Angina Drugs

Question 1

List the ani-anginal agents

Answer 1

Vasodilators = nitrates, CCB

Cardiac depressants = CCB, beta-blockers

Potassium Channel activators

Perhexiline

Question 2

What two nitrates are used in angina treatment?

Answer 2

Glyceryl trinitrate

Isosorbide dinitrate

Question 3

What will happen with constant/freq nitrate exposure?

Answer 3

Tolerance is built

Responsiveness to nitrates is restored by interrupting therapy for 8-12 hours each day

Question 4

What are possible mechanism of nitrate tolerance

Answer 4

Reduced mitochondrial aldehyde dehydrogenase activity

Depletion of cellular -SH

Scavenging of NO

Dysfunctional guanylate cyclase = can’t activate phosphate

Question 5

What are some ADRs of nitrates?

Answer 5

Headaches (vasodilation), flushing, palpitations (compensatory due to dec PVR), dizziness, hypotension (vasodilation), halitosis (sublingual)

Contact dermatitis

Long-term therapy = methemoglobinemia

Question 6

Name the calcium antagonists used in angina treatment

Answer 6

Nifedipine, Verapamil

Question 7

What is the MOA of verapamil?

Answer 7

Acts mainly on heart to affect demand

dec Ca2+ influx during AP –> lows impulse conduction through the AV node —> reducing contractility —> slows HR

Question 8

what is the MOA of Nifedipine?

Answer 8

relaxes VSM, dilating blood vessels and reducing afterload on heart

Question 9

What is the MOA of nitrates?

Answer 9

Nitrate > taken up by VSM > Nitrate converted to NO by sulfhydryl groups > activates guanylate cyclase > cGTP > cGMP > dec intracellular Ca2+ > vasodilation

Question 10

Name the beta-adrenoceptor antagonists used to treat angina

Answer 10

Propanolol (non-selective)

Atenolol (cardio selective)

Question 11

What is the MOA of beta-adrenoceptor antagonists?

Answer 11

Block regional blood flow blocking of beta adrenoreceptors

Dec heart contractility and rate –> dec O2 demand of heart (potential inc perfusion of ischaemic tissue)

Lowered HR = heart spends more time in diastole —> greater coronary blood flow

Question 12

Name the potassium channel activators (PCAs) used to treat angina

Answer 12

Nicorandil, diazoxide, minoxidil

Question 13

What additional effect does Nicorandil have?

Answer 13

Relaxes venous vascular system by inc cGMP

Question 14

What is the MOA of PCAs?

Answer 14

Activating ATP-sensitive potassium channels –> opens/prolongs open state of potassium channel —> potassium efflux –> hyperpolarization of cell membrane –> prevent intracellular penetration of Ca2+ through voltage-dependent Ca2+ channels

Question 15

List the ADR of nicorandil

Answer 15

Nausea, flushing, headache, myalgia

Question 16

List the ADRS of diazoxide

Answer 16

hyperglycaemia (slows the release of insulin from the pancreas), tachycardia, headache, flushing, oedema, GIT

Question 17

List the ADRs of minoxidil

Answer 17

nausea, tachycardia, hypertrichosis (excessive hair growth)

Question 18

What is perhexiline?

Answer 18

It is an antianginal drug used to treat refractory angina in Aus/NZ

It is a narrow therapeutic index drug

Question 19

What is the MOA perhexiline?

Answer 19

Inc ATP levels via inhibition of mitochondrial carnitine palmitoyl transferase

Question 20

What enzyme is perhexiline metabolised by?

Answer 20

CYP2D6, has many polymorphisms

Question 21

What are the indications of perhexiline toxicity?

Answer 21

Dizziness, headache, ataxia, hepatotoxicity, peripheral neuropathy, tremors, hypoglycaemia, hyperlipidaemia, seizures, polyradiculoneuritis