PREMEDICATION DRUGS

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PREMEDICATION DRUGS

• DR.SUDHIR
• MUBARAK AL KABEER HOSPITAL

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PREMEDICATION- DEFINITION

• Premedication refers to the administration of
  drugs in the period 1 2 hours before induction
  of anaesthesia

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OBJECTIVES

• Allay anxiety and fear
• Reduce secretions
• Enhance the hypnotic effects of G.A agents
• Reduce P.O.N.V
• Prodcuce amnesia
• Prevent aspiration
• Attenuate vagal reflexes
• Attenuate sympathoadrenal response

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ALLAY ANXIETY FEAR

• The best way to do this is by
  non pharmacological means
• Psychotherapy Reassurance
• Benzodiazepines- most commonly used drugs

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BENZODIAZEPINES

• Anxiolytic
• Amnesic
• Hypnotic
• Sedative
• Most commonly used premedication drug

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Mechanism of action- Site

• Modification of emotional response behaviour
  by suppressing the neuronal activity between
  limbic system and hypothalamus
• Decrease in alertness and arousal- by depressing
  interaction between limbic system and the RAS
• Anticonvulsant effect inhibition of amygdaloid
  nuclei
• Muscle relaxant suppression of polysynaptic
  reflexes in spinal cord ( central acting
  relaxant)

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Mechanism of action- Mode

• GABA mediated inhibitory effects
• GABAA RECEPTORS
• Cortex Limbic system
• GABAB brain stem spinalcord Baclofen
• GABAA RECEPTORS they are mebrane protein
  pentameric structure associated with chloride
  channel
• Three sububits ? ,ß, ?

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GABA binding site
Chloride channel
Benzodiazepine binding site
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GABA binding site
Chloride channel
Benzodiazepine binding site
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• Benzodiazepines enhance the efects of GABA on
  GABA receptor
• Thus they increase the frequency of chloride
  channel opening
• Channel opening times are unchanged (
  contatrast to barbiturates)
• Increased chloride ions cause neuronal hyper
  polarisation and thus inhibition
• Stage 3 sleep is increased
• Stage 4 sleep and REM sleep decreased

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Classification

• Long acting diazepam
• Medium acting temazepam
• Short acting - midazolam

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DRUG Dose (mg) Potency Half life Terminal (hrs) Active Metabol-ites Half lifes metabolites
FLUNITRAZEPAM 1 30 12-20 Y 25-30
TEMAZEPAM 20 1.5 4-10 Y
MIDAZOLAM 10 3 1-3 N
ALPROZALAM 0.5 60 10-12 Y
CHLORDIAZEPOXIDE 20 1.5 5-30 Y
CLONAZEPAM 6 5 20-60 N
DIAZEPAM 10 3 24-48 Y 50-120
LORAZEPAM 1 30 10-20 N
OXAZEPAM 30 1 6-25 N
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Diazepam

• Most commonly used
• Insoulble in water so formulated in propylene
  glycol, which is very irritant to veins.
• Diazemulus lipid emulsion
• Bioavailability 100
• Protein binding 90-95.
• Dosage
• Premedication 10-15 mg oral 1- 1.5 hrs preop
• Sedation- 7-15 mg i.v slowly, increments 1-2 mg
• Status epilepticus- 2mg every minute , max 20 mg
• Intensive care- not for infusion 5-10mg 4th
  hourly

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50 120 hrs
4-10 hrs
6-25 hrs
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Midazolam

• Imidazo benzodiazepine derivative
• It is this imidazole ring which imparts water
  solubility at pH lt 4
• At blood pH, drug becomes lipid soluble due to
  ring closure and penetrates brain rapidly in 90
  seconds peak effect 2- 5 mins
• Bioavailability 44
• Hepatic elimination( liver blood flow)
• Hydroxy-midazolam- active metabolite 1 hr-
  clinically important only after prolonged
  infusion in renal failure

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• Midazoalm is 1.5 -2 times more potent than
  diazepam ( ? )
• Dosage
• Premedication 15mg oral or 5mg I.M,nasal drops
• Sedation 2-7mg I.V incre 0.5 1 mg
• Status epilepticus not recommended ( ? )
• Intensive care 0.03 -0.2 mg/kg/hr

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Ring open
Ring closed
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• LORAZEPAM
• Longer duration(10-20 hrs)
• DOC liver failure
• CLONZEPAM
• Can be used in status epilepticus
• Seizure adjuvant
• FLUMAZENIL
• Competetive antagonist, reverses all effects
• Has slight intrinsic agonist property so can
  precipitate seizures ( INVERSE AGONISM )
• Short half life 1 hr, may need repeated
  injections or infusion
• 0.2 mg ,then 0.1 mg increments ( dont exceed 3
  mg)

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PHENOTHIAZINES

• They produce the following effects
• Central antiemetic action
• Sedation
• Anxiolysis
• H2 receptor antagonism
• ? adrenergic anatagonism
• Anticholenergic properties
• Potentiation of opiod analgesia
• Side effects extrapyramidal effects
• Promethazine trimeprazine ( children)

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ANTIMUSCURANIC DRUGS

• Used for there
• Antisialogue action
• Avoid bradycardia due to
• anaesthetic agents
• surgical stimulus( occulocardiac reflex,
  mesenteric traction)
• ? blocked or digitalised patients
• Intermittent suxamethonium
• Avoid reflex bronchospasm ( COPD)
• Children ( vagal predominance)
• Disadvantages
• Dry mouth ,palpitations, arrthymias, blurred
  vision
• Central anticholergic syndrome

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ATROPINE HYOSCINE
Dose 0.6mg 0.4mg
potency 1 2
Duration 1-1.5hrs 1-1.5hrs
CNS Central anticholenergic syndrome Yes -excitatory Yes- depression Motion sickness,vestibular disorders
Tachycardia More (initial bradycardia- partail agonist- M2 receptors less
Antisialogue less more
Bronchodilatation More less
Physiological dead space more less
Mydriasis Less More(cycloplegia)
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• GYCOPYRROLATE
• Synthetic antimuscuranic drug
• Ionised quaternary amine so doesnot cross BBB
  placenta
• Prolonged duration of action- 6hrs
• No or Less tachycardia
• Ideal for cardiac patients ( IHD)
• Pupillary and other changes minimal
• Antisialagogue action more
• Dose 0.1 0.4 mg

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a2 RECEPTOR AGONISTS

• Action they decrease noradrenaline release in
  both central and peripheral symp. N.
• CNS
• tractus solitarius hypotension bradycardia
• Locus coerulus sedation
• Vagal nuclei
• Spinal supraspinal level(non opioid) -
  Analgesia
• Peripheral
• Decrease cardiac rate
• Decrease smooth muscle tone
• Increase coronary blood flow
• Induce diuresis
• Platelet aggregation

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Anaesthesia - a2 agonists

• Decrese MAC requirements
• Attenuate sympathoadrenal responses associated
  with intubation and surgery
• CLONIDINE( 100-300 mics orally)
• DEXMEDETOMEDINE
• AZEPEXOLE
• Side effects dry mouth, sedation,depression,
  bradycardia, rebound hypertension

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Other drugs

• NSAIDS
• Diclofenac
• Ketorolac
• TAM mixture children
• ( trimeprazine,atropine,mefenamic acid)

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• ANTIEMETICS
• ANTACIDS
• NEXT CALSSES

THANK YOU
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• 8. Atropine
• a) may cause bradycardiab) dilates the pupil in
  premedicant dosec) has a shorter duration of
  action than glycopyrrolated) increases the
  physiological dead spacee) has both muscarinic
  and nicotinic effects

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• TTTTF

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• Flumazenil
• a) may induce panic attacks in susceptible
  patientsb) has anticonvulsant activity in
  patients with epilepsyc) has a long duration of
  actiond) may cause nausea and vomitinge) has
  inverse agonist action at benzodiazepine receptors

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• TFFTT

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• Glycopyrrolate
• a) can act at central cholinergic receptorsb)
  can increase the physiological dead spacec) can
  dilate the pupild) is equally effective when
  given orallye) is five times more potent as an
  antisialagogue than atropine

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• FTTFT c) hence use with caution in glaucoma.

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• Midazolam
• a) is an anticonvulsant b) is lipid soluble at
  physiological pH c) has no active metabolites
  d) has an elimination half-life of 2-4 hours e)
  can be administered as nasal drops for
  premedication  

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• TTFTT

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• Hyoscine
• a) causes tachycardiab) causes sedationc)
  causes mydriasisd) is an antiemetice) has a
  weaker antisialagogue effect than atropine

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• TTTTF

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• Hyoscine hydrobromide causesa) antiemesisb)
  somnolencec) pupillary dilatationd) tachycardia
  followed by bradycardiae) extrapyramidal
  symptoms

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• TTTTF

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• Chlorpromazinea) can cause dystonic
  reactionsb) antagonises apomorphine-induced
  vomitingc) is a dopamine antagonist at the
  chemoreceptor trigger zoned) is a weak
  alpha-adrenergic agoniste) undergoes extensive
  first-pass metabolism

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• TTTFT

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• Clonidinea) is an alpha-2 receptor agonistb)
  is a dopamine antagonistc) causes tachycardiad)
  inhibits salivatione) reduces the minimum
  alveolar concentration of halothane 

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• TFFTT