central nervous system.pptx
DESCRIPTION
drugs used for central nervous systemTRANSCRIPT
WELCOM
E
DRUGS ACTING ON
CENTRAL NERVOUS SYSTEM
Vaheeda rehman shaik,*129AISO605,Dept of pharmacology,Nimra college of pharmacy.
Central nervous system :• Brain • Brain stem• Spinal cord
ANTIDEPRESSANT& ANTIANXIETY
GENERAL ANAESTHETICS
SEDATIVES HYPNOTICS
ANTI PARKINSONIAN
DRUGS
ANTIEPILEPTICDRUGS
ANTIPSYCHOTIC &
ANTIMANIC
CNS
GENERAL ANAESTHETICS
INTRODUCTION
DEFINITION: General anaesthetics: These are drugs which produce reversible loss of all sensations and consciousness.
Anaesthesia means: an- without aesthesis- sensation
HISTORY
Alcohol, opium
Nitrous oxide
Ether
Chloroform
Cyclopropane
Thiopentone
Halothane
1844
1846
1847
1929
1956
1935
19th century
MECHANISM LIPID THEORY:
EFFECTS ON ION CHANNELS:
STAGES OF ANAESTHESIA
stage of analgesia stage of delirium/excitement stage of surgical anaesthesia stage of medullary paralysis
PROPERTIES OF AN IDEAL ANAESTHETIC
Patients• Non irritant• Not cause nausea/vomit• No after
effects• Fast Induction
and recovery
Surgeon• Immobility
• Muscle relaxant• Non
inflammable• Non explosive
• Provide adequate analgesia
Anaesthetist• Administration
easy• Ineffective to
organs• High Potency for
low conc• Cheap, non reactive, safety
TECHNIQUES OF INHALATION OF ANAESTHETICS
Open drop method
Through anaesthetic machines
a.Open systemb.Closed systemc.Semi closed system
CLASSIFICATIONGeneral anaesthetics
Inhalation
Gases VolatileLiquid
Intra venous
Inducing agents
Slower acting drugs
Balanced anaesthesia (both inhalational and i.v )
GASES: Nitrous oxide VOLATILE LIQUIDS: Ether Halothane Enflurane Isoflurane Desflurane Sevoflurane INDUCING AGENTS: Thiopentone sodium Methohexitone sodium Propofol Etomidate SLOWER ACTING DRUGS: BENZODIAZEPINES: Diazepam Lorazepam Midazolam DISSOCIATIVE ANAESTHESIA: Ketamine OPIOID ANALGESIA: Fentanyl
INHALATIONAL GENERAL ANAESTHETICSGASEOUS:
NITROUS OXIDE:Pharmacokinetics:• Onset of action ------- quick and smooth•Metabolism ------ does not occur• Excretion ------ quickly removed by lungs• MAC ------ 105%•Recovery ------- rapid• Second gas effect and diffusion hypoxia occurs• Dose ------- 70% Nitrous oxide, 25-30% of oxygen, 0.2-2% another potent drugAdvantages:•Cheap and very commonly used• Non toxic to lever, kidney, brainUses:• Nitrous oxide(50%) along with oxygen can be used for obstetric and dental
VOLATILE LIQUIDS:
ETHER: (DIETHYL ETHER)
Pharmacokinetics:• Induction is prolonged and unpleasant with struggling• Recovery ------ slowMechanism: • Reduces Ach output from motor nerve endingsAdvantages:•Potent drug, produce good analgesia•Still using in developing countries because it is cheap• Can be given by open drop methodAdverse effects:• Post anaesthetic vomit and nausea•Breath holding, salivation and marked respiratory secretions
•Premedication atropine given
HALOTHANE(FLUOTHANE) :
Pharmacokinetics: •Induction ------ reasonably quite and pleasant•Metabolism: 20% by liver, remaining exhaled out• Elimination: 24-48 hrs after prolonged administration• Recovery: smooth and reasonably quick• Dose :------ for induction --- 2-4% for maintenance --- 0.5-1%•causes direct depression of myocardial contractility by reducing intracellular calcium concentration and sympathetic activity fails to increase Adverse effects: •Malignant hyperthermia• Metabolite of halothane causes chemical and immunological injury• Repeated use causes hepatitis(1 in 10,000)• Cardiac output is reduced with deep anaesthesia• BP falls• Vascular bed dilates• Heart rate reduces, tachyarrhythmia occurs• Greater depression of respiration, breathing shallow
INTRAVENOUS GENERAL ANAESTHETICS
INDUCING AGENTSTHIOPENTONE SODIUM:• Derivative of thiobarbiturate (ultra short acting)Pharmacokinetics:• Highly soluble in water•Distribution: depends on organ blood flow (brain gets large amount)•Metabolism: hepatic• Elimination t1/2 is 7-12 hrs•Dose: injected I.V (3-5mg/kg) as 2.5%solution• Must prepare freshly before injectionPharmacology:•Produce unconsciousness in 15-20 seconds•Consciousness is regained in 6-10 min • t1/2 of distribution phase is 3minAdverse effects:•laryngospasm is a main adverse effect• Recovery with shivering and delirium• Other uses: control of convulsions
PROPOFOL:Pharmacokinetics: • I.V given for both induction and maintenance• Distribution t1/2 2-4 minutes(rapidly)• Elimination t1/2 (100 min) shorter than thiopentone due to rapid metabolism• Unconsciousness occurs 15-45 seconds and lasts 5-10 min• Suitable for outpatient surgeryAdvantages:• Post operative nausea and vomiting –low• Patient acceptability is very goodAdverse effects:• Excitatory effects and involuntary movements noted for some patients• Fall in BP- due to vasodilation• Bradicardia is frequent• Dose dependent respiratory depression• Pain during injection is also frequent- can be minimized by combining with lidocaine• Dose: 2mg/kg i.v bolus --- for induction 9mg/kg/hr -----------for maintenance
SLOWER ACTING DRUGSBENZODIAZEPINES:Pharmacokinetics: • Distribution: t1/2 of diazepam is 15 min•This is a premedication product• Now frequently using for inducing, maintenance, and supplement anaesthesia as well as conscious sedation• Dose: 0.2-0.3mg/kg or equivalent diazepam•Unconsciousness in 5-10 min• Amnesia persists------ 2-3 hrs• Sedation persists------ 6hrs or more•Post operative nausea and vomiting is absenceAdverse effects:• Injected i.v produce sedation and amnesia• If large doses given recovery delays• BZD’s are poor analgesics• An opioid or nitrous oxide is added if produced pain• Involuntary movements are not stimulated• Requires neuromuscular blockers• Uses: now preferred for endoscopies, angiographies, fracture setting etc
COMPLICATIONS OF GENERAL ANAESTHESIA
During anaesthesi
a
•Respiratory depression•Cardiac arrhythmias, asystole, fall in BP•Aspiration of gastric contents•Laryngospasm and asphyxia•Fire and explosion (rare)•Delirium, convulsions, excitatory effects•Recall of events during surgery
After anaesthesi
a
•Nausea and vomiting•Persisting sedation•Pneumonia, atelectasis•Organ toxicities•Nerve palsies•Emergency delirium•Cognitive defects
DRUG INTERACTIONS
• Antihypertensive's-general anaesthetics: BP fall
• Corticosteroid-anaesthetics: cardiovascular collapse Treatment: give 100mg of hydrocortisone
• Insulin need of a diabetic is increased during general anaesthetics
• Neuroleptics, opioids, clonidine and monoamine oxidase inhibitors potentiate anaesthetic effect
• Halothane sensitizes heart to Adr
PREANAESTHETIC MEDICATION Preanaesthesia: agents which show synergic effect on the
anaesthetic drugs
Advantages of preanaesthetics:
Decrease acidity and volume of gastric juice: less damages if aspirated Anti emetic effect extending to the postoperative period Decrease secretions and vagal stimulation Supplement analgesic action of anaesthetics and potentiate them: less anaesthetic is needed Amnesia for pre and postoperative events Relief of anxiety and apprehension preoperatively and to facilitate smooth induction
Examples:
Sedatives-anti anxiety drugs Opioids Anticholinergics Neuroleptics H2 blockers Antiemetics
SEDATIVES AND
HYPNOTICS
INTRODUCTION
DEFINITION: SEDATIVE: drug that subdues excitement and calms the subject without inducing sleep
HYPNOTIC: drug that induces and/or maintains sleep, similar to normal arousable sleep
Sedative
Hypnotic
General anaesthesia
STAGES OF SLEEP Stage 0 (awake) Stage 1 (dozing) Stage 2 (unequivocal sleep) Stage 3 (deep sleep transition) Stage 4 (cerebral sleep) REM sleep (paradoxical sleep)
Sedatives and
Hypnotics
CLASSIFICATION
Barbiturates:
• Long acting: phenobarbitone
• Short acting: Butobarbitone, Pentobarbitone
• Ultra short acting: Thiopentone, Methohexitone
Benzodiazepines:• Hypnotic: Diazepam Flurazepam Nitrazepam Alprazolam Temazepam Triazolam
• Antianxiety: Diazepam Chlordiazepoxide Oxazepam Lorazepam Alprazolam
• Anticonvulsant: Diazepam Lorazepam Clonazepam Clobazam
BARBITURATES: PHARMACOKINETICS:
Well absorbed from g.i. tract Widely distributed in body Rate of entry into CNS is dependent on lipid solubility High lipid soluble has instantaneous entry Less lipid soluble takes longer and enters very slowly REDISTRIBUTION: its imp in case of highly lipid soluble After i.v injection consciousness is regained in 6-10 min due to redistribution Ultimate disposal occurs by metabolism t1/2 of elimination phase is 9 hours METABOLISM: intermediate lipid solubility primarily metabolized in liver by oxidation, dealkylation, and conjugation plasma t1/2 12-40 hrs EXCRETION: low lipid solubility excreted unchanged in urine t1/2 of phenobarbitone is 80-120 hrs
PHARMACOLOGY: CNS: Barbiturates produce dose dependent effects Sedation Sleep Anaesthesia Coma HYPNOTIC DOSE: (100-200mg of short acting barbiturates) Shorten time taken to fall sleep & increase sleep duration Sleep arousable, but subject may feel confused & unsteady if waken early Night awakening are reduced REM and 3,4 sleep decreased REM –NREM sleep cycle disrupted Effect of sleep progressively reduces if taken every night When drug is discontinued rebound increase in REM sleep and night mares Takes several days for normal pattern restore After a night dose hang over may occur SEDATIVE: (smaller dose of long acting barbiturates) Given at day time can produce drowsiness, reduction in anxiety & excitement They have no analgesic action Smaller dose may even cause hyperalgesia Barbiturates have anticonvulsant activity Barbiturates depress all areas of CNS
OTHER SYSTEMS: RESPIRATION: depressed by relatively higher doses Neurogenic, respiratory centers depressed Barbiturates donot have selective antitussive actions CVS: decrease in BP & heart rate Toxic doses produce marked fall in BP due to ganglionic blockade, vasomotor centre depression and direct decrease in cardiac contractility Reflex tachycardia can occur, Dose producing cardiac arrest is about 3 times larger than that causing respiratory failure SKELETAL MUSCLE: Anaesthetic doses reduce muscle contraction SMOOTH MUSCLES: Hypnotic dose- tone and motility of bowel reduced Action on bronchial, and uterine muscles is not significant KIDNEY: Reduce urine flow by decrease BP and increase ADH release
USES: Enzyme inducing property of phenobarbitone can be utilized to clearance of congenital nonhaemolytic jaundice adjuvant in psychosomatic disorders
ADVERSE EFFECTS: SIDE EFFECTS: hang over, mental confusion, traffic accidents IDIOSYNCRASY: excitement HYPERSENSITIVITY: Rashes, Swelling of eyelids, lips TOLERENCE AND DEPENDENCE: Tolerance due to repeated use Withdrawal symptoms are – excitement , hallucinations, delirium convulsions, and death ACUTE BARBITURATE POISONING: patient will be flabby, comatose with shallow and failing respiration fall in BP and cardiovascular collapse renal shut down, pulmonary complications Lethal dose depends on lipid solubility it is 2-3g for more lipid soluble agents 5-10g for less lipid soluble agents TREATMENT: gastric lavage, alkaline diuresis, haemodialysis etc
DRUG INTERACTIONS:
Barbiturates - warfarin, tolbutamide, griseofulvin etc: induce metabolism and reduce their effectiveness
Sodium valproate – phenobarbitone: increase plasma concentration
Phenobarbitone – phenytoin and imipramine: competitively inhibits and induces metabolism
Phenobarbitone – griseofulvin: decreases absorption from g.i.t
ANTI-EPILEPTICDRUGS
INTRODUCTION
DEFINITION: EPILEPSY: group of disorders of CNS characterized by paroxysmal cerebral dysrhythmia, manifesting as brief episodes(seizures) of loss or disturbances of consciousness with/without characterized body movements(convulsions) sensory or psychiatric phenomena
ANTIEPILEPTICS: drugs which reduces epilepsy (mainly seizures) in human body
TYPES OF SEIZURESGTCS
Absence seizures
Atonic seizures
Myoclonic seizures
Infantile spasms
Generalized
seizures
SPS
CPS
SPS/CPS
Partial seizures
CLASSIFICATION•Barbiturates•Deoxybarbiturates• Hydantoin• Iminostilbene• Succinamides• Aliphatic carboxylic acid• Benzodiazepines• Phenyltriazine• Cyclic GABA analogue• Newer drugs
• Prolongation of sod channel inactivation• Facilitation of GABA mediated chlorine channel opening• Inhibition of T type calcium current
Based on
chemical structure
Based on
mechanism of action
• Barbiturates: phenobarbitone• Deoxybarbiturates: primidone• Hydantoin: phenytoin, fosphenytoin• Iminostilbene: carbamazepine, oxcarbazepine• Succinamides: ethosuximide• Aliphatic carboxylic acid: valproic acid, divalproex• Benzodiazepines: clonazepam, diazepam, lorazepam• Phenyl triazine: lomatrigine• Cyclic GABA analogue: gabapentin• Newer drugs: vigabatrin, topiramate, tiagabine, zonisamide,
BASED ON CHEMICAL NATURE:
BASED ON MECHANISM OF ACTION: Prolongation of sod channel inactivation:• Phenytoin• Carbamazepine• Valproate• Lomatrigine• Topiramate• Zonisamide Facilitation of GABA mediated chlorine channel opening:• Barbiturate• Benzodiazepine• Vigabatrin• Valproate• Gabapentine• Tiagabine Inhibition of T type calcium current:• Ethosuximide• Trimethadione• Valproate
PHENYTOIN PHARMACOKINETICS:
Absorption: • oral route • 80-90% bound to plasma protein
Metabolism: • Hepatic• t1/2 is 12-24 hrs
Excretion:• 5% unchanged in urine
PHARMACOLOGY:
Mechanism:•Therapeutic level:• Prolongation of sodium channel inactivation•At high concentration:•Reduction in calcium influx•Inhibition of glutamate and facilitation of GABA responses
Action of phenytoin:• On Tonic clonic epilepsy
ADVERSE EFFECTS:
At therapeutic level:• Hypersensitivity• Megaloblastic anemia• Osteomalacia• Hyperglycemia• Foetal hydantoin syndrome• Hirsutism• Gum hypertrophy
At high plasma levels:• Fall in BP, cardiac arrhythmias---when i.v injected• Nausea, vomiting• Drowsiness, hallucination, mental confusion
Anti-parkinsonian
drugs
INTRODUCTION
DEFINITION: Parkinsonism: A group of neurological disorders marked by hypokinesia, tremor, muscular rigidity
Antiparkinsonians: Drugs that have a therapeutic effect in parkinsonismBellad
onna alkaloi
ds
Levodopa
CLASSIFICATION
Drugs effecting brain dopaminergic system
• Dopamine precursor: LEVODOPA• Peripheral decarboxylase inhibitors: CARBIDOPA• Dopaminergic: BROMOCRIPTINE• MAO-B inhibitors: SELEGILINE• COMT inhibitors: ENTACAPONE• Dopamine facilitator: AMANTADINE
Drugs effecting brain cholinergic system
• Central anticholinergics: PROCYCLIDINE• Antihistamines: PROMETHAZINE
LEVODOPA
PHARMACOKINETICS:
Absorption:• Small intestine• Bioavailability: Gastric emptying Amino acids present in food
Metabolism:• First pass metabolism• Plasma t1/2 of levodopa is 1-2 hrs
Excretion: through urine
PHARMACOLOGY:
CNS:• Hypokinesia and rigidity resolved first later tremor•D1 like (D1, D5): excitatory• D2 like (D2, D3, D4): inhibitory
CVS:• Tachycardia
CTZ:• Nausea and vomiting
ENDOCRINE:• Inhibit prolactin release
ADVERSE EFFECTS
At initiation of therapy:• Nausea and vomiting• Postural hypotension• Cardiac arrhythmias• Exacerbation of angina• Alteration in taste sensation
After prolonged therapy:• Abnormal movements• Behavioral effects• Fluctuation in motor performance
INTERACTIONS:
antihypertensives – levodopa Non selective MAO inhibitors – levodopaAtropine and anticholinergic – levodopa Pyridoxine - levodopa
ANTI-PSYCHOTIC
DRUGS
INTRODUCTION
DEFINITION:
Psychosis: A severe mental disorder in which thought and emotions are so impaired that contact is lost with external reality
Antipsychotics: class of medicines used to treat psychosis and other mental and emotional conditions
•Aliphatic side chain: CHLORPROMAZINE•Piperidine side chain: THIORIDAZINE•Piperazine side chain: TRIFLUOPERAZINE
Phenothiazines
•HALOPERIDOL•PENFLURIDOL
Butyrophenones
•FLUPENTHIXOLThioxanthenes
•LOXAPINE•PIMOZIDE
Other heterocyclic's
•CLOZAPINE•OLANZAPINE•ZIPRASIDONE
Atypical antipsychotics
CLASSIFICATION
neuroleptics
CHLORPROMAZINE PHARMACOKINETICS:
Absorption: • Oral• Highly bound to plasma and tissue proteins
Metabolized:• Liver metabolism• By CYP 2D6
Elimination:• t1/2 is variable and 18-30 hrs
PHARMACOLOGY:
CNS
• In normal individuals:• Psychomotor slowing• Emotional quietening
• In psychotic patients:• Anxiety is relieved• Hyperactivity, hallucinations, and delusions are suppressed• Chlorpromazine lowers seizures & can precipitates fits in untreated epilepsy
MECHANISM OF ACTION:
LOCAL ANAESTHETICS:• Potent as procaine but not used because of irritant action
CVS:• Hypotension
SKELETAL MUSCLE:• No effect
ENDOCRINE:• Increase prolactin results in gynaecomastia & galactorrhoea• Reduce gonadotropin secretions• Decreased in ADH release– more urine
Anti manic drugs
Antimanic drugs: mood stabilizers
Example: lithium carbonate
hallucinogens
Indole amines
cannabinoids
ANTI-DEPRESSANT
DRUGS
INTRODUCTION
DEFINITION: Depression: state of low mood and aversion to activity that can have a negative effect on a person’s thought behavior, feelings, world view and physical well being
Antidepressants: drugs which have the effect on depression/ drugs for the treatment of depression
CLASSIFICATION
RIMAs •Moclobemide•Clorgyline
TCAs •NA+5-HT reuptake inhibitors: Imipramine, doxepin•Predominantly NA reuptake inhibitors: Amoxapine
SSRIs •paroxetine•Fluoxetine
Atypical •Amineptine •Trazodone
Tricyclic antidepressants
PHARMACOKINETICS:
Absorption:• Oral• Highly bound to plasma and tissue proteins
Metabolism:• Liver
Excretion:• Through urine over 1-2 weeks
PHARMACOLOGY:
CNS:
• In normal individuals:• Peculiar clumsy feeling• Tiredness, light headache, sleepiness, difficulty in thinking
• In depressed patients:• Mood is gradually elevated• Patient become more communicative• Produce convulsions on over dose
MECHANISM OF ACTION:
Inhibition of nerve terminal NE neuronal uptake system
Increase in synaptic concentrations of NE
Desensitization of nerve terminal 2-adrenoceptors
Increase in neuronal NE release
Further increase in synaptic concentrations of NE
Desensitization of postsynaptic -adrenoceptors with nochange in postsynaptic 1-adrenoceptor sensitivity
Mechanism of action
ANS:• Dry mouth, blurring of vision• Constipation, urinary hesitancy
CVS:• Tachycardia• Postural hypotension• ECG changes and cardiac arrhythmias
ADVERSE EFFECTS:
• Sweating and fine tremors•Postural hypotension• Sedation, mental confusion and weakness• Increased appetite and weight gain• Seizures threshold is lowered• Cardiac arrhythmias especially in ischemic heart disease• Rashes and jaundice due to hypersensitivity • Anticholinergic: dry mouth, bad taste epigastric distress• Acute poisoning
INTERACTIONS:
• Phenytoin, phenylbutazone, aspirin, and CPZ – TCAs• Phenobarbitone – imipramine• TCAs – CNS depressants • MAO inhibitors - TCAs
ANTIANXIETY DRUGS Anxiety: it is an emotional state, unpleasant, uneasiness, discomfort, and concern or fear about some defined or undefined future threats
Antianxiety: drugs which are aimed to control the symptoms of anxietyClassification:Benzodiazepines: Diazepam Chlordiazepoxide OxazepamAzapirones: Gepirone IspapironeSedative antihistaminic: HydroxyzineBeta blockers: Propranolol
REFERENCES Essentials of MEDICAL PHARMACOLOGY: KD Tripathi
RANG and DALE’S pharmacology
BASIC AND CLINICAL PHARMACOLOGY –LANGE
modern pharmacology with clinical applications – Lippincott www.doctors.ac.in
www.wikipedia.org
www.surgeryencyclopedia.com
THANK YOU