Antihypertensive Flashcards
Discuss ACE ihibitor overdose
Relatively benign - prinicpal effect is mild to moderate hypotension usually responsive to fluid therapy alone
Discuss risk assessment of ACEi
Generally benign irrespective of dose
Mild hypotension may occur usually is apparent within 2 horus of ingestion
Discuss TM and TK of ACEI
TM: Bind to ACE in a reversible manor prevenitng conversion of angiotensin 1 to 2 - leads to reduction in vasoconstriction also impairs amount of circulating aldosterone which can lead to hyper K and hypo Na
TK: Well absorbed orally with peak levels within 1-2 horus
Many are prodrugs which requrie hepatic activation
Most eliinated via the kidneys
Discuss Management
Resus
- ABCD
- 10-20ml/kg of cyrstaloid if hypotens
D: Charcoal if within 1 hour but is unlikely to alter clinical course
E: nil
A: nil
D: Home after observation and nromal bloods
Discuss risk assessment of B-blocker overdose
With the exception of sotalol and propanol isolated B blocker overdose results in little or no toxicity and does not require specific care. In contrast both propanalol or sotalol OD may be life threatening
Toxcitiy does not correlate well with ingested dose
The following factors increase risk of severe toxicity
- ingestion of proanolol or sotalol
-underlying pulonary or CVS comordbity
-coingestion or regular treatment with CA channel blockade or digoxicn
-Threshold dose for severe toxicity with propanolol may be as little as 1 g
-toxicity usually manifest within the first few hours with the exception of OD with controlled released preparations of sotalol
-PR prolongation in the absence of bradycardia is an early sign of toxicity
Children: there is a risk of toxocity following ingestion of any dose of propanolol or sotalol
Discuss TM and TK of beta blockers
TM: antaognism at both Beta 1 and 2 receptors. Excessive beta adrenergic blockade leads to decreased intracellular cAMP concentration and resultant blunting of the metabolic chronotropic and inotropic effects of catecholamines.
Proanolol also has Na blockade effects leads to QRS widening and vetnricular dysrhythmias and being lipid soluble crosses the BBB and exerts direct CNS toxicity
Sotalol also block cardiac K channels interfering with cardiac repolarisation and leading to QT prologation
TK:
Rapidly absorbed fromt he GIT with peak serum concenration occuring from 1-3 hours. Rapid distrubeted with varibale VD depnding on agent. Propanolol is distinguished from other agents due to its lipid solubility
Discuss clinical features of B lockade overdose
Occur within 4 hours manifested by fall in heart rate.
CVS
- hypotension and brady
- bradydysythmia incuding sinus brady, 1st -3rd degree HB junctional and ventricular bradycardia
-QRS widening and Ventricular tachydysrythmia observed with propanalol
-QT prolongation and torsade with sotalol
CNS
Delirum coma and siezures ( propanalol)
Other
- Bronchospasms, pulmonary oedema
- hyperkalaemia
- hypo/hyperglycaemia
Discuss management
Resus
- Prompt intuabtion and ventialtion and administration of bicarb are necessary to control ventricular dysrhtyhmias (prop managed as per TCA overdose)
Immediate life threat
- Bradycardia or hypotension
- – atropine 10-30 mic/kg (temporising)
- – isoprenaline infusion 4 mic/min
- adrenaline infusion
- –Hiet
Wide QRS
-Sodi bic 1-2mEqkg boluses over 1-2 minutes
Torsades
- isoprenaline
- overdrive pacing
- magnesium
D: Charcoal/intralipid
E: nil
A: HIET
D: asymptomatic at 6 hours can be discharge home
Discuss risk assessment of Ca channel blockade overdose
Verapamil and diltiazem commonly cause cardiovascular collapse following overdose which can be delayed 4-16 hours after ingestion of extended release.
- As little as 2-3 times the normal therapeutic dose of verapamil or diltiazem XR can cause severe toxicity in susceptible patients
- All deliberate poisonings are regarded as potentially serious
- ingestion of >10 tabas of verpamil or diltiazem in an adult is likley to be life threatening
- onset at 2 hours in standard release and 16 hour for XR preparations
- Coingestion with other cardiotoxic drugs increases risk of serious intoxication
Children - ingestion of 2 or more tablets of any strength verapamil or diltiazem is potentially lethal.
Discuss TM and TK of CA channel blockers
TM: Ca channel blockers prevent the opening of L-Type calcium channels resulting in reduced influs of ca - important to cardiac myoctyes, vascular smooth muscle and islet beta cella
Verapamil and diltiazem cause central cardiac effects and peripheral vasoidlation. The dihydropyridines chiefly cause the alter but due to loss of recepotr selectivity in massive OD can cause caridac depression.
Ca channgels also impair insulin release and cause insulin resistance in the periphery
TK: Well absorbed orally with peak levels at 1-2 hours and 6-12 for XR. In OD peak levels may not be reached until 6 hours for standard preparation and 22 horus for XR. High VD, protein bound
Hepatic metabolism
High first pass effect after absorption giving bioavilability of approx 40%
Discuss clinical features of calcium channel OD
CVS
- bradycardia, first degree heart block and hypotension are early signs - can progress to 2nd or 3rd degree block
- progression to refractory shock and death may occur
- myocardial ischaemia stroke or nonocclusive mesenteric ischaemic may complicated the clinical picture
CNS
- Seizure and coma are rare usually due to coingestion
Metabolic
- hyperglycaemia and lactic acidosis occur in severe intoxication
Discuss management of Ca channel overdose
RESUS
ABCD
- Mentation and airway protective reflexes are usually preserved until cardiac arrest.
-early invasive BP is useful
-Hypotension refractory to initial fuid jresusciation indicates the osnet of significant toxicity and is an indication to start HIET’
-Catechoolamines are rarely effective in signifaicnt CA channel blockade still used
-Methylene blue can be considered if refractory shock persist
- ventricular pacing should be used to bypass AV bock and rates should not exceed 60BPM - electrical capture is often difficult to achieve and may not be associated with improved perfusion
-ECMO, intraoartic balloon pump and bypass have been successfully used as extraordinary manoeuvres
D: Activated charcoal -present within 1hour for standard and 4 hours for XR
-Administer charcoal to all intuabted patients
-Whole bowel irrigation may be considered after a dose of activated charcoal in co-operaitve patientw tih ecidence of established toxicity and who present wihtin 4 horus of self poisoning with >10 tab of verpamil XR or diltiazem XR
-Intralipid can be considered
E: Rarely indicated - albumin dialysis
A: HIET, CA
D: Clincally well patient with normal ECG at 4 hours for standard and 16 hours for extended release can be discharged home
Discuss risk assessement of clonidine
Produces varying degrees of CNS depression and mild CVS effects. Classically intoxication manifests clinically with the triad of drowsiness, miosis and bradycardia.
Clinical effects correlate poorly with ingested dose. Significant CNS depression may occur with doses >20 mic/kg but alrge doses are sometimes tolerated with minor effects
Onset is usually rapid within 2 hours of ingestion and alwasy wihtin 6 hours
Children: ingestion of 2 tablets is potentially lethal wihtout supportive care
->10mic/kg - brady and hypotension
>20 mic/kg: respiratory depression or apnoea
DIscuss TK and TM of clonidine
TM: centrally acting A2 adreneric agonist. Acts as a sympathoplegic agent, decreasing CNS outflow. Also increases endthelial NO levels and decrease renin activity
TK: Clonidine is rapidly and completely absorbed with peak concentration and therapeutic effects occuring wihtin 1-3 hours. Clonidine has a large VD 3-6 L/K
It is metabolised in the liver but half the ingested dose ie eleminated uncahnged in the urine
Elimiantion half life is 6-24 hours
Protein biding is approximatly 20-40%
Discuss clicnial features of clonidien od
Rapid onset
-transient early hypertension is reported in 20-50% of cases
-lethargy miosis slurred speech and ataxia usually occur wihtin 2 hours and alwasy wihtin 6 hours. Patients can often be roused with stimulus only to become deeply somnolent again
-severe intoxication is associated with coma, bradycardia and hypotension. Sinus brady as low as 30 is common and is frequently presnet wihtout hypotension or signs of decreased end organ perfusion, heart block has been reported
Resolve within 24 hours
