Angiotensin II Receptor Antagonists
These drugs are similar to ACE
inhibitors in that they inhibit the effects of angiotensin II, but instead of
blocking the forma-tion of angiotensin II, they act as antagonists at its
receptors. Angiotensin II receptor antagonists selectively bind and, therefore,
block the AT(1) receptor subtype. This class of drug blocks the vasoconstrictor
and aldosterone-secreting effects of angiotensin II on smooth muscle and the
adrenal gland. The benefit of this different mode of action is that the
bradykinin system is unaffected, and hence cough and angioneurotic oedema do
Examples include losartan, tasosartan, and valsartan.
■■Dizziness, insomnia, headache, muscle cramps, and leg pain
occurred during clinical studies. Hyperkalaemia (greater than 20% increase in
serum potassium) occurred during clinical trials with valsartan.
drugs can potentially cause oliguria and azotaemia in patients whose renal
function may depend on function of the renin-angiotensin-aldosterone system
(e.g. severe CHF or renal artery stenosis).
hepatotoxicity has been reported.
has also been reported.
II receptor antagonists should be discon-tinued as soon as possible when
pregnancy is detected. Severe foetal deformity has been reported in humans and
animal models. Foetal death has been reported in one case following exposure to
losartan during weeks 20 to 31 of pregnancy. Oligohydramnios was present along
with a pattern of foetal abnormalities associated with angiotensin II
hyperkalaemia. Bradycardia could occur from parasympathetic (vagal)
· Symptomatic and supportive measures.
· Monitor renal and liver function
tests in symptomatic patients or following significant overdose.
· Monitor blood pressure and heart
rate frequently following a significant ingestion. Consider cardiac monitoring.
· If hypotensive, give 500 to 2000 ml
crystalloid initially (20 ml/kg in children) and titrate to desired effect
(stabi-lisation of vital signs, mentation, urine output); adults may require up
to 6 to 10 L/24 hours. Central venous or pulmonary artery pressure monitoring
is recommended in patients with persistent hypotension. Vasopressors should be
used in refractory cases unresponsive to repeated doses of noradrenaline and
after vigorous intravenous crystalloid rehydration.
Based on the high degree of protein binding of most of these
agents, haemodialysis would not be effective.
Most cases of antihypertensive drug overdose are accidental
(for e.g. in children), or suicidal. Paediatric poisoning arises out of
parental negligence rendering these and other dangerous pharmaceutical
preparations easily accessible to toddlers. Tragically, deaths have occurred in
Among the various antihypertensives, the beta blockershave
frequently been implicated in serious poisoning, with propranolol being the
commonest agent implicated. Reserpine increases suicidal tendency among
Extended (or sustained) release antihypertensives are
generally associated with prolonged and more profound effects in overdose.
Calcium channel blockers are increasingly being reported in
serious overdoses, while the safest drugs appear to be ACE inhibitors.
An abuse potential for clonidine has been identified in
treatment-seeking opiate abusers, particularly those with concurrent cocaine
use. Chewing of clonidine patches has been reported as a mechanism of abuse in
drug-seeking individuals. Two patterns of
clonidine use included: illicit use to decrease opiate withdrawal as well as
for its sedating effect, and, illicit use for its psychoactive effects,
including the interaction with methadone, in addition to decreasing opiate
withdrawal. Physical withdrawal symptoms were reported in 57% of 30 patients
abusing clonidine when the drug was stopped.
· Hypoxic-ischaemic encephalopathy
with permanent mental regression has been reported in a 3-year-old boy
following clonidine poisoning in a case of Munchausen by proxy. Prior to this
event, the boy had several lethargic episodes during hospitalisations when the
mother was present. Hypothermia, respiratory depression and arterial
hypotension also occurred during some of these episodes.