Pharmacology Notes

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ANXIOLYTICS & HYPNOTIC DRUGS Classification: 1. Benzodiazepines 2. Barbiturates 3. Non benzodiazepine and non barbiturates 4. Buspirone 5. adrenoceptor antagonist 6. Diphenhydramine is an antihistamine used as sleeping pills particularly in wakeful children 1. Benzodiazepines: i) Midazolam: is ultra short acting , used as I.V. anaesthetic Ii)Alprazolam: has anxiolytic & anti depressant property iii)Diazepam: Used I.V for the treatment of status epilepticus iv) Clonazepam: is an anxiolytic drug especially in mania v)Flumazenil: Benzodiazepam antagonist vi) 1-selective Benzodiazepam: will be having anxiolytic property but no sedation vii) 2- selective Benzodiazepam: anxiolytic and muscle relaxant property

Benzodiazepam doesnot effect random eye movement sleep(REM) Benzodiazepam doesnot effect growth hormone secretions Mostly they undergo metabolism by glucoronidation Hydroxy diazepam is called as Timazepam Hydroxy nor diazepam is called as Oxazepam Ioverdoses Benzodiazepam prolongs sllep without serious depression of respiratory (or) cardiovascular functions Short acting benzodiazepams cause severe withdrawal symptoms Severe psychological & physiological dependence occurs with Benzodiazepams Fumazenil can be used to reverse the effects of Benzodiazepines over doses Half life of Fumazenil 2hrs Fumazenil when given with Tricyclic anti depressants(TCA) precipates convulsions Is a partial 5HT-1a agonist Ipsapirane & Jepirone are analogues to Buspirone 5HT receptors are anti inhibitory in nature Buspirone also shows activity of non- adrenergic in local cerulus region It takes several days to weeks to show action It is ineffective in controlling franic attacks (or)severe anxiety states It does not produce sedation or motor in- coordination




They are potent cyp enzyme inducers Phenobarbitol is used for treatment of epilepsy Thiopental ultra short acting Given I.V. for anaesthetic action Barbiturates are dangerous to patients suffering from metabolic diseases like porphyration condition


Serotonin selective reuptake inhibitors(SSRI) such as fluoxatin, peroxitin, sulfranil can also be used for anxiety disorders

Anti-epileptic drugs: like -pentin , vigabatrin, Tiagabine , valproate can also be used as anxiolytic 5HT3- receptor antagonists: Ondansetron can also show anxiolytic activity ANALGESICS Morphine:

Supra spinal analgesia of morphine is because of -receptor antagonistic property For final analgesic action & receptors Respiratory depression, pupil constriction, euphoria & physical dependence is due to -receptors Disphoria is due to receptors Respiratory depression by opiates is not accompanied by depression of medullary centres controlling cardiovascular function Respiratory depression is most common cause of opiate poisoning Pin point pupil is characteristic of opiate poisoning Morphine inhibits peristaltic movements resulting in constipation Opiates should be avoided in biliary colic pains due to gall stones It increases concentration of amylase & lipases in plasma Morphine releases histamines from mast cells & causes itching at the site of injection Promotes bronchoconstriction & hypotension where as pethidine doesnot produce these effects is a phenomena of raising & stiffening of tail of rat & mice given opiate drugs It is the technique for screeing morphine like drugs Opiates suppresses immune system which produces tolerance and dependence Clonidine & ketamine are used to Alliviate avstinence syndrome Half life of morphine 3-6hrs Morphine 6-glucuronate is more active analgesic than morphine Morphine 3-glucuronate acts as antagonist for analgesic effect of morphine Morphine glucuronates undergoes extrinsic hepatic cycle Morphine like drugs have longer duration of action in Neonates because of low conjugation reaction hence contraindicated during child birth

Strace state:


Unwanted effects: Coma, respiratory depression with characteristic constricted pupil Diamorphine:

Di-acetylated derivative of morphine also called as Heroin Can cross BBB more rapidly than morphine 3 methyl morphine or 3 methoxy morphine Oral analgesic for mild pains Doesnot produce Euphoria Used in combination with paracetamol for analgesic action Most common side effect Constipation Mostly used as anti-tussive agents in cough syrups


Pethidine: 2

Also called as mepridine It produces restlessness Metabolism is mainly due to N-methylation Pethidine is preferred to morphine during labour because it doesnot reduce force of uterine contraction Excitement, hyperthermia, convulsions when given along with MAO inhibitors Metabolite of pethidine is norpethidine is responsible for these side effects Highly potent Used in severe chronic pains 1000 times more potent than morphine Used for veterinary purposes Is a longer acting opiod analgesic Half life 24hrs Less sedation Widely used for treating morphine & diamorphine addiction It is a mixed agonist & antagonist with analgesic action similar to morphine Produces dysphoria, nightmares & hallucinations Hallucinations occur because pentazocin acts on -receptor which is not opiod receptor Pure partial receptor agonist It doesnot have any side effects like euphoria, dysphoria, respiratory depression It is a shorter acting drug produces sedation & atropine like side effects Weak agonist at receptors Weak inhibitor of nor adrenergic reuptake opiod antagonists:

Side effects:

Pentanide & Isopentanyl phosphate:








Higher doses mimic the actions of morphine Can produce physical dependence & also withdrawal syndromes First pure opiod antagonist with affinity for all 3 opiod receptors Also shows ocupuncture analgesia which is associated with opiod release Fo treatment of respiratory depression caused by opiates during labour Halflife 2-4hrs should be given repeatedly Precipitation and withdrawal syndromes


Clinical use:

Side effect

Naltrexone: Similar to naloxane but longer acting Paracetamol: 3

Analgesic & anti-pyretic effect by lacking anti-inflammatory effects Selective to COX 3 enzyme Half life 3hrs Overdoses produce severe hepatotoxicity

Tricyclic antidepressants(TCA): Amipramine & Amytryptaline: for treatment of neuropathic pains Antiepileptic drugs:

-pentin, phenytoin, carbamazepine are used for neuropathic pain ketamine an analgesic drug shows wind up phenomemon I.V. lignocaine is effective in neuropathic pain

Enkephalins: Ex: Thiorphan Metabolic degradation of opiate peptides & acts as analgesic drugs Epibatidine:

Nicotinic Ach receptor agonist Also a potent analgesic drug Agonist at cannabinoid receptor Also acts as an analgesic drug ANTIDEPRESSANTS

Tetrahydro cannabinol:

Classification: i)Mono Amine Uptake Inhibitors: a)Non selective: TCAs (e.g.imipramine,amitriptyline) b)Other Non selective: TCAs: Venlafaxine, Duloxetin, Buproprion, St.Johns wort Nortryptaline & Desipramie: Selective for noradrenaline reuptake Clomipramine: Used for antidepressant and antianxiety Venlafaxine:

Used for treatment resistant patients Rapid action than other antidepressants Safer in higher doses Hyperforin should not be taken with cyclosporin or other antidiabetic dugs because their activity decreases Cyp enzyme inducer weak inhibitor of dopamine & NA uptake mechanism mainly used in depression associated with anxiety slow release formulations are used to treat nicotine dependence hydroxyl desmethyl imipramine selectively inhibits NA uptake & has no effect on 5HT TCAs produces sedation except Buproprion which produces insomnia In higher doses TCA prolongs QT interval

St.johns wort(Hypericum):


Imp points:


TCA potentiates action of alcohol as anaesthetic agents & causes severe respiratory depression For moderate to severe endogenous depression especially with psychomotor features like insomnia Sedating antidepressant drug amitryptiline is used For short term treatment of nocturnal aneuresis in older children Imipramine is used

Selective Serotonin Reuptake Inhibitors(SSRI): Fluoxetine, fluvoxamine, paroxetine, sertaline, citalopram-these are used for treatment of anxiety disorder known as obsessive compulsive disorder Fluoxetine:

long acting SSRI half life 48hrs

Peroxitin & fluoxotin: should not be used in combination with TCA because they are cyp enzyme inhibitor Unwanted effects:

Insomnia, loss of libido and failure of orgasm In combination with MAO Is, SSRIs can cause serotonin syndrome characterized by tremors, hyperthermia, & cardiovascular collapse Selective serotonin reuptake inhibitor Active in E form


MAOI: EX:Phenelzine, tranylcypramine, and iproniazid

Irreversibly inhibits MAO enzyme Selegaline is specific selective MAO B inhibitor Meclobimide, clorgiline MAO A selective MAOI areused in the treatment of parkinsonism NA & 5HT are selective substrates for MAO enzyme Phenylethylamine & benzylamine are specific substrates for MAO B Dopamine & Tyramine are non selective Non selective MAOI promote cheese reaction Moclobimide, selegaline, clorgiline do not provoke cheese reaction MAOI should not be given with pethidine TCAs should not be taken with MAOI

Miscellaneous antidepressants: Trazadone: is a weak 5HT uptake inhibitor, also inhibits 5HT & H1 receptors Nefarodone & Mianserin:

similar to that of Trazadone safer in high do