antiparkinsonian drugs

extrapyramidal motor disorder

• rigidity, tremor, hypokinesia
• secondary -defective posture gait, mask face, sialorrhoea
• progression to immovable, inbreathable – chest inf, embolism.

DOPAMINERGIC PRECURSOR -LEVODOPA

• high first pass metabolism in git liver. 95% decarboxylated in perihery. DA acts on heart, bv, CTZ -tachycardia, postural hypoTN, vomiting. Tolerance dev. [Rx- antidopaminergic domperidone bocks only  CTZ]
• 1-2% crosses BBB into DAneurones, stored & released- alerting response on behavior. rigidity, hypokinesia resolve first. other symptoms gradually.
• initial ADRs [tolerance dev]- arrhyth, postural hypoTN, vomiting, altered taste.
• late ADRs [no tolerance]- involuntary movts [tics,grimacing, choreoathetoid], abn behavior [anxiety, mania, depr, hallucinations, psychosis, incr sex activity], ON-OFF effect [disease progression -inability store relese, synthesis moment basis -rapid unpredictable fluctuations in motor control].  Rx- divided dose & frequent administration.

PERIPHERAL DECARBOXYLASE INH -CARBIDOPA, BENSERAZIDE

• administered along with ldopa -prolongs peripheral t1/2 [less DA form -less vomiting, tachycardia, hypoTN], incr & sustained availability to brain, so less dose is needed & on-off effect is minimised. increased response is noted.
• ADRs: early & intense involuntary, behavior abn, postural hypoTN.

DA agonists -bromocriptine, ropinirole, pramipixole.

MAO-B[brain] inh of DA -selegiline

DA facilitator -amantadine

anticholinergics -benzhexol, procyclidine, biperiden, cycrimine, ethopropazine.

opiods

MOA: opiod receptors[3- in git & limbic reinforcing] are prejunctional inhibitory to excitatory NT in CNS & MYENTERIC PLEXUS.

AGONIST [morphine, dynorphin, encephalins]  cause intracellular decr cAMP, opens K channels & suppress Ca channels —> decr intracellular levels of Ca –> decr excitatory NTs release.

MORPHINE -

• natural alkaloid acting on all 3 receptors. has both CNS depr & stimulant action. poor oral bioavailability.  its effects are potentiated by CPZ,TCA,MAOi, Amphetamine, Neostigmine.
• specific strong analgesic – visceral>somatic, nociceptive receptor> neuritic damage pain. decr sympth autonomic effects of excess pain- sinking, nausea, apprehension, sweat,  palpitation, incr/decr BP, incr resp.  Rx- MIischemic pain,  cancer, neurogenic shock [tauma, burn], postoperative.
• in apprehensive subjects – decr central sympth stimulation –> calming mood, decr concentration & initiative. Rx- MI, Internal bleeding [hematemesis, threatening abortion], preanaesthetic.
• Sedation without motor incoordination. use: anaesthetic.
• high sensitivity to antitussive action [dry cough]
  
• dose dependent decr resp[decr drives,rate, tidal vol -apparant decr O2 need- accumulatedCO2] & vasomotor centre [greater sys vasodil (shifts pulmn edema),incr ICP, postural hypoTN, decr Presis & preload CO, reflex tachycardia. use-acuteLVF.  CI: LABOR -foetal apnoea [quicker- poor BBB], resp insufficiency [emphysema], head inj [incr ICP from vasodil + overriding signs -resp decr, miosis, sedation, vomiting].
• relaxes smms [git,ut,uterus,bronchi] & incr sphincter spasm – chronic constipation, urinary hesitency, prolonged labor, ppt asthma. CI: biliary colic,diverticulitis, pancreatitis, BPH eldermales.
• pokilothermic.
• decr hypothalamus-pituitary action: decr FSH,LH,ACTH -steroids, sex hormones. incr ADH, GH, Prolactin.

tolerance dev to all except constipation & miosis

• stimulates: CTZ -vomiting, EWnucleus -miosis, incrIOP, vagal tone -bradycardia, cortex-hippocampus -rigidity, convulsions, rapid iv euphoria; sympth stimulation -mild hyperglycemia.
• H release -itch, lip swelling, urticaria, brconstr.
• high abuse -phy&psy dependence.
• withdrawl symtoms- mydriasis, lacry, sweat, goose flesh,  diarrhoea, abd colic, anxiety, insomnia, rapid wt loss. Rx-METHADONE.
• POISONING- CNSdepr: coma, decr resp BP, pin point pupils, pulm edema. Rx- KMnO4 lavage, opiod antagonist.

CODEINE-

• less potent & eficacious
• sub-analgesic doses: higher affinity to antitussive receptors [dry cough]
• analgesic doses: decr diarrhoea & improve concistency in colostomy.

PHOLCODEINE- less constipating.

contrast with PETHIDINE-

• synthetic
• good oral but accumulates os no repeat doses.
• only receptor
• more potent analgesic & preanaesthetic
• few CVeffects
• decr only tidal vol resp
• less smms spasm -miosis constipation urinary retention use- preferred in biliary colic
• less foetal apnoea use- preferred opiod analgesic during labor
• miosis+ no corneal reflex since corneal anaesthesia
• less H -safer in asthma
• anticholinergic- dry mouth, blurring
• withdrawl symptoms less severe.
• no abuse since slow tolerance, dependence
• poisoning - CNSexcitation tremor, mydriasis, delirium, convulsions, hyperreflexia.

FENTANYL- high lipid solubility

• BBB -short acting anaesthetic
• transdermal -chr cancer pain

METHADONE- long acting

• less kick abuse
• late mild withdrawl symtoms
• Rx- wean from opiod dependence

PURE OPIOD ANTAGONISTS: act on all receptors, morphine dependence diagnosis -ppt withdrawl symptoms

NALOXONE -iv short acting, Rx- alchohol & morphine poisoning, reverse apnoea [foetal/intraoperative]

more potent NALTREXONE -oral long acting, Rx- opiod & alcohol deaddiction.

alcohol

alcohol has low safety margin to anaesthesia & death.

[conc: 30-100 euphoria lack caution & self criticism, 100-150 thought clouding decr memory, 150-200 ataxia, 200-300 stupor]

disulfiram

• irreversible[7-14days] inhibitor of aldehyde dehydrogenase causing acetaldehyde accumulation.
• aldehyde syndrome: flush, burning, sweating, headache, vertigo, risk of severe rxns.
• use: alcohol deaddiction in phy not dependent addicts.

methanol poisoning-

• slowly  metabolised to formic acid –> retinal damage, acidosis.
• CNSdepr –> decr HR,BP,resp.
• vomiting, headache.

Rx:

• 10%ethanol to saturate enz & decr metabolism [disadv- unstable conc, no iv preparation, long treatment, risk intoxication & hypoglcemia]
• alcohol dehydrogenase inh -FOMEPIZOLE
• folate to hasten formic acid removal.

antipsychotics

MOA: block D2 receptors in limbic & mesocortical regions.

• initial adaptive incr in DA turnover [antiemetic(drug/disease induced)  but no extrapyramidal effects]
• later tolerance to enhancing effect of DA turnover in basal ganglia [dev of extrapyramidal effects], but not in limbic area [continued antipsychotic action]

high potency drugs: ADR-extrapyramidal motor disturbances [parkinsonian rigidity tremor mask facies shuffling gait rabbit syndrome-after yrs; ms dystonia grimacing torticollis; akathesia restlessness Rx-propranolol; malignant neuroleptic synd fever BP HR tremor rigidity Rx-dantrolene, bromocriptine; late tardive dyskinesia lick chew pout puff] -reduce dose, add antich antipark-benzhexol, cycrimine, ethopropazine…

• haloperidol [no incr wt], trifluperidol – acute schizo
• piperazine: fluphenazine
• penfluridol – chronic schizo
• flupenthixol – negative schizo
• pimodine [arrhyth] – schizo maintenanace

atypical/ second generation drugs: less extrapyramidal effects [uncommon tardive dyskinesia]

• respiridone -[less extrapyrmdl & seizures] [incr prolactin, postural hypoTN, agitation]
• olanzepine -schizo,bipolar,mania [less extrapyrmdl & prolactin] [dry mouth, constipation,incr wt, seizures, agranulocytosis]
• clozapine -resistant schizo [less extrapyrmdl & prolactin] [incr wt,HR,BP, sedation,seizures, agranulocytosis, urinary incontinence,salivation, myocarditis]

low potency drugs [antipsychotic effect dev after wks]: ADRs- sedation, ppt seizures, poikilothermia[decr temp], jaundice, rash, urticaria.

• chlorpromazine
• triflupromazine
• thioridazine [blue exposed skin, opaque cornea]

TOLERANCE dev to Sedation & HypoTN.
no dependence.

pharmacological actions: uses & ADRs.

• decr irrational behavior, aggressiveness, hallucinations, delusions. Rx- functional pschoses [schizo(+>-),paranoia,acute mania], resistant anxiety, initially in organic diseases. [NEUREOLEPTIC syndrome in normal people:decr initiative, psycomotor slowing, indifferent, emotional quietening, sleep (different from CNSdepr)] potentiate all CNSdepressants so used in anesthesia.
• low potent drugs have blocking[postural hypoTN,hypoTN by vasodil/water retention/no presyn & central vaso tone inh, palpitation, impotence] & anticholinergic [dry mouth, blurring vision, constipation, urinary hesitancy]  [atypical clozapine causes myocarditis,salivation by central action, pimodine is arrhyth]
• high potency drugs are antiH.
• decr skms spasm by central action. Rx- intractable hiccups, tetanus, Gilles de la Tourette, huntingtons chorea.
• incr blood glucose & lipids –>wt gain.
• incr prolactin by pituitary Dblock.
• decr gonadotropin –> amenorrhoea, infertility, gynecomastia, galactorrhoea.
• decr ACTH –> no incr steroid during stress.
• decr ADH –>polyuria.

lithium carbonate

• prolonged administration stabilises mood in bipolar & acute mania, recurrent depression, cluster headaches [by displacing Na & modifying membrane property in brain cells & decreasing NA,DA,inositol]
• Li2CO3 is converted to LiCl in stomach /w ic hygroscopic & irritant. decr ADH,thyroxine,blood glucose. tolerable ADRs:vomiting,diarrhoea,polyuria[Dinsepidus],polydipsia, incr wt by edema, goitre, hypoglycemia. CI: DM,Sick sinus.
• excreted in saliva,sweat,milk,crosses placenta. CI:pregnancy,brestfeeding [foetal goitre, cardiac defects].
• low TI & individual variation, hence divide dose to avoid high peaks & monitor serun levels after 12hrs [toxic>1.5mEq].  toxicity: tremors,ataxia,nystagmus,slur,incoordination,hyper-reflexia, drowsy,delirium,coma,convulsions, hypoTN, albuminuria, arrhythmias.  Rx: amiloride[not vasopressin], osmotic diuresis, [HCO3]- infusion, >4 toxicity requires hemodialysis.
• most reabsorbed in renal PCT. so blood levels rise in renal insufficiency, diuretic drugs, Na restriction.
• incr WBC –>use in leucopenia, agranulocytosis.

antiepileptics

Epilepsy-

• focal origin –>spread –>postictal depr.
• unconscious + convulsions/sensory/psychiatric effects.
• primary -genetic
• secondary -head trauma/surgery/ischemia/tumor/cyst –>early responds w/ all drugs, late [8mos-2yr] Rx w/ PB,P.

40% GENERALISED- both hemispheres.

• GTC/grand mal- 1-2min commonest, aura-cry-unconscious-tonicspasm-clonic jerking-froth incontinence -sleep CNSdepr confusion, febrile convulsions.
• Abscence/petitmal- children, thalmcort T Ca++ 3cycles/sec spike wave, stare 0.5min
• atonic- ms relax
• myoclonic- momentary contr of limb/body [phy while passing thr deep sleep]

60% PARTIAL- one part of hemisphere.

• simple/cortical/somatosensory- conscious+convulsions/sensory perception
• complex/temporal/psychomotor- unconscious+bizarre behavior/emotio/puposeless movts.

Tcurrent Ca++ Ch inh	VA, Ethosuccimide.
Na+ Ch inh	VA, Phenytoin,CBZ.
GABA potentiation	VA,Clonazpm, Phenytoin,CBZ, Phenobarbitone,
Glutamate inh	Phenytoin,CBZ, Phenobarbitone
Ca++ influx inh	Phenytoin,CBZ, Phenobarbitone

GTC/Grandmal	Phenytoin,CBZ,VA, PB. New drugs: Lamotrigine [monotherapy] adjuvants- Gabapentine, Topiramate.
Abscence	VA,Ethosuc, Clonazpm,
Atonic, Myoclinic	VA,Clonazpm,
Infantile spasm	CORTICOSTEROIDS, [adjuvant:VA,Clonazpm]
Simple partial	Phenytoin,CBZ,VA,PB New drugs: adjuvants- Gabapentine, Topiramate.
Complex partial	CBZ, Phenytoin,VA, PB New drugs: Tigabine, Vigabatrin.
Secondarily GTC	Phenytoin,CBZ, VA

	oral, PPB, t1/2	metblsm,urine excr, enzinduc.
PB	slow, yes, long	yes,yes,yes
P	slow,yes -displaced by VA,progressive incr.	metab inh by AMA & Warfarin, 5% excr unchanged, inducer.
CBZ	slow, yes, decr by autoinduc	metab inh by AMA, active metabolite, auto+others induc[P,VA,PB,steroids]
E	slow, NO, 48hrs	25% exc unchanged.
VA	good, yes, long action.	complete, active metabolite, inducer.
C	good, yes, 24hrs.	complete

	ALLERGY [rash, lupus]	CNS [drowsy, vertigo, ataxia]	GIT [epigastric pain, vomiting]	TERATOGEN	MISC
PB	in some similar to P	sedation, decr memory & IQ, behaviour abn.
P	neutropenia, megalo[folate] anaemia.	+excitement	+	fetal hydantoin syndrome [cleft, microcephaly]	gum hyper, hirsutism, osteomalasia, hyperglycemia.
CBZ	agranulocytosis, aplastic anaemia, hepatitis.	+neurotoxic, coma, covulsions, CVcollapse.	+	minor malformtn [incr W/ VA]	incr ADH -water retention, hyponatremia.
E	dyscrasia, fatal BM depr		+++		headache, tiredness
VA	thrombocytopenia, pancreatitis, fulminant hepatitis in children.	+tremor	+anorexia	neural tube defects [incr W/ CBZ]	alopecia, curling of hair, incr blood NH3.
C		little sedation, behavior abn, ataxia

	SEIZURE TYPE	OTHER USES
PB [cheapest, least toxic]	4th choice- GTC,SP,CP.
P [CI in females]	1st choice- GTC,SP. 2nd choice- CP.	iv FOXPHENONIUM in status epilepticus, arryth by digitalis, 2nd chice in trigeminal neuralgia.
CBZ	1st choice in CP. 2nd choice in GTC,SP.	1st choice in trigeminal neuralgia, alt to Li in bipolar
E [exclusive action on thalamocortex]	2nd choice in Abscence.
VA [prevents kindling & secondGTC] [CI in children] [w/ Clonazpm ppt abscence seizure]	1st choice in Abscence,atonic, myoclonic. adj in GTC,SP,CP.	alt to Li in bipolar.
C	absence

treatment of epilepsies: cause should be searched & removed, initiate Rx early to decr the propensity to further attacks, if monotherapy fails combine drugs w/ diff MOAs,atleast 3yrs or lifelong, withdrawl should be gradual [since ppt status epilepticus, abrupt only if toxicity] if no family history, recent onset, chilhood, primaryGTC, no cerebral disorder/EEG.

febrile convulsions[GTC]- <5yr age , some become chr. prevention: temp rise should be dampened w/ paracetmol/cooling, intermittent prophylaxis w/ diazepam at onset of fever.

status epilepticus- sudden severe continous

• diazepam/clonazepm ivbolus then slow to control fits
• phenobarbitone/phenytoin after convulsions
• general anaesth, crurarization, positive pressure resp for refractory fits.

NEWER DRUGS:

• LAMOTRIGINE -Rx both mania,depressive phases of bipolar disorder.
• GABAPENTINE, PREGABALIN -Rx for nerve pain associated with diabetes/herpes zoster.

sedative hypnotics

ascending dose affect on CNS depression:  sedation–>hypnosis–>general anaesthesia.

SEDATION=decr responsiveness,motor activity,ideation.
HYPNOTIC=induces/maintains sleep. [NREM-1234[night terrors]-BP HR resp steady, 20-30%REM-darting eyes, dreams, HR BP resp fluctuate].

Non-BDZ hypnotics = no REM alteration/daytime sedation/rebound/dependence… Used for shortterm Rx of insomnia/wean oof chr use of BDZs : Eszopiclone, zolpidem, zaleplon[rapid action t1/2 2.5hrs]

Melatonin receptor agonist: Ramelteon.

other drugs with hypnotic action: antiH[diphenhydramine,promethazine], amitryptiline, chlorpromazine, anticholinergic[hyoscine], opiods[morphine,pethidine].

BARBITURATES	BENZODIAZEPINES
MOA: GABA potentiation & mimetic by interacting with barbiturate site of GABA Cl- channel	only GABA potentiation [less CNS depr] by binding to BDZ site of GABA Cl- channel
general depressant to all body cells. CNS[RAS] is most sensitive.	specific depr of CNS :RAS, limbic, midbrain, cerebellum, medulla. selective: hypnotic, anxiolytic, anticonvulsant, ms relaxn.
hypnosis[quick, long sleep] ADRs: disrupted REM-NREM cycle. long acting drug causes hangover [sedate, irritable, lethargy,dizzy]. chr use-accumulates -tolerance & dependence[phy&psych -withdrawl symtoms:excite, hallu, delirium, convul, death]. abrupt disuse of short acting drug causes rebound anxiety,nightmares. depr resp, BP, HR, GFR-urine. decr GI spasms	hypnosis[quick,long sleep] estazolam , flurazepam, temazepam insomnia>3wk -long acting drug[to decr rebound,withdrawl symtoms]1dose/3days. insomnia>3days[bereavement] -low dose of long/short[esp elders] acting drug. insomnia 1-3 days[jetlag,new place] short acting drug.Adv: less disrupted sleep cycle, wake refreshed -no sedation, mild tolerance/dependence/withdrawl/rebound symptoms. NO resp/cvs depr. DECREASES stress ulcers & nocturnal gastric secr.
sedation[drowsy+antianxiety+less excite] -long acting drug is used. tolerance develops on chr use. ADRs: impairs memory,judgement, euphoria, hyperalgesia.ADJUVANT IN PSYCHOSOMATIC DISORDERS	not used for sedation since less CNSdepr & tolerance develops.i.v.inj causes analgesia+amnesia+anxiolytic ADJUVANT WITH NSAIDs & SPASMOLYTICS. use: alcohol withdrawl, ECT, elctrical cardioversion of arryhtmia, cardiac cath, endoscopy, obstetric.
anaesthetic: ultra short acting -THIOPENTONE. Skms relax by blocking NMJ.	preanaesthetic & i.v anaesthetic. central action of ms relax. ADR:CI in cvs/resp insufficiency since causes mild decr in BP,resp.
specific anticonvulsant action -no tolerance develops -PHENOBARBITONE	tolerance develops to anticonvulsant action, so used only in acute conditions:CLONAZEPAM, DIAZEPAM, CLOBAZAM. status epilepticus febrile convulsions tetanus eclampsia convulsant drug poisoning
enzyme induction [PHENOBARBITONE used for jaundice Rx in neonates]	NO induction
ultra short acting drugs [6-10hrs redristributed] THIOPENTONE. short acting drugs [metabolished in 24hrs] BUTOBARBITONE. long acting drugs [excreted in 100hrs -hastened by alkalization] PHENOBARBITONE.	single dose/short acting drug [quick redristribution]MIDAZOLAM repeated dose/long acting drug [long t1/2 DIAZEPAM, FLURAZEPAM, NITRAZEPAM accumulation/metabolites]
CI: apnoe, porphyria, emphysema, renal/liver disease.	CI: apnoea, labour[neonate resp depr]
acute poisoning [suicide, addict-tolerance, amnesia, dependence] -bullea, coma, depr resp, BP, HR, GFR-urine. Rx -activated charcoal lavage, alk urine by mannitol/NaHCO3 [if long acting drug], dopamine[pressor+renal], O2, i.v fluids, hemodialysis.	high therapeutic index -no severe toxication [only amnesia, ataxia, vertigo, impaired psychomotor -esp elderly] abuse with ultrarapidly absorbed MIDAZOLAM [since more withdrawl symtoms -anxiety, malaise, insomnia, less appetite,  nightmares] Antidote -FLUMAZENIL.

general anaesthetics

GA = reversible loss of sensation[esp pain] & consciousness [RAS,thalamus,hippocampus] w/ ms relaxn & loss of reflexes [spinal cord]

GA, BDZ, barbiturates, propofol -decr synaptic transmission [LA- block axon conduction] by interacting(do not bind) w/ ligand gated ion channels:

• GABA[inh NT] Cl-
• glycine Cl-
• nicotinic cation
• N2O,Ketamine inh –> NMDAglutamate[exc] Ca++

4 stages seen with traditional GAs:

1. analgesia -Nresp, Nreflexes[eyelashes,swallow], conscious[dream like]
2. delirium[cutshort w/ preanaesth & quicker induction] -irregular resp, ms tone incr[clenched,incontinence], BP rises, incr secretions, unconscious.
3. surgical -eyes fixed, pupil starts dil,no light reflex, decr resp,BP, ms tone.
4. medullary paralysis[robbed w/ atropine,morphine,ms relax] -dil pupil, resp & circulation stops, BP very low, flabby ms. medullary vital centres are depressed last at incr depth of GA. [frist are brain higher centres & spinal cord lower centres]

LIGHT anaesthesia =incision causes reflex incr in BP & resp , endotr tube causes cough,vomit,laryngospasm. nowadays aim is LIGHT GA + IV analgesic,amnesic,ms relax.

IDEAL GA:

• cheap, easy storage, unreactive, easy adm, nonirritant, noninflmmable (cautery)
• potent, adequate analgesia & ms relx, no decr BP,  non toxic to organs, versatile,
• fast & smooth – ind & recovery, rapid controlability

ADRs:

during anaesthesia:

• secretions,laryngospasm, acid pneumonitis
• decr resp & BP
• arrythmia
• awareness
• excitation [iv GA + phenothiazines,hyoscine] [Rx decr w/  opiods]

after anaesthesia:

• vomiting
• pneumonia
• sedation, impaired cognition, emergence delirium
• organ toxicity
• nerve palsy

INTERACTIONS:

• severe decr BP with antiHTNsives
• opiods, neuroleptics, MAOinh, clonidine potentiate GA
• halothane + A –>arrythmia
• A insufficiency & CV collapse  w/ corticosteroids [Rx- hydrocorticosone intraoperatively]
• incr insulin need in DM [Rx- plain insulin]

PREANAESTHESIA:

• Anxiety,Amnesia, sedation, smooth induction, analgesia w/ thiopentane/halothane  – BDZ,FENTANYL
• preoperative pain only – MORPHINE,PETHIDINE [CI: fever] [ADRs: DECR RESP & bp, INCR ASTHMA, INTERFERES PUPIL SIGNS, DELAY RECOVERY, NO AMNESIA, CONSTIPATION, URINARY RETENTION, FLUSHING]
• secretions & laryngospasm, vagal stimulation from bradycardia & hypotension -ATROPINE/HYOSCINE [emergency delirium,pupil dil] /GLYCOPYROLATE[less CNS effects]
• antiemetic -ONDENSETRON, DOMPERIDONE, PROMETHAZINE[antiH-sedation,anticholinergic esp children]
• decr acid reflux -PPI,H2blockers-ranitidine/fano

INHALATIONAL GA [N2O gas, liq Ether, halothane, en/iso/des/sevoflurane] -diffuse pulm alveoli, potency=MAC[min alv conc to enter CNS]

INDUCTION, RECOVERY: potentiated w/

• high potency[MAC]
• low potency ->high conc in inhaled mixture [irritancy limits conc] –>SECOND GAS EFFECT= high conc[N2O] of one decr alv gas vol, incr diffusion of anther[halothane] GA given at same time.
• incr resp rate –>can be incr by CO2
• matched alv ventilation perfusion ratio [mismatched in emphysema..]
• incr blood & tissue insolubility [low: halothane, ether, enflurane] [high: N2O,iso/des/sevoflurane --> quickly escape during recovery causing alv DIFFUSION HYPOXIA -->100% O2 inhalation after N2O is given in low CardioPulm reserve]
• cerebral vasodil [incr by CO2]
• blood flow high in brain> ms> adipose
• quick elimination [slow-->halothane]

ADMINESTRING METHODS:

• OPEN DROP -ether[cheap] liq poured[no apparatus required] & vapour inhaled [wasteful, conc cannot be determined]
• MACHINE -gas cylinders, vaporisers, flow meters, unidirect valves, corrugated tube, reservoir bag. [conc can be controlled]
  • OPEN -fresh dose[more drug is required] is given[conc controlled] while exhaled escapes out without rebreathing.
  • CLOSED -exhaled circulated[conc cant be controlled] thr sodalime[absorbing CO2] & is rebreathed [expensive(flurane)/explosive ones dont escape]
  • SEMICLOSED -partial rebreathing thr valve.

I.V inducing agents:

• cause rapid induction of unconsciousness in 1 arm brain circulation t=11sec.
• reduce dose of maintenance anaesthetic
• used solely or supplemented w/ analgesics,ms relax.
• ADRs: excitation occurs w/ phenothiazines/hyoscine  Rx: opiods

ideal characters –>	cheap, nonirritant,noninflmmable easy storage, unreactive versatile,easy adm
N2O	gas,cheap,nonirritant, noninflm,
ETHER	volatile liquid, cheap, irritant, inflammable
HALOTHANE [most popular]	volatile liquid, little expensive, nonirritant, noninflm
ENFLURANE	nonirritant, noninflm.
ISOFLURANE	costly, slight irritant
DESFLURANE	irritant- cough,laryngospasm.
SEVOFLURANE	degraded by sodalime so high flow open sys ->expensive, nonirritant
THIOPENTANE SOD. [commonest]	fresh prep, nonirritant, extravasation causes pain & necrosis.
PROPOFOL	inj causes pain
BDZs.	irritant [D>L>M] large dose by slow iv [burn,thrombophlebitis]
KETAMINE	cortical,subcortical action [not RAS]
FENTANYL

ideal characters –>	fast & smooth – ind & recovery , elimination, rapid controlability
N2O	quick smooth induction[but thiopentone is added], rapid recovery,only mild nausea, quick elimination [lowblood soluble]–> diffusion hypoxia.
ETHER	prolonged unpleasant induction [high blood solubility, secretions (Rx atropine preanaesth)], slow recovery -marked vomiting.
HALOTHANE	intermediate solubility, quick pleasant induction, quick smooth recovery -mild shivering, prolonged elimination -CNS depr for hrs.
ENFLURANE
ISOFLURANE	rapid induction & recovery [less soluble]
DESFLURANE	very fast ind & rec [very low solubility]–> brief rise in BP,HR.
SEVOFLURANE	rapid ind&rec, rapid control of depth
THIOPENTANE SOD.[iv anaesth]	ultra short action -high tissue solubility [instant brain- unconscious immediately but back diffusion-consciuos in 8-12min] secretions,intubation cause laryngospasm [Rx preanaesth atropine/Sch. residual CNSdepr for 12hrs -delirium, shivering, postanaesth pain & rstlessness
PROPOFOL [iv anaesth]	shrt action [30sec-->10min] rapidly metabolised excitation, involuntary movts in few.
BDZs. [slow acting iv]	faster onset [M>D>L] 5,10min–>1hr, 2hr amnesia, 6hr sedation.
KETAMINE [slow acting iv]	short action [1-->15min amnesia for 1-2hrs.
FENTANYL [slow acting iv]	short action[30-50min] postanaesth vomiting,itching.

ideal characters –>	potent,adequate analgesia & ms relx no decr BP,  non toxic to organs, use.
N2O	low potency -used in high conc –>second gas effect, good analgesic, poor ms relax, vitals not affected, used as adjuvant/carrier, solely in dental,obstetric analgesia.
ETHER	potent, good analgesic & ms relax, BP maintained by reflex sympth, nontoxic. used in developing countries since cheap & by opendrop[no apparatus].
HALOTHANE	potent, poor analgesic & ms relax [so req N2O,opiods,NMblockers], Arryhtmogenic,decr CO,BP,GFR-urine, resp, mismathches alv-vent perfusion ratio by vasodil, live rtoxicity, malignant hyperthermia [incr ms Ca-contr-heat esp w/SCh Rx-dantrolene,HCO3-,cooling], preferred in asthma,ext/int version in late pregnancy since inh br/uterus const.
ENFLURANE	better ms relax little cardiac depr, greater resp depr-acidosis, ppt seizures
ISOFLURANE	more potent, cardiac depr, greater resp depr, slightly more secretions, nontoxic. use:neurosurgery since no seizure ppt.
DESFLURANE	less potent-used in high conc, marked resp depr nontoxic used in out-patient surgery since less postanaesth CNSdepr.
SEVOFLURANE	potency,solubility,ADRs intermediate between iso&des. little cardiac & resp depr used in out-patient surgery since less postanaesth CNSdepr.
THIOPENTANE SOD.	poor analgesic & ms relax –>use opiods,N2O. transient cardiac & resp depr CIs: long operations, shock/sepsis, porphyria. used solely in short painless surgeries, ECT, narcoanalysis, communication w/maina.
PROPOFOL	transient cardiac depr, dose dependent resp depr, CI: children, high doses- resp depr, heart failure, metabolic effects. use: intubation sedation in ICU, out-patient surgery[no CNS depr/laryngospasm, low nausea]
BDZs.	potency [D>L=M] poor analgesic & ms relax[+opiod/N2O,NMblocker], decr resp,HR,BP. Antidote Flumazenil. use: endoscopy,catheter & angio, fracture setting, ECT, sedation w/LA.
KETAMINE [dissociative+anaesthesia]	emergence delirium, hallucinations, involuntary movts. N resp,reflexes, incr ms tone. incr HR,BP,CO CI: HTN, ischemic HD. use: burns/bleeding/hypovolemic shock, asthma, H&N surgery, short conscious operation, repeated use.
FENTANYL	potent opiod analgesic drowsy but conscious & can be commanded. resp & cardiac depr -Antidote Naloxone. use: painful surgery, burns, post-operative pain [iv BDZ,Thiopentane]