Pharmacokinetics & drug interactions of antihypertensives

Question 1

Pharmacokinetics

Answer 1

• Accumulation
• Absorption
• Distribution
• Metabolism
• Excretion

Question 2

How can ADME be effected

Answer 2

• Rate and extent to which drugs are absorbed
• Rate and path of elimination from the body
• Relationship between drug and plasma

Question 3

Absorption

Answer 3

• Route of administration significantly affected
• Oral most common
• pH effects drug solubility

Question 4

Distribution

Answer 4

• Anti-hypertensive drugs often target specific sites such as blood vessels and kidney
• Proteins binding effect distribution slower

Question 5

Metabolism

Answer 5

• Most are metabolized in liver by haptic enzymes
• Cytochrome P450 mostly metabolize
• Broken down result in formation of active and inactive metabolites

Question 6

Elimination

Answer 6

Rate of drug elimination is due to GFR rate and other factors

Question 7

Additive interaction

Answer 7

• Addition of two drugs which causes and equal effect to sum of individual effect

Question 8

Synergistic interaction

Answer 8

• Combination of drugs cause greater effect - control BP

Question 9

Antagonistic interaction

Answer 9

• Interaction of two drugs cancels out the individual effects

Question 10

ACEi (Ramipril)

Answer 10

• Producing prodrugs which inhibits ACE
• Low angiotensin II and RAAS activity
• Decrease blood flow and decrease blood volume
• decrease sympathetic activity

Question 11

Side effects of Ramipril

Answer 11

• Hypotension
• Hypokalemia
• Dry cough
• Bad taste

Question 12

ACE inhibitor food interaction

Answer 12

• High sodium and potassium meals counteracts effects of ACE inhibitors
• Increase BP and interfere with balance of electrolytes

Question 13

Drug to Drug interaction with ACEi

Answer 13

• Concurrent use of ACEi and non-steroidal anti-inflammatory drugs reduce effectiveness of ACE
• Increase risk of renal impairment by contacting vasodilatory effects

Question 14

Drug and herbal interaction with ACEi

Answer 14

• St John warts with ACEi induce the distribution metabolism and excretion so ACEi breaks down faster
• Doesn’t reach therapeutic effect

Question 15

CYP450 inducers

Answer 15

• Concurrent use of rifampin antibiotic is a potent CYP450 inducer
• Accelerate breakdown of ACEi reducing the effectiveness not reaching therapeutic effect

Question 16

CYP450 inhibitors

Answer 16

• Fluoxetine which a serotonin reuptake inhibitor and CYP450 repressor inhibit metabolism
• Increase levels in blood therefore more side effects

Question 17

Losartan

Answer 17

• Blocking the AT1 receptor
• Opens up the arteries lowering BP and increasing blood to heart
• Metabolized by CYP450

Question 18

Losartan drug to drug interaction

Answer 18

• Co-administer ARB with Ketoconazole cause further decrease in BP which leads to fainting

Question 19

Losartan and food interaction

Answer 19

• Grapefruit inhibit metabolism of ARB
• Increase drug level in blood
• prolong low BP with side effects

Question 20

Drug herbal interaction losartan

Answer 20

• St john warts acts as a drug inducer of CYP3A4 increase metabolism of ARB
• Unable to control BP reduced effectiveness

Question 21

CYP450 inducer with Losartan

Answer 21

• Rifampin is potent inducer of CYP3A4
• Lowers plasma concentration requires higher dosage

Question 22

CYP450 inhibitor

Answer 22

• Co-administer with CYP2C9 fluconazole involved in metabolism and repressing cytochrome P450
• Enhance therapeutic effect

Question 23

Pharmacokinetic drug interaction when taking losartan

Answer 23

• Hypokalemia
• Hypotension
• Renal impairment

Question 24

Calcium channel adverse effect

Answer 24

• Bradycardia
• Abnormal pain and nausea
• Dizzy drowsy and flushing

Question 25

Calcium channel interaction with statin

Answer 25

- Increase serum levels of the statins causing statin toxicity and muscle pain

Question 26

Calcium channel and grapefruit interaction

Answer 26

- Acts as a CYP450 inhibitor with an increase of CCB in blood cause increase side effect

Question 27

Hawthorn and Calcium channel blocker interaction

Answer 27

- Cause Additive effects as it is a mild vasodilator enhance antihypertensive effects

Question 28

Indapamide

Answer 28

- Inhibit NA+/Cl- co-transporter reducing sodium reabsorption - Decrease peripheral resistance - Decrease systolic BP

Question 29

Adverse effects of indapamide

Answer 29

- Postural hypotension - Hypoglycemia - Hypokalemia - Cardiac arrythmias - Electrolyte imbalance

Question 30

Drug interaction indapamide

Answer 30

ACE and ARB cause very rapid fall in blood pressure

Question 31

Alpha-blockers and indapamide

Answer 31

- Hypotensive effect during first dose

Question 32

Indapamide interaction with NSAID

Answer 32

- Combination of NSAID with diuretics - Inhibits renal blood flow and decreases the efficacy of thiazides

Question 33

Licorice with indapamide

Answer 33

- Decreased potassium levels and increased BP - Inhibition of cortisol breakdown cause water retention

Question 34

Carbamazepine and CYP450 inducer

Answer 34

- Antiepileptic with CYP450 inducer increase metabolism of thiazide reducing blood levels

Question 35

Amiodarone and CYP450 repressor

Answer 35

- Inhibit metabolism of thiazides increase blood levels diuretic and antihypertensive

Question 36

Inhibitors of CYP450 SICKFACE.COM acronym

Answer 36

- Sodium valproate - Isoniazid - Cimetidine - Ketoconazole - Fluconazole - Amiodarone - Chloramphenicol - Erythromycin - Ciprofloxacin - Omeprazole - Metronidazole (increase BP)

Question 37

Inducers of CYP450 BS CRAP GPS

Answer 37

- Barbiturates - St johns wart - Carbamazepine - Rifampin - Alcohol (Chronic) - Phenytoin - Griseofulvin - Phenobarbital - Sulfonylureas (Decrease BP)