Pharmacokinetics & drug interactions of antihypertensives Flashcards
Pharmacokinetics
- Accumulation
- Absorption
- Distribution
- Metabolism
- Excretion
How can ADME be effected
- Rate and extent to which drugs are absorbed
- Rate and path of elimination from the body
- Relationship between drug and plasma
Absorption
- Route of administration significantly affected
- Oral most common
- pH effects drug solubility
Distribution
- Anti-hypertensive drugs often target specific sites such as blood vessels and kidney
- Proteins binding effect distribution slower
Metabolism
- Most are metabolized in liver by haptic enzymes
- Cytochrome P450 mostly metabolize
- Broken down result in formation of active and inactive metabolites
Elimination
Rate of drug elimination is due to GFR rate and other factors
Additive interaction
- Addition of two drugs which causes and equal effect to sum of individual effect
Synergistic interaction
- Combination of drugs cause greater effect - control BP
Antagonistic interaction
- Interaction of two drugs cancels out the individual effects
ACEi (Ramipril)
- Producing prodrugs which inhibits ACE
- Low angiotensin II and RAAS activity
- Decrease blood flow and decrease blood volume
- decrease sympathetic activity
Side effects of Ramipril
- Hypotension
- Hypokalemia
- Dry cough
- Bad taste
ACE inhibitor food interaction
- High sodium and potassium meals counteracts effects of ACE inhibitors
- Increase BP and interfere with balance of electrolytes
Drug to Drug interaction with ACEi
- Concurrent use of ACEi and non-steroidal anti-inflammatory drugs reduce effectiveness of ACE
- Increase risk of renal impairment by contacting vasodilatory effects
Drug and herbal interaction with ACEi
- St John warts with ACEi induce the distribution metabolism and excretion so ACEi breaks down faster
- Doesn’t reach therapeutic effect
CYP450 inducers
- Concurrent use of rifampin antibiotic is a potent CYP450 inducer
- Accelerate breakdown of ACEi reducing the effectiveness not reaching therapeutic effect
CYP450 inhibitors
- Fluoxetine which a serotonin reuptake inhibitor and CYP450 repressor inhibit metabolism
- Increase levels in blood therefore more side effects
Losartan
- Blocking the AT1 receptor
- Opens up the arteries lowering BP and increasing blood to heart
- Metabolized by CYP450
Losartan drug to drug interaction
- Co-administer ARB with Ketoconazole cause further decrease in BP which leads to fainting
Losartan and food interaction
- Grapefruit inhibit metabolism of ARB
- Increase drug level in blood
- prolong low BP with side effects
Drug herbal interaction losartan
- St john warts acts as a drug inducer of CYP3A4 increase metabolism of ARB
- Unable to control BP reduced effectiveness
CYP450 inducer with Losartan
- Rifampin is potent inducer of CYP3A4
- Lowers plasma concentration requires higher dosage
CYP450 inhibitor
- Co-administer with CYP2C9 fluconazole involved in metabolism and repressing cytochrome P450
- Enhance therapeutic effect
Pharmacokinetic drug interaction when taking losartan
- Hypokalemia
- Hypotension
- Renal impairment
Calcium channel adverse effect
- Bradycardia
- Abnormal pain and nausea
- Dizzy drowsy and flushing
Calcium channel interaction with statin
- Increase serum levels of the statins causing statin toxicity and muscle pain
Calcium channel and grapefruit interaction
- Acts as a CYP450 inhibitor with an increase of CCB in blood cause increase side effect
Hawthorn and Calcium channel blocker interaction
- Cause Additive effects as it is a mild vasodilator enhance antihypertensive effects
Indapamide
- Inhibit NA+/Cl- co-transporter reducing sodium reabsorption
- Decrease peripheral resistance
- Decrease systolic BP
Adverse effects of indapamide
- Postural hypotension
- Hypoglycemia
- Hypokalemia
- Cardiac arrythmias
- Electrolyte imbalance
Drug interaction indapamide
ACE and ARB cause very rapid fall in blood pressure
Alpha-blockers and indapamide
- Hypotensive effect during first dose
Indapamide interaction with NSAID
- Combination of NSAID with diuretics
- Inhibits renal blood flow and decreases the efficacy of thiazides
Licorice with indapamide
- Decreased potassium levels and increased BP
- Inhibition of cortisol breakdown cause water retention
Carbamazepine and CYP450 inducer
- Antiepileptic with CYP450 inducer increase metabolism of thiazide reducing blood levels
Amiodarone and CYP450 repressor
- Inhibit metabolism of thiazides increase blood levels diuretic and antihypertensive
Inhibitors of CYP450
SICKFACE.COM acronym
- Sodium valproate
- Isoniazid
- Cimetidine
- Ketoconazole
- Fluconazole
- Amiodarone
- Chloramphenicol
- Erythromycin
- Ciprofloxacin
- Omeprazole
- Metronidazole
(increase BP)
Inducers of CYP450
BS CRAP GPS
- Barbiturates
- St johns wart
- Carbamazepine
- Rifampin
- Alcohol (Chronic)
- Phenytoin
- Griseofulvin
- Phenobarbital
- Sulfonylureas
(Decrease BP)
