Anti-Hypertensive Drugs II

Question 1

What is Clonidine/Catapres™ (also methyldopa)?

Answer 1

Clonidine is a sympatholytic medication used to treat high blood pressure, attention-deficit/hyperactivity disorder, anxiety disorders, withdrawal (from either alcohol, opioids, or smoking), migraine, menopausal flushing, diarrhea, and certain pain conditions. It is classified as a centrally acting α2 adrenergic agonist.

Drug costs $4 (generic) to $37 (branded) to $108 (Catapress™ patches) per month)

Question 2

To what drug class does clonidine belong?

Answer 2

Pharmacologic class => central α2 agonist

Therapeutic class–antihypertensive, adjunct to Rx of opioid withdrawal, prophylaxis of migraine

Question 3

Describe the pharmacodynamics of clonidine.

Answer 3

Stimulates α2 adrenoceptors in brainstem => down-regulation of sympathetic output

Question 4

Describe the pharmacokinetics of clonidine.

Answer 4

• Onset 1 h, duration 8 h
• F~85%
• Also available as cutaneous patch

Question 5

What toxicity is associated with clonidine?

Answer 5

• Withdraw gradually because of risk of rebound HTN
• Risk of bradycardia in sinus node disease
• Letharagy, fatigue, depression

Question 6

What interactions should be noted in patients taking clonidine?

Answer 6

• Additive effects with most other antihypertensives

- Additive sedation with other CNS drugs

Question 7

What special considerations should be made for patients on clonidine?

Answer 7

• Pregnancy class C

- Avoid in patients with renal insufficiency

Question 8

What is the route/dose for clonidine?

Answer 8

• Begin with 0.1 mg po bid, up to 1.2 mg per day

- Transdermal begin with 0.1 mg per 24 h as a 7-day patch

Question 9

What should be monitored in patients on clonidine?

Answer 9

BP and HR, fatigue

Question 10

What is Trimethaphan/Arfonad™ ?

Answer 10

Trimethaphan is a drug that counteracts cholinergic transmission at the ganglion type of nicotinic receptors of the autonomic ganglia => blocks both the sympathetic nervous system and the parasympathetic nervous system.

It acts as a non-depolarizing competitive antagonist at the nicotinic acetylcholine receptor, is short-acting, and is given intravenously ONLY => NOT for long term management of HTN

Question 11

To what drug class does Trimethaphan belong?

Answer 11

Pharmacologic class => ganglionic transmission blocker

Therapeutic class => antihypertensive

Question 12

Describe the pharamcodynamics of Trimethaphan.

Answer 12

• Blocks nicotinic transmission within both sympathetic and parasympathetic ganglia (NN receptors)
• Produces veno- and vaso-dilatation

Question 13

Describe the pharmacokinetics of Trimethaphan.

Answer 13

• Useful only when given iv
• Produces fall in BP within minutes
• Partly metabolized, and partly excreted by kidneys

Question 14

What toxicity is associated with Trimethaphan?

Answer 14

• Watch out for sudden, severe drop in BP and HR

- Reduction in just about any sympathetic or parasympathetic response

Question 15

What drug interactions are associated with Trimethaphan?

Answer 15

Additive effects with most other anti-hypertensives

Question 16

What special considerations should be accounted for in patients on Trimethaphan?

Answer 16

• Patients are quite miserable, hence only used during general anesthesia
• Helps to tilt patient to help control BP

Question 17

What are the indications/dose/route for Trimethaphan?

Answer 17

• Given by iv infusion => only to treat HTN crisis or for controlled hypotension during cardiovascular surgery

Question 18

What should be monitored in patients on Trimethaphan?

Answer 18

Minute to minute monitoring of BP (and HR)

Question 19

What is Reserpine?

Answer 19

Reserpine is an indole alkaloid, antipsychotic and antihypertensive drug, although because of the development of better drugs for these purposes and because of its numerous side-effects, it is rarely used today.

The antihypertensive actions of reserpine are a result of its ability to deplete catecholamines from peripheral sympathetic nerve endings.
- Controls HR, increases contractility and peripheral vascular resistance

• NOT USED TODAY FOR LONG TERM MANAGEMENT OF HTN

Question 20

What drug class does reserpine belong to?

Answer 20

Pharmacologic class => Rauwolfia alkaloid (used to treat HTN)
Therapeutic class => antihypertensive

Question 21

Describe the pharmacodynamics of Reserpine.

Answer 21

• Binds to vesicles that contain NE or serotonin, preventing their uptake, and ultimately depleting the neuron of NE (or serotonin)
• This effect takes 2-3 weeks to develop, and includes neurons and also the adrenal medulla

Question 22

Describe the pharmacokinetics of Reserpine.

Answer 22

• Good oral bioavailability, but biologic effects take 2-3 weeks to develop (via slow depletion of NE from vesicles)

Question 23

What toxicity is associated with Resperine?

Answer 23

• Dizziness
• Orthostatic hypotension
• Depression

Question 24

What interactions should be considered in patients on Reserpine?

Answer 24

Additive effects with most other anti-hypertensives

Question 25

When was Reserpine approved by the FDA and what is historically significant about Reserpine?

Answer 25

• Approved by the FDA in 1953
• First antihypertensive drug approved, and first sympatholytic drug approved by the FDA
• in 1960’s, drugs included only reserpine, HCTZ, and hydralazine

Question 26

What are the indications/douse/route for Reserpine?

Answer 26

• For HTN

- 0.1-0.2 mg po q day

Question 27

What should be monitored in patients on Reserpine?

Answer 27

BP, sympathetic tone, depression