Материал: MasterPass _ Pharmacology in 7 Days for Medical Students
THERAPEUTIC USES AND SIDE EFFECTS
Cyclophosphamide: side effects
1Bone marrow suppression (→ pancytopenia).
2Haemorrhagic cystitis. It is caused by one of the break down products of cyclophosphamide called acrolein. This side effect can be avoided by concomitant use of mercaptoethanesulfonate (mesna) and advising the patient to take lot of drinking water. Mesna ‘traps’ acrolein and thus reduces the incidence of haemorrhagic cystitis – an example of ‘rescue therapy’.
3Sterility.
4Alopecia.
5Cardiac dysfunction.
6Pulmonary toxicity.
7Syndrome of inappropriate antidiuretic hormone secretion (SIADH).
8NVD.
Doxorubicin and daunorubicin: side effects
1Bone marrow suppression (→ pancytopenia).
2The most distinctive side effect of these anthracyclines is cardiotoxicity (arrhythmias; cardiomyopathy; CHF). It can be avoided by ‘rescue therapy’ with dexrazoxane. As we know that anthracyclines generate free radicals, which in turn block the synthesis of RNA and DNA. Dexrazoxane administration inhibits free radical formation and thus prevents cardiotoxicity.
3Alopecia.
4NVD.
Amphotericin B: therapeutic uses
1As an I/V infusion: Amongst all the antifungals, amphotericin B has the widest spectrum of activity. It is used for a variety of systemic fungal infections caused by Aspergillus, Blastomyces, Candida albicans, Cryptococcus, Histoplasma and Mucor.
2Intrathecal infusion for fungal meningitis. Intrathecal infusion is dangerous as it can lead to neurotoxicity in the form of neurological damage and seizures.
3Topically: For mycotic corneal ulcers and keratitis.
Nystatin: therapeutic uses
1Oral candidiasis.
2Oesophageal candidiasis (in immunocompromised patients).
Griseofulvin: therapeutic uses
1 Dermatophytosis of skin and hair.
Metoclopramide: therapeutic uses
1To prevent NV due to gastroduodenal, hepatic and biliary diseases.
2Used in some patients with non-ulcer dyspepsia.
3Gastro-esophageal reflux.
4In post-op conditions.
5In high doses to prevent NV associated with cytotoxic drug therapy/radiotherapy.
6Used in radiology for speeding the transit of barium during intestinal followthrough examination.
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PHARMACOLOGY IN 7 DAYS FOR MEDICAL STUDENTS
Metoclopramide: side effects
1Extrapyramidal side effects (tremors; rigidity; bradykinesia). The classical symptoms of Parkinsonism are the same (i.e. tremors; rigidity; bradykinesia).
2Drowsiness.
3Hyperprolactinemia.
Sodium nitroprusside: therapeutic uses
1 It is only used in hypertensive emergencies as an intravenous infusion.
Sodium nitroprusside: side effects
1Excessive hypotension.
2Tachycardia.
3When infusion is continued for several days, it can lead to accumulation of cyanide/ thiocyanate in the blood.
Oxytocin: therapeutic uses
1Induction/augmentation of labour.
2Post-partum uterine haemorrhage.
3Incomplete abortion.
4Impaired milk ejection.
5Oxytocin challenge test (to know placental circulatory reservoirs). An abnormal response suggests intrauterine growth retardation and may require immediate caesarean delivery.
Prostaglandins (PGs): therapeutic uses
1Facilitation of labour at term (softening of cervix).
2Induction of labour.
3Abortifacient (vaginal suppository or oral dinoprostone, mifepristone).
Ergometrine: therapeutic uses
1 PPH (if oxytocin is ineffective to control atonic uterus). Dose: 150–250microgram I/V.
Aluminium hydroxide: therapeutic uses
1Peptic ulcer disease.
2Hyperphosphatemia in renal impairment.
Sucralfate: therapeutic uses
1Peptic ulcer disease.
2Upper GI bleeding in critically ill patients.
3Prevention of stress-related bleeding.
Misoprostol: therapeutic uses
1 NSAID-induced peptic ulcers (incidence 20% is reduced to 3%).
Colloidal bismuth compounds: therapeutic uses
1Peptic ulcer disease.
2Eradication of H. Pylori.
3Traveller’s diarrhoea.
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5
Drug differences
Table 5.1 Differences between atropine and hyoscine
|
Atropine |
Hyoscine |
Source: |
Atropa belladonna and |
Hyoscyamus niger and |
|
Dhatura stramonium |
Scopolia canolica |
Chemistry: |
Ester of tropic acid and |
Ester of tropic acid and |
|
tropine |
scopine |
Mechanism of action: |
Antimuscarinic, competitive |
Antimuscarinic, competitive |
|
antagonist of acetylcholine |
antagonist of acetylcholine |
Duration of action: |
Prolong |
Short |
Peripheral antimuscarinic |
More prominent on heart, |
More prominent on eyes, |
action: |
GIT and bronchial muscle |
salivary and bronchial |
|
|
secretion and sweat |
Action on CNS: |
Stimulation, followed by |
Depression from the |
|
depression |
beginning (in the presence |
|
|
of pain, there may be |
|
|
excitement) |
Loss of memory: |
Not seen |
It causes amnesia to recent |
|
|
events. It is thus more |
|
|
commonly used as a pre- |
|
|
anaesthetic medication as |
|
|
compared to atropine |
Motion sickness and |
Less useful |
More useful |
Parkinsonism: |
|
|
Toxicity: |
Restlessness, excitement, |
Drowsiness |
|
mania and delirium |
|
Dose: |
0.25Ð2 mg |
0.3Ð0.6 mg |
|
|
|
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Table 5.2 Differences between non-opioids (NSAIDs) and opioids
|
Non-opioids (NSAIDs) |
Opioids |
Source: |
Synthetic |
Natural opium alkaloids/semi-synthetic/synthetic morphine |
|
|
substitutes |
Structure: |
Heterogeneous |
Phenanthrene compounds, benzyl-isoquinoline compounds |
Type of pain |
Somatic pain arising from musculoskeletal structures |
Deep visceral pain |
relieved: |
|
|
Mechanism of |
¥ |
Inhibition of prostaglandin synthesis by inhibiting the cyclo- |
action: |
|
oxygenase enzyme |
|
¥ |
Inhibits generation of nociception by inhibiting the peripheral |
|
|
nociceptors |
|
¥ |
No action on speciÞc opioid receptors (µ, κ, δ, ε, σ) |
¥Decreased nociception input, decreased processing and integration, decreased transmission, decreased perception and decreased emotional reaction to pain. Decreased release of neurotransmitters (especially excitatory neurotransmitters like glutamic acid). By causing hyper-polarisation due to increase in potassium efßux
¥Acts on opioid receptors (µ, κ, δ, ε, σ)
CNS devpression: |
Do not depress CNS |
Depress CNS |
(continued)
STUDENTS MEDICAL FOR DAYS 7 IN PHARMACOLOGY
Table 5.2 Differences between non-opioids (NSAIDs) and opioids (continued)
Non-opioids (NSAIDs) |
Opioids |
Pharmacological ¥ Acts as analgesics, antipyretic, anti-inßammatory, antiplatelet actions and effects: (at low doses) and uricosuric (at high doses)
¥No antispasmodic effect on GIT smooth muscles (unlike morphine which commonly causes constipation, NSAIDs do not cause constipation)
¥Acts only as analgesics. Also produce euphoria, sedation, hypnosis and cough suppression. No antipyretic and antiinßammatory effects
¥Morphine-like alkaloids produce constipation through decreased intestinal peristalsis which is mediated by effects on opioids receptors in the enteric nervous system. Hence clinically used as antidiarrhoeal agents
¥Also opioids alone produce contraction of sphincter pupillae (→ miosis), truncal rigidly, contraction of biliary smooth muscle (→ biliary colic), contraction of sphincter of Oddi (reßux of biliary and pancreatic secretion) and
relaxation of uterine smooth muscle (→ prolongation of labour)
Tolerance and |
Do not produce tolerance/dependence |
dependence: |
|
Withdrawal |
Do not produce withdrawal syndrome |
syndrome: |
|
Side effects: |
Mainly due to inhibition of prostaglandin synthesis like peptic |
|
ulceration, upper GI bleed, bleeding tendency, precipitation |
|
of an acute attack of asthma (due to ↑ synthesis of |
|
leukotrienes), ReyeÕs syndrome (hepatic fatty degeneration and |
|
encephalopathy), ARF, interstitial nephritis, respiratory alkalosis |
|
(at high doses) and metabolic acidosis (at toxic doses) |
Produce tolerance/dependence
Produce withdrawal syndrome
Mainly due to CNS depression. Most serious is depression of the respiratory centre; others include ↑ ICP, postural hypotension, urinary retention, constipation, itching around nose and urticaria
DIFFERENCES DRUG
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