5-

ppt slide no 5 content not found
Slide 6-

NA (noradrenaline) = NE (norepinephrine)
Slide 7-

Rauwolfia serpentina (a small indian shrub) Reserpine Ajmaline
Slide 8-

Pathogenesis of depression The idea that depression must be associated with decreased functional amine-dependent synaptic transmission provided the basis for amine hypothesis of depression. By extension, drugs that increased amine function in appropriate synaptic areas would relieve depression. The amine hypothesis has provided the major experimental models for the discovery of new antidepressants. All currently available antidepressants, except bupropion, are classified as having their primary actions on the metabolism, reuptake, or selective receptor antagonism of 5-HT, NA, or both.
Slide 9-

The effects of DA, 5-HT and NE on the brain functions (NE) (DA) (5-HT)
Slide 10-

Raised neurotransmitter concentrations produce immediate alterations in postsynaptic receptor activation, leading to changes in second messenger (intracellular) systems and to gradual modifications in cellular protein expression. Antidepressants increase a cyclic AMP response-element binding (CREB) protein which in turn is involved in regulating the transcription of genes that influence survival of other proteins including brain derived neurotrophic factor (BDNF) which exerts effects on neuronal growth. The role of BDNF in depression is supported by the observation that stress both reduces its expression and impairs neurogenesis.
Slide 11-

ppt slide no 11 content not found
Slide 12-

The monoamine hypothesis of depression is an oversimplification (only deficieny of NA, 5-HT, and DA) of a complicated picture. Other systems that are implicated in the etiology of depression (and which provide potential targets for drug therapy) include the hypothalamo-pituitarythyroid axis and the hypothalamo-pituitary-adrenal axis (HPA). The finding that 50% of depressed patients have elevated plasma cortisol concentrations constitutes evidence that depression is associated with increased HPA drive.
Slide 13-

Monoamine Reuptake Inhibitors α2-adrenergic blockers MAO inhibitors (1a) Drugs Desipramine Nortriptyline (1b) Prodrugs Amitriptyline Clomipramine Doxepin Imipramine (2) Selective NARIs Reboxetine (3) Selective SSRIs Citalopram, Fluoxetine Escitalopram, Fluvoxamine Paroxetine, Sertraline Mianserin* Mirtazapine Trazodone (1) Tricyclic antidepressants (non-selective inhibitors) Moclobemide (MAO-A) Nialamide (MAO-A & B) Selegiline (irreversible MAO-B) - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
Slide 14-

Structural relationships between various tricyclic antidepressants (TCAs). Their structures are similar to phenothiazines.
Slide 15-

Selective serotonin reuptake inhibitors (SSRIs).
Slide 16-

Pharmacokinetics The antidepressants are generally well absorbed after oral administration. Steady-state plasma concentrations of TCAs show great individual variation but correlate with therapeutic effect. Antidepressants in general are inactivated princi- pally by metabolism by hepatic cytochrome P450 enzymes (2D6 and 3A4). Other cytochrome enzymes are CYP 1A2 inhibited by the SSRI fluvoxamine, and induced by cigarette smoking, caffeine and the atypical antipsychotics (clozapine and olanzapine).
Slide 17-

Several of these drugs produce active metabolites which prolong their action (e.g. fluoxetine is metabolized to norfluoxetine, t1/2 200 h). The meta- bolic products of certain TCAs are antidepressants too, e.g. nortriptyline (from amitriptyline), desipramine (from imipramine). Half-lives of TCAs and SSRIs are long (> 15 h). Around 7% of the Caucasian population have very limited CYP 2D6 enzyme activity. Such “poor metabolizers” may find standard doses of tricyclic antidepressants intolerable and it is often worth starting at a very low dose.
Slide 18-

Clinical indications The major indication is to treat depression, but a number of other uses have been established by clinical experience. Antidepressants may benefit most forms of anxiety disorder (panic disorder, generalized anxiety disorder, post-traumatic stress, obsessive-compulsive disorder, and social phobia), migraine. SSRIs are effective in milder cases of the eating disorder bulimia nervosa, particularly fluoxetine (in higher doses than are required for depression). Antidepressants appear to be ineffective in anorexia nervosa.
Slide 19-

SSRIs (selective serotonin reuptake inhibitors) are used in: panic disorders chronic anxiety depression bulimia neurosa (fluoxetine – in higher doses)
Slide 20-

Schematic representation of the time course of panic treatments Adapted from Bennett and Brown (2003)
Slide 21-

Mode of use The action of TCAs in ameliorating mood is usually absent in the first 2 weeks of therapy and at least 4 weeks must elapse to constitute an adequate trial. Where a minimal response is noted in this period, it is reasonable to extend the trial to 6 weeks to see if further benefit is achieved. Dose titration is often necessary. By contrast, patients may experience unwanted drug effects immediately on starting treatment (and they should be warned), but such symptoms often diminish with time. TCAs are given either in divided doses or, for the more sedative compounds, as a single evening dose.
Slide 22-

SSRIs have advantages over tricyclics in simplicity of introduction and use. Dose titration is often unnecessary since the minimum therapeutic dose can usually be tolerated as a starting dose. Divided doses are not required and administration is by a single morning or evening dose. Patients commencing treatment on SSRIs are more likely to reach an effective dose than those starting on TCAs. Venlafaxine is licensed for treatment-resistant depression by gradual dose titration. There is some need for dose titration when using MAOIs.
Slide 23-

Side effects of TCAs Anticholinergic (atropine-like): dry mouth, blurred vision, accommodation disturbances, increased ocular pressure, con- stipation, urinary retention, sweating, adynamic ileus (very rare). CNS: dizziness, tiredness, confusion, tremor, insomnia, seizures, exacerbation of psychotic symptoms. CVS: postural hypotension, sinus tachycardia, arrhythmia. Blood: leucopenia, agranulocytosis, thrombocytopenia, Haemolytic anaemia. Other ADRs: impaired respiration, libido changes, tinnitus, GI complaints, liver function disturbances, increased body weight.
Slide 24-

ppt slide no 24 content not found
Slide 25-

Precautions: close supervision, especially in early phase of treatment (suicide risk of TCAs). The possibility of unmasking a latent psychosis should be considered. A switch into a manic or hypomanic condition may occur (“switch process”). Caution should be exercised in CVD, history of urinary retention, narrow-angle glaucoma, and thyroid disease. Side-effects of SSRIs (mainly during the 1st and 2nd weeks of treatment): CNS: head- ache, restleness; CVS: bradycaria; GIT: nausea, diarrhoea The serotonin syndrome is a rare but dangerous complication with features restlessness, tremor, hуperthermia, convulsions, coma and death. Risk is increased by co-administration with MAOIs, the antimigraine drug sumatriptan, and St. John’s Wort.
Slide 26-

ppt slide no 26 content not found
Slide 27-

Trazodone acts by antagonism of central presynaptic alpha-2-adrenoceptors. It is an option for depressed patients where heavy sedation is required. Trazodone also has the advantages of lacking antimuscarinic effects and being relatively safe in overdose. Males should be warned of the possibility of priapism (painful penile erections), due to the blockade of peripheral postsynaptic alpha-1-adrenoceptors. Mianserin has the advantages of lacking antimuscarinic effects too, but can cuases aplastic anaemia.
Slide 28-

Side-effects of MAOIs Moclobemide (selective reversible MAO-A inhibitors) CNS: insomnia, restlessness, confusion, dizziness. CVS: arrhythmia, tachycardia, palpitations, Nialamide (irreversible nonselective MAO-A & B inhibitors) can cause high blood pressure. The following foods and beverages should be avoided – tyramine containing nutrition: maturated cheese (“cheese syndrome” – high blood pressure), yogurt, broad (fava) beans, green bean pods, chocolate, smoked or pickled fish, meat extracts containing brewer's yeast, fermented ausages (e.g. salami); red wine, sherry, beer and excessive amounts of alcohol; bananas, avocados, pineapple, coconuts etc.
Slide 29-

Agomelatine (Valdoxan®) is a melatonergic agonist (MT1- and MT2-receptors) and 5-HT2C antagonist. It has no effect on monoamine reuptake and no affinity for α, β adrenergic, histaminergic, cholinergic, dopaminergic and benzodiazepine receptors. Agomelatine is indicated for the treatment of major depressive episodes in adults. It not use in chlidren below 18 years of age due to a lack of data on safety and efficacy. OTHER ANTIDEPRESSANTS:
Slide 30-

Many patients with mild to moderate depression are aware of the benefits of the herbal remedy St. John’s Wort. The major active antidepressive constituents are thought to be hyperforin and hypericin. Some believe that hyperforin is the major constituent responsible for antidepressant activity. It inhibits the reuptake of 5-HT, DA, and NA. Hyperforin also has affinity for GABA and glutamate receptors. Hypericum perforatum L.
Slide 31-

St. John’s Wort Many patients with mild to moderate depression are aware of the benefits of the herbal remedy St. John’s Wort. The major active antidepressive constituents are thought to be hyperfurin and hypericin . Some believe That hyperfurin is the major constituent responsible for antidepressant activity. It inhibits the reuptake of 5-HT, DA, and NA (NE). Hyperfurin also has affinity for GABA and glutamate receptors.
Slide 32-

Use of St. John’s Wort is complicated by the lack of standardization of the ingredients. Those who wish to take St. John's Wort should be made aware that it may cause dry mouth, dizziness, sedation, GI disturbance and confusion. It induces hepatic CYP 1A2 and CYP 3A4 with the result that the plasma concentration and therapeutic efficacy of warfarin, oral contraceptives, some anticonvulsants,antipsychotics and HIV protease/reverse transcriptase inhibitors are reduced. Concomitant use of tryptophan and St. John’s Wort may cause serotoninergic effects including nausea and agitation.
Slide 33-

Electroconvulsive therapy (ECT) involves the passage of a small electric charge across the brain by electrodes applied to the frontotemporal aspects of the scalp with the aim of inducing a tonic-clonic seizure. ECT requires the patient to be receiving a general anaesthetic. It may cause memory deficit although this is generally transient. ECT is usually reserved for psychiatric illness where pharmacotherapy has been unsuccessful for instance the severely depressed patient who has stopped eating or drinking. Modern-day ECT is a safe and effective alternative to pharmacotherapy and remains a first-line option in clinical circumstances where rapid, response is desired, when it can be life-saving.
Slide 34-

Mood stabilizers In bipolar affective disorder patients suffer episodes of mania, hypomania and depression, classically with periods of normal mood in between. Manic episodes involve greatly elevated mood, often interspersed with periods of irritability or undue excitement, accompanied by biological symptoms (increased energy, restlessness, decreased need for sleep, increased sex drive), loss of social inhibitions, irresponsible behaviour and grandiosity. Psychotic features may be present, particularly disordered thinking, manifested by grandiose delusions and “flight of ideas” with rapid speech.
Slide 35-

Hypomania is a less dramatic and dangerous presentation but retains the features of elation or irritability and the biological symptoms, abnormalities in speech and in social conduct to overfamiliarity and mild recklessness. Depressive episodes include depressive symptoms described before and may include psychotic features. Lithium salts are ineffective for prophylaxis of bipolar affective disorder in around 35% of patients and cause severe unwanted effects. The search for alternatives has produced drugs that are more famous as anticonvulsants (carbamazepine and sodium valproate, and possibly lamotrigine).
Slide 36-

The main effect of lithium is probably to inhibit hydrolysis of inositol phosphate, so reducing the recycling of free inositol for synthesis of phosphatidylinositides. These intracellular molecules are part of the transmembrane signaling system that is important in regulating intracellullar calcium ion concentration, which subsequently affects neurotransmitter release. Other putative mechanisms involve the cyclic AMP “second messenger” system and monoaminergic and cholinergic neurotransmitters.
Slide 37-

Action of lithium on the IP3 and DAG second-messenger system. The schematic diagram shows the synaptic membrane of a neuron. (PIP2 – phosphatidylinositol-4,5-bisphosphate; PLC – phospholipase-C; G – G-coupling protein). Result: activation of protein kinase C, mobilization of intracellular Ca2+, etc. Lithium, by inhibiting the recycling of inositol substrates, may cause depletion of the second-messenger source PIP2 and therefore reduce the release of IP3 and DAG.
Slide 38-

The therapeutic plasma concentration is close to the toxic concentration (low therapeutic index). Lithium is a small ion that, given orally, is rapidly absorbed throughout the gut. High peak plasma concentrations are avoided by using sustained-release formulations which deliver the peak plasma lithium concentrations in 5 h. With chronic use the plasma t1/2 of lithium is 15–30 h. Lithium is usually given 12-hourly to avoid unnecessary fluctuation (peak and trough concentrations) and to maintain a plasma concentration just below the toxic level. A steady-state plasma concentration will be attained after about 5–6 days (i.e. 5 x t1/2).
Slide 39-

Lithium carbonate is effective treatment in 75% of episodes of acute mania or hypomania. Because its therapeutic action takes 2–3 weeks to develop, lithium is generally used in combination with lorazepam or diazepam (or with a neuroleptics where there are also psychotic features). For prophylaxis, lithium is indicated when there have been two episodes of mood disturbance in two years.
Slide 40-

Lithium is also used to augment the action of antidepressants in treatment-resistant depression. The difference between therapeutic and toxic doses is narrow and therapy must be guided by monitoring of the plasma concentration once a steady state is reached. Increments are made at weekly intervals until the concentration lies within the range of 0.4–1 mmol/L (maintenance at the lower level is preferred for elderly patients). The plasma concentration should be checked every 3 months. Thyroid function and renal function (plasma creatinine and electrolytes) should be measured before initiation and every 3 months during therapy.
Slide 41-

Side-effects of Lithium CNS: ataxia, dysarthria, choreoathetoid disturbances, extrapyrimidal symptoms, confusion, tremor, epileptic seizures, spasms, stupor, sedation, lethargy. CVS: arrhythmia, hypertension, circulatory collapse. Other effects: weight increase, muscular hypotonia, anorexia, nausea, vomiting, thirst, rash etc.
Slide 42-

The manic phase in bipolar affective disorder often requires treatment with neuroleptics (chlorpromazine, haloperidol), though lithium or valproic acid supplemented with high-potency benzodiazepines (eg, lorazepam or clonazepam) may suffice in milder cases. Recent controlled trials support the efficacy of monotherapy with atypical antipsychotics (olanzapine) in the acute phase (up to 4 weeks) of mania.
Slide 43-

Psychostimulants Psychostimulants have predominant cortical action. Their psychic effects are more important than those on medullary vital centres. (1) Methylxanthines Three methylxanthines are pharmacologically important: caffeine, theophylline, and theobromine. All of them occur naturally in certain plants. Only caffeine is used as a CNS stimulant. It is widely consumed in the form of beverages, including as infusions or decoctions, derived from these plants.
Slide 44-

Coffea arabica (seeds) In an average cup of coffee: Caffeine 75 mg Theobroma cacao (cocoa) In an average cup of cocoa: Caffeine 4 mg Theobromine 200 mg Cola acuminata (Guru nuts) In 330 ml bottle of cola drink: Caffeine 50 mg Methylxanthines (purine alkaloids) Caffeine, Theophylline, Theobromine Thea sinensis (leaves) In an average cup of tea: Caffeine 50 mg Theophylline 1 mg
Slide 45-

Actions of methylxanthines They block adenosine-1-receptors. Adenosine acts as a local mediators in CNS, CVS and other systems. Adenosine contracts bronchial muscles, dilates cerebral blood vessels, depresses cardiac pacemaker and inhibits gastric secretions. Methylxanthines inhibit phosphodiesterase which degrades intracelullarly cAMP. Theophylline-containing preparations enhance cAMP accumulation. It results in bronchodilation, vasodilation and cardiac stimulation (including tachycardia). Caffeine and theophylline are CNS stimulants, primarily affect the higher centres. Caffeine (150 to 250 mg) produces a sense of wellbeing, alertness, beats boredom, alleviates fatigue; thinking becomes clear, improves performance and increases motor activity.
Slide 46-

As a CNS stimulant caffeine is more active than theophylline. In higher doses caffeine causes nervousness, restlessness, panic, insomnia, and excitement. Still higher doses produces tremor, arrhythmia, delirium, and convulsions. Methylxanthines, especially caffeine, also stimulate medullary vagal, respiratory and vasomotor centres (analeptic effect). Vomiting in higher doses is due to both to gastric irritation and stimulation of chemoreceptor trigger zone (CTZ). Methylxanthines directly stimulate the heart and increase force of myocardial contraction. They tend to increase heart rate by direct action, but also decrease it by vagal stimulation. Net effect is variable. Tachycardia is more common with theophylline.
Slide 47-

Cardiac output is increased. This action is more marked in CHF patients. At high doses cardiac arrhythmias may be produced. Methylxanthines, especially theophylline, dilate systemic blood vessels, including coronaries. Cranial vessels are constricted by caffeine: this is one of the bases of its use in migraine. Effect of blood pressure is variable and unpredictable. Usually a rise in systolic and fall in diastolic BP is observed. Antiasthmatic (bronchodilatation) effect of theophylline is more potent then those of caffeine.
Slide 48-

ATP 3’, 5’-AMP cAMP Lipolysis (–) AC PD Cholesterol synthesis Caffeine > 300 mg/d: 5–6 coffee cups daily (+) (+) Hypercholesterolemia
Slide 49-

Methylxanthines are mild diuretics. They act by inhibiting tubular reabsorption of Na+ and water. Theophylline and theobromine are more potent diuretics than caffeine. At high dose caffeine enhances the contractile power of skeletal muscle: it increases release of Ca2+ from sarcoplasmatic reticulum by direct action. In addition, caffeine facilitates neuromuscular transmission by increasing ACh release. Its central action relieves fatigue and increases muscular work. Methylxanthines enhance secretion of acid and pepsin in the stomach, even on parenteral application. They are gastric irritants – theophylline more than caffeine.
Slide 50-

Caffeine is an alkaloid with pKb 0.8. It is rapidly absorbed after oral administration. It is < 50% bound to plasma proteins. Its t1/2 is 4 h. Caffeine is nearly completely metabolized in the liver by demethylation and oxidation, and excreted in urine. Caffeine is to be avoided in peptic ulcer patients. It is not contraindicated in gout because it is not converted in the body to uric acid. Moderate coffee drinking does not contribute to development of hypertension. Uses of caffeine In analgesic drug combinations: caffeine benefits headache probably by allaying fatigue and boredom. Migraine attacks: in combination with ergotamine. To counteract hypnotic overdose, but its value is doubtful, better not to be used.
Slide 51-

Caffeine is an alkaloid with pKb 0.8. It is rapidly absorbed after oral administration. It is < 50% bound to plasma proteins. Its t1/2 is 4 h. Caffeine is nearly completely metabolized in the liver by demethylation and oxidation, and excreted in urine. Caffeine is to be avoided in peptic ulcer patients. It is not contraindicated in gout because it is not converted in the body to uric acid. Moderate coffee drinking does not contribute to development of hypertension. Uses of caffeine In analgesic drug combinations: caffeine benefits headache probably by allaying fatigue and boredom. Migraine attacks: in combination with ergotamine. To counteract hypnotic overdose, but its value is doubtful, better not to be used.
Slide 52-

(2) Amphetamines
Slide 53-

Amphetamines are central indirect adrenomimetics. Higher central and peripheral activity ratio is exhibited by dextro- amphetamine and methylamphetamine (methamphetamine). Amphetamines stimulate mental than motor activity. Convulsive doses are much higher. Abuse potential of the amphetamines is very high!
Slide 54-

Methylphenidate is chemically and pharmacologically similar to amphetamine. Both act by releasing NA and DA in the brain. Both produce increase in mental activity at doses which have little action on other central and peripheral functions. Methylphenidate is considered superior to amphetamine for treatment of hyperkinetic children (attention deficit disorder) because it causes less tachycardia and growth retardation. Behaviour and learning ability are improved in 75% of cases. Methylphenenidate can also be used for concentration and attention defect in adults, and for narcolepsy. Side effects of methylphenidate are anorrhexia, insomnia, abdominal discomfort, and bowel upset.
Slide 55-

(3) Cocaine is an alkaloid from the leaves of Erythroxylon coca, a South American plant. The natives of Peru and Bolivia habitually chew these leaves. Cocaine is used sometimes in ocular anaesthesia as eyes drops. It should be never be injected because it can causes tissue necrosis. After system absorption cocaine produces prominent CNS stimulation with marked effect on mood and behaviour (a sense of wellbeing, delays fatigue and increases power of endurance). In susceptible individuals it produces strong psychological, but not physical dependence. Cocaine is unique among drugs of abuse, because it is does not produce tolerance on repeuted use. It also stimulate vagal, vasomotor, vomiting and thermoregulatory centres. In periphery it blocks reuptake of NA and adrenaline and acts indirectly as a sympathomimetic.
Slide 56-

Nootropic drugs (cognition enhancers) Piracetam is a cyclic GABA derivative without GABA like activity. Piracetam selective improves efficiency of higher encephalic integrative activity by: Enhancement of learning and memory Facilitation of interhemisphere information transfer Increased tonic cortical control of subcortical areas Improves ATP/ADP ratio in encephalon Stimulates synaptic transmission, etc.
Slide 57-

The indications of piracetam are: Senile dementia of Alzheimer type, multi-infarct dementia, etc. Mental retardation and learning problems in children Cerebrovascular accident: to hasten recovery To reduce impairment of consciousness following brain trauma or brain surgery, memory impairment after electroconvulsive therapy, and central vertigo. The validity of evidence for drug induced cognition enhancement has not been established. ADRs: gastric discomfort, excitement, insomnia, dizziness, skin rash. Pramiracetam has similar properties and indications.
Slide 58-

www.medpharm-sofia.eu > 600 files& > 300 links