Материал: MasterPass _ Pharmacology in 7 Days for Medical Students
PHARMACOLOGY IN 7 DAYS FOR MEDICAL STUDENTS
Table 5.3 Differences between morphine and pethidine
|
Morphine |
Pethidine |
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Source: |
Natural |
Synthetic |
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Chemistry: |
Phenanthrene derivative |
Phenylpiperidine derivative |
||
Pharmacokinetics: |
¥ |
Route of administration: S/C, |
¥ |
Route of administration: Oral, |
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|
I/M, I/V, epidural, intrathecal |
|
S/C, I/M |
|
|
and per-rectal |
¥ |
Bioavailability: 50% |
|
¥ |
Bioavailability: 25% |
¥ |
Plasma protein binding: 60% |
|
¥ |
Plasma protein binding: |
¥ |
Onset of action: quick |
|
|
33% |
¥ |
Duration of action: short |
|
¥ |
Onset of action: slow |
|
(2Ð4hrs) |
|
¥ Duration of action: longer |
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|
|
|
|
(3Ð5hrs) |
|
|
Metabolism: |
Glucuronidation in liver |
Demethylation in liver |
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Metabolites: |
Morphine-3-glucuronide and |
Normepridine (→ CNS |
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|
Morphine-6-glucuronide. Both |
stimulation; but no analgesic |
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|
metabolites are active |
property) |
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Pharmaco- |
¥ |
Receptors: µ predominantly |
¥ |
Receptors: κ predominantly |
dynamics: |
¥ |
Potency: more as analgesic |
¥ |
Potency: 1/10th as analgesic |
|
¥ |
Sedation: more marked |
¥ |
Sedation: less marked |
|
¥ |
Miosis: present |
¥ |
Miosis: absent |
|
¥ |
Corneal anaesthesia and |
¥ Corneal anaesthesia and loss |
|
|
|
loss of corneal reßex: absent |
|
of corneal reßex: present (on |
|
¥ |
Bronchoconstriction: present |
|
parenteral administration) |
|
¥ |
Cough suppression: present |
¥ |
Bronchoconstriction: absent |
|
¥ Effect on heart rate: |
¥ |
Cough suppression: absent |
|
|
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bradycardia |
¥ Effect on heart rate: |
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|
¥ |
Antimuscarinic effects: |
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tachycardia |
|
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absent |
¥ |
Antimuscarinic effects: present |
|
¥ |
Spasmogenic effect: present |
¥ |
Spasmogenic effect: absent |
|
¥ |
Urinary retention: present |
¥ |
Urinary retention: absent |
|
¥ |
Constipation: more marked |
¥ |
Constipation: less marked |
|
¥ |
Pregnancy and lactation: |
¥ |
Pregnancy and lactation: can |
|
|
contraindicated because |
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be given (no effect on labour) |
|
|
morphine delays labour |
¥ |
Withdrawal syndrome: short- |
|
¥ |
Withdrawal syndrome: long- |
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lived (4Ð6 days) |
|
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lived (8Ð10 days) |
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|
Therapeutic uses: |
Analgesic, LVF with massive |
Analgesic (for short procedures |
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pulmonary oedema, pre- |
like upper/lower GI endoscopy, |
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anaesthetic medication and |
cystoscopy, I/V ascending |
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anxiety |
pyelography) |
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Excretion: |
Not affected by acidiÞcation |
AcidiÞcation of urine increases |
||
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of urine |
excretion |
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134
DRUG DIFFERENCES
Table 5.4 Differences between heparin and warfarin
|
Heparin |
Warfarin |
Source: |
Bovine lungs, porcine intestinal |
Semi-synthetic |
|
mucosa |
|
Chemistry: |
Mucopolysaccharide |
Coumarin derivative |
Structure: |
Large polymer, acidic |
Small, lipid-soluble |
Route of |
Parenteral (S/C, I/V) |
Oral |
administration: |
|
|
Site of action: |
Blood |
Mechanism of |
It binds to antithrombin-III |
action: |
(ATIII) forming a heparin-ATIII |
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complex. This complex binds |
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and irreversibly inactivates |
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thrombin (activated factor |
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II), factors IXa, Xa, XIa, XIIa, |
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and XIIIa. In the presence |
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of heparin, ATIII proteolyses |
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clotting factors 1000-fold |
|
faster than in its absence |
Liver
Warfarin inhibits Vit-K dependent synthesis of factors X, VII, IX and X in the liver by inhibiting the enzyme Vit-K epoxide reductase
Onset of action: Quick (in seconds). Since heparin acts by inactivating the pre-formed clotting factors, it produces its therapeutic effect immediately
Slow (36Ð48hrs). Since warfarin acts by inhibiting the synthesis of clotting factors, its therapeutic effect is produced only when the pre-formed clotting factors having t½ of 8Ð60hrs are eliminated from the circulation. Also, whereas effect of warfarin can be reversed by giving Vit-K, it only occurs when Vit-K causes the synthesis of new clotting factors Ð a process that takes 6Ð24hrs. More rapid reversal requires transfusion of fresh
frozen plasma (FFP) that contains normal clotting factors
Effect on vascular |
Vasodilatation |
Nil |
tone: |
|
|
Duration of action: |
Short (10Ð15 min) |
Long (4Ð7 days) |
Protein binding: |
Nil |
Extensive |
Metabolites: |
Uroheparin |
S-warfarin-7-hydroxy warfarin; |
|
|
R-warfarin-warfarin alcohol |
Half-life: |
40Ð90 min |
15Ð70hrs |
|
|
|
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|
(continued) |
135
PHARMACOLOGY IN 7 DAYS FOR MEDICAL STUDENTS
Heparin |
Warfarin |
Therapeutic uses: Used when anticoagulation is needed immediately, i.e. on starting anticoagulant therapy, heparin is given Þrst, followed 24hrs later by warfarin. Important
therapeutic indications include DVT, pulmonary embolism, acute MI (in combination with thrombolytics for revascularisation), atrial
Þbrillation, coronary angioplasty and placement of coronary stents (in combination with glycoprotein IIb/IIIa inhibitors), CVA, haemodialysis/peritoneal dialysis, anticoagulation during pregnancy and to preserve blood in vitro
Warfarin is used for chronic anticoagulation (starting 24hrs after commencement of heparin therapy) in all of the clinical situations described for heparin (except during pregnancy). Heparin-warfarin combination therapy is continued for 4Ð5 days, followed by warfarin monotherapy for months or may be more depending upon the indication
Pregnancy and |
Safe |
lactation: |
|
Adverse effects: Bleeding (commonest side effect), thrombocytopenia, osteoporosis, transient alopecia, allergic reactions (like asthma, urticaria and anaphylactic shock)
Drug interactions: Nil
Antidote: Protamine sulphate 1% I/V is the antidote for unfractionated heparin; it only partially reverses the effects of LMW heparins
Contraindicated (teratogenic: causes bone defects and multiple haemorrhages in the developing fetus)
Bleeding (commonest side effect), teratogenicity, decreased production of Protein C (→ development of a period of hypercoagulability; heparin is thus always started before warfarin therapy to avoid the development of hypercoagulability)
Cytochrome P450-inducing drugs → ↑ warfarin clearance → ↓ anticoagulant effect. Cytochrome P450-inhibiting drugs → ↓ warfarin clearance → ↑ anticoagulant effect
Vit K (phytomenadione) I/V
136
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DRUG DIFFERENCES |
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Table 5.5 Differences between cimetidine and ranitidine |
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Cimetidine |
Ranitidine |
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Chemistry: |
Imidazole derivative |
Furan derivative |
Duration of action: |
Short (4Ð6hrs) |
Long (8Ð12hrs) |
Bioavailability: |
60% |
50% |
Plasma protein binding: |
20% |
15% |
Binding with cytochrome |
Present |
Negligible |
P450: |
|
|
Increase in cell-mediated |
Yes |
No |
immunity: |
|
|
Hepatic blood ßow: |
Decreased |
Decreased |
Crossing of blood brain |
Poor |
Very poor |
barrier (BBB): |
|
|
Potency: |
Less |
5Ð10 times more potent |
Elimination t½: |
2Ð3hrs |
2Ð3hrs |
Drug interactions: |
Interferes with hepatic |
Negligible |
|
metabolism of drugs |
|
|
like digoxin, warfarin, |
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|
benzodiazepines, beta- |
|
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blockers, etc. |
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Toxicity: |
CNS: lethargy, hallucinations, |
Endocrine: DoesnÕt cause |
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convulsions |
hyperprolactinemia. |
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Endocrine: Unlike ranitidine, |
Hepatotoxicity: Less potent |
|
cimetidine causes |
inhibitor of hepatic drug |
|
hyperprolactinemia (→ |
metabolising enzyme |
|
gynecomastia in males and |
(CYP450) |
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galactorrhea in females) |
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Hepatotoxicity: As compared |
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to ranitidine, cimetidine is a |
|
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potent inhibitor of hepatic |
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drug metabolising enzyme |
|
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(CYP450) |
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Dose: |
800 mg/day in divided doses |
300 mg/day in divided doses |
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137
PHARMACOLOGY IN 7 DAYS FOR MEDICAL STUDENTS
Table 5.6 Differences between adrenaline and noradrenaline
|
Adrenaline |
Noradrenaline |
||
Source: |
Adrenal medulla |
Postganglionic sympathetic |
||
|
|
|
nerve endings |
|
Chemistry: |
Catecholamine (contains |
Catecholamine (does not |
||
|
methyl group) |
contain methyl group) |
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Receptors stimulated: |
α1, α2, β1, β2, β3 |
α1, α2, β1 |
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Effects on the |
Rate: ↑ |
Rate: ↓ |
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cardiovascular system: |
¥ |
Force of contraction: ↑ |
¥ |
Force of contraction: little |
|
¥ |
Excitability and |
|
effect |
|
|
conductivity: much |
¥ |
Excitability and |
|
|
increased |
|
conductivity: increased |
|
¥ |
Coronary blood ßow: ↑ |
¥ |
Coronary blood ßow: ↑ |
|
¥ |
Cardiac output: ↑ |
¥ |
Cardiac output: no change |
|
¥ |
Arteriolar tone in |
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or ↓ |
|
|
the skeletal muscles: |
¥ |
Arteriolar tone in |
|
|
vasodilatation |
|
the skeletal muscles: |
|
¥ |
Arteriolar tone in skin and |
|
vasoconstriction |
|
|
viscera: vasoconstriction |
¥ |
Arteriolar tone in skin and |
|
¥ |
Total peripheral resistance: |
|
viscera: vasoconstriction |
|
|
↓ |
¥ |
Total peripheral resistance: |
|
¥ |
Systolic blood pressure: ↑ |
|
↑ |
|
¥ |
Diastolic blood pressure: ↓ |
¥ |
Systolic blood pressure: ↑ |
|
|
|
¥ |
Diastolic blood pressure: ↑ |
Effects on smooth |
¥ |
Intestine and bladder: relax |
¥ |
Intestine and bladder: relax |
muscles: |
¥ |
Bronchi: relax |
¥ |
Bronchi: little effect |
|
¥ |
Sphincter: constrict |
¥ |
Sphincter: constrict |
|
¥ |
Uterus: inhibition of uterine |
¥ |
Uterus: stimulation of |
|
|
contraction |
|
uterine contraction |
|
¥ |
Eye: mydriasis |
¥ |
Eye: mydriasis |
Metabolism |
↑ |
|
InsigniÞcant effect |
|
(glycogenolysis and O2 |
|
|
|
|
consumption): |
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138