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7. PHARMACOLOGY II-1.pdf
1. Kenya Medical Training College
Department of Orthopaedic and Trauma
Medicine
PHARMACOLOGY II
Year: 2022 Semester: 2 Session 7&8
Topic: Steroids and Opioids
Date: 17th May 2022
By: Carol Babu
2. Learning Objectives
1. Define steroids
2. Explain dosing of steroids
3. Classify steroids
4. Describe the mode of action of steroids
5. Discuss clinical uses and side effects of steroids
6. Define opioids
7. Classify opioids
8. Mechanism of action of opioids
9. Tolerance to opioids
10.Clinical uses of opioids
3. Steroids
• Corticosteroids are important therapeutic agents
used to treat allergic and inflammatory disorders
or to suppress undesirable or inappropriate
immune system actions.
• Synthetic drugs that closely resemble cortisol
4. • Physiologically, steroids are normally produced by
adrenal cortex through cholesterol metabolism and
are grouped into:
Glucocorticoids- Mainly hydrocortisone (Cortisol)
Mineralocorticoids- Aldosterone
Androgens – Dihydroepiandrosterone (DHEA) and
estrogen (sex hormones)
5. Glucocorticoids
• Cortisol is the prototype and is synthesized from
cholesterol mainly in zona fasciculate of the
adrenal glands.
• Normally 20mg of cortisol equivalent of 5mg of
predinsolone is secreted daily.
• It stimulates glucose production from proteins
(gluconeogenesis) and may stimulate fat acid
synthesis leading to fat deposition
6. Dosing for Glucocorticoids
• Hydrocortisone is the agent of choice for
physiologic replacement. Usual dosing strategies
to mimic normal cortisol production is 20 mg
each morning and 10 mg at 4:00 pm.
• During periods of stress, doses of up to 300 mg
daily may be required to prevent signs and
symptoms of adrenal insufficiency, including
hypoglycemia, hypotension, and cardiovascular
collapse.
7. Dosing for Glucocorticoids
• Dosage titration and optimization of chronic
therapy may be required to prevent symptoms.
• Fludrocortisone is a synthetic form of
aldosterone that can be added to improve overall
control of adrenal insufficiency and is generally
dosed at 0.1 mg daily.
8. Functional classification of steroids
1. Anabolic steroids(Androgens)
• Interact with androgen receptor and enhance
muscle mass, athletes performance, male sex
hormones
2. Glucocorticoids
• Regulate metabolism, immune function, anti-
inflammatory activity
10. 3. Mineralocorticoids
• Maintain blood volume and renal excretion
• Used for replacing steroids the body isn't
producing
• Example: Fludrocortisone
4. Progestins
• Development of female sex organs and
characteristics
12. Mode of action
• Inhibit the formation of leukotrienes and
prostaglandins (inflammatory mediators)
• Inhibit WBC migration
• Stabilisation of the mast cell by inhibiting the
release of allergic mediators.
14. Clinical Uses
• Steroids generally decrease inflammation and
reduce the activity of the immune system
• The indications include:
Addisons disease and Congenital Adrenal
Hyperplasia –Steroids are used as natural
replacements
Inflammatory bowel disease
Autoimmune diseases; SLE
Rheumatoid arthritis
18. • Hypertension
• Hyperglycemia
• Mood and behavior changes
• Others: Increased risk of developing cataracts,
blurred vision, glaucoma
19. Controlled drugs (Class I drugs)
Opioids
Terms used
• Opium-A derivative of poppy papaver
somniferum plant which has been used for social
and medicinal purposes to produce euphoria,
analgesia, sleep and to prevent diarrhoea
20. • Opiod -Substance whose physiological activities
are like opium
• Opiate -A derivative of opium
• Narcotics -Substances that cause stupor or
alteration of sensibility or consciousness.
Narcotics cause physical dependence
• Narcosis -Sleep
23. Mechanism of action
• Opiods act as first messengers and bind to receptors;
mu, delta, kappa and sigma
Pharmacological effects
1.CNS -Sensory and affective analgesia
Euphoria
Dysphoria
Dose dependence sedation but not amnesia
24. Causes dependence respiratory depression by
blunting the respiratory centre's response to
carbondioxide and hypoxia
Cough suppression
Miosis (pin point pupils) by binding to the
Edingerwestaphal nucleus near the lateral geniculate
body of the eye
Truncal rigidity
Convulsions
Hypothermia
25. 2. RS- Respiratory depression
3. CVS- Bradycardia, Vasodilation
NB:
• All opioids cause bradycardia and vasodilation
except pethidine which causes tachycardia because
of its effect on muscarinic receptors
• A patient in hypovolaemic shock will get worse if
given morphine resulting in bradycardia
• A patient with heart attack will have a worsened
tachycardia if given pethidine
26. 3. Smooth muscle
a) Stomach
Decreased gastric emptying
Decreased HCl acid secretion
b) Intestines
Opiods act as absorbagogues and increase viscosity
Increased resting tone
Decreases secretion
27. c) Large colon
Decreases peristalsis and cause constipation
d) Biliary tract
Biliary colic
Constriction of sphincter of Oddi
28. 4. Skin
Cutaneous dilatation esp. upper part of the body
Pruritus due to histamine release
5. Immune system
Chemotaxis of polymorphonuclear cells
Macrophage superoxide production
Mast cell serotonin release
Decreased lymphocyte antibody production and
release
29. Tolerance and dependence of opioids
Tolerance
• Decrease in response to the same dose or need to
increase the dose to get the same response
• Can be acute or chronic
• Acute tolerance is referred to as tachyphylaxis
30. Dependence
• Disturbance in the homeostatic set point of the
organism if the product of the drug is stopped.
• Physical dependence begins to occur within
24hrs esp. with morphine if given 4hrly
Addiction -Maladaptive behaviour
31. Therapeutic uses of opiods
• Analgesia -Potent analgesics in acute pain,
chronic pain as in terminal illnesses
• Pulmonary edema
• Antitussives (Cough suppression) such as
Dextromethophan
Codeine (Lictus codeine)
Levoproxyphan
• Anti-diarrhoeals - Loperamide, Diphenoxylate
33. Morphine
• The prototypical opioid
• Can be given orally, parenterally or intrathecally
• It is hydrophilic and has a delayed onset or peak
effect
34. Pharmacokinetics
• Oral morphine undergoes extensive presystemic
metabolism; conjugation in the gut wall and liver
with 20-30% of the drug reaching systemic
circulation
• Metabolism is mainly in the liver and kidney
• In the liver, it is conjugated to glucuronide
• It is excreted in bile with 10% of the drug
excreted renally
35. Bioavailability
• Oral as compared to parenteral route is 25 -33%
because the drug undergoes significant first pass
effect
• In acute painful conditions as in surgery, it
should be given parenterally
• In change over from Iv to oral, it is important to
note that only about 25% of the drug will be
available for systemic effect, therefore, multiply
the IV dose by 3-4 times the oral dose
36. Side effects
• Respiratory depression which is dose dependent
• Addiction
• Tolerance
• Morphine causes release of histamine
• Emetogenic
• Bradycardia
• Constipation
37. Clinical uses of Morphine
• Moderate to severe pain but do not relieve
neuropathic pain
• Post- surgery to relieve pain and anxiety
• Palliative care- chronic pain in cancer patients
38. Contraindications
• Hypothyroidism
• Hypotension
• Bronchial asthma
Drug interaction
• Morphine is potentiated by mono-amine oxidase
inhibitors (MAOI)-antidepressants
• Alcohol produces additive effect
• Neuromuscular blocking agents- Anaesthetics
Dose – 30ug/kg; 1-3mg IV, 10mg IM
39. Tolerance and Dependence
• Acquired tolerance develops over days with
continued frequent use and passes off over a few
days to weeks
• Physical dependence occurs within 24hrs if the
drug is given every 4hrs
• Abrupt withdrawal of morphine after chronic
exposure provokes rebound or a withdrawal
syndrome (“Noradrenergic storm”).
40. • Features of withdrawal syndrome include:
• Anxiety
• Restlessness
• Frequent yawning
• Profuse sweating
• Severe twitching of muscles
• Dilated pupils
• Leg and abdominal cramps
• Vomiting and diarrhoea
NB: Treatment for tolerance/dependence -
Methadone and monitoring of temp and BP
41. Morphine overdose
• Presents with respiratory depression
• Miosis
• Bradycardia
• Circulatory collapse from hypoxia
Treatment for overdose -Naloxone and close
cardiovascular monitoring
42. Pethidine
• Less potent than morphine
• Structurally resembles atropine
• It is available orally and parenterally
• It is more lipid soluble than morphine and
bioavailability is about 60%
• It causes addiction and tolerance
• Metabolism is in the liver and excretion of the
metabolites or parent drug is via bile and urine
• It is contraindicated in Space Occupying Lesion
(SOL) as it increases Inter Cranial Pressure (ICP). It
is also contraindicated in epileptic patients.
43. Drug interaction
• Pethidine inhibits the re-uptake of monoamines
leading to euphoria and circulatory collapse as
additive effects
• Pethidine does not interfere with uterine
contraction and is a useful drug as an obstetric
analgesia
• It is less likely to cause urinary retention and has
a shorter duration of analgesia compared to
morphine
Dose - Oral 50-100mg
- S/c or IM 25-100mg
44. • A synthetic analgesic opioid modified from
codeine
• Inhibits neuronal noradrenaline uptake and
enhances serotonin release
Mechanism of action
• Agonist at opioid receptors
45. Effects of tramadol
• More emetogenic-Causes nausea and vomiting
than the other opioids.
• Has less respiratory effect, less likely to
constipate and addict than the other opioids
• It is epileptogenic
• It is effective in mild-moderate pain but less
effective in severe pain
46. Potency
• Mild-moderate pain-Equivalent to pethidine
• Not very useful in severe pain for example pain
in bone fractures
NB: It is preferable to give it with an
antiemetic
48. Pharmacokinetics
• Diamorphine is usually converted to morphine
within minutes of administration
• The greater potency of diamorphine is due to the
metabolite 6-acetlymorphine which is active
• It causes rapid relief of pain
49. Uses of heroine
• Acute pain as in MI
• Palliative care in chronic pain
• Patient controlled analgesia
• Severe cough (Linctus)
Abuse -Heroine is the most potent of all
dependence producing opioids
50. Methadone
• Structurally similar to morphine
• It is a prodrug that is converted to morphine
• Has less respiratory depression
• It is less potent than morphine
• Its usefulness is in the management of opiod
addicts because it causes less physical
dependence
• Analgesia may last for as long as 24hrs (The
principal feature of methadone is its duration of
action)
51. • Methadone also causes vomiting but less
common than morphine
Uses
Opiod withdrawal syndrome
Maintenance programmes for opiod addicts
Chronic pain in palliative care
52. • Methylmorphine
• It binds to mu receptors with 10% being converted
to morphine
• Available as oral tablets, linctus
• Potency is 1/3 that of morphine
• Has cough suppressant effect - used as anti-tussive
in cough mixtures
• Has a long half life hence useful in long term pain
but lacks efficacy for severe pain
• Safe even in pts with head injury or brain tumors
and is occasionally combined with Aspirin or
paracetamol
53. Fentanyl
• A very potent opiod analgesic with potency being
1000 times that of morphine
• It is highly lipid soluble and is useful for severe pain
• It has less histamine releasing effect, therefore
confers cardiostability
• Has a short half life and is used intravenously
• It blunts the stress reponse to surgery
54. • It can cause or provoke asthmatic attack even
without histamine release
• Respiratory depression can come much later
despite its short half –life
• It can cause severe muscle rigidity
• Dose 0.5-1ug/kg
Assignment -Read on Sufentanyl, Remifentanyl
56. Naloxone
• A competitive antagonist of opioids at u, delta, k
and sigma receptors
• It is a derivative of oxymorphine
• It is used orally because it undergoes high
presystematic elimination when swallowed
• Given Iv, it causes reversal of opioid induced
respiratory depression in 1-2 min, reversal of
analgesia and depressed consciousness is slower.
57. • It has no abuse potential
• Very high doses cause:
Cardiovascular effects; high BP, vasoconstriction
and tachycardia.
Increased secretion of hormones; LH, FSH, GH
especially in women
• Can cause rebound release of catecholamines,
pulmonary edema and ventricular arrhythmias
58. Therapeutic uses
• Reversal of effects in opiod overdose
• Diagnosis of suspected opiod overdose or
dependence
• Treatment of alcoholism
• Dose 0.4mg as titrated dose slowly; starting at
0.1mg and then build up slowly
• For continous IVI, the dose is 2.5ug/kg/hr
59. Side effects
• Reversal of analgesia
• Reversal of anaesthesia
• Sympathetic arousal
• Nausea and vomiting when given rapidly
60. Naltrexone
• Available only in the oral formulation
• Has a longer half life with duration of effect
lasting 1-3 days
• The active metabolite is 6-Beta-naltrexone
• It does not reduce craving as does the agonist
methadone
61. Uses
• Alcohol dependence heroine intoxication by
blocking the euphoric effect and therefore
preventing relapse
