Материал: MasterPass _ Pharmacology in 7 Days for Medical Students
DRUG DIFFERENCES
Table 5.7 Differences between methyl dopa and clonidine
Methyldopa |
Clonidine |
Structure: |
Structural analogue to levodopa |
Mechanism of |
It is a pro-drug. After having |
action: |
being converted to alpha-methyl- |
|
norepinephrine, it acts as an |
|
agonist on the postsynaptic |
|
α2-receptors in the CNS → ↓ |
|
sympathetic outßow from the |
|
centre to periphery |
2-imidazole derivative
It is an active drug that acts as an agonist on the postsynaptic α2-receptors in the CNS → ↓ sympathetic outßow from the centre to periphery
Pharmacokinetics: On oral administration, absorption is incomplete and slow with extensive Þrst-pass metabolism. Elimination is mainly through liver metabolism and some through renal excretion
Being lipid-soluble, GI absorption of clonidine is rapid. Elimination is mainly through renal excretion
Route of |
Oral, sometimes I/V in |
Oral and transdermal (I the form |
administration: |
emergencies |
of patch), but never I/V |
T½ |
2hrs |
8Ð12hrs |
Bioavailability: |
25% |
95% |
Dose-response |
Increasing doses are not more |
Increasing doses are more |
curved: |
effective |
effective (and also more toxic) |
Reduction in |
No |
Yes |
dosage required |
|
|
in moderate renal |
|
|
insufÞciency: |
|
|
Pharmacologic It reduces blood pressure chießy effects: by reducing peripheral vascular resistance
It reduces blood pressure both by reducing heart rate (and thus cardiac output) and peripheral vascular resistance
Therapeutic uses: |
Mild to moderate cases of |
Mild to moderate cases of |
|
hypertension, hypertensive crisis |
hypertension, diabetic diarrhoea |
|
and carcinoid syndrome |
(→ ↑ Na+ and H2O reabsorption |
|
|
and ↓ secretion of HCO3) |
|
|
and alcohol/tobacco/opioid |
|
|
withdrawal syndrome. It is |
|
|
contraindicated in hypertensive |
|
|
crisis |
|
|
|
|
|
(continued) |
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PHARMACOLOGY IN 7 DAYS FOR MEDICAL STUDENTS
Methyldopa |
Clonidine |
Toxicity: Causes sedation (commonest side effect), extrapyramidal signs (Parkinsonism), ↑ prolactin secretion (→ lactation), positive CoombÕs test, hemolytic anaemia, hepatitis and drug fever
Common side effects include sedation and dry mouth. It also causes depression. In case depression develops during the course of the therapy, clonidine should be withdrawn. If withdrawn suddenly after protracted use, clonidine can
precipitate hypertensive crisis. It should, therefore, be withdrawn gradually. In case hypertensive crisis develops, it is treated
by reinstitution of clonidine or administration of α- and β-blockers
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6
Miscellaneous
Halothane
Advantages
1Good physical properties.
2Used to produce controlled hypotension and bloodless field during plastic/vascular surgery.
3Potent anaesthetic.
4Produces bronchodilatation (useful in asthmatic patients).
5Potent relaxant of masseter muscles.
6Potent inhibitor of laryngeal and pharyngeal reflexes.
7Does not cause bronchospasm, laryngospasm and coughing.
Disadvantages
1Poor analgesic.
2Poor muscle relaxant.
3Profound hypotension, if given in more than 2% concentration.
4Increases para-sympathetic tone, leading to bradycardia.
5Sensitises ventricular muscle and conduction tissue to adrenaline, causing arrhythmias.
6Hepatotoxic and respiratory depressant.
7Expensive, and special apparatus is needed for administration.
8Can cause malignant hyperthermia (ryanodine receptors).
9Genetic mutations → more binding of Ca++ with the receptors.
Nitrous oxide
Advantages
1Rapid induction and recovery.
2Non-inflammable, non-irritating and non-explosive (however supports combustion).
3Very potent analgesic (30–40% analgesia; 65–70% loss of consciousness; and 80% plane 1 of surgical anaesthesia).
4Used in procedures of short duration (tooth-extraction, obstetrical analgesia, cleansing and debridement of wounds and cauterisation).
5Induction and maintenance of anaesthesia, along with I/V thiopentone-gas- oxygen-halothane technique called balanced-anaesthesia.
6Safe. No organ toxicity (respiratory, renal, CVS, or hepatic).
7Measurement of cerebral and coronary blood flow by Fick’s Principle.
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PHARMACOLOGY IN 7 DAYS FOR MEDICAL STUDENTS
8Decreases the dose of general anaesthetic. When combined → decreased complications and decreased recovery period from anaesthesia.
Disadvantages
1Not a potent anaesthetic and muscle relaxant, so violent excitement can occur.
2Second gas effect leading to transient hypoxia.
3CO2 accumulation and hypoxia→ cardiac irregularities during anaesthesia.
4Specialised apparatus to control its administration.
5Administration for more than 7 hours, leads to bone-marrow depression (leukopenia and anaemia).
6Prolonged administration → peripheral neuropathy, megaloblastic anaemia (due to interference with vitamin B12 metabolism) and abortion.
Ketamine
Advantages
1Effective by both intravenous and intramuscular routes.
2Anaesthesia is accompanied by profound analgesia.
3Does not produce vomiting, hypotension and bronchospasm.
4Less respiratory complications, due to less impairment of laryngeal/pharyngeal reflexes.
5Useful for poor risk geriatric/elderly and unstable patients.
6Used in low doses, as outpatient anaesthesia.
Disadvantages
1No muscle relaxation.
2Tends to raise heart rate, intraocular and intracranial pressures.
3Cannot be used for surgery on larynx, pharynx and bronchi.
4Poor in relieving visceral pain.
5Emergence phenomenon (characterised by bad dreams, post-op disorientation and sensory/perceptual delusions). Its Rx is diazepam, before the operation.
Thiopentone sodium
Advantages
1Ease of administration.
2Non-explosive.
3Induction and recovery is rapid and pleasant.
4No irritation of mucous membranes.
5No sensitisation of myocardium to adrenaline.
6No/less incidence of post-op vomiting and excitement.
7Low incidence of post-anaesthetic complications.
Disadvantages
1Stages of anaesthesia cannot be recognised.
2Pupils remain normal or constricted.
3During induction, unpleasant and fatal reactions (like apnea, coughing, hiccough, laryngospasm and bronchospasm) may develop.
4Depression of myocardium, respiratory and vasomotor centres.
5Rapid injection can lead to hypotension and cardiac arrhythmias.
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MISCELLANEOUS
6Intra-arterial injection→ severe pain and gangrene.
7Inadequate muscle relaxation.
8Laryngeal and pharyngeal reflexes are not abolished.
9Regurgitation due to relaxation of gastro-esophageal sphincter.
10Injury to surrounding nerves and tissues.
11Thromboembolism.
12Can precipitate porphyria in susceptible individuals.
Preference of benzodiazepines over barbiturates
1High margin of safety (i.e. 10 times the normal dose can be given without harmful effects).
2Least drug interactions, since no effect on the drug metabolising cytochrome P450 enzyme system in the liver.
3Selectivity of action (i.e. like barbiturates, benzodiazepines are not a general CNS depressant – they act mainly on limbic system).
4Lack of interactions (i.e. neither enzyme inhibitors nor enzyme inducers).
5Do not cause hyperalgesia.
6Fewer incidences of drug dependence/addiction.
7Less severe withdrawal syndrome.
8Less severe tolerance.
9Least alteration in sleep pattern.
Digoxin toxicity: features
1Arrhythmias (especially AV block).
2Nausea, vomiting, diarrhoea.
3Headache; dizziness.
4Seizures.
5Xanthopsia (yellow vision).
6Skin reactions.
7Impotence.
Digoxin toxicity: causes
1Electrolyte disturbances (↓ K+; ↓ Mg++; ↑ Ca++).
2Renal impairment.
3Hypothyroidism.
4Drug-induced (ACEI7; Ca-channel blockers; amiodarone8; quinidine; cyclosporine).
Digoxin toxicity: management
•Prevent absorption: gastric lavage; activated charcoal (if patient comes within 6–8hrs of ingestion).
•Correct electrolyte disturbances (↓ K+; ↓ Mg++; ↑ Ca++). K+ should not be raised above the level of 5 mEq/L.
•For bradyarrhythmia: Atropine.
•For symptomatic bradycardia that has failed to respond to atropine: Temporary pacemaker.
7 ACEI reduce renal clearance of digoxin → digoxin toxicity.
8 Amiodarone displaces digoxin from the binding proteins → digoxin toxicity.
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