Notes drugss

Anti Parkinsonism
Levadopa Bromocriptine Amantidine Anticholinergic Tremor and rigidity Increase dopamine activity Inhibit peripheral metabolism by L-dopa by inhibit COMT Prolonged L-dopa action F : well Metabolism : liver Block muscarinic receptor Restore balance between cholinergic and dopaminergic activity Selegiline MAO inhibitor Adjunctive drug Entacapone COMT inhibitor Benzotripine, Trihexyphenidyl Antimuscarinic agent Tremors and rigidity

Clinical used Classification MOA

Dopaminergic agents Parkinson disease Parkinson disease improve bradykinesia Hyperprolactinemia Dopamine precursor Dopamine agonist Cross BBB

PK

Toxicity

Orally T : 1- 3 hrs F : delay if with food Metabolise : liver + intestine Excretion : urine a. Levadopa (alone) i. Nausea ii. Vomiting iii. Hypotension iv. Arrhythmia b. Levadopa + carbidopa i. Confusion ii. Hallucination iii. Dyskinesia Food natural amino acids (milk i. Pyridoxine (vit B6) ii. MAO A - inhibitors

Orally 1st pass effect Excrete : faeces

Orally T : 2-4hrs Exrete : urine

5-10mg (in morning)

i. GIT nausea vomit ii. CVS hypotension, painless digital vasospasm iii. CNS confusion, hallucination, delusion iv. Dyskinesia Psychosis Coronary disease Active peptic ulcer

i. CNS Confusion hallucination ii. Livedo reticularis iii. Postural hypotension

i. Insomnia ii. Dizziness iii. Nausea

i. ii. iii. iv.

Dyskinesia vomitting Nausea Diarrhea

Contraindication

Drug interaction

Antiepileptic drugs
Carbamazepine (CBZ) Clinical used Most epilepsy Choice : GTC + PS Treat trigerminal neuralgia Phenytoin (0 order kinetic) Most epilepsy except absences Phenobarbital GTC + PS Mostly infant seizure Ethosuximide Absences seizure ONLY Sodium valproate i. F: >90% protein binding T : 24hrs F : 100% T : 2-6 days Elimination : hepatic metabolism and renal excretion F : 100% T : 40 hrs Orally Metabolize : hydroxylation i. Gastric irritation ii. Fatigue + headache + dizziness iii. Teratogenic i. ii. iii. iv. v. vi. Wide spectrum ( GTC + PS + Abs + myoclonic + atonic) Bipolar disorder Migraine Neuropathic pain Block HFRF : blockade of transmembrane Na+ channels Increase GABA and reduce aspartate F : >80% T : 10 hrs protein binding Inhibit own mechanism Gastric irritation + nausea + vomit Weight gain/ appetite Fine tremor Idiosycncratic thrombocytopenia Idiosyncratic hepatotoxicity Teratogenic effects Benzodiazepine Status epilepticus

MOA

Block Na channel Inhibit firing mechanism i. F = slow absorption Autoinduction hepatic enzyme Slow release (prvnt autoinduction) GIT irritation Nausea vomitting CNS Diplopia Dizziness Ataxia Hyponatremia and H2O intoxication Idiosyncratic blood dyscrasia Skin allergy (Steven Johnson syndrome- SJS) Teratogenic

Block Ca2+ channel Block Na channel

Unknown

Inhibit Ca channel (thalamocortical activity)

Rapid onset

PK

Toxicity

ii.

iii. iv. v. vi.

Drug interaction

Induction of enzyme : level OCP - estrogen Phenytoin, valproate, clonazepam Warfarin, theophylline Inhibition of enzyme : level Cimetidine Erythromycin Valproic acid Isoniazid

Impaired brainstem and cerebellar fx Nystagmus Ataxia Diplopia Vertigo Dysarthria Drowsiness Cognitive impairment ii. Chronic connective tissue Gum hyperplasia Hirsutism Coarsening of facial iii. Skin rash Acne SJS iv. Folate deficiency megaloblastic anemia v. Vitamin D deficiency (osteomalacia) vi. Teratogenic Warfarin - enzyme

CNS i. Sedation and fatigue (adult) ii. Hyperactive + aggression (child) iii. Nausea + vomit iv. Tolerance v. Dependence vi. hepatic enzyme

Non narcotic drugs Acetaminophen Analgesic Antipyretic Ibuprofen Rheumatoid osteoarthritis Aspirin i. Antipyretic and analgesic ii. External application ( iii. CVS platlet aggregation iv. Colon cancer Reverse inhibit Blocked PG synthesis COX Inhibits cyclooxygenase Inhibit synthesis of activity PG Orally F : stomach and small intestine T : 15mins GIT i. GIT Nausea Vomit Bleed ii. BV Inhibit platlet aggregation Prolonged bleed time iii. Respiration Metabolic acidosis Respiratory depression iv. Metabolic process Hyperthermia v. Hypersensitivity Urticaria Bronchoconstriction Edema Indomethacin Rheumatoid Gout Ankylosing spondylitis Mefenamic acid Diclofenac Rheumatoid arthritis Osteoarthritis Ankylosing spondylitis Allupurinol GOUT (hyperuricemia)

Clinical used

MOA

Inhibit COX-3

COX inhibitors Inhibit phospholipase A and C

Inhibit COX and phospholipase A

PK

Toxicity

Orally T : 2-3 hrs Metabolite : liver and kidney Skin rash Renal tubular necrosis Hypoglycemia Hepatic necrosis (potent)

Excretion : urine

Orally T : 2hrs

i. GIT Diarrhea GI hemorrhage Abdominal pain pancreatitis ii. CNS Headache Dizziness Confusion Depression iii. BV Thrombocytopenia Aplastic anemia iv. Metabolic process Hyperkalemia v. Renal Renal papillary necrosis

i. GIT Diarrhea ii. Hemolytic anemia

i. GIT Diarrhea Vomit nausea ii. hepatic enzyme level increase

i. GIT Nausea diarrhea ii. Hypersensitivity

Cranial Nerve
No I II III IV V Cranial nerve Olfactory Optic Oculomotor Trochlear Trigerminal Nucleus name Anterior olfactory Lateral geniculate Oculomotor Edinger-westphal PS Trochlear Principle Spinal Mesencephalic Motor Abducens Motor Solitary Superior salivatory Vestibular cochlear Nucleus ambiguous Inferior salivatory Solitary Nucleus ambiguous Dorsal motor vagal Solitary Nucleus ambiguous Spinal accessory Hypoglossal Nucleus location Olfactory tract Thalamus Midbrain Pons Medulla Pons/midbrain Pons Pons Function Smell Vision Eye movement (elevate, adduct) Pupil dilate Eye movement (depression of adduct eye) Facial sensation Mastication Symptom/ sign Anosmia Blindness Eye deviate out&down Loss of papillary/ accommodation reflex Diplopia, lateral deviation of eye Facial anesthesia Loss of facial pain sensation Weakness/ loss of mastication Medial eye deviation Paralysis of facial nerve Loss of taste Dry mouth, loss of lacrimation Vertigo, nystagmus, disequilibrium Loss of hearing Loss of taste (post 1/3) Loss of gag reflex Dysphagia and hoarseness of voice Tachycardia, loss of cough reflex Loss of taste Head turning/shoulder- shrugging Weakness Atrophy of tongue muscle Deviation on protrusion, fasciculation

VI VII

Abducens Facial

VIII IX

Vestibulocochlear Glossopharyngeal

Medulla

Vagus

XI XII

Accessory Hypoglossal

Medulla cervical cord Medulla

Eye movement (abduction) Facial expression Taste Salivation, lacrimation Balance Hearing Taste Salivation Innervations of pharynx Swallowing/talking Cardiac, GIT, respi taste Pharynx/larynx muscle Neck/ shoulder mvmnt Tongue movement

SEDATIVE AND HYPNOTIC

Benzodiazepine Anxiety Sedation & amnesia before medical or surgical procedure Anticonvulsant eg Diazepam (iv) Insomnia (short term) Muscle relaxant (neuromuscular disorders) Flumazenil BDZ overdose Reverse BDZ after anaesthesia Do not antagonize GABA or other sedative hypnotics Barbiturate Anticonvulsant Anaesthetics Neonatal jaundice -increase glucuronyl -transferase affinity -increase bilirubin conjugation eg Phenobarbitone GABA mimetic effect high dose, mati. Low therapeutic index. Classification Ultrashort triazolam, midazolam Short lorazepam, temazepam Intermediate oxazepam Long diazepam, chlordiazepoxide BDZ antagonist (antagonize GABA-A receptor) Non-BDZ Ultra short acting thiopentone to induce anesthesia Short acting pentobarbitone Long acting: phenobarbitone anticonvulsant Bind to GABA receptor Increase GABA affinity receptor Prolonged Cl channel open Anti-anxiety drug Non-benzodiazepine Hypnotics Serotonin derivative (penial gland) Novel hypnotic drug Buspirone Anxiety Zolpidem Hypnosis Insomnia Melantonin Insomnia Jet leg Ramelton Insomnia Chloral hydrate old agent, seldom used prodrug: metabolised to trichloroethanol in liver CH + ethanol: severe depression of CNS trichloroethanol inhibits conversion of ethanol to aldehyde

Clinical used

MOA

Enhanced inhibitory action of GABA Bind to GABA-A receptor Cl channel open Cl influx Hyperpolarization Inhibit AP Absence of GABA, BDZ ineffective Increased dose of BDZ does not further increase CNS depression (subanesthetic level)

Competitive antagonist at BDZ receptor

Act on 5HT-1A partial agonist receptor give BDZ + Buspirone initially >>>2 weeks>>stop BDZ, maintain with Buspirone

Bind to BDZ receptor Increase inhibition effects of GABA

Agonist in MT receptor in brain

PK

A : complete, oral D : short, intermediate, long M : hepatic/liver E : urine (as glucuronides)

A: IV D : 2 hrs (short) Cross BBB

A: oral , complete D : fast M: liver E: urine

A: oral (hi 1st pass effct)

A: oral D: T : 2-4hrs M: liver E: urine

A: oral D:2-5 hrs M: liver

Pharmacology effects

PK: lipophilic, iv & im, cross BBB & placenta , highly bound to plasma protein, metabolismlonger duration, excretion kidney i. Sedation (decrease spontaneous reaction and dec ideation, low therapeutic dose) ii. Hypnosis iii. Subanaesthesia (premedication before anesthesia, post op, cant produce anesthesia) iv. Anticonvulsion v. Muscle relaxant (high dose) inhibit NMJ vi. Respiratory Hypnosis dose respi depression in pt w pulmonary disease Anaesthesia respi depression, hypotension & tachycardia vii. CVS Hypotension Tachycardian

i.

ii. iii.

iv.

CNS Depression Anti-anxiety Sleep effect Respiratory Hi : resp collapse CVS Hi : depress contract, Cv collapse Liver Induce hepatic enzyme F

physical & psychology dependence withdrawal sydrome: -anxiety

Anti-anxiety effect is seen after 2 weeks (not suitable for panic disorder) does not potentiate the effects of other CNS depressant No tolerance, no dependence no hypnosis, anticonvulsion & muscle relaxant effects oral, high first pass effect

Less anxiolytic, anticonvulsant, muscle relaxant Less rebound Risk of dependence Deep refresh sleep

-tremor

-convulsion Toxicity i. ii. iii. iv. v. vi. Sedation and confusion Anterograde amnesia Total amnesia Ataxia Cognitive impairment Paradoxical aggression (disinhibition) i. ii. iii. iv. Anxiety Confusion Tachycardia Induce withdrawal syndrome i. Mental and psychomotor disturbance Hypersensitivity Physical & psychological disturbance No antidote Tachycardia Nervousness Headache GIT distress GIT disturbance Drowsiness (day) Tachycardia Depression Vivid dream Headache i. ii. Dizziness Fatigue CH + ethanol: severe depression of CNS trichloroethanol inhibits conversion of ethanol to

ii. iii.

iv.

No mental & psychomotor disturbance

aldehyde Contraindication Pt w respiratory insufficiency -sleep apnoea -hepatic insufficiency Nursing mothers BDZ overdose not fatal in normal indiv. Liver dysfunction

Fatal if taken with other CNS depressant (alcohol) Antidote: flumazenil - Mental & psychomotor function disturbances ---drowsiness, confusion, incoordination - After effects --- prolonged disturbance of mental & psychomotor after waking up -Psychological effects ---paradox: nightmare ---depression, suicidal tendency ---hallucination L Tolerance, physical & psychological dependence

Adverse

- when taken more than 2 weeks - mild compared to other sedative hypnotic - withdrawal syndrome: insomnia, anxiety, nightmare (stop Rx gradually)

Anesthesia

anaesthesia local/ regional induc2on surgery end mixed general induc2on sleep maintain unconsious end