Anesthesiology

Lec:-3

Premedication
Definition : -Drugs administration before anaesthesia.

 ● Aims ( Indications) (goal) :-

1-◗ Provide anxiolysis. (relief anxiety ) Ex.
(Diazepam ).

2-◗ Provide analgesia. ((relief pain) Ex. (Opioid )

(analgesia is Lack of sensation of pain from a normally painful
stimulus.).

3- ◗ Provide smooth induction of anaesthesia.

4-◗ Reduced upper airway and salivary gland secretions for successful
intubation. Ex. Atropine

5-◗ Reduced risk of awareness (awareness ) awareness is a

Postoperative recall of events occurring during general anaesthesia.) .

6- Reduced PONV.(postoperative nausea and vomiting )

Ex. ( Metoclopramide ).

7-◗ Reverse respiratory depression secondary to narcotics or sedative.

Ex. (flumazenil ).

8-◗ Reduced risks of specific complications associated with anaesthesia

and surgery or the preexisting patient’s condition. Ex.:-

A - Bradycardia, e.g. in ophthalmic surgery (Atropine ).

B - Hypertensive response to tracheal intubation (Antihypertensive ).

C - Aspiration pneumonitis. ( Aspiration of gastric contents is a

rare ,but potentially fatal, and oft en litigious event that can complicate
anesthesia.) Ex ( Antiemetic )

D - Adverse drug reactions, (side effects ) Ex. hypotension following

thiopental injection .
E – Bronchospasm e.g. (Asthmatic patients ).

F – DVT (deep venous thrombosis) e.g. (Anticoagulant drugs.).

 Drugs uses for premedication include:-

1-◗ Opioid analgesic drugs, e.g. morphine. ( analgesic and
sedative)

2-◗ Benzodiazepines, e.g. diazepam, lorazepam (sedative, anxiolytic).

3-◗ Anticholinergic drugs, e.g. atropine, hyoscine, glycopyrronium

(reduced salivation, reduced secretion.).

4-◗ Antiemetic drugs, e.g. metoclopramide ( Antiemetic ).

7-◗ H2 receptor antagonists, e.g. ranitidine, cimetidine (prophylactic

for Aspiration pneumonitis which increase gastric PH).

8-◗ Antacids, e.g. sodium citrate (prophylactic for Aspiration

pneumonitis).

9-◗ In addition, certain drugs already taken regularly by the patient are
usually continued up to and including the day of surgery, e.g.

 Antiarrhythmic drugs,
 Antihypertensive drugs,
 Drugs used in ischaemic heart disease
 Drugs used in asthma,
 Anticonvulsant drugs.

● Many anesthetists do not routinely prescribe premedication because of

disadvantages (Sid effect ) of preoperative drugs which include :-

( Side effects of premedication ):-

1) ◗ Excessive sedation.
2) ◗ Pain due to I.M injections.
3) ◗ Nausea and vomiting (with opioids).
4) ◗ Dry mouth with anticholinergic drugs.
5) ◗ Delayed recovery.
 Analgesic Agents

 Analgesia. Is Lack of sensation of pain from a normally painful

stimulus.
 Analgesic drugs are agents have ability to reduce pain sensation
without inducing sleep;

Analgesic Agents May be divided into:

A. ◗ Opioid analgesic drugs.

B. ◗ Prostaglandin synthesis inhibitors : it's called NSAIDs.(Non-
steroidal anti-inflammatory drugs), Aspirin,Voltarin
paracetamol.
C. ◗Adjuncts: i.e. reduce pain or pain sensation by alternative means:
e.g. antidepressant drugs, corticosteroids, gabapentin, muscle
relaxants, e.g. diazepam. Caffeine

 OPIOIDS
Opioid analgesic drugs. Opium and morphine have been used for
thousands of years; morphine was isolated in 1803 and codeine in 1832.

May be divided into ;-

 naturally occurring drugs (e.g. morphine, codeine),

 semisynthetic drugs e.g. diamorphine, dihydrocodeine)
 synthetic opioids e.g. Pethidine, fentanyl.
Clinical uses (Indications)
 General analgesic drugs, For premedication and Anesthetics in
large dose.
 Anxiolytics.
 Cough suppression.
 Treatment of chronic diarrhea.

Mechanisms of Action

Opioids bind to specific receptors (agonist) located throughout the

central nervous system and other tissues.

There are Four major opioid receptor types :-

 mu ( μ ) receptor .
 kappa (κ), receptor
 delta (δ), receptor .
 sigma (σ). receptor

binding of an Opioids (agonist) to an opioid receptor causes neural cell

membrane hyperpolarization (decrease neural activity).

Neuroendocrine response
The neuroendocrine stress response to surgical stimulation is measured in
terms of the secretion of specific hormones, including catecholamines,
antidiuretic hormone, thyroxin, insulin, and cortisol.

So Large doses of opioids (typically fentanyl or sufentanil) block the

release of these hormones in response to surgery .

1. Morphine hydrochloride.
Naturally Opioid analgesic drug, in use for thousands of years as
opium derived from poppy seeds.

Used mainly for

 Premedication and as an analgesic drug.

 Useful also in pulmonary oedema.
SEs:-

1. Histamine release,
2. Addiction.
3. Respiratory complication

2. Pethidine hydrochloride(meperidine).
Synthetic opioid analgesic drug, developed in Germany in 1939. One-
tenth as potent as morphine, with duration of 2–4 h and half-life of about
3–4h .hepatic metabolism to norpethidine, an active substance (half-life
20–40 h).

Used also in obstetric analgesia and anaesthesia (50– 150 mg im , max

400 mg/day), and has been given by subarachnoid injection (50–100 mg).

3. Fentanyl citrate.
Synthetic opioid analgesic drug, derived from Pethidine. Developed in
1960. Its 100 times as potent as morphine. used as perioperatively
analgesic, for sedation (e.g. on ICU) and in chronic pain as
Transdermal patch, sublingual lozenges and induction of anesthesia
in large dose.

 Use also in spinal opioid analgesia and anaesthesia

Postoperative respiratory depression is possible if large doses are used.

4. Tramadol
Tramadol is Synthetic opioid analgesic drug , Its analogue of codeine,
is a unique drug with a complex mode of action.

◗ It has one-tenth the potency of morphine.

◗ Tramadol is used in the treatment of moderate to severe pain.

◗ Tramadol is well absorbed orally, has little respiratory depression when

compared to with analgesic doses of morphine.

◗ Low potential for abuse and physical dependence, although abuse has
been reported. At present, it is not subject to controlled-drug restrictions

Non-steroidal anti-inflammatory drugs

(NSAIDs)
(Prostaglandin synthesis inhibitors)
Group of chemically dissimilar compounds have the fallowing similar
effects :-

 Anti-inflammatory.
 Antipyretic.
 Analgesic actions.
 Antiplatelet action.

 Mechanisms of Action
Arachidonic acid ( part of cell membrane) release during cellular damage
due to inflammation

Arachidonic acid and by aid cyclooxygenase (COX) enzyme it convert

to prostaglandin which is responsible of inflammatory symptom(pain,
redness etc. ) and thrombosis.

Agents that inhibit COX enzyme reduce prostaglandin release that for it
called Prostaglandin synthesis inhibitors or NSAID
COX enzyme is 2 types COX-1 and COX-2, have differing distribution
in tissue.

1. COX-1 are widely distributed throughout the body,

including the CNS ,gut and platelets.

2. COX-2 produced in response to inflammation.

SO :- Prostaglandin synthesis inhibitors( NSAIDs ) Classified into

1. Non selective COX inhibitors :- inhibit both types of enzyme

( aspirin , mefenamic acid, diclofenac ,indometacin ,ibuprofen)

2. selective COX-2 inhibitors : inhibit COX type 2 (acetaminophen

[paracetamol], celecoxib, etoricoxib)

1. Aspirin
2. Paracetamol (Acetaminophen).
3. Diclofenac sodium (Voltaire).
4. Peroxicam (feldin)
5. Meloxicam (mobic)
6. Ketorolac

 Anticholinergic (Antimuscarinic )
( Muscarinic antagonist) Drugs
Its Muscarinic antagonists, block muscarinic cholinergic (ACh)
receptors, (Muscarinic Parasympathetic receptors antagonists)
producing mydriasis and bronchodilatation, increasing heart rate,
and inhibiting salivary secretions (antisialagogue effect.).
Commonly used muscarinic antagonists include :-

 Atropine,
 Scopolamine,
 Glycopyrrolate,
 Ipratropium bromide.

 Indication:-
 1) During reversal of neuromuscular agent to avoid the risk of
profound bradycardia, heart block, and asystole. Ex(Atropine with
Neostigmine)
2) Atropine is potent treating for bradyarrhythmias.
3) Ipratropium bromide, is available in a metered-dose inhaler for the
treatment of bronchospasm (asthma , acute chronic obstructive
pulmonary disease).
4) Peptic ulcer healing, e.g. pirenzepine.
5) Antispasmodic

1. Atropine sulphate.
2. Hyoscine hydrobromide.
3. Glycopyrrolate.

 ANTACIDS
 Mechanism of Action
Antacids neutralize the acidity of gastric fluid by providing a base
(usually hydroxide, carbonate, bicarbonate, citrate, or trisilicate) that
reacts with hydrogen ions to form water. Antacids have an immediate
effect

 Clinical Uses
Common uses of antacids include the treatment of:-

 Gastric and duodenal ulcers,

 GERD.
 Zollinger– Ellison syndrome.
 In anesthesia provide protection against the harmful effects of
aspiration pneumonia by raising the pH of gastric contents.

 H2 -Receptor Antagonists
(Cimetidine, Ranitidine)
 Mechanism of Action
H 2 -Receptor antagonists include cimetidine, famotidine, nizatidine, and
ranitidine . These agents competitively inhibit histamine binding to H 2
receptors, thereby reducing gastric acid output and raising gastric pH.

 Clinical Uses
 Prophylactic for aspiration pneumonitis.

 Peptic duodenal and gastric ulcers.

 GERD.( gastroesophageal reflux disease)

 Zollinger– Ellison syndrome.

 PROTON PUMP INHIBITORS (PPIs)

(omeprazole, Lanzoprazol)
 Mechanism of Action
By decreasing gastric fluid volume and hydrogen ion content, H 2
blockers reduce the perioperative risk of aspiration pneumonia.

These agents, including (omeprazole , lansoprazole, rabeprazole ,

pantoprazole)

It bind to the proton pump of parietal cells in the gastric mucosa and
inhibit secretion of hydrogen ions and increase gastric PH educing gastric
acid output and raising gastric pH..

 Clinical Uses (indicated)

 Duodenal ulcer.
 GERD. gastroesophageal refl ux disease
 Zollinger– Ellison syndrome.

 METOCLOPRAMIDE (Meclodin)
 Mechanism of Action
Is Antiemetic drug, Metoclopramide acts peripherally on lower
esophageal sphincter by increases lower esophageal sphincter tone,
speeds gastric emptying, and lowers gastric and centrally as a dopamine
receptor antagonist.
Metoclopramide effective as prophylaxis for those at risk for aspiration
pneumonia and PONV.

 Side Effects
 Extrapyramidal uncommon and reversible.

 Metoclopramide-induced increases in prolactin secretion

(gynecomastia).

 Contraindication
patients with complete intestinal obstruction.

 5HT RECEPTOR ANTAGONISTS

(Ondansetron-Zofran)
Selectively block serotonin 5-HT 3 receptors, which are located
peripherally (abdominal vagal afferents) and centrally appear to play an
important role in the initiation of the vomiting reflex.

 Clinical Uses:- Administered at the end of surgery. All these

agents are effective antiemetics in the postoperative period.

 DEXAMETHASONE
Dexamethasone (Decadron) in doses as small as 4 mg has been shown
to be as effective as Ondansetron in reducing the incidence of PONV.

Dexamethasone should be given at induction time as opposed to the end

of surgery, and its mechanism of action is unclear.