Transcript PREMEDICATION DRUGS

PREMEDICATION
DRUGS
DR.SUDHIR
MUBARAK AL KABEER HOSPITAL
PREMEDICATION- DEFINITION
Premedication refers to the administration of
drugs in the period 1 – 2 hours before
induction of anaesthesia
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
ALLAY ANXIETY & FEAR
 The best way to do this is by
non –pharmacological means
 Psychotherapy – Reassurance
 Benzodiazepines- most commonly used drugs
BENZODIAZEPINES
 Anxiolytic
 Amnesic
 Hypnotic
 Sedative
 Most commonly used premedication drug
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)
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 – ά ,β, γ
GABA binding site
Chloride channel
Benzodiazepine binding site
GABA binding site
Chloride channel
Benzodiazepine binding site
 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
Classification
 Long acting – diazepam
 Medium acting – temazepam
 Short acting - midazolam
DRUG
Half life
Active Half lifes
Terminal Metabol metaboli
tes
-ites
(hrs)
Dose
(mg)
Potency
FLUNITRAZEPAM
1
30
12-20
Y
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
LORAZEPAM
1
30
10-20
N
OXAZEPAM
30
1
6-25
N
25-30
50-120
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
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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
50 – 120 hrs
4-10 hrs
6-25 hrs
Midazolam
 Imidazo – benzodiazepine derivative
 It is this imidazole ring which imparts water solubility
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at pH < 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 hrclinically important only after prolonged infusion in
renal failure
 Midazoalm is 1.5 -2 times more potent than
diazepam ( ? )
 Dosage:
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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
Ring open
Ring closed
 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 ( don’t exceed 3
mg)
PHENOTHIAZINES
 They produce the following effects
 Central antiemetic action
 Sedation
 Anxiolysis
 H2 receptor antagonism
 ά – adrenergic anatagonism
 Anticholenergic properties
 Potentiation of opiod analgesia
 Side effects
: extrapyramidal effects
 Promethazine & trimeprazine ( children)
ANTIMUSCURANIC DRUGS
 Used for there :
 Antisialogue action
 Avoid bradycardia due to
 anaesthetic agents
 surgical stimulus( occulocardiac reflex, mesenteric
traction)
 Β blocked or digitalised patients
 Intermittent suxamethonium
 Avoid reflex bronchospasm ( COPD)
 Children ( vagal predominance)
 Disadvantages :
 Dry mouth ,palpitations, arrthymias, blurred vision
 Central anticholergic syndrome
ATROPINE
HYOSCINE
Dose
0.6mg
0.4mg
potency
1
2
Duration
1-1.5hrs
1-1.5hrs
CNS
Yes -excitatory
Yes- depression
Central anticholenergic
syndrome
Tachycardia
Motion sickness,vestibular
disorders
More
less
(initial bradycardia- partail
agonist- M2 receptors
Antisialogue
less
more
Bronchodilatation
More
less
Physiological
dead space
more
less
Mydriasis
Less
More(cycloplegia)
 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
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Antisialagogue action more
 Dose
0.1 – 0.4 mg
α2 RECEPTOR AGONISTS
 Action : they decrease noradrenaline release in both
central and peripheral symp. N.
 CNS :
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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
Anaesthesia - α2 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
Other drugs
 NSAIDS
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Diclofenac
Ketorolac
TAM mixture – children
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( trimeprazine,atropine,mefenamic acid)
 ANTIEMETICS
 ANTACIDS
 NEXT CALSSES
 8. Atropine:
 a) may cause bradycardia
b) dilates the pupil in premedicant dose
c) has a shorter duration of action than
glycopyrrolate
d) increases the physiological dead space
e) has both muscarinic and nicotinic effects
 TTTTF
 Flumazenil:
 a) may induce panic attacks in susceptible
patients
b) has anticonvulsant activity in patients with
epilepsy
c) has a long duration of action
d) may cause nausea and vomiting
e) has inverse agonist action at
benzodiazepine receptors
 TFFTT
 Glycopyrrolate:
 a) can act at central cholinergic receptors
b) can increase the physiological dead space
c) can dilate the pupil
d) is equally effective when given orally
e) is five times more potent as an
antisialagogue than atropine
 FTTFT c) hence use with caution in
glaucoma.
 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
 TTFTT
 Hyoscine:
 a) causes tachycardia
b) causes sedation
c) causes mydriasis
d) is an antiemetic
e) has a weaker antisialagogue effect than
atropine
 TTTTF
 Hyoscine hydrobromide causes:
a) antiemesis
b) somnolence
c) pupillary dilatation
d) tachycardia followed by bradycardia
e) extrapyramidal symptoms
 TTTTF
 Chlorpromazine:
a) can cause dystonic reactions
b) antagonises apomorphine-induced
vomiting
c) is a dopamine antagonist at the
chemoreceptor trigger zone
d) is a weak alpha-adrenergic agonist
e) undergoes extensive first-pass metabolism
 TTTFT
 Clonidine:
a) is an alpha-2 receptor agonist
b) is a dopamine antagonist
c) causes tachycardia
d) inhibits salivation
e) reduces the minimum alveolar
concentration of halothane
 TFFTT