PREMEDICATION

PRESENTER-DR.SRISHTI
MODERATOR-DR.R.PAL( PROFESSOR)
DR.P. JAIN(ASSOCIATE PROFESSOR)
DEFINITION-Premedication is the administration of medication before a
treatment or procedure. It is commonly used prior to anesthesia for surgery.
 HISTORY OF PREMEDICATION
• The concept of anesthetic premedication was initially developed to counteract the side effects of general
anesthesia when ether and chloroform were widely used as inhalational anesthetics in the 1850 s.

• Diethyl ether has long duration of induction time. Patients often suffered a long period of involuntary
movement, anxious feeling, and excessive salivation before they could finally be put to sleep. Such
behaviors can be attributed mainly to the high blood solubility of diethyl ether.
• Guedel's signs were used to describe the long induction time of ether anesthesia, which included four
stages (analgesia stage, excitement stage, surgical anesthesia stage, and respiratory paralysis stage)

in 1864 it was found that subcutaneous morphine can relax patients and intensify chloroform anesthesia.
 CURRENT PRACTICE OF PREMEDICATION
In current practice of anesthesia patient is premedicated with a purpose not as
a routine procedure . This can be explained because
• the induction time of general anesthesia in current practice is much shorter
than that of ether anesthesia.
• now routinely intravenous anesthetics are used as induction agents; for
most intravenous agents, onset of action occurs within 60 seconds.
• When patients are premedicated, they must be put into surveillance to
monitor the vital signs and the potential side effects of medication
 AIMS OF PREMEDICATION

1. To produce Amnesia & Analgesia

2. Provide effective prophylaxis against Post operative nausea
vomiting(PONV)
3. To decrease anxiety
4. Decrease gastric pH and risk of regurgitation and aspiration
5. Prevent allergic reactions,
6. Suppress reflex responses to surgical stimuli,
7. Decrease anesthetic requirement for the surgical procedure
 Factors to be considered before premedication

• Patient physical status

• Age
• Type of surgery
• Timing of surgery
• History of drug allergy , nausea and vomiting
 ANXIOLYSIS AND SEDATION
• Relieving anxiety is most important goal in present day practice. Both
psychological and pharmacological approaches are effective in decreasing
preoperative anxiety.
• Pre operative visit of anesthetist clearing patients doubts ,fears myths
,explaining technique can be very helpful in decreasing anxirty.
• Pharmacological approach include following class of drugs
1. Benzodiazepine(midazolam ,lorazepam , diazepam)
2. Barbiturates(phenobarbitone)
3. Others (promethazine)
 BENZODIAZEPINES
• Benzodiazepine binds to the GABA A (interface betweenα and γ subunit)
receptor increases the frequency of openings of the associated chloride ion
channel. Benzodiazepine-receptor binding by an agonist facilitates binding of
GABA to its receptor.
• Chemical structure of benzodiazepines includes a benzene ring and a seven
member diazepine ring ,imidazole ring of midazolam contributes to its
water solubility. Diazepam and lorazepam are insoluble in water so
parenteral preparations contain propylene glycol.
AGENT USE ROUTE DOSE
MIDAZOLAM Premedication oral 0.25–1 mg/kg
Intravenous 0.05–0.1 mg/kg
intranasal 0.2–0.3 mg/kg

buccal 0.07 mg/kg

sublingual 0.1 mg/kg

LORAZEPAM Premedication oral 0.05 mg/kg

DIAZEPAM Premedication oral 0.2-0.5 mg/kg
i.v. 0.1-0.2 mg/kg
ALPRAZOLAM premedication Oral 0.5 mg

• Midazolam is most commonly used premedication in adults and children, due to quicker onset and
short duration of action.
• Time of action: 2-3 minutes
• Duration of action:30-50 minutes
• Diazepam and lorazepam have long half-life& longer duration because of their affinity for the receptor.Because of their
duration, lorazepam and diazepam are not useful in instances in which rapid awakening is necessary, such as outpatient
anesthesia.
• Clinical effects comes 30 to 60 minutes after oral administration of lorazepam. Peak plasma concentrations may not
occur until 2 to 4 hours.
• Their use may be more suited for those patients already taking chronic benzodiazepines for anxiety and who may need
the anxiolysis prior to arrival in the preoperative area.
• Metabolism- by hepatic microsomal enzymes,(hydroxylation) metabolites of benzodiazepines are excreted chiefly in
the urine.
• SIDE EFFECTS
1. Cardiovascular-Benzodiazepines decreases arterial blood pressure , cardiac output, and peripheral vascular resistance
slightly.
2. Respiratory-depress the ventilatory response to CO2. Ventilation must be monitored in all patients receiving
intravenous benzodiazepines.
3. Nausea/vomitsing
4. Hiccups
5. Cough
 ANALGESIA

• AGENTS COMMONLY USED IN PRE MEDICATION ARE

1. OPIOIDS
2. NSAIDS{diclofenac ,paracetamol, ketorolac }
 ANALGESIA
OPIOIDS

• Opioids are agents of choice for pre operative analgesia

• Four major opioid receptor types have been identified - mu (μ, with subtypes μ1 and μ2), kappa (κ), delta (δ),
and sigma (σ).
• Present in brain and spinal cord also vascular tissues, cardia, airway/lung, gut and cells of the immune system

• Mechanism of action -opioid receptors couple to G proteins; Acute opioid effects are mediated by inhibition of
adenylyl cyclase and activation of phospholipase C. Opioids inhibit voltage-gated calcium channels. Opioid
receptor activation inhibits the presynaptic release &postsynaptic response to excitatory neurotransmitters (eg,
acetylcholine s, substance P) released by nociceptive neurons.
Exogenous opioid Agonists: Morphine, Codeine, Meperidine, Fentanyl, Sufentanil, Remifentanil, Methadone,
Tramadol.
According to the strength or potency based on the plasma concentrations at which they exert their effects the plasma
concentration causing a 50% effect opioid can be classified as:-
1. Strong - fentanyl, sufentanil, and remifentanil
2. intermediate - morphine, methadone, oxycodone, and buprenorphine
3. Weak -codeine and tramadol.

• Opioids are weak bases. When dissolved in solution, they are dissociated into ionized and free-base fractions, with
the relative proportions depending on the pH and p Ka

Ionized fraction
Less lipid soluble
•Attached to plasma proteins and not available to diffuse to the action site (the receptor)
However -it is the “effective” form of the molecule –the receptor recognizes the ionized form

Base (free) fraction

More lipid soluble –free to diffuse to the action site thus highly lipid-soluble opioids have a more rapid onset of action
• ABSORPTION –oral , rectal ,SC , IM routes,Nasal route.,patch (fentanyl)
• METABOLISM- (liver) CYP3A4 & CYP2D6 are involved in biotransformation to metabolite like
morphine-6-glucuronide, morphine-3-glucuronide
• EXCRETION- M6G & M3G are excreted by glomerular filtration
• Chronic renal failure can cause elevated levels of these metabolites & lead to adverse effects like
seizures &CNS depression DRUG DOSE
• DOSE Sublingual morphine 0.5 mg/kg
Intravenous morphine 0.05–0.1 mg/kg

SC OR IM morphine 0.1–0.2 mg/kg

fentanyl 1-3 mg/kg
Morphine( oral) 10-30mg every 4 hrly
Tramodol (iv) 2-8 mg/kg
MORPHINE FENTANYL
Onset 1-2 min onset-<60 sec
Half life 2hrs Half life 90 min
Duration upto 3-4 hrs duration about 30-60 min
EFFECTS
•CVS-hypotension, secondary to a decrease in the systemic vascular resistance,
•RS-respiratory depression with decreased ventilatory response to hypoxia and hypercapnia
•CNS- Morphine is a potent analgesic agent and may also cause drowsiness,relief of anxiety,
and euphoria ,miosis.
•GIT AND UT-Opioids decreases gastrointestinal motility and decreases gastric acid,
•biliary, and pancreatic secretions. These increases the tone of the ureters, bladder detrusor
muscle,
•and sphincter, and may precipitate urinary retention.
SIDE-EFFECTS
Respiratory depression, nausea and vomiting, hallucinations , pruritis,constipatin ,dry mouth.
 DICLOFENAC
• It is a phenylacetic acid derivative.
• Forms available-tablets ,IV ,IM injection ,gel ,suppositories,patch
• Main actions -Analgesic, anti-inflammatory, and antipyretic.
• Indicated for management of mild-to-moderate pain and moderate-to-
severe pain alone or in combination with opioid analgesics or paracetamol.
Used to decrease pain sensation without loss of consciousness.
• Mode of action -Diclofenac is a non-specific inhibitor of COX which converts
arachidonic acid to cyclic endoperoxidases, thus preventing the formation
of prostaglandins, thromboxanes , and prostacylin. Prostaglandins are
involved in the sensitization of peripheral pain receptors to noxious stimuli.
• Dose 1-1.5 mg/kg
• Metabolism and excretion –through liver (hydroxylation),and renal route.
• GIT-Diclofenac causes gastrointestinal damage , dyspepsia, nausea, bleeding from gastric and
duodenal vessels, mucosal ulceration, perforation, and diarrhoea .
• RS -Bronchoconstriction and eosinophilia
• GU -The plasma renin activity and aldosterone concentrations are reduced
• Metabolic/other Diclofenac interferes with neutrophil function, reversibly inhibits platelet aggregation
SIDE EFFECTS
increase incidence of MI , HTN , heart failure
Affects platelet function
GI side effects-ulcers,perforation
Renal injury-may cause AKI
 PARACETAMOL
• It is acetanilide derivative.
• Preparations –tablets, suppositories , intravenous
• Mechanism of action-The drug inhibits
• COX isoenzymes COX-1 and COX-2, particularly in areas of low inflammation.
Prostaglandin synthesis within the CNS (Anterior hypothalamus)is inhibited which
accounts for the antipyretic effect .As analgesic acts centrally by activating serotonergic
pathways &peripherally by blocking impulse generation within the bradykinin-sensitive
chemoreceptors responsible for the generation of afferent nociceptive impulses.
• DOSE 10-30mg/kg
• half-life is 2–4 hours in normal adults,4-5 hrs in neonates
• METABOLISM &EXCRETION- Occurs predominantly in the liver (glucuronide) by
CYP2E1 to highly reactive intermediate metabolite (N-acetyl-p-benzo-quinoneimine
(NAPQI)) which, in turn, is inactivated by conjugation.
excretion is through kidney.
• Toxicity/side effectss Gastrointestinal disturbances, skin reactions, and
idiosyncratic haemopoietic disorders (thrombocytopenia, neutropenia) may
occur with therapeutic doses.
• Overdose of paracetamol leads to Hepatoxicity due to metabolite NAPQI
that causes direct liver cell damage and glutathione depletion leading to liver
failure.
• N-acetyl cysteine is the drug of choice in toxicity which inhibits NAPQI and
replenish the glutathione(precursor for glutathione)
 ASPIRATION PREVENTION

• Anesthetic agents can decrease lower esophageal sphincter tone and decrease gag reflex,
increasing the risk for passive aspiration.
• Approaches to prevent aspiration-
1. Fasting
2. Rapid sequence induction
3. Cricoid pressure(Sellick maneuver)
4. Drugs- Different combinations of premedications are used to,reduce gastric volume, increase
gastric pH, or augment lower esophageal sphincter tone.
These agents include antihistamines, antacids,proton pump inhibitors and metoclopramide .
 PROTON PUMP INHIBITORS
• These agents, including omeprazole , lansoprazole ,rabeprazole , esomeprazole and
pantoprazole .
• They bind to proton pump of parietal cells in the gastric mucosa and inhibit secretion of
hydrogen ions.
• PANTOPRAZOLE OMEPRAZOLE
Dose 40 mg dose20 mg
Onset <1 hrs 2-3 hrs
Duration >24 hrs duration>24 hrs

SIDE EFFECT-nausea, abdominal pain, constipation ,Diarrhoea

• These are primarily eliminated by the liver, repeat doses should be decreased in patients with
severe liver impairment.
• PPIs can interfere with hepatic P-450 enzymes, decreasing the clearance of diazepam,
warfarin, and phenytoin.
• PPI can decrease clopidogrel effectiveness,as clopidogrel require P-450 for its activation.
 H2-Receptor Antagonists
• H2-Receptor antagonists include ranitidine , cimetidine and famotidine,
nizatidine.
• Competitive inhibition of histamine at H2-receptors of the gastric parietal
cells, which inhibits gastric acid secretion, gastric volume, and decreases
hydrogen ion concentration.
• These drugs affect the pH of only those gastric secretions that occur after
their administration.
• Adult dose of ranitidine (oral) 50 mg ,onset 1-2 hrs , duration 10-12 hrs.
• Binds to the cytochrome P-450 and affect metabolism of drugs like
propranolol, diazepam, theophylline, phenobarbital, warfarin, and
phenytoin.
• Side effects-long term use may cause hepatotoxicity, nephritisb,
thrombocytopenia , granulocytopenia.s
 PROKINETIC-METOCLOPRAMIDE

• Metoclopramide peripherally facilitates acetylcholine transmission at selective

muscarinic receptors and centrally as a dopamine receptor antagonist.
• Its action as a prokinetic agent is abolished by anticholinergic agents. It does not
stimulate secrtions.
• It also acts as anti emetic agent by blocking dopamine receptors in chemoreceptive
trigger zone.
• metoclopramide increases lower esophageal sphincter tone, speeds gastric emptying, and
lowers gastric fluid volume.
• Dose-(0.25 mg/kg) onset of action is 3-5 mins(i.v.)
• Side effects-Rapid intravenous injection may cause abdominal cramping, Sedation,
• nervousness, and extrapyramidal signs.
• It is contraindicated in patients with complete intestinal obstruction, parkinson disease.
• metoclopramide is excreted in the urine, its dose should be decreased in patients with
kidney dysfunction
 ANTACIDS
• Antacids neutralize the acidity of gastric fluid by providing a base
(hydroxide, carbonate, bicarbonate, citrate) that reacts with hydrogen ions
to form water.
• DOSE-15 to 30 mL orally, 15 to 30 min prior to induction
• Antacids provide protection against the harmful effects of aspiration
pneumonia by raising the pH of gastric contents but they increase
intragastric volume.
• Aspiration of particulate antacids (aluminum or magnesium hydroxide)
produces abnormalities in lung function . Nonparticulate antacids (sodium
citrate or sodium bicarbonate) are much less damaging to lung alveoli if
aspirated.
 POST OPERATIVE NAUSEA VOMITING(PONV)
5-HT3 RECEPTOR ANTAGONISTS
Serotonin, 5-hydroxytryptamine (5-HT), is present in large quantities in
platelets and the GI tract . It is also important neurotransmitter in multiple
area of CNS.
1. 5-HT3 receptor mediates vomiting and is found in the GI tract and the
brain .
2. The 5-HT2Areceptors mediates smooth muscle contraction
&plateletaggregation
3. 5-HT4 receptors in the GI tract mediate secretion and peristalsis
4. 5-HT6 and 5-HT7 receptors present in the limbic system (depression).
• All ex receptor are coupled to G proteins but 5-HT3 receptor are mediated
via an ion channel.
• Ondansetron, granisetron, tropisetron, and dolasetron selectively block
serotonin 5-HT3 receptors
• These are located peripherally (abdomen)and centrally (chemoreceptor trigger
zone of the area postrema and the nucleus tractus solitarius).
• The 5-HT3 receptors of the chemoreceptor trigger zone in the
area postrema reside outside the blood–brain barrier .
• Dose- 4-8 mg over 2-5 minutes before induction of anesthesia
• Half life- 3-4 hours
SIDE EFFECTS
1. Most common side effect is headache and diarrhea
2.Transient increase in plasma concentration of liver transaminase enzyme
3. Cardiac arrhythmias are reported after iv administration
4.Slight QT interval prolongation
DEXAMETHASONE
• Dexamethasone in doses as small as 4 mg has been shown to be as
effective as ondansetron in reducing the incidence of PONV.
• Its mechanism of action is unclear.
• It should be given at induction.
• Obese and diabetic patient are at increased risk of hyperglycemia when
they receive single dose of dexamethasone.
 ANTISIALOGOGUES
• They decrease the secretions and helps reduce vagally mediated bradycardia and hypotension.
• These agents are atropine ,glycopyrrolate, scopolamine , hyoscine
• Mechanism of action-anticholinergics binds to the acetylcholine receptors & competitively blocks
binding by acetylcholine and prevents receptor activation.
• EFFECTS
A. Cardiovascular
Blockade of muscarinic receptors in the sinoatrial node produces tachycardia.
This effect is especially useful in reversing bradycardia due to vagal reflexes.
B. Respiratory
The anticholinergics inhibit respiratory tract secretions, from the nose to the
Bronchi.
C. Cerebral
Anticholinergic medications can cause stimulation or depression, depending on drug choice and
dosage. Cerebral stimulation may present as excitation, restlessness, or hallucinations. Cerebral
depression, including sedation and amnesia, are prominent after scopolamine.
• D. Gastrointestinal
Salivary and gastric secretions are reduced by anticholinergic drug . Decreased intestinal motility
and peristalsis prolong gastric emptying time.
• E. Ophthalmic
Anticholinergics cause mydriasis (pupillary dilation) and cycloplegia (an inability to accommodate
to near vision).
• F. Genitourinary
Anticholinergics decrease ureter and bladder tone as a result of smooth
muscle relaxation and lead to urinary retention.

ATROPINE
Atropine is a tertiary amine.
Dose-0.01 to 0.02 mg/kg

Metabolism: Liver and Excreted inUrine

Half-Life: 2.5 hrs
Onset: <1 hrs & Duration: 4hrs
Atropine has particularly potent effects on the heart and bronchial smooth
muscle and is the most efficacious anticholinergic for treating bradyarrhythmia’s.

• SIDE EFFECT-Blurred vision , Dry eyes , Ocular pressure increased , Constipation

• CONTRAINDICATION-angle closure glaucoma , myasthenia gravis, obstructive uropathy.
GLYCOPYRROLATE
• premedication dose is 0.005 to 0.01 mg/kg up to 0.2 to 0.3 mg in adults
• Onset: 1 min (IV)
• Duration 30 mins
• glycopyrrolate cannot cross the blood–brain barrier and is almost devoid of central nervous
system and ophthalmic activity due to its quaternary structure.
• SIDE EFFECT Anticholinergic symptoms (mydriasis, hyperthermia, tachycardia, cardiac
arrhythmia) ,Dry mouth , Dry skin , Anhidrosis , Flushing
• Contraindication-angle-closure glaucoma, obstructive uropathy, GI obstruction, paralytic ileus,
intestinal atony of elderly.