Hypotensive states (shock, spinal anaesthesia, hypotensive drugs) One of the pressor agents can be used along with volume replacement for neurogenic and haemorrhagic shock; also as an expedient measure.....
THERAPEUTIC USES
1. Vascular Uses
Hypotensive states (shock, spinal
anaesthesia, hypotensive drugs) One of the pressor agents can be used along
with volume replacement for neurogenic and haemorrhagic shock; also as an
expedient measure to maintain cerebral circulation for other varieties of
shock. They should not be used in secondary shock when reflex vasoconstriction
is already marked. Use in cardiogenic shock is tricky, because attempts to
raise BP may also increase cardiac work. Slow i.v. infusion of
dopamine/dobutamine is more appropriate in this situation; use of NA is
practically obsolete. Adr 0.5 mg injected promptly i.m. is the drug of choice in
anaphylactic shock (see p. 82). It not
only raises BP, but counteracts bronchospasm/ laryngeal edema that may
accompany. Because of the rapidity and profile of action Adr is the only life
saving measure. Oral ephedrine has been used to treat postural hypotension due
to autonomic neuropathy (diabetes, parkinsonism, idiopathic) or advanced age.
However, it is not satisfactory because it cannot mimic selective NA release
that occurs only on standing. Elastic stockings and use of fludrocortisone to
expand plasma volume are more helpful.
Along with local anaesthetics Adr 1 in 200,000 to 1 in 100,000 for infiltration,
nerve block and spinal anaesthesia. Duration of anaesthesia is prolonged and
systemic toxicity of local anaesthetic is reduced. Local bleeding is minimised.
Control of local bleeding From skin and mucous membranes, e.g. epistaxis : compresses
of Adr 1 in 10,000, phenylephrine/ephedrine 1% soaked in cotton can control
arteriolar and capillary bleeding. NA 8 mg in 100–200 ml saline put in stomach
through a tube can control bleeding from gastric erosions and stress ulcers.
Nasal decongestant In colds, rhinitis,
sinusitis, blocked nose or eustachian tube—one of the αagonists is used as
nasal drops. Shrinkage of mucosa provides relief, but aftercongestion, atrophy
of mucosa on prolonged use are still a problem. The imidazolines should be used
in lower concentrations in infants and young children, because they are more
sensitive to central effects of these drugs. Nasal decongestants should be used
very cautiously in hypertensive patients and in elderly males.
Pseudoephedrine,
PPA, and phenylephrine have been used orally as decongestants, but effective
doses will constrict other blood vessels as well and cause rise in BP. However,
they do not produce aftercongestion.
Peripheral vascular diseases like Buerger’s
disease, Raynaud’s phenomena,
diabetic vascular insufficiency, gangrene, frost bite, ischaemic ulcers, night
leg cramps, cerebral vascular inadequacy : vasodilators including isoxsuprine
have been used, but are far from satisfactory in most cases, because often the
capacity of the affected vessels to dilate is severely limited, and ischaemia
itself is a potent vasodilator.
2. Cardiac Uses
Cardiac arrest (drowning, electrocution, StokesAdams syndrome and other causes) Adr may
be used to stimulate the heart; i.v. administration is justified in this
setting with external cardiac massage.
Partial or complete AV block Isoprenaline may be used as
temporary measure to maintain sufficient ventricular rate.
Congestive heart failure (CHF) Adrenergic inotropic drugs are not useful in the routine
treatment of CHF. However, controlled short term i.v. infusion of DA/dobutamine
can tide over acute cardiac decompensation during myocardial infarction,
cardiac surgery and in resistant CHF.
3. Bronchial Asthma
Adrenergic drugs, especially β2 stimulants are the
primary drugs for relief of reversible airway obstruction.
4. Allergic Disorders
Adr is a physiological antagonist of histamine which is an important
mediator of many acute hypersensitivity reactions. It affords quick relief in
urticaria, angioedema; is life saving in laryngeal edema and anaphylaxis. It is
ineffective in delayed, retarded and other types of allergies, because
histamine is not involved.
5. Mydriatic
Phenylephrine is used to facilitate fundus examination;
cycloplegia is not required. It tends to reduce intraocular tension in wide
angle glaucoma. The ester prodrug of Adr dipivefrine is a second
choice/adjuvant drug for open angle glaucoma.
6. Central
Uses
Hyperkinetic children (minimal brain dysfunction,
attention deficit hyperkinetic disorder): Amphetamines have an apparently
paradoxical effect to calm down hyperkinetic children. This disorder is
recognized as the mildest grade of mental retardation or a reduction in the ability
to concentrate, i.e. the span of time for which attention can be focused on a
subject is abbreviated. Amphetamines by increasing attention span improve
behaviour and performance in studies ; tolerance to this effect does not
develop. However, growth retardation may occur due to reduction in appetite.
The riskbenefit ratio of such therapy needs to be considered in individual
patients.
Narcolepsy Narcolepsy is sleep occurring in fits and is adequately
controlled by amphetamines. Development of tolerance, abuse and behavioural
abnormalities are the calculated risks of such therapy. Imipramine like drugs
are generally tried first.
Epilepsy Amphetamines are
occasionally used as adjuvants and to
counteract sedation caused by antiepileptics.
Parkinsonism Amphetamines improve
mood and reduce rigidity
(slightly) but do not benefit tremor. They are occasionally used as adjuvants
in parkinsonism.
Obesity The anorectic drugs can help the obese to tolerate a
reducing diet for short periods, but do not improve the longterm outlook. Their
use (for 2–3 months) may be considered in severe obesity, but not for cosmetic
reasons in mild to moderate obesity. In the absence of dietary restriction none
of them has any significant weight reducing effect, and lifestyle modification
is required to maintain weight loss. Tolerance develops to the anorectic action
of all available drugs. Most subjects tend to regain weight after the slimming
regimen is over. Currently, sibutramine is being used, though its longterm
safety is not established.
The
newer approaches being developed for control of obesity are:
Orlistat An inhibitor of gastric and pancreatic lipase;
it interferes with
digestion and absorption of dietary triglycerides. Absorption of cholesterol
and fat soluble vitamins is also impaired. It has facilitated weight loss in
clinical trials. Fluid motions, steatorrhoea, abdominal pain, nausea,
flatulence and vitamin deficiency are the side effects.
Olestra is a sucrose polyester which can be used as a cooking medium in place of fat but is neither
digested nor absorbed. Its acceptability is inconsistent.
Leptin (the endogenous slimming peptide) analogues, neuropeptide Y
antagonists and β3 adrenergic agonists are under investigation as antiobesity drugs.
Rimonabant A selective cannabinoid (CB1) receptor antagonist that blocks hunger promoting action
of cannabis has been found in clinical trials to decrease appetite and help
weight reduction by the obese. Neusea is a side effect. Rimonabant has also
been tried to help smoking cessation.
7. Nocturnal Enuresis In Children
And Urinary Incontinence
Amphetamine affords benefit both by its central
action as well as by increasing tone of vesical sphincter.
8. Uterine Relaxant
Isoxsuprine has been used in threatened abortion
and dysmenorrhoea, but efficacy is doubtful. Selective β2 stimulants, specially
ritodrine, infused i.v. have been successfully used to postpone labour but
maternal morbidity and mortality may be increased due to their cardiac and
metabolic actions and incidents of pulmonary edema.
9. Insulin Hypoglycaemia
Adr
may be used as an expedient
measure, but glucose should be given as soon as possible.
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